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Contents Solid Organ Transplantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...................... Joshua O. Benditt, MD, FCCP Infections in AIDS Patients and Other Immunocompromised Hosts . . . . . . . . . . . . . . . . . . . . . .................. George H. Karam, MD, FCCP Nervous System Infections and Catheter Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .................... George H. Karam, MD, FCCP Bradycardias Diagnosis and Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .................... James A. Roth, MD Upper and Lower GI Bleeding in the ICU . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .................... Gregory T. Everson, MD Tachycardias Diagnosis and Management. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .................... James A. Roth, MD Heart Failure and Cardiac Pulmonary Edema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ................... Steven M. Hollenberg, MD, FCCP Acute Coronary Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .................... Steven M. Hollenberg, MD, FCCP Shock . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...................... John P. Kress, MD, FCCP Mechanical Ventilation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .................... Gregory A. Schmidt, MD, FCCP Hypertensive Emergencies and Urgencies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .................... R. Phillip Dellinger, MD, FCCP Critical Illness in Pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .................... Mary E. Strek, MD, FCCP Venous Thromboembolic Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..................... R. Phillip Dellinger, MD, FCCP Weaning From Ventilatory Support . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .................... Scott K. Epstein, MD, FCCP Trauma and Thermal Injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .................... David J. Dries, MD, MSE, FCCP Postoperative Critical Care Management and Selected Postoperative Crises . . . . . . . . . . . . . ................. Jonathan S. Simmons, DO, MSc, FCCP Acute Respiratory Distress Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .................... John P. Kress, MD, FCCP Coma, Delirium, and Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .................... Scott K. Epstein, MD, FCCP Abdominal Problems in the ICU . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ................... David J. Dries, MD, MSE, FCCP ACCP Critical Care Medicine Board Review th Edition iii Hypothermia, Hyperthermia, and Rhabdomyolysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .................. Janice L. Zimmerman, MD, FCCP Ventilatory Crises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..................... Gregory A. Schmidt, MD, FCCP Poisonings and Overdoses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..................... Janice L. Zimmerman, MD, FCCP Anemia and RBC Transfusion in the ICU . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .................... Karl W. Thomas, MD, FCCP Endocrine Emergencies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..................... James A. Kruse, MD Coagulopathies, Bleeding Disorders, and Blood Component Therapy . . . . . . . . . . . . . . . . . . . ................. Karl W. Thomas, MD, FCCP Hemodynamic Monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .................... Jesse B. Hall, MD, FCCP Nutritional Support in the Critically Ill Patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ................. John W. Drover, MD AcidBase Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .................... Gregory A. Schmidt, MD, FCCP Issues in Postoperative Management Postoperative Pain Management and Intensive Glycemic Control . . . . . . Michael A. Gropper, MD, PhD, FCCP Seizures, Stroke, and Other Neurologic Emergencies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .................... Thomas P. Bleck, MD, FCCP Resuscitation Cooling, Drugs, and Fluids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ................... Brian K. Gehlbach, MD Issues in Sedation, Paralytic Agents, and Airway Management . . . . . . . . . . . . . . . . . . . . . . . . ................. Michael A. Gropper, MD, PhD, FCCP Severe Pneumonia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...................... Michael S. Niederman, MD, FCCP Acute Kidney Injury in the Critically Ill . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .................. Richard S. Muther, MD Antibiotic Therapy in Critical Illness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .................. Michael S. Niederman, MD, FCCP Electrolyte Disorders Derangements of Serum Sodium, Calcium, Magnesium, and Potassium .............. Richard S. Muther, MD iv Contents ACCP Critical Care Medicine Board Review th Edition The American Board of Internal Medicine ABIM is not afliated with, nor does it endorse, preparatory examination review programs or other continuing medical education. The content of the ACCP Critical Care Medicine Board Review th Edition is developed independently by the American College of Chest Physicians ACCP, which has no knowledge of or access to ABIM examination material. The views expressed herein are those of the authors and do not necessarily reect the views of the ACCP. Use of trade names or names of commercial sources is for information only and does not imply endorsement by the ACCP. The authors and the publisher have exercised great care to ensure that drug dosages, formulas, and other information presented in this book are accurate and in accord with the professional standards in effect at the time of publication. However, readers are advised to always check the manufacturers product information sheet packaged with the respective products to be fully informed of changes in recommended dosages, contraindications, etc., before prescribing or administering any drug. Copyright by the AMERICAN COLLEGE OF CHEST PHYSICIANS. Copyright not claimed on material authored by the US Government. All rights reserved. No part of this book may be reproduced in any manner without permission of the publisher. Published by the American College of Chest Physicians Dundee Road Northbrook, IL Telephone Fax ACCP Web site www.chestnet.org Printed in the United States of America First Printing ISBN Authors Joshua O. Benditt, MD, FCCP Director of Respiratory Care Services Division of Pulmonary and Critical Care Medicine University of Washington School of Medicine Seattle, WA Thomas P. Bleck, MD, FCCP Chairman of Neurology, Evanston Northwestern Healthcare and Professor and Vice Chair for Academic Programs Department of Neurology Northwestern University Feinberg School of Medicine Evanston, IL R. Phillip Dellinger, MD, FCCP Professor of Medicine Robert Wood Johnson Medical School Director, Division of Critical Care Medicine Director, Medical/Surgical Intensive Care Unit Cooper University Hospital Camden, NJ David J. Dries, MD, MSE, FCCP Assistant Medical Director for Surgical Care HealthPartners Medical Group John F. Perry, Jr., Professor of Surgery University of Minnesota Regions Hospital St. Paul, MN John W. Drover, MD Associate Professor Chair and Medical/Director Critical Care Program Queens University Kingston General Hospital Kingston, ON Canada Scott K. Epstein, MD, FCCP Dean for Educational Affairs and Professor of Medicine Tufts University School of Medicine Pulmonary, Critical Care and Sleep Medicine Division Tufts Medical Center Boston, MA Gregory T. Everson, MD Professor of Medicine Director of Hepatology University of Colorado School of Medicine Denver, CO Brian K. Gehlbach, MD Assistant Professor of Medicine University of Chicago Section of Pulmonary and Critical Care Chicago, IL Michael A. Gropper, MD, PhD, FCCP Professor and Vice Chair Department of Anesthesia and Perioperative Care Director, Critical Care Medicine University of California, San Francisco San Francisco, CA Jesse B. Hall, MD, FCCP Professor of Medicine Anesthesia and Critical Care The University of Chicago The Pritzker School of Medicine Chicago, IL Steven M. Hollenberg, MD, FCCP Professor of Medicine Robert Wood Johnson Medical School University of Medicine and Dentistry of New Jersey Director, Coronary Care Unit Cooper University Hospital Camden, NJ George H. Karam, MD, FCCP Paula Garvey Manship Professor of Medicine Louisiana State University School of Medicine New Orleans, LA Head, Department of Internal Medicine Earl Long Medical Center Baton Rouge, LA John P. Kress, MD, FCCP Assistant Professor of Medicine Section of Pulmonary and Critical Care University of Chicago Chicago, IL James Kruse, MD Chief, Critical Care Services Bassett Healthcare Cooperstown, NY Richard S. Muther, MD Medical Director Division of Nephrology Research Medical Center Kidney Associates of Kansas City PC Kansas City, MO Michael S. Niederman, MD, FCCP Chairman, Department of Medicine Professor of Medicine Winthrop University Hospital Vice Chairman, Department of Medicine SUNY at Stony Brook Mineola, NY James A. Roth, MD Director of Electrophysiology Associate Professor of Cardiovascular Medicine Medical College of Wisconsin Milwaukee, WI Gregory A. Schmidt, MD, FCCP Professor, Division of Pulmonary, Critical Care, and Occupational Medicine Department of Internal Medicine University of Iowa Iowa City, IA Jonathan S. Simmons, DO, MSc, FCCP Clinical Assistant Professor CoDirector, Critical Care Fellowship Program Chair, Disaster Preparedness and Emergency Management Departments of Anesthesia and Emergency Medicine Surgical Intensive Care Unit University of Iowa Hospitals and Clinics Iowa City, IA Mary E. Strek, MD, FCCP Associate Professor of Medicine Section of Pulmonary and Critical Care University of Chicago Chicago, IL Karl W. Thomas, MD, FCCP Assistant Professor Division of Pulmonary Diseases Critical Care, and Occupational Medicine University of Iowa Iowa City, IA Janice L. Zimmerman, MD, FCCP Head, Division of Critical Care Medicine and Director, Medical Intensive Care Unit Department of Medicine The Methodist Hospital Houston, TX ACCP Critical Care Medicine Board Review th Edition v DISCLOSURE OF AUTHORS CONFLICTS OF INTEREST The American College of Chest Physicians ACCP remains strongly committed to providing the best available evidencebased clinical information to participants of this educational activity and requires an open disclosure of any potential conict of interest identied by our authors. It is not the intent of the ACCP to eliminate all situations of potential conict of interest, but rather to enable those who are working with the ACCP to recognize situations that may be subject to question by others. All disclosed conicts of interest are reviewed by the educational activity course director/chair, the Continuing Education Committee, or the Conict of Interest Review Committee to ensure that such situations are properly evaluated and, if necessary, resolved. The ACCP educational standards pertaining to conict of interest are intended to maintain the professional autonomy of the clinical experts inherent in promoting a balanced presentation of science. Through our review process, all ACCP CME activities are ensured of independent, objective, scientically balanced presentations of information. Disclosure of any or no relationships will be made available onsite during all educational activities. The following authors of the Critical Care Medicine Board Review th Edition have disclosed to the ACCP that a relationship does exist with the respective company/organization as it relates to their presentation of material and should be communicated to the participants of this educational activity Authors Thomas P. Bleck, MD, FCCP Relationship Grant monies sources other than industry NINDS, NIAD Grant monies industryrelated sources ALSIUS, NovoNordisk, Actelion Consultant fee USAMRICD Speakers bureau PDL BioPharma Steven M. Hollenberg, MD, FCCP Michael S. Niederman, MD, FCCP Speakers bureau NovartisMakers of Valsartan Consultant fee, speaker bureau, advisory committee, etc Pzer, Inc., Merck amp Co., Inc., ScheringPlough, OrthoMcNeil, Nektar, Cerexa Grant monies from sources other than industry Nektar to study aerosolized amikacin in VAP therapy. Brahms to study procalcitonin James A. Roth, MD Mary E. Strek, MD, FCCP Advisory committee Medtronic Regional Advisory Board Member Grant monies industryrelated sources AstraZeneca LP, GlaxoSmithKline The following authors of the ACCP Critical Care Medicine Board Review th Edition have disclosed to the ACCP that he or she may be discussing information about a product/procedure/technique that is considered research and is not yet approved for any purpose Thomas P. Bleck, MD, FCCP John W. Drover, MD Michael S. Niederman, MD, FCCP Nicardipine for subarachnoid hemorrhage several drugs for status epilepticus Parenteral glutamine Aerosolized amikacin The following authors of the Critical Care Medicine Board Review th Edition have indicated to the ACCP that no potential conict of interest exists with any respective company/organization, and this should be communicated to the participants of this educational activity Joshua O. Benditt, MD, FCCP R. Phillip Dellinger, MD, FCCP David J. Dries, MD, FCCP John W. Drover, MD Scott K. Epstein, MD, FCCP Gregory T. Everson, MD Brian K. Gehlbach, MD Michael A. Gropper, MD, PhD, FCCP Jesse B. Hall, MD, FCCP George H. Karam, MD, FCCP John P. Kress, MD, FCCP James A. Kruse, MD Richard S. Muther, MD Gregory A. Schmidt, MD, FCCP Jonathan S. Simmons, DO, FCCP Karl W. Thomas, MD, FCCP Janice L. Zimmerman, MD, FCCP vi Needs Assessment Rely on the ACCP Critical Care Medicine Board Review to review the type of information you should know for the Critical Care Subspecialty Board Examination of the American Board of Internal Medicine ABIM. Designed as the best preparation for anyone taking the exam, this comprehensive, examfocused review will cover current critical care literature and management strategies for critically ill patients. The ABIM Critical Care Subspecialty Board Examination tests knowledge and clinical judgment in crucial areas of critical care medicine. This premier course will review the information you should know for the exam. 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The major issues that are likely to be seen in the critical care setting regarding solid organ transplantation are complications in the postoperative period related to mechanical surgical procedure complications. and lymphocytes are recruited to areas of infection or tissue injury is induced through nonspecic mechanisms of cellular response. Natural immunity refers to the nonspecic reaction whereby the recruitment of inammatory cells such as macrophages. Once . liver transplantation.Solid Organ Transplantation Joshua O. MD. infection. This form of immunity is specic and results in the memory and specic recognition of foreign tissues and infectious agents. Benditt. and an understanding that overimmunosuppression results in its own complications and is to be avoided. Rejection Immunobiology A basic understanding of the immune system is important to understand the process of solid ACCP Critical Care Medicine Board Review th Edition organ rejection as well as the antirejection medications that are used to try to prevent this problem. and complications related to the antirejection medicines themselves. This occurs through cell surface recognition molecules known as the major histocompatibility complex MHC proteins on the cell surface of cells in the transplanted organ. Although there is signicant overlap and interaction between the innate and the adaptive systems. kidneypancreas transplantation. one of the major limitations to increasing the number of transplants performed is the imbalance between the limited supply of donor organs and the large and growing number of patients on organrecipient waiting lists. which react to those foreign agents. Currently. lung transplantation Overview of Solid Organ Transplantation Solid organ transplantation has increased in frequency dramatically over the past decades largely due to advances in the understanding and management of rejection immunobiology. which then presents this foreign antigen fragment on its cell surface to T cells that are destined for activation. kidney transplantation. A portion of the MHC molecule is usually then cleaved and processed by the APC. Key to this process is the recognition of the transplanted organ as foreign. The major response of the host to the transplanted organ is the activation of Tcell lymphocytes in the host that results in a cascade of reactions that are designed to destroy the transplanted foreign body. Adaptive immunity involves the recognition of the presence of specic cell surface proteins on infectious agents or transplanted organs that results in the activation of T and B lymphocytes. A brief review of the rejection immunobiology will be presented here. polymorphonuclear leukocytes. it is the latter that is more involved in solid organ transplant rejection. The APCs bind to the T cells through the foreign antigen fragment as well as a second costimulatory receptor on the Tcell surface. pertinent immunobiology and an approach to the major complications seen following the transplant procedure Identify the usual clinical course and major complications of liver transplantations Identify the usual clinical course and major complications of kidney and kidneypancreas transplants Identify the usual clinical course and major complications of lung and heart transplantation Key words heart transplantation. Survival following solid organ transplantation has also increased with better antirejection medications. These MHC proteins are recognized by antigenpresenting cells APCs that may be T cells or macrophages. rejection. FCCP Objectives Review the main principals of solid organ transplantation. Reviews of this topic are referenced in the bibliography The immune system is composed of the following two parts natural immunity and adaptive immunity. Tacrolimus FK is a macrolide that has essentially the same mechanism of action as cyclosporine. paresthesias. gingival hyperplasia. but less hypertension. and is effective in the treatment of acute rejection. as well as the treatment of established rejection. Drugs or Compounds That Affect Cyclosporine Levels Increase Levels Diltiazem Nicardipine Verapamil Fluconazole Itraconazole Ketoconazole Clarithromycin Erythromycin Lansoprazole Rabeprazole Cimetidine Methylprednisolone Allopurinol Bromocriptine Metoclopramide Colchicine Amiodarone Danazol Grapefruit juice Decrease Levels Nafcillin Rifabutin Rifampin Carbamazepine Phenobarbital Phenytoin Octreotide Ticlopidine Oristat St. Hyperacute rejection is seen within minutes to hours of transplantation and is mediated by preformed antibodies that cause vascular injury. kidney. Acute rejection is dened as occurring between week and months following transplantation. There are marked individual variations in the absorption and metabolism of cyclosporine. Johns wort Immunosuppression Immunosuppression is required to prevent the rejection of the transplanted organ. hypertension. vary signicantly from one institution to another. tacrolimus is more effective than cyclosporine in preventing acute and chronic rejection. resulting in the blockade of Tcell activation. In liver. Several patterns of rejection have been described in solid organ transplantation. gingival hyperplasia. neurotoxicity eg. It is these processes that lead to the rejection and dysfunction of the transplanted solid organ. In comparison with cyclosporine. Azathioprine is a purine analog that inhibits lymphocyte proliferation. Acute rejection is the most common cause of graft failure and is mediated by Tcellmediated cytotoxicity. dyslipidemia. and help for macrophages to induce delayed type hypersensitivity responses. and cholestasis are important toxicities. activation of the T cell occurs. This Tcell activation leads to the rejection cascade that includes the following clonal expansion of B cells that produce antibodies to molecules on the transplanted organ cell surfaces. Diarrhea. and leukopenia are the principal side effects of mycophenolate Solid Organ Transplantation Benditt . Leukopenia. Accelerated rejection is an uncommon form of antibodymediated rejection that is seen several days after transplantation and is characterized by vascular necrosis. Mycophenolate mofetil is a more selective inhibitor of purine synthesis that appears to be more effective than azathioprine at preventing acute rejection. Table . tremors. Cyclosporine is a fungal cyclic peptide that inhibits the transcription of interleukin IL and the expression of IL receptors. There is no specic treatment but this form of rejection usually can be avoided by pretransplant crossmatching. Important side effects include nephrotoxicity. tacrolimus is associated with more neurotoxicity. induction of CDpositive T cells that mediate cytotoxicity. Most centers use a combination of agents in low doses to minimize the toxicity of individual drugs. Chronic rejection generally appears months after the transplant procedure and is characterized by a slowly progressive course associated with the presence of brosis on histologic analysis of the transplanted organ. hyperlipidemia.this binding of the two ligands occurs. The approaches to induction and maintenance immunosuppression. nephrotoxicity. and hypertrichosis. and glucose intolerance. and lung transplant recipients. The kidney and heart are particularly susceptible. or hirsutism. Sirolimus is a newer agent that has effects similar to those of cyclosporine and tacrolimus and is used more commonly in renal transplantation or in situations in which rstline immunosuppression protocols have not been entirely effective. Cyclosporine is metabolized by the hepatic cytochrome p system and is subject to many drug interactions Table . the precise timing of dosages and monitoring of drug levels are essential. and seizures. emesis. hepatitis. Modern immunosuppression regimens are designed to interfere with this process in a number of ways. B. Routine testing includes serology testing for CMV. VZV. Symptomatic disease develops in to of primary infections and approximately of secondary infections. PTLD presents to weeks after transplantation with an infectious mononucleosislike syndrome or diverse local manifestations that may involve any lymphatic tissue. osteoporosis. Polyclonal and monoclonal antibodies are used to deplete the T cells that mediate acute rejection. and the chest radiograph evaluated for granulomatous disease. The peak incidence of EBVrelated PTLD is to months after transplantation. antigen recognition. or culture. OKT also increases the risks of cytomegalovirus CMV infection and EpsteinBarr virus EBVrelated posttransplant lymphoproliferative disorder PTLD. Pretransplant identication of latent infections in the donor and recipient is essential in dening risks. and C. and immunizations should be brought up to date. and Listeria. Initial treatment with OKT. a murine monoclonal antibody to the Tcell receptor. such as histoplasmosis and coccidioidomycosis. to of heart transplants. hyperlipidemia. Active infection viral replication will develop in most patients at risk. HSV. chills. The manifestations of CMV disease vary with the organ transplanted. Candidiasis and aspergillosis are the major fungal infections occurring in the rst few months after transplantation. Staphylococci and Gramnegative bacilli are the most common early bacterial pathogens. hyperglycemia. myopathy. to of liver transplants. and a capillary leak syndrome resulting in hypotension and pulmonary edema. Toxoplasmosis and Pneumocystis carinii pneumonia may develop after the rst posttransplant month. CMV is the bane of transplantation. secondary or reactivation infection develops in seropositive recipients. Herpes simplex virus HSV often reactivates in the initial weeks after transplantation. kidneys. The risk of CMV disease is increased in patients who are treated with antithymocyte globulin or OKT. The diagnosis is made by . and cataracts. Suspected infection should be approached with an assessment of risks and an aggressive effort at specic diagnosis. Indolent infection of the oral cavity and sinuses should be excluded. The PTLD is caused by EBV infection. CMV disease can be prevented by the use of screened blood products. and leukopenia. Dermatomal reactivation of ACCP Critical Care Medicine Board Review th Edition varicellazoster virus VZV also occurs in this time frame. or brain. nucleic acid identication. CMV and hepatitis C infections typically present after the rst month. often elicits fever. oral valganciclovir prophylaxis. hepatitis A. but the reactivation of endemic mycoses and cryptococcosis may present later. followed later by infections caused by Legionella. lungs.mofetil. A tuberculin test should be performed. and Tcell proliferation. HIV. Nosocomial infections are prominent in the early posttransplant course. basiliximab and daclizumab are associated with less toxicity. Complications of Solid Organ Transplantation The complications of solid organ transplantation are most commonly divided into infectious and noninfectious complications. Prophylaxis is effective against many latent and some acquired infections. and of kidney transplants. Infectious Complications Infectious complications are most often divided into early and late infections. Mycobacteria. Primary infection occurs when a seronegative patient receives an organ from a seropositive donor. and occurs in to of lung transplants. Corticosteroids are nonspecic antiinammatory agents that inhibit cytokine production. Newer mouse/human chimeric monoclonal antibodies to IL receptors eg. and by prophylactic or preemptive treatment at the earliest sign of viral replication with ganciclovir and hyperIg. The risk of PTLD is increased by treatment with antiTcell antibodies. and relevant endemic mycoses. the GI tract. and new opportunistic infections related to the intensity and duration of immunosuppression. and herpesvirus is increasingly recognized to weeks posttransplant. CMV disease is treated with ganciclovir. Antithymocyte and antilymphocyte globulin may cause serum sickness. and is diagnosed by antigen detection. thrombocytopenia. followed by the reactivation of latent infections in the graft or host. Nocardia. Each of these categories is then divided along temporal lines. with or without CMV Ig. and possibly others. Routine surveillance is helpful for the preemptive management of CMV infections. EBV. toxoplasmosis. The familiar side effects of corticosteroids include Cushing syndrome. The criteria for transplantation have been difcult to evaluate as patients either survive to full recovery or die rapidly.. irrespective of the grade of encephalopathy or grade III or IV encephalopathy. and there is an uncertain role for acyclovir or ganciclovir. rejection. liver transplantation is used in cases of fulminant hepatic failure. A listing for liver transplantation usually occurs at this point or with a higher score. autoimmune hepatitis. and serum bilirubin level of mg/dL mol/L Liver Transplantation Background Liver transplantation is a treatment for both acute and chronic liver failure. Ln serum bilirubin in milligrams per deciliter .demonstrating the EBV genome in association with benign or malignant lymphatic proliferation. but metabolic alkalosis develops as the liver metabolizes citrate. which is dened as the onset of liver failure with encephalopathy within a short period of time weeks. These noninfectious complications will be discussed in more detail with each of the specic transplant types. Ln INR . and others. Treatment strategies include reduced immunosuppression. as noted above. A mild metabolic acidosis may be present initially. Local resection may be helpful. Kings College Hospital Criteria for Liver Transplantation in Patients With Fulminant Hepatic Failure Conditions Acetaminopheninduced disease Criteria Arterial pH . Chronic liver failure cirrhosis that is uncompensated is considered to be treatable by liver transplantation. prothrombin time of s. nonB hepatitis. In the acute setting. Myocardial depression is a poor prognostic sign. They also can be divided into early and late complications. Hyperglycemia is common. Blood products are usually replaced empirically for evident bleeding and a fall in hematocrit. Ln serum creatinine in milligrams per deciliter . graft dysfunction related to ischemia. The cardiac output is generally high. which is a rapid measure of the time to the onset of clotting. although many centers monitor coagulation with thromboelastography. and cytotoxic chemotherapy. and rejection. Calcium may be depleted by the citrate in blood products. halothane hepatitis. prothrombin time of s. circulatory instability is common and usually volumeresponsive. and those related to the toxicities of the immunosuppressant drugs. The decision to consider liver transplantation will depend on the severity of the disease as well as the quality of life and the absence of contraindications. duration of jaundice before onset of encephalopathy of d. The system currently in place to characterize the severity of liver disease appropriate for transplantation is known as the Model for Endstage Liver Disease or MELD score. or idiosyncratic drug reactions. Typical Postoperative ICU Course Liver transplant recipients require ICU care for to days after surgery. Decient clotting factor levels and thrombocytopenia contribute to a signicant bleeding diathesis. and potassium levels may be high or low. A score of is the usual indication for referral to a liver transplant center. Table . Cases of fulminant hepatic failure that may require transplant include acetaminophen toxicity. Noninfectious Complications Noninfectious complications consist of complications related to the surgical procedure itself. acute viral hepatitis. mg/dL mol/L All other causes of Prothrombin time of s fulminant hepatic irrespective of the grade of failure encephalopathy or any three of the following variables irrespective of the grade of encephalopathy age yr or yr. and serum creatinine level of . etiology of nonA. preservation. The score is calculated as . the rate of clot Solid Organ Transplantation Benditt . and the systemic vascular resistance is low. and reperfusion. The Kings College criteria Table are the most commonly used prognostic criteria to decide on the suitability of a patient for liver transplantation. After the rst few months. The score is also used for prioritization on the waiting list. Noninfectious problems in the rst few weeks after solid organ transplantation include surgical complications. interferon. chronic rejection is a signicant problem as are the side effects of immunosuppressant medications. Acute rejection is the most common cause of liver dysfunction after transplantation. and shock. hypoglycemia. metabolic acidosis. Important signs of a functioning graft are the production of goldenbrown bile. Most patients can be extubated within to h. the absence of metabolic acidosis. Respiratory muscle weakness. a bile leak with or without evidence of liver injury. and the site of infection often involves the transplanted liver or the reconstructed biliary tree. CMV infection will be evident in approximately of liver transplant recipients. The signs of graft failure include poor bile formation. ARDS occurs in of liver graft recipients. The diagnosis is made by duplex ultrasonography. Most patients experience at least one episode. Primary graft failure occurs in to of patients receiving liver transplants and usually is a consequence of ischemic injury. and severe metabolic alkalosis may contribute to delayed weaning. The serum bilirubin level may rise initially because of hemolysis. Hepatic artery thrombosis occurs in about of patients and presents in one of the following four ways massive liver necrosis eg. Neurologic dysfunction after liver transplantation may be caused by hepatic encephalopathy. intraabdominal bleeding may be related to necrosis of a vascular anastamosis. and pulmonary edema. hepatic vein. and half of these cases will be symptomatic. drug toxicity. Noninfectious Complications Hemorrhage in the rst h usually is caused by diffuse oozing in the setting of a coagulopathy and is managed with blood products. Biliary complications occur in up to of patients. particularly in the rst weeks after grafting. and surgical wound infections are the most common foci of bacterial infection. and urinary tract infections. and venulitis. and the resolution of encephalopathy. or as an asymptomatic nding on a routine ultrasound. The peak onset of CMV infection is . tenderness. renal insufciency. Biliary obstruction may be caused by the kinking of the bile duct or drainage tubes. Later. cholangitis. pleural effusions. Grampositive cocci and Gramnegative bacilli are the predominant pathogens. ICU readmission is rarely required. Hepatic vein thrombosis is rare. ductal injury. and failure to resolve encephalopathy and coagulopathy. and presents with ascites and variceal hemorrhage. peritonitis. rising enzymes. deterioration in mental status. dysfunction of the sphincter of Oddi. impaired mental status. intracranial hemorrhage. Most patients respond to therapy with pulse steroids or antiTcell antibodies. elevated levels of hepatocellular enzymes and bilirubin are nonspecic. Portal vein thrombosis is less common. The prothrombin time and partial thromboplastin time should improve daily and should be normal within h. followed by pneumonia. fever. and presents with liver failure and massive ascites. The clinical signs eg. Intraabdominal abscesses. and the treatment is operative repair or retransplantation. recurrent bacteremia from hepatic abscesses. before brainstem herniation from cerebral edema occurs. GI hemorrhage may result from stress ulceration or the development of portal hypertension.formation. Prophylactic systemic and topical antibiotics are commonly used but are of unproven value. the restoration of clotting. and maximum clot elasticity. fever. The treatment is retransplantation within h. air embolism. In most cases. or portal vein. usually to days after transplantation. Seropositivity for CMV is the most important risk factor for CMV disease. or infection. Infection Bacteria are the most important causes of infection after liver transplantation. with or without graft dysfunction. preoperative shunting caused by the hepatopulmonary syndrome improves over days to months posttransplant. but liver enzyme levels should fall each day. catheter sepsis. ACCP Critical Care Medicine Board Review th Edition or strictures. usually as a consequence of sepsis. the abdominal wound. The diagnosis is conrmed with a liver biopsy nding that demonstrates mononuclear cell portal inltration. Bile leaks are caused by traumatic or ischemic injury to the common bile duct. Common noninfectious pulmonary complications of liver transplantation include atelectasis. Biliary complications are diagnosed by cholangiography and are managed with surgical or endoscopic repair. and enlargement of graft and laboratory features eg. Vascular complications include thromboses of the hepatic artery. Patients should be awake and alert within h. Background Kidneypancreas transplant is considered for patients with renal failure and type I diabetes. and to of these patients will be symptomatic. HSV mucositis reactivates in to of seropositive patients and can be prevented or treated with acyclovir therapy. diabetes or hypertension is the cause of chronic renal insufciency in most recipients. and Listeria usually occur to months after transplantation. Opportunistic infections caused by Legionella. days after transplantation. Anecdotal reports have suggested that the treatment of CMV disease with ganciclovir is benecial. Nocardia. require ICU care in the immediate postoperative period. when compared with maintenance dialysis. and to of these patients will have clinical disease. malaise. renal vein thrombosis. refractory cases are conrmed by renal biopsy. In the United States. Hepatitis is the most common involvement in the liver. Primary CMV infection develops in to of seronegative recipients of a kidney from a seropositive donor. Surgical complications such as renal artery thrombosis. The onset of infection is usually to months after transplant. followed by pulmonary aspergillosis. the number of patients awaiting transplant far outstrips the supply of donor organs available and has resulted in many patients requiring ongoing dialysis with its associated morbidities. and lymphoceles occur in of patients. The most common manifestation is a mononucleosislike syndrome that is characterized by fever. Acute rejection is empirically treated with corticosteroids. Typical Postoperative ICU Course KidneyPancreas Transplant Patients who have undergone renal transplantation rarely. Volume overload and graft dysfunction occasionally lead to pulmonary edema. myalgias. from an abdominal or vascular source. living related donors. The Solid Organ Transplantation Benditt . Fungal infections are less common in renal graft recipients than in other organ transplant patients. usually in the rst months. Candidemia. CMV infection develops in to of seropositive recipients. Unfortunately. A successful kidney transplant improves the quality of life and reduces the mortality risk for most patients. Pneumocystis infections are rare in patients receiving prophylaxis. Ganciclovir appears to be effective in treating CMV disease in the setting of renal transplantation. Bacterial infections of the wound. CMV disease can be prevented in highrisk patients by longterm day ganciclovir prophylaxis or by preemptive treatment at the rst sign of viral replication. is the leading mycosis. Acute rejection occurs in to of patients within the rst months and is suspected by a rise in creatinine level that is not attributable to cyclosporine toxicity. and neutropenia. Sources for renal allografts include cadaveric donors. and the respiratory tract also may complicate the early postoperative course. They are generally extubated in the recovery room and brought to a nonICU hospital oor. IV catheter sites. urine leaks. The mononucleosislike CMV syndrome is the most common manifestation of CMV disease in renal transplant recipients. Fungal infections complicate to of liver transplants. Infectious Complications Urinary tract infections are common soon after renal transplantation and can be prevented with prophylaxis using antibiotics. resulting in the high levels of graft survival that are seen. Chronic rejection develops in to of patients. Kidney Transplant Background Kidney transplantation is the treatment of choice for patients with endstage renal disease. and are more common in liver transplants than in the transplantation of other organs. CMV pneumonia will develop in about of symptomatic patients. and living unrelated donors. if ever. Human leukocyte antigen matching of the donor and the recipient is routinely performed. Hyperacute rejection from preformed antibodies causes immediate graft failure and is usually detected in the operating room. Noninfectious Complications Serious noninfectious complications are uncommon after renal transplantation. frequent in the rst month after transplantation but may appear a year or more postoperatively. The task force of the American College of Cardiology and the American Heart association recommended the use of exercise testing with ventilatory gas analysis for this purpose. hematuria. and abdominal abscesses caused by bacteria or fungi are particularly ACCP Critical Care Medicine Board Review th Edition Noninfectious Complications The early complications of heart transplantation include those of cardiac surgery in general. Infectious Complications Infections also are more common in patients who receive kidneypancreas transplants than in recipients who receive kidney transplants alone because of the additional surgery and the need for more immunosuppression. the liver is the most common site of tissue infection in the form of hepatitis. and tight glucose control with an insulin drip to keep the pancreas at rest. Active CMV infection will develop in most patients who are at risk. Acute pancreatic rejection occurs in of cases. Noninfectious Complications Complications are more common after kidneypancreas transplantation than after kidney transplantation alone. Loss of sodium bicarbonate in the urine may cause signicant dehydration and metabolic acidosis. Wound infections. Also. Pancreatic rejection is diagnosed by an abrupt fall in urinary amylase levels. Patients are routinely extubated within h and discharged from the ICU within h. In general. Most cases of pancreatic rejection fail to respond to corticosteroids and require repeated courses of OKT.major reported benet is an improved quality of life due to avoidance of the need for insulin and dialytic therapy. but several days are often required for full graft function. more commonly than kidney rejection. urinary tract infections. The development of left lowerlobe atelectasis . and urethral stricture. and is more refractory to therapy with corticosteroids. Surgical complications include vascular thrombosis. Glucose regulation may normalize within hours. some centers conrm rejection histologically by cystoscopic biopsy. and treatment with lowdose isoproterenol or pacing is often required for to days. New York Heart Association class III or IV that have not responded to maximal medical management. Heart Transplant Background Typical Postoperative ICU Course Patients require ICU monitoring of uids and electrolytes. although sequential kidney then pancreas transplantation or pancreas transplantation alone is performed. Cardiac output is initially ratedependent in the denervated heart. a distribution that has not changed appreciably in many years. and the right ventricle recovers more slowly than the left. Published recommendations for considering transplantation in patients with cardiac conditions are for those with advanced disease generally. survival appears to be better with a simultaneous pancreas transplantation. bicarbonate loss due to secretion by the pancreas into the bowel or bladder where the pancreas implant is placed can lead to metabolic acidosis. For those patients with type I diabetes mellitus undergoing cadaveric transplantation but not living donor transplantation. Most procedures are performed as simultaneous transplants. perforation of the duodenal segment. Judging when in the course of chronic heart failure transplantation should be considered is difcult. Underlying coronary artery disease and nonischemic cardiomyopathy each account for about of cases. the peak oxygen uptake measured on cardiopulmonary exercise testing appears to provide the most objective assessment of functional capacity in patients with heart failure and may be the best predictor of when to list an individual patient for cardiac transplantation. and the majority of these infections will be symptomatic with a viremic syndrome. Usual Postoperative Course Cardiac function is depressed for several days postoperatively. VZV typically reactivates in a dermatomal distribution to months after transplantation. Gramnegative bacilli and Staphylococcus aureus are frequent pathogens. Legionella pneumonia and wound infections are important in the rst months after heart transplantation. CMV pneumonia develops in of infected patients. Refractory patients usually respond to antiTcell treatment. Any lymphatic tissue may be involved. The severity of rejection is graded by the degree of lymphocytic inltration and myocyte necrosis. arrhythmias. Treatment with prostaglandin E. Treatment with pyrimethamine and sulfadiazine is effective if instituted promptly. but hemorrhage is unusual. Persistent pulmonary hypertension is an important early problem that may lead to right ventricular failure. and catheterrelated infections are common in the rst month after transplantation.and mediastinal uid collection is common in most patients. Active CMV infection will develop in most seropositive patients and seronegative recipients of hearts from seropositive donors. The resection of localized tumors and treatment with acyclovir may be helpful. The diagnosis is supported by seroconversion and conrmed by the demonstration of tachyzoites in tissue. Clinical signs of rejection such as fever. brain. Pyrimethamine also may be effective in preventing primary infection. nitric oxide. usually with a mononucleosislike syndrome. PTLD is probably caused by EBV. Most cases respond to a reduction in immunosuppressive therapy. P carinii pneumonia develops in of cardiac transplant patients without prophylaxis but is now rare. Nocardia infection of the lung may present at any time after the rst postoperative month and may disseminate to the brain or bone. Toxoplasmosis is an important consideration when a seronegative recipient receives a heart from a seropositive donor. and the risk is markedly increased by treatment with OKT. The lung is the primary site of infection. Accelerated coronary atherosclerosis is the leading cause of death year after heart transplantation. PTLD develops in to of heart transplant recipients. Ganciclovir appears to be effective in the treatment of CMV disease in heart transplant patients. The role of ganciclovir in prophylaxis is uncertain. The reactivation of oral and genital HSV infection is common in the rst few months after heart transplantation. Calcium channel blockers and hydroxymethylglutaryl coenzyme A reductase inhibitors may slow the development of allograft vasculopathy. particularly in hospitals with contaminated water supplies. Lung Transplant Background Lung transplantation is relatively infrequent compared to other transplants because of the Solid Organ Transplantation Benditt . Serious morbidity and mortality are largely limited to patients with primary infection. The cumulative incidence is approximately per year. postoperative left ventricular dysfunction. and volume overload. lungs. HSV and VZV infections usually remain localized and respond to treatment with acyclovir. heparinprotamine reactions and reperfusion injury may alter lung permeability. usually in the rst month. Rejection may occur any time after heart transplantation and is diagnosed histologically from routine surveillance endomyocardial biopsies. usually presenting to months after transplantation. mediastinum. and assist devices may be effective. Most episodes respond to treatment with pulse corticosteroids and/or increased doses of cyclosporine. as well as the GI tract. Reactivation of latent toxoplasmosis in seropositive recipients is not clinically signicant. Primary infection presents to weeks after transplantation with fever and nonspecic signs involving the heart. Infectious Complications Nosocomial bacterial pneumonia. Pulmonary edema is a frequent occurrence because of pretransplant congestion. or brain. or soft tissues. heart failure. and/or liver. but dissemination is evident in half of the cases at diagnosis. empyema. myocardial infection may mimic rejection. and pericardial friction rubs are unreliable. Atypical mycobacterial infections have been reported in of heart transplant recipients. Aspergillosis is the most common fungal infection after heart transplantation. about one third of patients require treatment for rejection. mediastinitis. lungs. eyes. developing in to of recipients. Mild cases may resolve spontaneously. kidneys. usually involving the lung. One third of these infections will be symptomatic. inotropes. later. and cardiogenic pulmonary edema. Care must be taken to avoid airtrapping in an emphysematous native lung. and stents are occasionally required for the management of stenoses. Bleeding is particularly common in heartlung ACCP Critical Care Medicine Board Review th Edition transplants because of the extensive mediastinal dissection and the need for heparinization during bypass. however. The lymphatics are severed in the transplanted lung. Lung transplantation can be unilateral or bilateral. Airway dehiscence. Reexive coughing is lost in the denervated lung. Patients receiving singlelung transplants for primary pulmonary hypertension often are heavily sedated for to h before extubation to reduce pulmonary arterial hypertensive crises. CMV is the principal concern. Noninfectious Complications Hemorrhage early after lung transplantation is usually from the mediastinum or pleura. Transbronchial biopsy specimens demonstrate the characteristic perivascular mononuclear inltrates with a sensitivity of to and a specicity of . Infection and edema are the major alternative considerations in the rst few weeks after transplantation. and impaired gas exchange. time on the waiting list was used to order lung transplant recipient waiting lists. and other factors that predict mortality and prevent death while the patient is on the waiting list. Lung transplantation is performed for a wide variety of diagnoses. Bilateral bronchial anastomoses require less mediastinal dissection and are associated with less bleeding than tracheal anastomoses. Phrenic nerve paralysis resulting from thermal or mechanical injury occurs in of patients. particularly for younger recipients. lung transplantation after donation from a living related person. and pulmonary toilet is critical for secretion management. and responds to therapy with isoproterenol. there is an increasing trend toward bilateral transplant for all diagnoses. impairing extravascular uid clearance and rendering the graft particularly susceptible to edema. and new or changing inltrates seen on a chest radiograph the chest radiograph is usually normal when rejection occurs month after transplantation. and most patients will experience at least one episode within the rst postoperative month. Lung rejection is more common than heart rejection in heartlung transplants. Acute rejection occurs as early as days after lung transplantation. The response peaks to days after transplantation and resolves gradually thereafter with careful uid management and diuresis. and the exclusion of infection. with gradual recovery over several weeks. The pulmonary reimplantation response is evident in most patients. fatigue. however. The clinical features include alveolar and interstitial inltrates seen on a chest radiograph. hypoxemia. a fall in FEV. Cardiac function may be impaired if cardiopulmonary bypass was required all heartlung transplants and some lung transplants. Currently. This is a form of reperfusion injury that results in noncardiogenic pulmonary edema.pulmonary injury or infection that so often occurs in cadaveric donors. cough. Strictures now develop in about of cases. rejection. and include lowgrade fever. dyspnea. The diagnosis is made by the clinical presentation and time course. and bronchomalacia were major causes of morbidity and mortality in the early years of lung transplantation. Patients with cystic brosis also are at increased risk of hemorrhage because pleural adhesions often must be severed to remove the native lungs. Usual Postoperative Clinical Course Volume overload and pulmonary edema are common early problems. The injury is often temporary. more recently a lung allocation score has been devised that includes the type and severity of disease. Because of this. is currently being performed at a few centers. The use of telescoping bronchial anastomoses has markedly reduced the incidence of airway complications. stenosis. Bronchoscopy is helpful in excluding infection and conrming rejection. There may be . Previously. a decline in lung compliance. the majority of individuals on the waiting list have COPD. Most patients can be extubated within h. Cardiac output is ratedependent in denervated hearts. Independent lung ventilation through a doublelumen endotracheal tube may be necessary in some singlelung transplant recipients to improve ventilationperfusion matching or reduce airtrapping. The clinical manifestations are nonspecic. although native strains of Pseudomonas cepacia and Pseudomonas aeruginosa are problematic in patients with cystic brosis. Repeated episodes of acute rejection and CMV infection are possible risk factors. or dissemination from a cutaneous or vascular site. Invasive aspergillosis typically presents as a focal pneumonia or necrotizing airway infection. EBVrelated PTLD occurs in approximately of lung allograft recipients. and a positive BAL culture nding is predictive of histologic evidence of infection only in the highest risk patients ie. with half of the cases presenting in the rst year. but CMV infection may increase the risk of acute and chronic rejection. The clinical diagnosis hinges on a spirometric demonstration of signicant declines in FEV and the midexpiratory phase of forced expiratory ow. Most patients respond to a reduction in the immunosuppressive regimen. Obliterative bronchiolitis may present any time after the second postoperative month. but the optimal regimen has not been dened. Acyclovir appears to be effective in preventing the reactivation of HSV. In singlelung transplant recipients. seronegative recipient/seropositive donor. CMV pneumonitis is the most common manifestation of CMV disease in lung allograft recipients. infection in the native lung is a signicant problem. relying heavily on bronchoscopy. but the risk and severity of symptomatic CMV disease are highest in seronegative patients who receive a lung from a seropositive donor ie. and chest radiograph ndings are usually normal. HSV mucositis develops in of seropositive lung transplant recipients in the absence of acyclovir prophylaxis. Obliterative bronchiolitis is the major manifestation of chronic rejection in the transplanted lung and a leading cause of late mortality. Treatment is administered with increased immunosuppression. although any lymphoid tissue may be involved. Bacterial pneumonia is most frequent in the early postoperative period. and pneumonia develops in half of these patients. Most patients respond promptly to therapy with pulse corticosteroids. The typical case presents within the rst months after transplantation with nodular inltrates in the lung allograft. Some centers have found transbronchial biopsies to be helpful. Patients may complain of dyspnea or cough. those with a primary infection. The reported mortality rate for patients with fungal infections after lung transplantation has ranged from to . Bacterial infections usually respond to treatment with antibiotics. Treatment with OKT is an additional risk for CMV. Primary HSV infections are rare. The chest radiograph is nonspecic. Transbronchial biopsies are required to identify Solid Organ Transplantation Benditt . the validity of this practice has not been tested by controlled trial. Pulmonary function may stabilize with treatment but rarely improves. Typical nosocomial pathogens are the usual culprits. Positive blood and BAL cultures active infection will develop in most seropositive recipients a median of days after transplantation in the absence of prophylaxis. Most centers advocate an aggressive approach to etiologic diagnosis. late bacterial infections are particularly common in patients with obliterative bronchiolitis. CMV disease is more common in lung allograft recipients than in other solid organ transplant patients. nonresponders are treated with antiTcell antibodies. The mortality rate of patients with obliterative bronchiolitis is within years of diagnosis. but no strategy has been demonstrated to be effective. Bacteria are the most common agents of infection after lung transplantation. but purulent bronchitis often presents weeks to months after transplantation. Candidiasis is the most common mycosis and may involve the mediastinum.a role for identifying donorsensitized lymphocytes by BAL. Infectious Complications Infection is the leading cause of death after lung transplantation. and most infections are located in the thorax. Prophylaxis with ganciclovir may be effective in preventing or delaying CMV disease in atrisk patients. The incidence of obliterative bronchiolitis increases over time and is found in to of patients who survive for years after undergoing transplantation. Prophylactic broadspectrum antibiotics are routinely administered for the rst to h after transplantation. empirically or guided by cultures from the donor and recipient respiratory tracts. Fungal infections occur in to of lung transplant recipients. the airway anastomosis. disease. The roles for antifungal prophylaxis and aggressive treatment of mucosal isolates are unclear. The direct mortality rate from CMV disease in treated patients is about . . et al. et al. Becker BN. Estenne M. Dykstra DM. Knoop C. Curr Opin Crit Care .viral inclusions and to exclude rejection. Presentation and early detection of posttransplant lymphoproliferative disorder after solid organ transplantation. Eur Respir J . van Imhoff GW. Semin Respir Crit Care Med . Steinman TI. McGilvray ID. Trends and results for organ donation and transplantation in the United States. patient selection and timing of referral for lung transplantation. Becker YT. Guidelines for the referral and management of patients eligible for solid organ transplantation. Becker BN. et al. J Am Soc Nephrol . Greig PD. Bibliography Bakker NA. Verschuuren EA. Port FK. Frost AE. Odorico JS. Transpl Int . Acute and chronic rejection after lung transplantation. Simultaneous pancreaskidney and pancreas transplantation. The treatment of CMV pneumonitis in lung transplant recipients with ganciclovir is probably effective but has not been prospectively studied. Merion RM. Indications. Estenne M. Critical care of the liver transplant patient an update. et al. Transplantation . Glanville AR. ACCP Critical Care Medicine Board Review th Edition . Am J Transplant . Notes Solid Organ Transplantation Benditt . Once a pathogen is ingested by these cells and is intracellular. humoral immunity. IL. MD. Although multiple factors are involved. secrete interferongamma IFN. the key to polarization of Th cells into the Th phenotype is interleukin IL. FCCP Objectives Propose an approach to the immunocompromised patient based on identication of defects in three major host defense systems Review the likely pathogens. In questionable circumstances. and cellmediated immunity. which are involved with type immunity. Th cells are involved with type immunity. the Th outcome is favored over the Th differentiation because IL dominates IL. and therapeutic options in patients with neutropenia Summarize the various limbs in humoral immunity. Recent attention has been focused on the concept of type and type immunity as they interrelate with humoral and cellmediated immunity.Infections in AIDS Patients and Other Immunocompromised Hosts George H. . stimulate high titers of antibody production. and are associated with suppression of cellmediated immunity and with strong humoral immunity. and IL. Th cells. All T helper lymphocytes start out as naive Th cells. When integrated into the traditional approach of cellmediated immunity and humoral immunity. IL. are capable of polarizing or differentiating into either Th or Th effector cells. after being activated.as the cytokines chiey responsible for their proinammatory effect. a basic consideration is whether the patient is a normal host or one who is immunocompromised. whereas IL is needed for Th polarization. their clinical presentations.. with T helper type Th and T helper ACCP Critical Care Medicine Board Review th Edition type Th cells being the most relevant. and cellular host defense. Pathogens that classically infect patients with primary neutrophil problems are those that may be ingested without opsonization. Use of an approach that identies the defective limb of host defense allows for directed therapeutic decisions that are based on likely pathogens for the involved site. humoral immunity. cellmediated immunity. Karam. Subpopulations of CD lymphocytes are important in both humoral immunity and cellmediated immunity. which. These events may not occur until an activated T cell arrives at the site of danger and samples the local cytokine milieu to determine if an inammatory or antibody response is appropriate. which includes the three major categories of primary neutrophil defense. HIV. The Th cell is associated with strong cellmediated immunity and weak humoral immunity. killing is generally an easy process. neutropenia In the clinical approach to patients with fever presumed to be infectious in etiology. Primary Neutrophil Function The polymorphonuclear leukocyte is the major phagocyte for both primary neutrophil defense and humoral immunity. The system of neutrophil defense has been described as being responsible for defending against organisms that are easy to eat and easy to kill. type and type immunity have important therapeutic implications in the care provided for immunocompromised patients. are inuenced by IL. and lymphotoxin. including barrier systems such as skin and mucous membranes which are protective against infection or foreign bodies such as intravascular and urinary catheters which predispose to infection. A traditional method has been to consider host defense in immunocompromised patients as being in one of two categories mechanical factors. with particular attention to the clinical situations of asplenia and splenic dysfunction Outline the categories and clinical presentations of pathogens likely to be encountered with decits of cellmediated immunity Focus on the broadening number of clinical issues in patients whose cellmediated immunity defect is on the basis of HIV infection Key words asplenia. and intracellular killing which may occur via either oxygendependent or oxygenindependent mechanisms. Infections due to bacteria are classically encountered when the neutropenia is either rapid in development or profound especially with counts cells/mm. ingestion the process of attaching to the pathogen and then getting that pathogen within the cell. neutrophil dysfunction may occur on either a qualitative or quantitative basis. Recognition of this fact allows for an understanding of the organisms that classically infect neutropenic patients. neutropenic patients. clinically present as the entity interchangeably referred to as either granulocytopenia or neutropenia. and those patients have a lower incidence of bacteremia. a calculated granulocyte count of cells/mm indicates absolute neutropenia.An important pathophysiologic consideration is that polymorphonuclear leukocytes may have either an extravascular or intravascular location. In conditions such as aplastic anemia or HIVassociated neutropenia. a granulocyte count . most notably Candida spp Filamentous fungi. The pathogens most likely to infect neutropenic patients are listed in Table . chemotaxis movement to the site of infection. Conditions Causing Neutrophil Dysfunction Qualitative Defects Impaired diapedesis Impaired chemotaxis Impaired ingestion Impaired intracellular killing Quantitative Defects Neutropenia Acute leukemia Invasion of bone marrow by neoplasms Treatment with agents toxic to marrow Drug idiosyncrasy Splenic sequestration syndromes HIVassociated neutropenia Idiopathic chronic neutropenia Table . Although any of the enterobacteriaceae eg. these phagocytes go to two major sites the subepithelial area of skin and the submucosal area of the GI tract. As represented in Table . These patients are more likely to experience Gramnegative bacteremia and fungemia. Quantitative defects. as might be predicted from the loss of subepithelial and submucosal polymorphonuclear leukocytes. Qualitative defects characteristically occur in children and are associated with polymorphonuclear leukocytes that are normal in number but abnormal in function. The bacteria characteristically involved are skin and gut ora. which are the more characteristic neutrophil problems in adults. In the guidelines of the Infectious Diseases Society of America IDSA for management of febrile. for most clinical purposes the granulocyte count is calculated by adding the percentage of polymorphonuclear leukocytes and band forms. including Bacteroides fragilis Fungi Yeasts. where killing takes place. Escherichia coli or Klebsiella may cause infection in this setting. the gut mucosa is usually intact. the clinician must assume that the patient has impaired natural defense against the pathogens defended against by this limb of host defense. After leaving the bloodstream. In the setting of neutropenia and fever. the most lifethreatening Table . The clinical course of patients with neutropenia is variable and may be explained in part by the integrity of the gut mucosa. and then multiplying the total WBC count by that percentage. Classic qualitative defects of polymorphonuclear leukocytes are related to dysfunction in one of the following processes diapedesis the ability to leave the intravascular space via endothelial channels. In contrast. patients who receive chemotherapeutic agents that cause mucositis have loss of both the mechanical barrier of gut mucosa and submucosal polymorphonuclear leukocytes. most notably Aspergillus spp Infections in AIDS Patients and Other Immunocompromised Hosts Karam . Important Pathogens Causing Infection in Neutropenic Patients Grampositive organisms Staphylococcus aureus Coagulasenegative staphylococci Viridans streptococci Enterococci Corynebacterium jeikeium Enterobacteriaceae Pseudomonas aeruginosa Anaerobes. cells/mm with a predicted decline to cells/mm should be considered neutropenia. Characteristic conditions that may lead to neutropenia are listed in Table . Although eosinophils are classied as granulocytes. which breach the mechanical barrier of the skin. intramural hemorrhage due to severe thrombocytopenia. Histologically. In recent years. neutropenic enterocolitis may involve the terminal ileum. have increased in part because of the expanded use of invasive devices such as intravascular catheters. the distal ileum and remaining colon are also frequently involved. Severe oral mucositis. The experience with antibiotic prophylaxis during the neutropenic period after autologous peripheral blood stem cell transplantation provides an important insight into a potential problem regarding viridans streptococci. The classic skin lesion that suggests such an infection is ecthyma gangrenosum. had a cutaneous rash. and alterations in GI tract ora. may not be optimal for preventing viridans group streptococcal bacteremia in neutropenic patients. All patients presented with fever and mucositis after a mean of . which in other reports has been associated on occasion with desquamation. two additional risk factors for viridans streptococcal bacteremia in neutropenic patients were cytosine arabinoside and antimicrobial ACCP Critical Care Medicine Board Review th Edition prophylaxis with either trimethoprim/ sulfamethoxazole or a uoroquinolone. a basic principle in empiric therapy of febrile neutropenic patients is coverage of P aeruginosa. Of the patients with serious complications of their streptococcal bacteremia. Pathogenetically. including ARDS plus septic shock cases. Ten of these cases were associated with serious complications. The important clinical nding of cavitary pulmonary inltrates may be a clue to infection by either Staphylococcus aureus or Corynebacterium jeikeium.pathogen is Pseudomonas aeruginosa. the infection involves dermal veins. Despite the use of levooxacin prophylaxis. and approximately one half were resistant to ceftazidime. but these ndings may be seen with other conditions including Clostridium difficile toxininduced colitis and ischemic colitis. abdominal pain. Although isodense cecal wall thickening is the most notable CT nding. Although other Gramnegative pathogens have been reported to cause such a process. days of neutropenia. infections caused by Grampositive organisms have signicantly increased in neutropenic patients. highdose chemotherapy with cyclophosphamide. In a recent prospective study of episodes of bacteremia in neutropenic patients with cancer. and allogeneic bone marrow transplantation were the only variables found to be signicantly associated with the development of complications. viridans streptococci caused a total of episodes . These lesions have a central area of hemorrhage surrounded by a halo of uninvolved skin with a narrow pink or purple rim. and the colon with the ascending portion the most frequently involved. In patients with complications. and septic shock cases. and diarrhea. ARDS cases. Although optimal therapy has not been definitively established. therefore. A conclusion of this paper was that the use of levooxacin may select viridans group streptococci with diminished susceptibility to levooxacin and other quinolones with enhanced activity against Grampositive organisms and. Streptococcus mitis. Ultrasound ndings include echogenic thickening of the mucosa and bowel wall. Patients characteristically present with the triad of fever. All six viridans group streptococcal isolates from these patients exhibited distinct patterns on pulsedeld gel electrophoresis. Because of this and despite the relative decline in the incidence of infection caused by this pathogen in neutropenic patients. who underwent transplantation over a month period in . Although the level of temperature elevation that mandates antimicrobial therapy in neutropenic patients may be influenced by the degree of . the cecum. and septic shock developed in days. These pathogens. Notable among the Grampositive pathogens is infection caused by viridans streptococci eg. of these pathogens showed diminished susceptibility to penicillin. viridans group streptococcal bacteremia developed in of patients . In a more recent review. the clinician should assume that ecthyma gangrenosum is caused by P aeruginosa until this pathogen has been excluded. Previously referred to as typhlitis because of the cecum as the predominant site in many cases. and clinically it may progress to bullae formation. A lifethreatening complication that may occur in patients who have received chemotherapy is neutropenic enterocolitis. which may result in the viridans streptococcal shock syndrome. which are listed in Table . the process may occur on several bases including destruction of GI mucosa by chemotherapy. conservative medical management appears to be effective for most patients. and whether vancomycin therapy is needed. The outcome among patients who received appropriate therapy was related to the duration of bacteremia. where the frequency did not change. and C jeikeium. a prospective. the incidence of P aeruginosa bacteremia decreased between the two study periods from . penicillin. or carbapenem. fever in neutropenic patients has been dened as a single oral temperature of . doubleblind. bacteremia. An ongoing controversy remains regarding whether an agent like vancomycin. Options in patients for monotherapy with vancomycin not being needed included one of the following agents cefepime or ceftazidime. all antimicrobial agents administered should be bactericidal. empiric antibiotics should be started after appropriate cultures are obtained. the recommendation for coverage against this pathogen in febrile neutropenic patients is prompted by the higher rates of mortality that may occur when this pathogen infects neutropenic patients. carbapenem plus vancomycin. to . For lowrisk adults only. in its most recent recommendations for management of febrile neutropenic patients the IDSA has offered suggestions for empiric antimicrobial therapy. In such patients. Of the neutropenic patients in this study who had P aeruginosa bacteremia and in whom therapy was delayed. cephalosporin cefepime or ceftazidime. known colonization with methicillinresistant S aureus or penicillin. In an update of these data from to in the same institution. The classic regimen has been an antipseudomonal lactam antibiotic eg.neutropenia. it was not presented as an option for monotherapy when vancomycin was not indicated. piperacillin or ceftazidime in combination with an aminoglycoside. positive results of Infections in AIDS Patients and Other Immunocompromised Hosts Karam . multicenter. A conclusion of the latter paper was that antibiotic regimens for empiric therapy in neutropenic patients and especially patients with acute leukemia should still provide coverage against P aeruginosa. three options were presented cefepime or ceftazidime plus vancomycin. In these recommendations. cases per . Even though an antipseudomonal penicillin was offered as an option in the IDSA guidelines for combination therapy without vancomycin and for therapy in which vancomycin was indicated. including the potential for acute mortality in neutropenic patients who are bacteremic with P aeruginosa. with or without an aminoglycoside. Inuenced by multiple factors. should be included in the initial regimen. Prior to the publication of the IDSA guidelines.and cephalosporinresistant S pneumoniae. with cure rates similar among patients who had bacteremia from to days but greater among patients with days of bacteremia for which the cure rate was only . Although some centers acknowledge a decreasing prevalence of infection caused by P aeruginosa. which would cover such pathogens as methicillinresistant S aureus. outcome was related to the interval between the onset of the bacteremia and the institution of appropriate therapy. with or without an aminoglycoside.C F or as a temperature of . an oral regimen using ciprooxacin plus amoxicillinclavulanate was suggested. admissions. cellulitis.and cephalosporinresistant Streptococcus pneumoniae. or imipenem or meropenem. Because of the risk of selecting vancomycinresistant enterococci or vancomycinresistant staphylococci with injudicious use of vancomycin. Because the patients do not have adequate neutrophils to provide natural host defense.C . the IDSA guidelines for management of febrile neutropenic patients discouraged vancomycin use in routine empiric therapy for a febrile neutropenic patient and recommended that this agent be used in the following settings clinically suspected serious catheterrelated infections eg. died within h and died within h. Options for combination therapy were an aminoglycoside plus an antipseudomonal penicillin. According to a review of episodes of Pseudomonas bacteremia in patients with cancer from to .F over at least h. it was noted that the initial evaluation should determine whether the patient is at low risk for complications with the specics dened in these guidelines. Overall cure rate was in the latter study period vs in the earlier study. randomized clinical trial showed piperacillintazobactam given as monotherapy to be as effective as the combination of piperacillintazobactam plus amikacin for the treatment for adults who were febrile and neutropenic. or an antipseudomonal penicillin plus an aminoglycoside and vancomycin. P aeruginosa bacteremia remained the most common in acute leukemia. In those patients in whom vancomycin is indicated discussed in the following paragraph. which has also been referred to as hepatosplenic candidiasis. comparative trials evaluating the relative efcacy of granulocyte colonystimulating factor vs granulocytemacrophage colonystimulating factor were available. uncontrolled primary disease. This illness may present as unexplained fever. Age years and posttreatment lymphopenia were mentioned as potentially being other highrisk factors. Certain patients with fever and neutropenia are at higher risk for infectionassociated complications and have prognostic factors that are predictive of poor clinical outcome. Because no largescale prospective. liposomal amphotericin B. but the benets in ACCP Critical Care Medicine Board Review th Edition these circumstances have not been proven. multiorgan dysfunction sepsis syndrome. which was recommended in the treatment of candidemia in nonneutropenic patients. indwelling catheters. pneumonia. The use of a colonystimulating factor in such highrisk patients may be considered. as adjuncts to progenitorcell transplantation. In the ASCO guidelines. neutropenic patients are at risk for candidemia. imaging studies may be negative. the most important pathogens to consider are Candida spp and Aspergillus spp. Potential clinical factors mentioned in the guidelines include profound neutropenia absolute neutrophil count / L. Clinical situations for which recommendations were made in adults include the following when the expected incidence of neutropenia is although there are some special circumstances detailed in the ASCO guidelines that might be a valid exception. and caspofungin. and hypotension or other evidence of cardiovascular impairment. Although the list of fungal organisms identied in neutropenic patients has increased signicantly in recent years. On the basis of neutropenia. patients may demonstrate bullseye liver lesions on ultrasound and hypodense liver defects on abdominal CT scan. Prolonged neutropenia is a major predisposition to fungal infection. and invasive fungal infection. During the period of neutropenia. colonystimulating factors were recommended after documented febrile neutropenia in a prior chemotherapy cycle to avoid infectious complications and maintain dose intensity in subsequent treatment cycles when chemotherapy dose reduction is not appropriate. In the guidelines of the IDSA for treatment of candidemia. right upper quadrant tenderness. germ cell tumors. but as the granulocyte count improves. The clinical presentation may range from unexplained fever to a septic appearance. dose reduction after an episode of severe neutropenia should be considered as a primary therapeutic option. Autopsy series have suggested that as many as of patients with evidence of metastatic candidal infections in visceral organs may have had negative antemortem blood cultures for Candida. The lungs are a prime . after completion of induction chemotherapy in patients years of age who have acute myeloid leukemia. Based on these data. and elevated alkaline phosphatase.blood cultures for Grampositive bacteria before nal identication and susceptibility testing. This was modied in the guidelines because there were no published regimens that have demonstrated diseasefree or overall survival benets when the dose of chemotherapy was maintained and secondary prophylaxis was instituted. particularly involving the mediastinum. was not included as a treatment option in neutropenic patients. and mucositis. The guidelines of the American Society of Clinical Oncology ASCO for colonystimulating factors were published in the Journal of Clinical Oncology. guidelines about the equivalency of these preparations were not proposed. it was recommended that. in the setting of many tumors but exclusive of curable tumors eg. Noteworthy is that uconazole. This recommendation is probably an acknowledgement of the evolving trend toward nonalbicans species of Candida and of the potential role of azole therapy in selecting for such pathogens. and after completion of the rst few days of chemotherapy of the initial induction or rst postremission course in patients with acute lymphoblastic leukemia. Aspergillus is a nosocomial pathogen that may be associated with vascular invasion and extensive tissue necrosis. the options for neutropenic patients included amphotericin B. Colonystimulating factors should be avoided in patients receiving concomitant chemotherapy and radiation therapy. The characteristic clinical infection in this setting is chronic disseminated candidiasis. but it was acknowledged that these have not been consistently conrmed by multicenter trials. hypotension. broadspectrum antibiotics. A structural part of these antibodies is a component referred to as the Fc segment. the skin lesions may be concentrically enlarging and necrotic. In a randomized trial comparing voriconazole with standard amphotericin B for primary treatment of invasive aspergillosis. There is not a consensus recommendation about when empiric antifungal therapy should be started for neutropenic patients who have persistent fever. Because of the nosocomial nature of this organism. A statistically signicant and noteworthy observation in this report was that patients receiving voriconazole had more episodes of transient visual changes than did those receiving liposomal amphotericin B . both agents were comparable in overall success. it has been the agent most often used. Because amphotericin B has activity against most Candida spp as well as Aspergillus. Of the various complement components. it is cleaved by C esterase to yield Cb. and because of the vascular invasion. infection of the paranasal sinuses and CNS may also occur. Once intracellular. there is an immediate need for host defense that cannot wait for antibody production. there is a requirement that certain organisms undergo opsonization. Liposomal amphotericin B has been shown to be as effective as conventional amphotericin B for empiric antifungal therapy in patients with fever and neutropenia. however. complement may serve as an opsonizer. and less nephrotoxicity. which produce as major opsonins IgG and IgM. which may be generated through two different pathways. More recently. with a spectrum of disease that includes pulmonary inltrates or cavitary lung lesions. the one most important for opsonization is Cb. and had fewer drugrelated adverse events p . randomized. voriconazole was demonstrated to be more effective than amphotericin B. international. but the IDSA guidelines for therapy in febrile neutropenic patients suggest beginning empirical antifungal treatment when there is persistent fever for days after antibacterial therapy is instituted in patients expected to have neutropenia for longer than to more days. a process in which those organisms are encased by a factor which then allows the phagocyte to attach. In a blinded. international multicenter noninferiority study of caspofungin mg daily. In situations such as the acute development of pneumococcal infection. The humoral immune system provides for such opsonization through its major components of antibody and complement and may be summarized as providing protection against pathogens that are hard to eat but easy to kill. A limitation of the classic complement pathway is the requirement for antibody production. and it is associated with fewer breakthrough fungal infections. In the classic complement pathway. These Fc segments attach to the Fc receptor on the phagocyte. The antibody component of humoral immunity is dependent on the transformation of B lymphocytes into plasma cells. less infusionrelated toxicity. Once C is activated. In addition to antibody. It is in this setting that the alternative complement pathway also known as the properdin system Infections in AIDS Patients and Other Immunocompromised Hosts Karam . it may be introduced into the skin with catheter insertion. Blood cultures are not likely to reveal this pathogen. With the lack of both intravascular and subepithelial polymorphonuclear leukocytes. mg on day vs liposomal amphotericin B mg/kg daily for therapy of persistently febrile neutropenic patients. Humoral Immunity To be ingested by polymorphonuclear leukocytes. Polymorphonuclear leukocytes have a receptor for this Fc segment.. which may take hours to develop. the formation of antigenantibody complexes turns on the complement cascade. multicenter trial found that voriconazole a new secondgeneration triazole with both Aspergillus and Candida activity was comparable to liposomal amphotericin B for empiric antifungal therapy. The IDSAs clinical guidelines for treatment of infections caused by Candida suggest starting antifungal treatment when there is persistent unexplained fever despite to days of appropriate antibacterial therapy. allowing the polymorphonuclear leukocyte to ingest the organism in a process that has been referred to as the zipper phenomenon of phagocytosis. caspofungin was associated with more successful outcome in patients with baseline fungal infections p . a randomized. these organisms are readily killed by the phagocyte.site of infection.An evolving body of clinical data regarding this topic has led to the recent comment that voriconazole will likely become the drug of choice for treatment of invasive aspergillosis. The characteristic pathogens infecting patients with impairment of immunoglobulin production are included in Table . Cb can be joined by factors B and D to form a C convertase. These lead to proteolytic cleavage of C to generate Cb. In addition to its opsonizing ability and its initiation of the membrane attack complex of complement. Major Clinical Situations Resulting in Disorder of Immunoglobulin Production Congenital agammaglobulinemias Common variable immunodeciency acquired hypogammaglobulinemia Heavy chain disease Waldenstrm macroglobulinemia Multiple myeloma Bcell lymphomas Chronic lymphocytic leukemia Tcell deciency states Hyposplenic states ACCP Critical Care Medicine Board Review th Edition . particularly echovirus . When bound by properdin. which is highly labile. Common variable immunodeciency CVI is associated with functional abnormalities of both B and T cells but is usually classied as a primary antibody deciency syndrome. Enteroviruses. CVI usually does not become clinically Table . Among the bacteria. with its resultant production of abnormal immunoglobulins occurring on the basis of Tcell deciency states in conditions such as HIV infection. the mortality in this setting remains high. Some clinical evidence exists that patients who have undergone splenectomy have a decrease in alternative pathwaymediated activation of C. including enteroviruses. with a high incidence of bacteremia and an increased risk of ARDS. In recent years. the one that most frequently causes an acute lifethreatening infection is S pneumoniae. and arboviruses. The major clinical situations that result in disorders of immunoglobulin production are summarized in Table . Despite appropriate antibiotics and supportive care. and neurologic problems. it has been noted that the severity of infection with S pneumoniae may be accentuated in patients with alcoholism or in those who are HIVinfected. hypocomplementemia. and this mechanism can lead to immediate opsonization. This has been referred to as chronic enteroviral meningoencephalitis. particularly echovirus Inuenza viruses Arboviruses Pneumocystis jiroveci formerly P carinii Giardia lamblia Asplenic State or Splenic Dysfunction Streptococcus pneumoniae Capnocytophaga canimorsus Babesia microti Plasmodium spp Haemophilus inuenzae Neisseria spp Table . the C convertase is stabilized and can then cleave more C to generate more Cb. inuenza viruses. Also included among the pathogens that infect patients with defects in immunoglobulin production are certain viruses. In both patient groups. edema. the alternative pathway is dependent on cell wall components such as teichoic acid and peptidoglycans found in Grampositive organisms and lipopolysaccharides found in Gramnegative organisms. Pathogens in Patients With Defective Humoral Immunity Disorders of Immunoglobulin Production Streptococcus pneumoniae Haemophilus inuenzae Encapsulated strains of Gramnegative bacilli Enteroviruses. with a resultant amplication of the alternative complement pathway. which may be multilobar. this pathogen may initially present as the etiologic agent of communityacquired pneumonia. An important consideration regarding infection with this pathogen is the increasing prevalence of penicillin resistance. asplenia or hyposplenic states. the common feature is encapsulation.becomes important. and impaired neutralization of toxins. Included in these processes is the lack of Bcell regulation. Instead of requiring an antigenantibody complex to turn on the cascade. have been associated with a clinical complex consisting of dermatomyositislike skin lesions. Of the pathogens defended against by humoral immunity. with the capsule essentially making them slippery and therefore dependent on opsonization for phagocyte attachment. Characterized by hypogammaglobulinemia and recurrent bacterial infections. There are four clinically relevant situations within the category of defective humoral immunity disorders of immunoglobulin production. and acute graftvshost disease in the first days posttransplant. interstitial pneumonia of infectious or idiopathic etiology. The valent pneumococcal vaccine is recommended for adults with functional or anatomic asplenia. The propensity for infection in these patients occurs on the basis of impairment of several immunologic functions relative to other lymphoid organs. untreated patients may develop a fulminant course that includes disseminated intravascular coagulation. In this patient population. Affected patients have an increased risk of autoimmune. IV immunoglobulin may be efcacious in patients with this clinical entity. Babesia microti and Plasmodium spp. Responsible for about of overwhelming infections in asplenic patients. dosing is more frequent than in prophylaxis for primary humoral immunodeciency. This reects the importance of local immunoglobulin production in the GI tract as a component of defense against G lamblia. Although S pneumoniae and Haemophilus inuenzae are pathogens encountered in patients with either disorders of immunoglobulin production or splenic dysfunction.apparent until the second or third decade of life. An important clinical clue to heighten awareness of both functional and anatomic asplenia is the presence of HowellJolly bodies on the peripheral blood smear. S pneumoniae should be given a particularly high index of suspicion because the clinical entity of postsplenectomy pneumococcal sepsis may initially present as only a ulike illness with fever and myalgias. the pathogens infecting the asplenic or hyposplenic patient are otherwise different. and alternative complementmediated activation of C may be decreased in patients after splenectomy. Its halflife of weeks allows for oncemonthly dosing for prophylaxis in patients with primary humoral immunodeficiency. purpura fulminans. For bone marrow transplant patients years of age. that infect erythrocytes to cause hemolytic states and that require removal of parasitized RBCs by the spleen as a protective defense. Patients with deciencies in the late complement components C through C may present with recurrent Neisseria spp infections. The total hemolytic complement CH is the best screening test for this population. are also important predispositions to infection. removing opsonincoated organisms or damaged cells from the circulation. Prevention of disease with vaccine is important in patients with defects in humoral immunity. shock. Even though recurrent bacterial infections of the respiratory tract are the most common. one can essentially exclude complement deciency. diarrhea due to Giardia lamblia is frequently encountered. although responses to vaccine may be attenuated. If the assay is normal. and botulism. as well as the hyposplenic states that occur in persons with sickle cell disease due to autoinfarction of the spleen and in patients with Hodgkin disease especially after therapy. tetanus. symmetrical peripheral gangrene. the spleen has a greater percentage of B lymphocytes and is therefore involved in the production of antibody to polysaccharide antigens. an Xlinked properdin deciency associated with absence of the alternative complement pathway may produce a similar picture of severe meningococcal disease. Completing the spectrum of clinical problems that may occur on the basis of defective humoral immunity is lessthanoptimal neutralization of toxins produced in diphtheria. Within the course of a few hours. granulomatous. Anatomic asplenia. the spleen participates as a phagocytic organ. chronic Infections in AIDS Patients and Other Immunocompromised Hosts Karam . In addition. and lymphoproliferative diseases. chronic cardiovascular disease. Capnocytophaga canimorsus produces an acute illness with eschar formation following dog bites to asplenic individuals. but anaphylaxis with such therapy has been reported. The important pathogens involved in infections in patients without a spleen or with splenic dysfunction are summarized in Table . Contraindications to its use include selective IgA deciency and severe systemic reactions to human immune globulin. Also included are two pathogens. concomitant infection of these two body sites should raise the suspicion of immunoglobulin deciency states such as CVI. it has been shown to decrease the risk of septicemia and certain other infections. IV gammaglobulin is a polyvalent antibody product containing the IgG antibodies that regularly occur in the donor population as well as traces of IgA and IgM and immunoglobulin fragments. and ultimately death. Because some of the common pathogens infecting the respiratory or GI tracts are dependent on antibody production for host defense. patients have a decrease in cellmediated immunity. provided that years has elapsed since receipt of the rst dose of pneumococcal vaccine. Hodgkin disease. HIV infection. H inuenzae B vaccines are immunogenic in splenectomized adults and may be considered for this group. When elective splenectomy is planned. which spontaneously reconstitutes itself within about months of delivery. especially corticosteroids and cyclosporine AIDS and HIVrelated disorders . and those receiving immunosuppressive chemotherapy including steroids. When restimulated. Although the need for revaccination of adults has not been determined. In an overall analysis not limited to immunocompromised patients. the predominant phagocytic cell in cellmediated immunity is the macrophage. if possible. and persons aged years if they received the vaccine years previously and were years old at the time of the primary vaccination. macrophages can readily ingest microorganisms but have a difcult time with intracellular killing. a Table . Irrespective of the mechanism. Immunosuppressive drugs including corticosteroids and cyclosporine and HIV infection are associated with defects in this limb of host defense. revaccination once was recommended for two groups persons aged years who are at highest risk for serious pneumococcal infection and those who are likely to have a rapid decline in pneumococcal antibody levels eg. and revaccination may be considered to years after receipt of the initial dose. other conditions associated with immunosuppression including transplantation. ciprofloxacin mg orally as single dose in nonpregnant adults. alcoholism. Both steroids and HIV infection decrease total T lymphocyte numbers. including macrophage activation factor. cyclosporine does not decrease lymphocyte numbers but decreases the functional capacity of lymphocytes to produce lymphokines. In contrast to polymorphonuclear leukocytes. lymphoma. these sensitized T lymphocytes produce a group of lymphokines. leukemia. ACCP Critical Care Medicine Board Review th Edition CellMediated Immunity The cellmediated immune system is dependent on the interrelationship of T lymphocytes with macrophages. This report noted that the vaccine provides an effective tool for reducing disease caused by drugresistant strains. functional or anatomic asplenia. Some of the disorders and clinical situations associated with defects in cellmediated immunity are listed in Table . With aging alone. the effectiveness of pneumococcal conjugate vaccine has been demonstrated to prevent disease in young children for whom the vaccine is indicated and may be reducing the rate of disease in adults. and H inuenzae B vaccination should precede surgery by at least weeks. including persons who have terminal complement component deciencies and those who have anatomic or functional asplenia. It is this substance that stimulates macrophages to better ingest and kill pathogens. In contrast. In contrast to primary neutrophil defense and humoral immunity. multiple myeloma. cerebrospinal uid CSF leaks. resulting in production of abnormal amounts of lymphokines like macrophage activation factor. or ceftriaxone mg IM as a single dose. generalized malignancy. in which the polymorphonuclear leukocyte is the major phagocyte.pulmonary disease. On initial exposure to an antigen. Prophylaxis options against meningococcal infection based on the patient population being treated include rifampin mg orally qh for days. Pregnant women in their third trimester have a transient loss of cellmediated immunity. In the review by the Centers for Disease Control and Prevention CDC. Important Clinical Situations Associated With Defects in CellMediated Immunity Aging During and following certain viral illnesses Thymic dysplasia Congenital situations associated with defects in cellmediated immunity Third trimester of pregnancy Lymphatic malignancies of Tcell origin Immunosuppressive therapy. and immunocompromised states including malignancy and HIV infection. chronic renal failure. chronic liver disease. antibody levels to N meningitidis rapidly decline over to years. This system may be summarized as providing protection against pathogens that are easy to eat but hard to kill. pneumococcal. Routine vaccination with the quadrivalent Neisseria meningitidis vaccine is recommended for certain highrisk groups. T lymphocytes become sensitized. meningococcal. diabetes mellitus. nephrotic syndrome. These reactions are not associated with changes in M tuberculosis bacteriology. viruses most characteristically. extrapulmonary TB has been reported in at least . With CD counts cells/ L. which is the temporary exacerbation of TB symptoms in the form of hectic fevers. lymphadenopathy. After initiation of antituberculosis therapy. and IDSA on the treatment of tuberculosis includes Infections in AIDS Patients and Other Immunocompromised Hosts Karam . worsening of chest radiographic findings. the cellular factor that binds to promoter regions of HIV. These reactions have been especially notable in individuals concurrently treated with antituberculosis and antiretroviral therapy. The rifamycins eg. When CD cells fall to / L. These individuals with drugsusceptible strains tend to respond well to standard antituberculous therapy given as a shortcourse regimen for months. Persons with serologic evidence of HIV infection and pulmonary TB fulll the case denition for AIDS. the pattern of typical reactivation TB with cavitary disease or upper lobe infiltrates is more common. and worsening of extrapulmonary lesions. In patients with CD counts at this level. it has attracted recent attention because of the copathogenesis that may occur in individuals who are dually infected with the intracellular pathogens M tuberculosis and HIV. Pathogens in Disorders of CellMediated Immunity Bacteria Mycobacteria Listeria Nocardia Rhodococcus Salmonella Legionella Brucella Bartonella formerly Rochalimaea Fungi Cryptococcus Histoplasma Coccidioides Blastomyces Candida Aspergillus Viruses Herpes simplex Varicellazoster Cytomegalovirus EpsteinBarr virus Polyoma viruses Adenoviruses Measles virus Parasites/Protozoa Pneumocystis Toxoplasma Strongyloides Giardia Cryptosporidium Isospora Trypanosoma Microsporidia Leishmania Amebae Others Treponema pallidum Chlamydiae Rickettsiae decrease in the production of macrophage activation factor decreases the stimulus for macrophages to optimally serve as the primary phagocytic cell in this host defense system. and a miscellaneous group some include spirochetes in this category. the pattern of disease is more typically middle to lower lobe disease with or without intrathoracic lymphadenopathy. and patients generally feel well with no signs of toxicity.Table . some patients experience a paradoxical reaction. CDC. Intracellular Bacteria Mycobacterium tuberculosis Although tuberculosis TB can be a problem in any patient with defective cellmediated immunity. fungi which often become clinically manifested in the setting of previous epidemiologic exposure. parasites and protozoa. rifampin and rifabutin accelerate the metabolism of protease inhibitors through induction of hepatic P cytochrome oxidases. DNA viruses. The pathogens infecting patients with defects in cellmediated immunity are summarized in Table and can be divided into ve categories bacteria having as a common characteristic an intracellular location. The presentation of TB in HIVinfected persons is variable and is inuenced by the level of immunosuppression. Such reactions have been attributed to recovery of delayed hypersensitivity response and an increase in exposure and reaction to mycobacterial antigens after bactericidal antituberculosis therapy is initiated. It has been suggested by some that myco bacteria and their products may enhance viral replication by inducing nuclear factor B. Rifabutin has comparable antituberculous activity but with less hepatic P cytochrome enzymeinducing effect than rifampin. including that with protease inhibitors. A noteworthy issue in HIVinfected patients is the interaction between antituberculosis drugs and antiretroviral therapy. The joint document of the American Thoracic Society. diarrhea. Mycobacterium avium Complex Among individuals with defective cellmediated immunity. it is recommended that HIVinfected persons with a tuberculin skin test with mm induration be given treatment for latent tuberculosis. To more accurately describe such therapy. In those patients with symptomatic disease. In a prospective cohort study of persons with HIV infection in the United States. The word preventive was inaccurate in that it referred to use of an agent such as isoniazid to prevent development of active TB in persons known or likely to be infected with M tuberculosis.to mm punctate lesions that are the hallmark of MAC disease in the gut. iniximab used to treat rheumatoid arthritis and Crohn disease. bone marrow. weight loss. in contrast to the reactivation that is common with TB. tuberculin positivity was also set at mm induration for patients with organ transplants and other immunosuppressed patients receiving the equivalent of mg/d of prednisone for month or more. anorexia. Some recent attention has focused on measures that foster type immunity as a means of treating patients with TB. Adherence of the organisms to the gut wall is the initial event in invasion. with extrapulmonary TB being especially noted. This is believed to occur on the basis of interference with enzyme metabolism rather than because of hepatic tissue destruction. it was not intended to imply prevention of true primary infection. a multidrug regimen is recommended that should . The other relates to the reports of liver failure and death after months of therapy with rifampin and pyrazinamide. GI tract mucosa. and lymph nodes although granuloma formation is minimal or absent.inhibitors eg. followed by entry into the lamina propria and then phagocytosis by macrophages. IL did not enhance bacillary clearance or improvement in symptoms in HIVseronegative adults with drugsusceptible TB. In patients with AIDS. respiratory secretions. including those who may not have responded to initial therapy. bilirubin. the terms preventive therapy and chemoprophylaxis were used to describe the status of persons with a positive tuberculin test but no symptoms or signs of active TB. Local replication of organisms leads to the endoscopically visible . stool. night sweats. A signicant change has recently occurred regarding TB infection. Based on such facts. serious pulmonary infection is not common in HIVinfected patients. there are several lines of evidence suggesting that most patients with disseminated MAC have recently acquired the organisms. the annual ACCP Critical Care Medicine Board Review th Edition risk of active TB among HIVinfected persons with a positive tuberculin test was . It acknowledged the role of LTBI as an important element in control of TB. Mycobacterium avium complex MAC classically infects HIVinfected persons when their CD cells are / L. For many decades. Two clinically relevant trends related to TB deserve comment. placebocontrolled. The clinical presentation is that of a wasting syndrome marked by fever. Despite positive sputum cultures. drugsusceptible pulmonary TB patients was conducted using adjunctive immunotherapy with recombinant IL. and malaise. which exceeds the standard estimated lifetime risk of approximately for the reactivation of LTBI in nonimmunocompromised persons with positive puried protein derivative tests. The organism is most characteristically isolated from blood. In this trial. in an ofcial statement in the American Thoracic Society introduced the terminology latent tuberculosis infection LTBI as a substitute for preventive therapy and chemoprophylaxis. cases per personyears of observation. smearpositive. A unique pathophysiologic abnormality seen in about of AIDS patients with MAC disease is marked elevations to times normal in serum alkaline phosphatase with little elevation of transaminases. or other parameters of hepatic function. The risk of TB increases with a higher dose and longer duration of corticosteroids. doubleblinded trial in HIVnegative. In the guidelines for treatment of LTBI.recommendations for use of rifamycins in the treatment of TB. One is an apparent increase in TB reactivation associated with tumor necrosis factor. a randomized. It has been noted that HIVinfected persons with a positive tuberculin skin test have about a chance per year of developing tuberculous disease. Because IL has a central role in regulating Tcell responses to M tuberculosis. Gram stain of the CSF is positive in only about one fourth of patients. weeks of therapy is recommended for serious infections. raw food from animal sources eg. unpasteurized milk. cavitary lesions. it has not been denitively proven that the combination is synergistic at the drug ratios that usually are achieved in serum or CSF. or in the absence of effective antiretroviral therapy. in up to of patients. especially with monotherapy. In this series. or amikacin as CIII recommendations. and Listeria has only recently been considered a cause of febrile GI illness in immunocompetent persons. Pustular skin lesions and neurologic disease in the form of encephalitis or brain abscess complete the triad of the most common presentations by this pathogen. The liver and kidneys are less likely to be involved. When it causes acute meningitis. Because the organism most commonly infects humans through the respiratory tract. recognizing that the aminoglycosides administered parenterally in adults will not cross the bloodbrain barrier but may help eradicate infectious sites outside the CNS. Bacteremia is another common presentation. trimethoprimsulfamethoxazole is possibly effective. Therapy is with highdose IV ampicillin or penicillin. the infection was common in AIDS patients as well as in transplant recipients. Listeria monocytogenes This intracellular Grampositive rod characteristically infects persons with malignancy. Additional drugs that may be added to this regimen include rifabutin as an A recommended agent or ciprooxacin. beef. which may take the form of nodular inltrates. the treatment guidelines recommend that adding a third drug be considered. About one third of patients in some series have no known risk factor. The most common clinical presentations are of CNS infection. sepsis. pork. complication of this localization. or foods made from raw milk notably. With advanced / L. diabetes mellitus. blood . Neonates and pregnant women are also at risk. Trimethoprimsulfamethoxazole is often used because of its convenient IV dosing.include either clarithromycin or azithromycin in combination with ethambutol. Nocardia asteroides These lamentous aerobic Grampositive rods are weakly acidfast and characteristically produce disease in patients who have lymphoreticular neoplasms or have received longterm corticosteroid therapy. In the report from the Johns Hopkins Hospital of patients diagnosed with nocardiosis over an year time span. disease developed in some despite prophylactic therapy against other pathogens with trimethoprim/sulfamethoxazole. Although rifabutin was the initial agent approved for prophylaxis against MAC infection. levooxacin. For penicillinallergic patients. Nocardia was isolated most commonly from the respiratory tract . or diffuse inltrates with or without consolidation. certain soft cheeses. with high immunosuppression CD mycobacterial loads. followed by soft tissue . and the acquisition of drug resistance is common. the classic pattern of infection is pulmonary disease. and CNS . or poultry. or renal transplantation followed by immunosuppressive therapy. with cerebritis or brain abscess being less frequent. In both groups of patients. more recent recommendations for the prevention of opportunistic infections in HIVinfected persons have listed azithromycin or clarithromycin as the agent of choice when the CD count is / L. Some favor the addition of a parenteral aminoglycoside with these agents even for treatment of meningitis. particularly cranial nerve involvement. Hydrocephalus may be a Infections in AIDS Patients and Other Immunocompromised Hosts Karam . Because of the intracellular location of the organisms. Listeria may be acquired via consumption of certain contaminated raw vegetables with coleslaw as a source in some outbreaks. or a ulike illness. The response to therapy is variable among patients. Extremely noteworthy is that cephalosporin therapy has no role in treating infection caused by Listeria. Listeria may be associated with a variable glucose level or with a CSF lymphocytosis or monocytosis. The infection has a predilection for the base of the brain with resultant focal neurologic signs. and the infection occurs with increased frequency with cirrhosis. Standard therapy is with sulfonamides. certain contaminated canned products with sterile canned corn kernels as the source in one outbreak. however. vancomycin. pyelonephritis. Like Nocardia. this partially acidfast. cavitary lung lesions with abscess formation may occur. and HIV infection. especially those with HIV infection. patients who receive corticosteroids. Compared with Shigella and Campylobacter. it has also been associated with neurologic and skin lesions. uoroquinolones. intracellular Grampositive rodcoccus was rst described in as the cause of disease in humans. The intracellular location has made the organism difcult to treat. ciprooxacin. glycopeptides eg. a disorder of monocyte deciency and dysfunction. aerobic. In individuals receiving corticosteroids. rifampin. there is a lower incidence of bloody diarrhea and fecal leukocytes with Salmonella infection. secondary antibacterial prophylaxis in HIVinfected persons. immunocompromised patients.Rhodococcus equi Formerly called Corynebacterium equi. Bacteremia is common in immunocompromised patients. The choice of agents used and the duration of therapy are dependent on both the patients host defense status and the site of infection. In those persons with HIV infection. Some have suggested that rifampin be Salmonella spp Patient populations with defective cellmediated immunity that develop bacteremia with this intracellular Gramnegative rod include those with hematologic malignancies. Even though the organism has been rarely reported to cause infection in immunocompetent patients. have an increased incidence of Legionella pneumonia. are the ones most likely to develop clinical disease due to this pathogen. the most common extrapulmonary site was reported to be the heart including myocarditis and pericarditis. it has been suggested that immunocompromised patients and patients with serious infections receive IV therapy with twodrug or threedrug regimens that include vancomycin. but recent reviews have suggested that the uoroquinolones may be more efcacious. and one would need to assume that such organ system involvement might be possible in immunocompromised patients. and pancreatitis. In vitro. aminoglycosides. imipenem. Legionella infection should be suspected in those individuals who do not respond to therapy with a lactam antibiotic. and imipenem. The most characteristic pattern of infection is described as a progressive pneumonia that may cavitate. More common is an illness associated with fever. R equi is usually susceptible to erythromycin. and crampy abdominal pain. In a review of Legionnaires disease. This pathogen causes more severe disease in transplant recipients. Patients with hairycell leukemia. systemic lupus erythematosus. and/or erythromycin. rifampin. Recurrent nontyphoidal bacteremia is considered an indication for ACCP Critical Care Medicine Board Review th Edition . aminoglycosides. often in association with drainage. Erythromycin has traditionally been considered the agent of choice for treatment of this infection. Because of increased efcacy and the fact that macrolides such as erythromycin may have pharmacologic interactions with immunosuppressive agents used in transplant patients. some investigators feel that a uoroquinolone should be added to the standard regimen for treating Legionnaires disease in transplant recipients with nosocomial pneumonia if the causative agent has not been identied. Fever with a scanty productive cough is often described. cellulitis. Oral antibiotics may be an option in certain immunocompetent patients with localized infection. Immunocompromised patients with legionellosis may present with variable patterns of multisystem disease. Other patterns of extrapulmonary involvement by Legionella may take the form of sinusitis. severe diarrhea. Dissemination seems to occur via bacteremic spread of the organism. and principles of therapy include a prolonged duration of antibiotics. and HIVinfected persons. including even those who are not immunocompromised. which has been stated to be sensitive and specic in diagnosing infection caused by Legionella pneumophila serogroup I. Legionella spp Legionella is a pathogen recognized to have the potential for causing acute mortality in patients with pulmonary infections. Useful in the acute diagnosis is the Legionella urinary antigen assay. a febrile typhoidal illness without diarrhea accounts for about of the disease caused by this pathogen. Fungi Cryptococcus neoformans Cryptococcal meningitis is an important infection in HIVinfected persons. These ndings make CSF studies such as India ink stain. Infection in the HIV population may present as a noninammatory infection of the CNS. and fungal culture mainstays in the diagnosis. the spectrum of brucellosis in immunocompromised hosts has not been frequently described. therefore. usually with CD counts cells/L. The organism has a propensity to enter the bloodstream and may be detected in routine blood cultures. Conclusions from this trial of AIDSassociated cryptococcal meningitis were that induction treatment for weeks with the combination of amphotericin B . The patterns of infection in HIVinfected persons include the following bacteremia in the absence of focal vascular proliferative response in tissue. mg/kg/d plus ucytosine mg/kg/d in patients who were tolerant of this agent. either alone or in association with other sites of involvement. and the clinical features are therefore different from what one might expect in classic forms of meningitis caused by other pathogens. The authors noted that high intracranial pressures have been associated with catastrophic neurologic deterioration and death in the absence of hydrocephalus. histopathology may be the study that directs further diagnostic evaluation. bacillary angiomatosis. The organism enters the body through the lungs. and normal protein. Peliosis hepatitis refers to the bloodlled peliotic changes in the parenchyma of the liver or spleen that occur because of infection with these two species. Because of the lack of inammation in the CNS. normal glucose. Erythromycin or doxycycline is considered the preferred agent. Based on the association between elevated intracranial Brucella spp Even though intracellular brucellae require cellmediated immunity for eradication. and peliosis hepatitis. and the associated nding of pulmonary inltrates in an HIVinfected person with meningitis should raise the suspicion of this diagnosis. The condition is associated with a unique vascular lesion that may involve virtually every organ system. Because these organisms are at present difcult to culture from blood or tissue. Of these. Because of the ability for splenic localization with the formation of suppurative lesions that might require splenectomy. Bacillary angiomatosis presents in the later phases of HIV infection. Species causing such a process include Bartonella henselae and Bartonella quintana. the CSF formula may include WBC/mm. skin lesions are the most commonly recognized. The resulting fungemia is often associated with multisegment pulmonary inltrates and with skin lesions. particularly when CD counts are cells/ L. The history is frequently of a subacute or chronic illness associated mainly with headache. and rifampin has the potential to induce the cytochrome P system and. Physical examination may not reveal classic ndings such as nuchal rigidity. this organism may cause further impairment of an otherwise compromised immune system. cryptococcal antigen. with characteristic lesions being red and papular and therefore resembling Kaposi sarcoma. Bartonella Formerly Rochalimaea spp The small Gramnegative organisms in this genus may be demonstrated with WarthinStarry staining or by electron microscopy. Of the patients in this study. but this must be taken in context with the facts that no prospective studies have evaluated such therapy.used as adjunctive therapy for severe Legionella infections. Lesions characteristically are associated with a long duration of symptoms or physical ndings prior to diagnosis. cause a signicant interaction with immunosuppressive therapy. but may also occur in other populations. including elderly persons. followed by therapy with uconazole mg/d orally for weeks is safe and effective and should be considered the treatment of choice. Infections in AIDS Patients and Other Immunocompromised Hosts Karam . The National Institute of Allergy and Infectious Diseases Mycoses Study Group and AIDS Clinical Trials Group reported their ndings in patients with cryptococcal meningitis treated in a doubleblind multicenter trial. of early deaths and of deaths during weeks through were associated with elevated intracranial pressure. More recently. tissue. mg twice daily when the patient no longer requires hospitalization for IV therapy. In those without AIDS who were sufciently ill to require hospitalization. and studies have identied uconazole as the agent of choice.. this fungal pathogen occurs most commonly in those individuals from endemic areas. IDSA guidelines for the management of cryptococcal meningitis in HIVinfected persons with opening CSF pressure of mm HO recommended lumbar drainage sufcient to achieve a closing pressure mm HO or of initial opening pressure. Histoplasma capsulatum The clinical entity of progressive disseminated histoplasmosis has become increasingly recognized because of HIV infection. For patients with AIDS. with replacement by itraconazole. amphotericin B . Although patients may present with such nonspecic ndings as fever. commonly mm HO. Although the organism may be isolated from sputum. The illness may resemble Pneumocystis pneumonia with diffuse reticulonodular inltrates. Recurrent cryptococcal infection should be suspected in patients whose serum cryptococcal antigen test results revert back to positive after discontinuation of maintenance therapy. Itraconazole mg tid for days and then bid for weeks was recommended for patients who have mild or moderately severe symptoms and do not require hospitalization. Maintenance therapy is required after completion of primary therapy. yeastlike organisms are the characteristic morphologic form of the organism. In an international observational study reported by the International Working Group on Cryptococcosis. It was noted that most patients respond quickly to amphotericin B and can then be treated with itraconazole mg qd or bid for to mo. and bone marrow involvement. to . it was suggested that measurement of intracranial pressure be included in the management of such patients. or CSF may serve as a more rapid diagnostic study.pressure and mortality in patients with cryptococcal meningitis. it was recommended that therapy be divided into an initial week intensive phase to induce a remission in the clinical illness and then followed by a chronic maintenance phase to prevent relapse. lymphadenopathy. Coccidioides immitis In HIVinfected persons as well as in transplant recipients. A subgroup may present with a septic syndrome that can include disseminated intravascular coagulation. In the IDSA guidelines for treating disseminated histoplasmosis. Small intracellular periodic acidSchiff positive. the H capsulatum polysaccharide antigen from blood. fatigue. manifested as dissemination to sites such as meninges. discontinuation of maintenance therapy for cryptococcal meningitis was stated to be safe if the CD cell count increases to cells/ L while the patient is receiving highly active antiretroviral therapy HAART. urine. The illness may occur on the basis of either reactivation or primary disease. immunocompromised patients were divided into those with AIDS and those without AIDS. and weight loss. it was recommended that in the absence of focal lesions. opening pressures mm HO should be treated with largevolume CSF drainage dened in this report as allowing CSF to drain until a satisfactory closing pressure had been achieved. Maintenance therapy with itraconazole for life was included in the recommendations. weakness. and ventriculoperitoneal shunts for asymptomatic patients with intracranial CSF pressure mm HO and for symptomatic patients with pressures mm HO. Amphotericin B was recommended for patients sufficiently ill to require hospitalization. mg/kg/d was recommended. Included in the recommendations were daily lumbar punctures. a characteristic presentation in about half of patients is ACCP Critical Care Medicine Board Review th Edition diffuse interstitial or miliary pulmonary inltrates that are associated with hypoxemia and mimic Pneumocystis jiroveci previously Pneumocystis carinii pneumonia. to complete a week total course of induction therapy. The classic clinical pattern of disease. These ndings were consistent with previous recommendations by the US Public Health Service and the IDSA that discontinuation of secondary prophylaxis may be an option when CD cells are to cells/ L for months. or blood. making the epidemiologic history of travel to or residence in endemic areas crucial. . These patients may concomitantly demonstrate reticuloendothelial involvement in the forms of hepatosplenomegaly. use of acetazolamide. At CD levels of cells/ L. invasive pulmonary or disseminated aspergillosis may occur. A recent trend has been toward nonalbicans strains of Candida and toward strains of Candida albicans that are uconazoleresistant. and notable risk factors for this include surgery particularly of the GI tract. oral candidiasis is the expected clinical entity.stimulates killing of this pathogen and reduces the frequency and severity of clinically apparent fungal infection. The echinocandin caspofungin has been recently approved for patients in whom amphotericin fails. Voriconazole is the preferred therapy for invasive aspergillosis in HIVinfected patients. In addition to being a nosocomial pathogen. Patients with chronic granulomatous disease have an increased incidence of infection with Aspergillus. This tends to present in the later stages of HIV infection. The IDSA guidelines for treatment of coccidioidomycosis offer recommendations for the management of meningitis. primary prophylaxis is not generally recommended. or ethanol use. In a randomized trial comparing voriconazole with standard amphotericin B for primary treatment of invasive aspergillosis. Aspergillus may cause infection in patients with defects in either neutrophil function or cellmediated immunity.based on an understanding of the role of type immunity in defending against certain fungal pathogens. of patients became colonized with fluconazoleresistant strains of C albicans. and intravascular catheters. therapy usually starts with amphotericin B. the immunocompetent host may develop bloodborne infection with this pathogen. These candidal infections generally respond well to therapy. and because of this. In such circumstances. it was noted that the presence of bilateral reticulonodular or miliary inltrates produced by C immitis usually implies an underlying immunodeciency state. Recurrent use of uconazole in HIVinfected patients has been associated with an increasing number of reports of Candida spp resistant to this agent. Lipid formulations of amphotericin have noteworthy roles in two circumstances for the patient who has impaired renal function or develops nephrotoxicity while receiving amphotericin B deoxycholate and for patients who have undergone bone marrow transplantation. The clinical presentation of odynophagia in a patient with oral candidiasis and a CD count of cells/ L strongly raises the diagnosis of Candida esophagitis. With CD counts in the to cells/ L range. In addition. infection with this agent may represent reactivation disease. Itraconazole has been suggested as an alternative form of therapy in certain settings of Aspergillus infection. including a role for oral uconazole in certain patients. voriconazole was demonstrated to be more effective than amphotericin B. This observation is important in that it conveys a treatment option for IFN. Several weeks of therapy is often required for improvement. women may develop recurrent vulvovaginal candidiasis. With HIV infection. broadspectrum antibiotics. Candida may present in a hierarchical pattern. hyperalimentation.skin. and joints. which Candida spp Host defense against Candida is provided by both neutrophils and cellmediated immunity. oral or IV for the rst days after transplantation. corticosteroid therapy. especially when CD cells are / L. In AIDS patients with the concomitant problems of neutropenia. An evolving body of clinical data regarding this topic has led to the recent comment that voriconazole. Treatment of these patients with recombinant IFN. at which point an oral azole may replace amphotericin. Patterns of azole use have probably contributed to such problems. This may be especially notable in patients who have received a bone marrow transplant or solid organ transplant. mg/kg/d and continued despite modest increases in serum creatinine. Infections in AIDS Patients and Other Immunocompromised Hosts Karam . The traditional treatment for Aspergillus has been amphotericin B given at maximum tolerated doses eg. Aspergillus spp As is the case with Candida. In a bone marrow transplant unit in which patients were given uconazole mg/d. is not altered by HIV infection. to . In the IDSA guidelines for the treatment of coccidioidomycosis. and of patients had at least one mouthwashing sample that yielded nonalbicans species of Candida during the course of their bone marrow transplantation. Aspergillus infection and its treatment provide some important insights into the evolving clinical importance of type immunity. including esophagitis. women with VZV pneumonia compared with matched control subjects identied cigarette smoking and skin lesions as markers for the development of varicella pneumonia in pregnancy. and a spectrum of neurologic diseases. or hepatitis are characteristic presentations. and this may be the initial clue to the diagnosis of HIV infection. Although serologic tests have previously been suggested to have a VaricellaZoster Virus As is the case with HSV infection. Herpes zoster may be multidermatomal in HIVinfected persons. In transplant patients. with hepatitis caused by HSV presenting most classically as the triad of high fever. Cytomegalovirus For perspective. possibly enhancing chronic rejection. acyclovirresistant strains have emerged. and the requirement for IV vs oral therapy. hepatitis. adrenalitis. Acyclovir. The spectrum of clinically active CMV infection in immunocompromised patients is broad and may vary according to the immunosuppressive condition. The virus may be present in the forms of latency infection without signs of active viral replication. the pattern of immunosuppression. leukopenia. and primary infection active infection in a previously nonimmune seronegative person. colitis. will likely become the drug of choice for treatment of invasive aspergillosis. In immunocompromised patients and pregnant women who are exposed to chickenpox and in whom there is no clinical or serologic evidence of immunity to VZV. superinfection with opportunistic pathogens. varicellazoster virus VZV may present differently according to the underlying type of immunosuppression. including a wide range of clinical illnesses. New approaches in both hematopoietic stem cell or solid organ transplant recipients emphasize the use of prophylactic or preemptive therapy based on CMV monitoring. and injury to the transplanted organ. encephalopathy. HIVinfected persons can have a vast array of clinical conditions caused by HSV. and markedly elevated aminotransferase levels. With the depression of cellmediated immunity that occurs during the third trimester of pregnancy. active infection viral replication in blood or organs. A recently published casecontrol analysis of pregnant ACCP Critical Care Medicine Board Review th Edition . it is important to recognize the three major consequences of cytomegalovirus CMV infection in solid organ transplantation recipients CMV disease.is available in both IV and oral formulations. These patients died of invasive bacterial and fungal infections at a rate greater than that of patients who did not have primary infection. the classic presentation has been chorioretinitis but may also include GI ulcerations. Treatment options for both varicella and zoster have been summarized. and it was hypothesized that primary CMV infection has immunomodulatory effects that predispose to such secondary infections. pneumonitis. Viruses Herpes Simplex Virus The patterns of herpes simplex virus HSV infection vary according to the underlying immunosuppression status. and meningoencephalitis. perianal ulcers often associated with urinary retention. there is increased risk of dissemination of VZV to the lungs during pregnancy. administration of varicellazoster immune globulin may prevent or signicantly modify VZV infection. pneumonitis. In HIVinfected patients. famciclovir. and a painful myeloradiculopathy. esophagitis. cutaneous dissemination may occur and may be associated with such visceral involvement as pneumonitis. Some immunosuppressed patients present with only a mononucleosislike syndrome consisting of fever and lymphadenopathy. Patients with hematologic or lymphoreticular neoplasms may develop disseminated mucocutaneous HSV lesions. A recent study addressed the impact of primary infection in bone marrow recipients who were CMVseronegative and who received stem cells from CMVseropositive recipients. However. and valacyclovir are discussed according to the disease. With both chickenpox and shingles in patients with solid and hematologic malignancies. hepatitis.. for which foscarnet may be the alternative therapy. Acyclovir remains the drug of choice for these infections. tracheobronchitis. pneumonitis. Although early studies indicated that EBV replicated in epithelial cells in the oropharynx. which acts as an oncogene and whose expression in an animal model has resulted in Bcell lymphomas. Secondary prophylaxis has been recommended but may be discontinued if the CD cell count reaches to cells/ L and remains at this level for months with no evidence of active CMV disease. Even though the nding of antibodies against EBV viral proteins and antigens is consistent with the fact that there is some degree of humoral immunity to the virus. DNA/RNAemia especially quantitative polymerase chain reaction is clinically useful. Important among the proteins produced by EBV is latent membrane protein . hairy leukoplakia presents as raised Infections in AIDS Patients and Other Immunocompromised Hosts Karam . studies are ongoing using valganciclovir as both preemptive and definitive therapy of CMV infections in transplant patients. prophylactic use use of antimicrobial therapy from the earliest possible moment. It has been suggested that therapy for EBV lymphoproliferative disease should include reduction in the dose of immunosuppressive medication when possible. valganciclovir an oral prodrug of ganciclovir has been approved as an effective treatment option. Bcell hyperplasia. The appearance of CMV protein pp in peripheral blood leukocytes has proved to be superior to tests based on virus isolation and has correlated with subsequent development of CMV disease. denitive recommendations for therapy are not available. An immune reconstitution syndrome including visual blurring months after successful therapy of CMV retinitis has been described in AIDS patients who have started HAART. denitions of CMV infection and disease were developed and published. This has led to the thought that resting memory B cells are the site of persistence of EBV within the body. What has not been denitively elucidated at the present time is the role of oral epithelial cells in the transmission and latency of EBV. In addition. In the therapeutic setting of CMV disease after solid organ transplantation. an approach to the management of CMV infection after solid organ transplantation has been recently published. but potential options have been reviewed. EpsteinBarr Virus The pathobiology of EpsteinBarr virus EBV is important in understanding the evolution of EBVassociated disease in immunocompromised patients. which in tissue may take the form of plasmacytic hyperplasia. preemptive use antimicrobial therapy before clinical signs of infection. In addition. or immunoblastic lymphoma. with antiCMV hyperimmunoglobulin preparations being useful adjuncts in seronegative recipients of seropositive organs and with foscarnet because of its inherent toxicity being considered as rescue therapy. nonmalignant hyperplastic lesion of epithelial cells seen most characteristically in HIVinfected patients. with the number of latently infected cells remaining stable for years. more recent studies suggest that B cells in the oropharynx may be the primary site of infection. and several clinically relevant messages provided it. the clinician needs to be aware of four types of treatment options therapeutic use treatment based on the presence of established infection. In addition to CMV antigenemia. and detection tests for both are methods of choice for diagnosis and monitoring of active CMV infection after organ transplantation. With detection of CMV antigenemia at a predened level. Completing the spectrum of EBV disease in immunocompromised patients is oral hairy leukoplakia. and deferred therapy initiation of therapy after onset of disease. it is the cellular immune response that is the more important for controlling EBV infection. For the purpose of developing consistent reporting of CMV in clinical trials. More specic. Although ganciclovir has for years been the mainstay of therapy for CMV retinitis in AIDS patients. serologies are not the most reliable studies in predicting the presence of CMV infection or clinical disease. an inability to control proliferation of latently EBVinfected cells may lead to EBV lymphoproliferative disease. Bcell lymphoma. In patients who have AIDS or have received organ or bone marrow transplants. In managing CMV infection. The role for prophylaxis against CMV was summarized based on the type of organ transplanted. IV ganciclovir may have a role in preventing CMV disease in certain patient populations. a common. In its classic presentation.potential role in directing CMV therapy in bone marrow transplant patients and heart transplant patients. IV ganciclovir is the drug of choice. In this primary demyelinating process involving the white matter of the cerebral hemispheres. and liver. and clinical efforts have recently focused on the role of immune reconstitution in modifying the clinical course of the illness. decreases in JC virus DNA to undetectable levels predicted a longer survival. the most characteristic disease entities are hemorrhagic and nonhemorrhagic cystitis. neurologic improvement or stability at months after therapy was demonstrated in of patients who received HAART in contrast to improvement in only of patients who did not receive HAART p . GI tract.. but EBV replication returned in normal tongue epithelial cells after valacyclovir treatment. Even with the overwhelming success of measles immunization programs. Fatal giantcell pneumonitis has been described in a young male measles vaccine recipient with AIDS. JC virus is the etiologic agent in progressive multifocal leukoencephalopathy PML. Primary infection with BK virus is generally asymptomatic and occurs in childhood. A feature on neuroradiology imaging studies is lack of mass effect. a study of serial tongue biopsy specimens from HIVinfected patients demonstrated EBV replication in normal tongue epithelial cells in contrast to the lack of active viral replication in certain EBVassociated malignancies and suggested that the tongue may be a source of EBV secretion into saliva. valacyclovir treatment completely abrogated EBV replication. and these occur most often in recipients of solid organ or bone marrow transplants. which may result in death. An exception has been use of measles vaccine. protection via vaccine is an important consideration. patients present subacutely with confusion. Adenoviruses In immunocompromised patients. Topics not evaluated in this study. especially on the lateral aspect of the tongue. Polyoma Viruses Including JC Virus and BK Virus Clinically important members of this class of doublestranded DNA viruses include BK virus and JC virus. a livevirus vaccine. The infections may have a fulminant course. liver. and brain are sites of both primary and reactivated BK virusassociated disease. the virus can remain latent in many sites. although IV ribavirin may be effective in some. This class of viruses has recently emerged as a major problem in some bone marrow transplant units. resulting in resolution of hairy leukoplakia when it was present. and visual disturbances. In a multicenter analysis of consecutive HIVpositive patients with PML.white lesions of the oral mucosa. but important in the understanding of EBV. A basic tenet in infectious diseases has been that livevirus vaccines should not be administered to immunocompromised patients. such potential for preventing neurologic progression and improving survival by controlling JC virus replication becomes clinically relevant. No drug has been shown to be denitively benecial in these patients. respiratory system. No denitive therapy ACCP Critical Care Medicine Board Review th Edition Measles Virus Because individuals are protected against measles by cellmediated immunity and since measles may cause severe illness in HIVinfected persons. in asymptomatic HIVinfected individuals and potentially in those with symptomatic HIV infection. Contributing to the ongoing attempts to elucidate the pathobiology of EBV. In this study. which may progress to cortical blindness or ataxia. the virus can reactivate and cause clinical disease. CSF is characteristically acellular. With cellular immunodeciency. these DNA viruses may produce generalized illness that classically involves the nervous system. lung. eye. In this clinical trial. disorientation. with the most notable being the kidney. and nephritis. this case has prompted reappraisal of recommendations and some have suggested that it may be prudent to withhold measlescontaining . are whether other oral epithelial cells support viral replication and whether oral epithelial cells participate with B cells in viral latency. Following primary infection. ureteric stenosis. These ndings are consistent with clinical experience that the lesions of hairy leukoplakia respond to antiviral therapy but recur once therapy is stopped. Although the kidney. is presently available for this infection. In the context that untreated PML may be fatal within to months. The dramatic decrease in the number of cases of PCP relative to the number of patients with HIV infection has been attributable to prophylaxis. Findings that support. the use of the acronym PCP is not precluded because it can be read Pneumocystis pneumonia. a WBC count . HIVassociated PCP has decreased. particularly in persons who have received bone marrow or solid organ transplantation.vaccines from HIVinfected persons with evidence of severe immunosuppression. and if that smear is negative. Also listed as alternative therapy for mild to moderate disease are dapsone plus trimethoprim. PCP may occur as part of the presentation of the acute retroviral syndrome. Although diffuse interstitial inltrates are the most characteristic pulmonary nding with PCP. cavitary lesions. Ongoing investigation has been focused on the development of a quantitative polymerase chain reaction assay that can be performed on oral washes or gargles and that might allow a clinician not only to diagnose PCP at an earlier stage than has traditionally been possible. or nodular lung lesions. it has been included in this section of pathogens that infect patients with defective cellmediated immunity. atovaquone. Host defense against Pneumocystis includes humoral immunity. Infections in AIDS Patients and Other Immunocompromised Hosts Karam . the organism that causes human Pneumocystis pneumonia has been recently renamed P jiroveci. with the lung being an important target organ. especially during the time of steroid withdrawal. the diagnosis of PCP in an HIVinfected patient with pulmonary inltrates include a CD cell count cells/ L. The spectrum of disease caused by these pathogens is evolving. because of the overwhelming predominance of infection by this pathogen in HIVinfected persons. Following the widespread use of HAART in the mids. This stain is performed rst on induced sputum. Following the onset of the AIDS epidemic in the early s. which is recommended for those patients with a CD cell count cells/ L. or trimetrexate with leucovorin. Direct immunouorescent staining using monoclonal antibody G which detects both cysts and trophozoites has been used for many years in the algorithm of the National Institutes of Health Clinical Center for diagnosing PCP. Emerging Viral Pathogens in Persons With Defects in CellMediated Immunity There have been increasing reports of infections caused by respiratory syncytial virus or parainuenza virus. Trimethoprimsulfamethoxazole is the current firstline therapeutic agent. then a BAL specimen is obtained for the same study. but despite this change. but do not prove. patients may present with focal inltrates. In the preAIDS era. In the review of PCP from the Clinical Center at the National Institutes of Health. cells/mm. Parasites and Protozoa P jiroveci Previously P carinii In recognition of its genetic and functional distinctness. These viruses should be considered to be among the pathogens that may cause pneumonia in patients with defects in cellmediated immunity. pentamidine has been recommended for severe PCP. and it has been recently reported that PCP may in certain settings be diagnosed more often in nonHIV immunocompromised patients than in those with HIV infection. Adjunctive corticosteroid therapy is recommended for patients with PCP whose room air Pao is mg Hg or whose arterialalveolar oxygen gradient is mm Hg. It was noted that traditional stains on sputum or from BAL specimens for the cyst form of P jiroveci have been the mainstay of diagnosis in most settings. Clindamycin/primaquine has been compared with trimethoprimsulfamethoxazole in a clinical trial and found to be a reasonable alternative therapy for mild to moderate PCP. The clinical setting in which P jiroveci pneumonia PCP develops continues to evolve. As alternative therapy. but also to distinguish between colonization and disease with P jiroveci. however. and an elevated serum lactate dehydrogenase. diagnostic studies for PCP were reviewed. PCP was most often diagnosed in HIVinfected persons. this pathogen was described as a cause of rapidly progressive infection in patients with malignant diseases. It is important that steroids are started at the time antipneumocystis therapy is initiated in an attempt to prevent the lung injury that may occur when this pathogen is killed. CD cells of total lymphocyte count. the clinical presentation of watery diarrhea. cramping. Imaging studies of the brain show multiple usually nodular contrastenhancing lesions. epigastric pain. the total duration of acute therapy should be at least weeks. Among patients with defects in cellmediated immunity. After acute therapy for toxoplasmic encephalitis. it classically presents as fever. The bacteremia occurs because of this organisms hyperinfection cycle. and meningitis. Because the disease is due to reactivation of latent infection in about of cases. or AIDS. bacteremia secondary to the hyperinfection is uncommon in two groups transplant recipients who receive cyclosporine because of the anthelminthic properties of this rejection agent. or inadequate clinical response to an optimal treatment regimen or to what the physician ACCP Critical Care Medicine Board Review th Edition Strongyloides stercoralis Infection with this parasite has often been described in patients with COPD who have been receiving chronic steroid therapy and who present with Gramnegative bacteremia. considers to be an effective prophylactic regimen against T gondii. and ascend to the glottis where they are swallowed into the intestinal tract to continue their process of autoinfection. and focal neurologic decits. headache. a seronegative recipient who acquires the parasite from a seropositive donor via a graft. ileus. diffuse pulmonary inltrates. Ivermectin may also be more effective than thiabendazole. toxoplasmosis results from reactivation of latent infection. Brain biopsy should be considered in immunocompromised patients with presumed CNS toxoplasmosis if there is a single lesion on MRI. anorexia. IgG antibody to Toxoplasma is generally present. found most commonly in the basal ganglia and at the graywhite matter junction. In the vast majority of immunocompromised patients. during which lariform larvae penetrate the intestinal mucosa. lung. and malaise in an HIVinfected patient . Toxoplasma gondii Patient populations at higher risk for toxoplasmosis include those with hematologic malignancies particularly patients with lymphoma. it seems that discontinuing prophylaxis in patients with adequate immune recovery is a useful strategy that should be widely considered. or kidney. but in heart transplant patients and in a small number of other immunocompromised patients. Mass effect is characteristic with these lesions. liver. Infection with this pathogen should be suspected in a patient with a defect in cellmediated immunity who presents with clinical features that include generalized abdominal pain. unless the CD cell count is cells/mm and the patient is concomitantly receiving corticosteroids. the highest risk of developing disease is in the setting of primary infection ie. Clindamycincontaining regimens may have a role in sulfaallergic patients. solid organ transplant including heart. recommendations for therapy have changed based on the recognition that thiabendazole may not be consistently efcacious and that albendazole may be superior. or a previous history of PCP. constitutional symptoms such as thrush or unexplained fever F for weeks regardless of the CD count. In recent years. maintenance therapy is recommended but may be discontinued when the CD cell count is /L for months. break into alveolar spaces. In HIVinfected persons. shock. In the classic setting. Based on several clinical investigations. empiric therapy with sulfadiazine and pyrimethamine is recommended. and HIVinfected patients. altered mental status. Cryptosporidium parvum Although selflimited diarrhea associated with waterborne outbreaks has been noted in normal hosts. neurologic disease is the classic pattern. Trimethoprimsulfamethoxazole given for PCP prophylaxis serves as primary prophylaxis for toxoplasmosis. but should not be used for therapy. Although pulmonary disease due to this pathogen is associated with nonspecific radiographic findings of which bilateral pulmonary interstitial inltrates are most common. a negative IgG antibody test result. pass to the lungs by way of the bloodstream. atulence. Eosinophilia is often absent in steroidtreated patients. especially in individuals whose CD count falls below cells/ L.. bone marrow transplant. visual disturbances. peritonitis. Effective antiretroviral therapy to increase CD count to cells/ L has been noted to result in complete. but it appears that the diamidine derivatives pentamidine. fumagillin has been suggested as being effective. It is contraindicated in patients with myocarditis. The modied trichrome stain has been used in clinical diagnostic laboratories to detect microsporidia in uids. Four clinical syndromes have been identied chronic diarrhea in of patients. No predictably effective antimicrobial therapy is available. and keratoconjunctivitis. focal neurologic decits. Albendazole may be the most effective drug to treat disseminated not ocular and intestinal infection attributed to microsporidia other than E bienuesi. and cystic. which are resistant to environmental extremes. or subcutaneous abscesses. with arrhythmias atrial and ventricular and sudden death occasionally. Clinical manifestations include mental status abnormalities. fumidil in saline eye drops and albendazole for management of systemic infection have been recommended. Enterocytozoon bienuesi produces a protracted diarrheal illness accompanied by fever and weight loss similar to that caused by Cryptosporidium. propamidine. Isospora belli Like cryptosporidiosis. Pneumonitis may also be a part of the clinical presentation. fever. lesions may take the form of ulcerative. but the BrownBrenn stain and the WarthinStarry silver stain are commonly used for detecting microsporidia in tissue culture. leishmaniasis has been increasingly described in HIVinfected persons from endemic regions and may take a chronic relapsing course. For GI infections caused by E bienuesi. it is reported to occur in to of patients with chronic diarrhea not attributable to other causes. Acanthamoeba spp may infect individuals with defects in cellmediated immunity including patients who have AIDS or have undergone organ transplantation and result in granulomatous amebic encephalitis. Treatment guidelines have recommended the initiation and optimization of antiretroviral therapy with immune reconstitution to a CD Leishmania spp In endemic areas of the world. nodular. Notable is that the drug may cause doserelated QT prolongation on ECG. Infections in AIDS Patients and Other Immunocompromised Hosts Karam . There are few data regarding therapy for granulomatous amebic encephalitis. or nephritis. choleralike disease . most notably hepatomegaly and splenomegaly. Recently. An important clinical clue may be preexisting skin lesions that have been present for months before CNS disease is clinically manifested. count cells/ L. meningismus. these pathogens infect patients with defective cellmediated immunity and cause a febrile illness with visceral involvement. Diagnosis is conrmed by nding characteristic acidfast oocysts on examination of feces. the pathogen is larger. Transmission electron microscopy with observation of the polar lament is considered the gold standard for diagnosis. Biliary tract symptoms similar to cholecystitis have been noted in of cases. microbiologic. sustained clinical. and very importantly. this pathogen is acidfast and can cause a very similar diarrheal illness. and dibromopropamidine have the greatest activity against Acanthamoeba. headache.suggests the diagnosis of cryptosporidiosis. oval. and ataxia. Enterocytozoon cuniculi has been described as an etiologic agent for hepatitis. Of these. Pentavalent antimonials with sodium stibogluconate as the representative agent may be useful for this infection. seizures. and management consists largely of symptomatic treatment of diarrhea. responds to therapy with trimethoprimsulfamethoxazole. transient diarrhea . hepatitis. Microsporidia These obligate intracellular protozoa are probably transmitted to humans through the ingestion of food contaminated with its spores. For ocular infection. Amoebae Naegleria and Acanthamoeba are freeliving amoebae that have the potential to infect humans. and relapsing illness . In contrast to cryptosporidiosis. and histologic resolution of HIVassociated cryptosporidiosis. . there was a switch to a marked increase in the level of IL messenger RNA. Although patients with a defect in this host defense system may be at increased risk for chlamydial ACCP Critical Care Medicine Board Review th Edition . administered as to million U IV qh or as continuous infusion for Trypanosoma cruzi With immunosuppression including HIV infection. The CSF uorescent treponemal antibody absorption test is less specic for neurosyphilis than the VDRLCSF. liposomal amphotericin B has been shown to be potentially effective because it targets infected macrophages and reaches high levels in plasma and tissues. particularly among persons with peripheral blood CD counts cells/mm. including unusually high. a characteristic clinical presentation of syphilis in the CNS is stroke in a young person. aberrant serologic responses are uncommon. such as dendritic cells. A reactive CSFVDRL and a CSF WBC count cells/mm support the diagnosis of neurosyphilis. Biopsy specimens from patients with localized infection with Leishmania braziliensis were consistent with a protective type immune response that included prominent messenger RNA coding for IL and IFN. The recommended regimen for the treatment of patients with neurosyphilis is aqueous penicillin G to million U/d. unusually low. infections. With HIV infection.Antimony resistance has been noted in some HIVinfected patients. As the lesions in patients became more destructive. However. This has implications for therapy. Such considerations are important. but the high sensitivity of the study has led some experts to believe that a negative CSF uorescent treponemal antibody absorption test excludes neurosyphilis. seizures. be aggressive. cognitive changes. which has included the use of IFN. such problems have not been classically described. and hemiparesis. Treponema pallidum Defense against this pathogen may include a role for macrophages and other antigenpresenting cells. Rickettsiae As with chlamydiae. Such data have been interpreted as an eloquent demonstration of the facts that type immunity is the key to protection against Leishmania infections in humans and that a high infectious burden suppresses the human immune system from mounting type responses.as an adjunctive agent for visceral leishmaniasis. Miscellaneous Pathogens Chlamydiae This group of intracellular pathogens has been listed in some recent reviews of pathogens defended against by cellmediated immunity. leishmaniasis is important. which is consistent with a failed type immune response. In addition to meningitis. and most specialists believe that both treponemal and nontreponemal serologic tests for syphilis can be interpreted in the usual manner for patients who are infected with both HIV and T pallidum. Recent reviews have not described immunocompromised patients as being at increased risk for infection by pathogens in this group. HIVinfected patients can have abnormal serologic test results. In addition to the characteristic lesions seen with Chagas disease. with neuroimaging studies showing large solitary or multiple ringenhancing lesions with surrounding edema. that process and present treponemal antigens to helper T cells. immunosuppressed patients have an increased incidence of neurologic disease. it may be nonreactive when neurosyphilis is present. treponemal infection is more likely to have an atypical clinical presentation. such as the CNS. reactivation of this pathogen can occur. in such situations. since HIV infection might be associated with mild mononuclear CSF pleocytosis cells/mm. patients may present with headache. Of the relevant disease models inuencing the understanding of the clinical signicance of type and type immunity. rickettsiae are intracellular pathogens defended against by cellmediated immunity. In both posttransplantation infection and HIVassociated infection. Although the VDRL test on CSF is the standard serologic test for neurosyphilis. or invade sites. or uctuating titers. et al. million U IM once daily plus probenecid mg orally times a day. et al. et al. . Bacteremia due to viridans group streptococci with diminished susceptibility to levooxacin among neutropenic patients receiving levooxacin prophylaxis. Sepkowitz KA. Khaliq Y. et al. Hepatic candidiasis in cancer patients the evolving picture of the syndrome. Infections caused by viridans streptococci in patients with neutropenia. Karam GH. humoral immunity. J Clin Oncol . . Clin Infect Dis . Bodey GP. . Type /type immunity in infectious diseases. Patterson TF. . Bodey GP. Litzow MR. Neutropenic enterocolitis spectrum of the disease and comparison of denite and possible cases. Razonable RR. Martino P. Serious complications of bacteremia caused by viridans streptococci in neutropenic patients with cancer. . Clin Infect Dis . Armitage JO. Recent experience with Pseudomonas aeruginosa bacteremia in patients with cancer retrospective analysis of episodes. .. Clin Infect Dis . Hughes WT. . . Shawker TH. et al. Edwards JE Jr. If compliance with therapy can be insured. Herbrecht R. American Society of Clinical Oncology. It is recommended that all HIVinfected persons be tested for syphilis and that all persons with syphilis be tested for HIV. Ozer H. regardless of stage. Pastakia B. Sobel JD. Pappas PG. Pseudomonas bacteremia. both for to days. MO MosbyYear Book. doubleblind. Medicine Baltimore . to days. Clin Infect Dis . et al. some experts recommend administering benzathine penicillin . et al. Guidelines for treatment of candidiasis. Update of recommendations for the use of hematopoietic colonystimulating factors evidencebased clinical practice guidelines. . Chatzinikolaou I. Summary The identication of a defect in neutrophil function. Kirkpatrick WR. et al. . Clin Infect Dis . Clin Infect Dis . ed. Arch Intern Med . an alternative regimen is procaine penicillin . White M. costeffective therapy and in improved patient outcome. . AbiSaid D. An approach to the immunocompromised patient based on pathogenesis of disease should result in more directed. Marron A. . Ann Intern Med . . et al. or cellmediated immunity allows the clinician to better focus on the most likely pathogens involved in an infectious process. N Engl J Med . Thaler M. Rolston KV. placebocontrolled trial comparing piperacillintazobactam with and without amikacin as empiric therapy for febrile neutropenia. An approach to diagnosing and treating infections in immunocompromised patients. Patterson TF. update of recommendations for the use of hematopoietic colonystimulating factors evidencebased. Tunkel AR. St Louis. References . Arch Intern Med . . J Clin Oncol . clinical practice guidelines. A multicenter. Treatment of opportunistic fungal infections. Martino R. Elting L. Jadeja L. Carratal J. treatment practices. Current therapy in critical care medicine. Spinal uid examination has been recommended for all HIVinfected persons with latent syphilis or with neurologic abnormalities. Infections in AIDS Patients and Other Immunocompromised Hosts Karam . Bennett CL. Some experts have recommended spinal uid examination for any HIVinfected person with syphilis. Bodey GP. Del Favero A. . Gomez L. . GonzlezBarca E. Clin Infect Dis . In Parrillo JE. et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. Invasive aspergillosis disease spectrum. guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Grifn FM. Rex JH. million IM once weekly for up to weeks on completion of the neurosyphilis regimen to provide a comparable total duration of therapy. Menichetti F. . Clin Infect Dis . Denning DW. Clin Infect Dis . Armstrong D. Armstrong D. Spellberg B. and outcomes. Because the duration of treatment recommended for neurosyphilis is shorter than for latent syphilis. . . et al. Hartel D. Am J Respir Crit Care Med . SS . Winston DJ. Metakis LJ. RR . Ann Intern Med . Donowitz G. Tuberculosis in patients with human immunodeciency virus infection. . National Institutes of Health. Targeted tuberculin testing and treatment of latent tuberculosis infection. Tuberculosis and acquired immunodeciency syndrome a historical perspective on recent developments. Voriconazole a new triazole antifungal agent. Clin Infect Dis . Markowitz N. Case records of the Massachusetts General Hospital Case . HIV Medicine ACCP Critical Care Medicine Board Review th Edition . . Hansen NI. Walsh TJ. The pathophysiology of disseminated Mycobacterium avium complex disease in AIDS. Am J Respir Crit Care Med .. Ssekasanvu E. Am J Med . . de Ciutiis A. Infect Med . Haas DW. Immunologic defect of the alternate pathwayofcomplement activation postsplenectomy a possible relation between splenectomy and infection. Lewis VA. MMWR Recomm Rep . Walsh RJ. N Engl J Med . A prospective study of the risk of tuberculosis among intravenous drug users with human immunodeciency virus infection. . and revisions in American Thoracic Society/CDC recommendationsUnited States. J Natl Med Assoc . Centers for Disease Control and Prevention. Sullivan KM. N Engl J Med . Barnes PF. Tuberculosis associated with iniximab. . Overwhelming postsplenectomy infection a critical review of etiologic pathogens and management. Case records of the Massachusetts General Hospital Case . . Incidence of tuberculosis in the United States among HIVinfected persons. Farley MM. Kauffman CA. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America. Baluta A. N Engl J Med . Hopewell PC. Liposomal amphotericin B for empirical therapy in patient with persistent fever and neutropenia. Polley MJ. Barza MJ. Weinberg ED. Horsburgh CR. Walsh T. . Vergis EN. American Thoracic Society. Havlir DV. . . Pregnancyassociated depression of cellmediated immunity. et al. a tumor necrosis factor neutralizing agent. et al. MMWR Morb Mortal Wkly Rep . et al. MMWR Recomm Rep . J Infect Dis . Johnson JL. Gershon S. Keane J. Wise RP. N Engl J Med . et al. Randomized trial of adjunctive interleukin in adults with pulmonary tuberculosis. N Engl J Med . Okwera A. Finberg RW. Rev Infect Dis . Centers for Disease Control and Prevention. . . Selwyn PA. Schooley RT. suppl SS . Centers for Disease Control and Prevention. N Engl J Med . Recommendations of the Advisory Committee on Immunization Practices ACIP use of vaccines and immune globulins for persons with altered immunocompetence. . . N Engl J Med . . Arndt C. . Update fatal and severe liver injuries associated with rifampin and pyrazinamide for latent tuberculosis infection. et al. . et al. Yu VL. Immunomodulatory and antimicrobial efcacy of intravenous immunoglobulin in bone marrow transplantation. Des Prez RM. Pappas P. N Engl J Med . Norris RP. Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. et al. . MMWR Recomm Rep . Treatment of tuberculosis. Whitney CG. Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. Johnson LB. et al. Prevention and control of meningococcal disease recommendations of the Advisory Committee on Immunization Practices ACIP. . Am J Respir Crit Care Med . Hadler J. Teppler H. Kopecky KJ. Decline in invasive pneumococcal disease after the introduction of proteinpolysaccharide conjugate vaccine. Prevention of pneumococcal disease recommendations of the Advisory Committee on Immunization Practices ACIP. N Engl J Med . RR . Jocom J. Parsonnet J. et al. Versalovic J. Centers for Disease Control and Prevention. N Engl J Med . RR . Listeriosis. Larsen RA. et al. Clin Infect Dis . Clin Infect Dis . Sarosi G. Verville TD. . Kubilis P. Powderly WG. . Fiorucci GC. MMWR Recomm Rep . Cloud GA. Sobel J. Ferrer A. Graybill JR. Cloud GA. Rex JH. et al. Clin Infect Dis . Saag MS. Clin Infect Dis . Garrido CS. Antimicrobial chemotherapy for Legionnaires disease a review. Kan VL. suppl SS Aureli P. . Nocardiosis. . Am Rev Respir Dis . et al. . Listeria monocytogenes clinical and experimental update. An outbreak of febrile gastroenteritis associated with corn contaminated by Listeria monocytogenes. . Weinstock DM. . J Infect Dis . Clin Infect Dis . Practice guidelines for the management of bacterial meningitis. Walensky RP. et al. . et al.S. Torres A. Caroli D. Severe communityacquired pneumonia epidemiology and prognostic factors. Practice guidelines for diseases caused by Aspergillus. ravuconazole. et al. N Engl J Med . Kaplan SL. Yu VL. Lerner PI. Marr KA. Stevens DA. International surveillance of bloodstream infections due to Candida species frequency of occurrence and in vitro susceptibilities to uconazole. . Stout JE. . Lorber B. Gregory SH. N Engl J Med . N Engl J Med . Edelstein PH. Prevalence of Bartonella infection among human immunodeciency virusinfected patients with fever. Saag MS. Ampel NM. Resistance of Candida species to uconazole. Legionellosis. Treatment of cryptococcal meningitis associated with . Association/Infectious Diseases Society of America. Rhodococcus equi infections of humans cases and a review of the literature. Clin Infect Dis . . N Engl J Med . Jones RN. and voriconazole of isolates collected from through in the SENTRY antimicrobial surveillance program. MMWR Recomm Rep . et al. et al. . . Miro JM. . A controlled trial of uconazole or amphotericin B to prevent relapse of cryptococcal meningitis in patients with acquired immunodeciency syndrome. Saag MS.. Rinaldi MG. Tunkel AR. Huycke MM. Sanchez MA. Clin Infect Dis . Clin Infect Dis . Wingard JR. van der Horst CM. the acquired immunodeciency syndrome. RR Wing EJ. Tye S. et al. .RR Guidelines for preventing opportunistic infections among HIVinfected persons recommendations of the U. Galgiani JN. Greeneld RA. . Brown AE. . Pfaller MA. . Molecular epidemiology of bartonella infections in patients with bacillary angiomatosispeliosis. Wheat J. suppl SS Koehler JE. et al. Clin Infect Dis . Diekema DJ. Candidemia in allogeneic blood and marrow transplant recipients evolution of risk factors after adoption of prophylactic uconazole. Lee L. Graybill RJ. Infections in AIDS Patients and Other Immunocompromised Hosts Karam . Discontinuation of maintenance therapy for cryptococcal meningitis in patients with AIDS treated with highly active antiretroviral therapy an international observational study. Treating opportunistic infections among HIVinfected adults and adolescents. et al. Clin Infect Dis . Clin Infect Dis . Practice guidelines for the management of cryptococcal disease. Sanchez MA. Pezzotti P. et al. Seidel K. White TC. et al. . Clin Infect Dis . . Public Health Service and the Infectious Diseases Society of America. Catanzaro A. Clinical signicance of nephrotoxicity in patients treated with amphotericin B for suspected or proven aspergillosis. . Practice guidelines for the management of patients with histoplasmosis. . Mussini C. . et al. Clin Infect Dis . . Antimicrob Agents Chemother . et al. et al. Judson MA. Hartman BJ. Graybill JR. Diagnosis and management of increased intracranial pressure in patients with AIDS and cryptococcal meningitis. Saag M. Saag MS. Pfaller MA. SerraBatlles J. . Clin Infect Dis . McKinsey D. Cloud CA. Koehler JE. N Engl J Med . Practice guidelines for the treatment of coccidioidomycosis. et al. A comparison of itraconazole versus uconazole as maintenance therapy for AIDSassociated cryptococcal meningitis. et al. Infect Dis Clin Pract . Moore RD. Rhodococcus equi an emerging pathogen. J Clin Microbiol . Medicine . A case series of patients with nocardiosis. J Infect Dis . . Management of cytomegalovirus infection and disease after solidorgan transplantation. Cohen JI. . Walker M. Ioannidis JPA. Risk factors and outcome of varicellazoster virus pneumonia in pregnant women. Yamamura M. BK virus a clinical review. . . Lerch RA. Laboratory diagnosis of Toxoplasma gondii infection and toxoplasmosis. Karavellas MP. Montoya JG. Clin Infect Dis . Azen SP. Reiss R. Pea JM. Discontinuation of Pneumocystis carinii prophylaxis in patients infected with human immunodeciency virus a metaanalysis and decision analysis. Cryptosporidiosis in patients with AIDS correlates of disease and survival. van der Bij. J Infect Dis . Storch GA. Decker LL. A new name Pneumocystis jiroveci for Pneumocystis from humans. Cohen JI. . N Engl J Med . Reploeg MD. et al. suppl SS . Pirmez C. . et al. Sexually transmitted diseases treatment guidelines . Clin Infect Dis . Clin Infect Dis . Neuroimaging ndings in patients with AIDS. J Infect Dis . Miller BL. A randomized trial of the discontinuation of primary and secondary prophylaxis against Pneumocystis carinii pneumonia after highly active antiretroviral therapy in patients with HIV infection. . et al. diagnosis. Ernest JM. suppl SS . sequelae. Persistent productive EpsteinBarr virus replication in normal epithelial cells in vivo. Walpita P. and treatment outcomes. Discontinuation of secondary prophylaxis against Pneumocystis carinii pneumonia in patients with HIV infection who have a response to antiretroviral therapy. Flaitz CM. Clin Infect Dis . Walling DM. Nichols WG. . Gooley T. . et al. Immune recovery vitritis and uveitis in AIDS clinical predictors. . Centers for Disease Control and Prevention. Mocroft A. Clark DP. et al. N Engl J Med . Clin Infect Dis . Microsporidiosis. Summary of the guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. The use of corticosteroids in Pneumocystis carinii pneumonia. Ammassari A. Babcock GJ. New insights into transmission. Clin Infect Dis . . Corey L. et al. Recent advances in varicellazoster virus infection. Clin Infect Dis . Giancola ML. . Parasitic central nervous system infections in immunocompromised hosts. Brunell PA. MacDonald JC. Bozzette SA. Harger JH. Moore RD. et al. J Clin Invest . J Infect Dis . De Luca A. Nichols CM. The effect of potent antiretroviral therapy and JC virus load in cerebrospinal uid on clinical outcome of patients with AIDSassociated progressive multifocal leukoencephalopathy. Volk M. Ledergerber B. EBV persistence in memory B cells in vivo. et al. et al. Didier ES. Uyemura K. J Infect Dis . . Ann Intern Med . et al. Trikalinos TA. High risk of death due to bacterial and fungal infection among cytomegalovirus CMVseronegative recipients of stem cell transplants from seropositive donors evidence for indirect effects of primary CMV infection. . Vaccineassociated measles pneumonitis in an adult with AIDS. JAMA . Clin Infect Dis . . Beard CB. Staus SE.. et al. RR ACCP Critical Care Medicine Board Review th Edition . Clin Infect Dis . Gill VJ. Ann Intern Med . Emerg Infect Dis . MMWR Recomm Rep . . Farr RW. EpsteinBarr virus infection. Stringer JR. Clifford DB. N Engl J Med . Weissman D. . et al. Ljungman P. Chang L. Fulminant hepatitis during herpes simplex virus infection in apparently immunocompetent adults report of two cases and review of the literature. . Miro JM. . . Cytokine patterns in the pathogenesis of human leishmaniasis. Thurnau GR. Walot I. Short S. Paya C. Dykewicz CA. . Clin Infect Dis . Miller RF. Grifths P. Retina . Zunt JR. de Quiros JCLB. J Infect Dis . J Infect Dis . Angel JB. et al. . Speich R. et al. et al. Manabe YC. and drug treatment of Pneumocystis carinii pneumonia. Denitions of cytomegalovirus infection and disease in transplant recipients. . Kovacs JA. Meshnick S. Immunity . . Notes Infections in AIDS Patients and Other Immunocompromised Hosts Karam . As summarized in Table . septic intracranial thrombophlebitis. encephalitis. or peritoneum can also result in morbidity and create diagnostic or therapeutic dilemmas for the clinician. on rare occasions patients may have a predominance of eosinophils in the CSF. urinary bladder. the median age of persons with bacterial meningitis increased from months to years. but eosinophilic meningitis is uncommon. this classically occurs because of acute inammation or with inltration of the meninges by granulomas or malignant cells. Gram stain and culture of CSF are highly specic but may have a median sensitivity of about . Helpful in understanding the pathogenesis of meningitis due to varied processes is the CSF glucose level. MD. In addition. Glucose enters the CSF by facilitated transport across choroid plexuses and capillaries lining the CSF space. Although consumption of glucose by white blood cells and organisms may contribute to low CSF glucose levels which is referred to as hypoglycorrhachia.. important clinical studies include stains and cultures. . spinal epidural abscess Introduction Infection affecting various parts of the nervous system has the potential to be lifethreatening or to result in severe sequelae if the infection is not appropriately diagnosed and treated. When such uid is obtained. and lymphocytic meningitis with a low glucose. the major mechanism for low glucose is impaired transport into the CSF. glucose. ACCP Critical Care Medicine Board Review th Edition The basic diagnostic tool in the diagnosis of meningitis is examination of cerebrospinal uid CSF.Nervous System Infections and Catheter Infections George H. . an approach for diagnosing the etiology of meningitis based on the CSF analysis would include three common categories polymorphonuclear meningitis. Karam. and brain abscess are the most frequently encountered. encephalitis. Levels are lower in cisternal and ventricular CSF than in lumbar CSF. Nervous System Infections Meningitis From to . the CSFtoblood glucose ratio is . Normally. Although infections such as meningitis. lymphocytic meningitis with a normal glucose. meningitis. the most helpful study in the initial approach to the patient with meningitis is a cell count with differential on the CSF. brain abscess. When protein levels exceed mg/dL. This review will attempt to summarize these infections as they relate to the critical care setting. cavernous sinus thrombosis. protein. the uid may appear xanthochromic. and botulism may present as emergent problems that require a high level of clinical suspicion for prompt diagnoses to be made. Protein is usually excluded from the CSF but levels rise after disruption of the bloodbrain barrier. FCCP Objectives Review clinical presentations of nervous system infections that may present as serious or lifethreatening processes Outline principles inuencing diagnosis and management of nervous system infections Present an approach to infections related to catheters placed in the vasculature. and cell count with differential. The diagnosis of meningitis is made by the nding of a CSF pleocytosis and may occur on the basis of both infectious and noninfectious processes. rabies. Infections associated with catheters placed in the vasculature. In the absence of a positive stain on the CSF. rabies. mg/dL are often indicative of subarachnoid block. making meningitis in the United States predominantly a disease of adults rather than of infants and young children. processes such as spinal epidural abscess. Extreme elevations ie. Usual elevations in patients with meningitis are in the to mg/dL range. catheterrelated infections. urinary bladder. or peritoneum Summarize existing opinions and data about management of catheterrelated infections Key words botulism. population in counties in four states revealed the following Streptococcus pneumoniae. Neisseria meningitidis. which has occurred as a result of vaccination against this pathogen. the single most important cause of a polymorphonuclear meningitis is bacterial infection.Table . herpes simplex or viral meningitis Partially treated bacterial meningitis Carcinomatous meningitis Subarachnoid hemorrhage Chemical meningitis Although not clinically common in the United States. penicillin G and ampicillin are equally effective. Trichinella spiralis.. Toxocara canis. Polymorphonuclear Meningitis Because of the acute inammation. or intermediate. An Approach to CSF Pleocytosis Polymorphonuclear Bacterial see Table Early meningitis Tuberculosis Fungal Viral Druginduced Parameningeal foci Brain abscess Subdural empyema Epidural abscess Sinusitis Mastoiditis Osteomyelitis Persistent neutrophilic meningitis Lymphocytic With Normal Glucose Viral meningitis Enteroviruses. .. Taenia solium. the problematic strains of S pneumoniae are those that are penicillinresistant. eosinophilic meningitis can occur. including poliovirus Herpes simplex virus usually type HIV Adenovirus Tickborne viruses Meningoencephalitis. . parameningeal foci. Although highdose penicillin . to . Compounding this problem is the inability of certain antibiotics to cross the bloodbrain barrier effectively enough to yield CSF levels signicantly above the MIC for the infecting organism. Gnathostoma spinigerum. Discussion in this syllabus will be limited to this topic. Likely etiologic agents for bacterial meningitis are summarized in Table from the perspectives of the age of the patient and underlying predispositions to meningitis. Listeria monocytogenes. U/kg/d has been useful in patients with pneumonia caused by strains of pneumococci with intermediate resistance.. Paragonimus westwermani. Strains with relative. Although pneumococci are the most common pathogens in bacterial meningitis. and persistent neutrophilic meningitis. In the differential diagnosis of polymorphonuclear meningitis. Because of the sequelae that may be associated with a delay in therapy. and Haemophilus inuenzae. Highlevel resistance to penicillin is dened as an MIC g/mL. group B streptococci. there are four major groups of disease bacterial infection. . This is most notable with bacterial meningitis. this process is usually associated with a low CSF glucose owing to impaired transport across the meninges. g/mL. resistance will have a penicillin minimal inhibitory concentration MIC of .. such high doses do not predictably lead to CSF levels of Nervous System Infections and Catheter Infections Karam . For pneumococcal meningitis caused by penicillinsusceptible strains. Presented in a different manner.. rates of meningitis per . and Baylisascaris procyonis. including viral causes Parameningeal foci Partially treated bacterial meningitis Listeria meningitis Spirochetal infections Syphilis Leptospirosis Lyme disease Rickettsial infections Rocky Mountain spotted fever Ehrlichiosis Infective endocarditis Immunemediated diseases Sarcoidosis Druginduced Lymphocytic With Low Glucose Fungal Tuberculous Certain forms of meningoencephalitis eg. The most notable change in etiologic agents over the past decade has been the dramatic decrease in the incidence of H inuenzae meningitis. and the characteristic pathogens causing such a process are Angiostrongylus cantonesis. . . to . the early meningeal response to any type of infection or inammation. g/mL. the Centers for Disease Control and Prevention CDC analyzed cefotaxime MIC data from the Active Bacterial Core Surveillance of the Emerging Infections Program Network from to . each year. To assess the effect of these new criteria on reporting of nonsusceptible S pneumoniae isolates. It was suggested that the regimen of a broadspectrum cephalosporin plus vancomycin be used if the S pneumoniae isolate is resistant to penicillin MIC g/mL and to ceftriaxone and cefotaxime MIC g/mL. Streptococcus pneumoniae Haemophilus inuenzae N meningitidis. For S pneumoniae from a meningeal source. N meningitidis S pneumoniae. g/mL. N meningitidis Enterobacteriaceae L monocytogenes S pneumoniae. clinical failures have been reported when these agents have been used for such strains. and resistant. to . Steroids given concomitantly for meningitis may further decrease vancomycins penetration. g/mL. The lessthanoptimal penetration of vancomycin into CSF has an impact on this therapeutic option. This analysis indicated that after the new criteria were applied. In .Table . including Klebsiella pneumoniae and Acinetobacter calcoaceticus when meningitis develops from a contiguous postoperative traumatic wound infection S aureus S aureus Coagulasenegative staphylococci Aerobic Gramnegative bacilli including Pseudomonas aeruginosa S pneumoniae. H inuenzae Gramnegative bacilli Staphylococci Coagulasenegative staphylococci S aureus Aerobic Gramnegative bacilli including P aeruginosa Propionibacterium acnes S pneumoniae Gramnegative bacilli S aureus yr yr to young adult Adults yr Alcoholic and elderly Closed skull fracture Open skull fracture Penetrating trauma. g/mL. Postneurosurgery CSF leak CSF shuntassociated Diabetes Defects in cellmediated immunity L monocytogenes Concern of bioterrorism Bacillus anthracis penicillin that exceed the MIC of intermediately resistant strains. . the Infectious Diseases Society of America IDSA published recommendations for the management of bacterial meningitis to update recommendations that have been available since . Even though cefotaxime or ceftriaxone has been recommended for pneumococci with intermediate susceptibility to penicillin. Clinical data on the efcacy of rifampin in patients with bacterial . S pneumoniae S pneumoniae. Likely Pathogens in Bacterial Meningitis Based on Patients Age or Underlying Conditions Neonates Enterobacteriaceae Group B streptococci Listeria monocytogenes Neisseria meningitidis. Because of the importance of S pneumoniae. a thirdgeneration cephalosporin was recommended. the National Committee for Clinical Laboratory Standards began offering differing cephalosporin breakpoints for pneumococcal susceptibility based on the site of infections. g/mL. H inuenzae Staphylococcus aureus Coagulasenegative staphylococci Gramnegative bacilli Gramnegative bacilli. vancomycin is the drug of choice. These recommendations have been repeated in subsequent National Committee for Clinical Laboratory Standards reports. the guidelines provided an approach to therapy of proven pneumococcal meningitis based on in vitro susceptibility. For penicillinsusceptible isolates. g/mL. including those strains demonstrating antibiotic resistance. For isolates with highlevel resistance. and resistant. . the ACCP Critical Care Medicine Board Review th Edition ceftriaxone and cefotaxime breakpoints were listed as follows susceptible. With intermediate susceptibility to penicillin MIC. This was in contrast to nonmeningeal breakpoints. A summary of the empiric therapy recommendations from those guidelines is included in Table . intermediate susceptibility. In December . the number of isolates dened as nonsusceptible to cefotaxime decreased . penicillin or ampicillin was suggested. to . g/mL. which were stated as follows susceptible. intermediate susceptibility. multicenter trial assessed the value of adjuvant treatment with dexamethasone compared with placebo in adults years of age or older with suspected meningitis who had cloudy CSF./mm. because administration of dexamethasone in this circumstance is unlikely to improve patient outcome. in patients with pneumococcal meningitis caused by highly penicillin. meningococcemia purpura fulminans and the WaterhouseFriderichsen syndrome. meningitis are lacking. doubleblind. with the rst dose administered to min before. A prospective. respiratory tract infections pneumonia.or cephalosporinresistant strains. bacteria in CSF on Gram staining. or vancomycin plus meropenem Adapted from Tunkel and colleagues. Not approved by the Food and Drug Administration FDA for meningitis. A report from Argentina described epidemic meningococcal disease in the northeastern part of that country associated with Nervous System Infections and Catheter Infections Karam . but some authorities would use this agent in combination with a thirdgeneration cephalosporin. The usual duration of therapy for pneumococcal meningitis is generally stated to be to days. focal infection conjunctivitis. or at least concomitant with. The epidemiology of meningococcal meningitis is evolving. The role of steroids in adults with meningitis has not been denitively established. demonstrable bacteria on Gram stain of CSF. or CSF shunt Recommended Drugs Vancomycin plus a thirdgeneration cephalosporin Vancomycin plus ampicillin plus a thirdgeneration cephalosporin Vancomycin plus ceftazidime or vancomycin plus cefepime. Early treatment with dexamethasone was shown to improve the outcome and did not increase the risk of GI bleed. especially college students or military recruits who live in relatively conned quarters. An early opinion by experts in the eld suggested that adult patients who might be candidates for steroid therapy in meningitis are those with a high CSF concentration of bacteria ie. It is this site from which disease may develop.Table . This statement was qualied in the IDSA guidelines for treatment of bacterial meningitis with the comment that rifampin should be added only if the organism is shown to be susceptible and there is a delay in the expected clinical or bacteriologic response. especially if there is increased intracranial pressure. Even though the data are inadequate to recommend adjunctive dexamethasone in adults with meningitis caused by bacterial pathogens other than S pneumoniae. it was acknowledged that some authorities would initiate dexamethasone in all adults because the etiology of meningitis is not always ascertained at initial evaluation. CSF Recommendations for Empiric Therapy of Meningitis When Lumbar Puncture Is Delayed or in Patients With a Nondiagnostic CSF Gram Stain Patient Group Age to yr Age yr Penetrating head trauma. purulent pericarditis. or postneurosurgery. The dose of dexamethasone used in this study was mg IV qh for days. Important in the pathogenesis of the clinical illnesses caused by the meningococcus is the organisms natural reservoir in the nasopharynx. It was stated that adjunctive dexamethasone should not be given to adult patients who have already received antimicrobial therapy. septic arthritis. FDAapproved for bacterial meningitis in pediatric patients mo old. the rst dose of antimicrobial therapy be given in adults with suspected or proven pneumococcal meningitis. otitis media. and chronic meningococcemia. or a CSF leukocyte count of . In the IDSA guidelines for the treatment of bacterial meningitis in adults. it was recommended that dexamethasone . mg/kg qh for to days. randomized. with or without vancomycin. epiglottitis. urethritis. meningococcal bacteremia. The infectious syndromes caused by N meningitidis are somewhat broad and include meningococcal meningitis. The traditional groups of patients at risk have included children and young adults. The illness may progress to acidosis. There were infections for which steroids were strongly supported or suggested as having a role. In contrast. tissue hypoxia. not all patients who die of meningococcemia have evidence of adrenal hemorrhage at autopsy. the potential for N meningitidis to cause purulent pericarditis should be noted. remains a drug of choice for treating meningitis caused by this pathogen. and meningococcemia was not one of those listed. The dual function of protein C as an anticoagulant and as a modulator of the inammatory response was recently reviewed in the context of experimental data showing that activated protein C replacement therapy reduces the mortality rate for fulminant meningococcemia. An additional observation from this study. During the very early stages of infection. Such data become especially noteworthy given the efcacy and safety data about recombinant human activated protein C in patients with severe sepsis. The potential for lactamaseproducing strains remains a concern. however. as penicillin will not eliminate organisms at this site. and coma. investigators have addressed other potential therapeutic modalities that may be benecial in patients with overwhelming meningococcal infection. Because fulminant meningococcal septicemia represents an extreme form of endotoxininduced sepsis and coagulopathy. shock. if any. This report. IDSA published a review of the role of steroids in patients with infectious diseases. which has been raised in previous studies. cortisol levels may be elevated. There are anecdotal reports in the literature of improved outcome in such patients treated with corticosteroids. and hemorrhagic adrenal infarction. implying that adrenal insufciency may not be the primary cause of circulatory collapse. massive adrenal hemorrhage with the resultant clinical entity of the WaterhouseFriderichsen syndrome. disseminated intravascular coagulopathy. meningococcal meningitis is usually acute and often associated with purpuric skin lesions although the Atlanta report noted that only of the adults with meningitis had a generalized rash. With meningococcemia. the role of steroids in meningococcemia is unresolved. In patients treated with penicillin for meningococcal meningitis. supporting the pathogenetic point that close connement allows aerosolization and spread of the organism from the nasopharynx. of steroids in management of patients with meningococcal meningitis. At the present time. ciprooxacin. Although meningitis is the characteristic infection caused by N meningitidis. Although variably reported through the years. which was titled Disco Fever. therefore. and this raises the issues of whether adrenal reserves may be decreased in certain patients and whether steroids may have a role. In . it would be helpful to have denitive recommendations about the role. and tracheobronchitis are important sources of bacteremic meningococcal disease. Pneumonia. These recommendations are similar to those for chemoprophylaxis for individuals exposed to a . The usual duration of therapy is generally days. sinusitis. diverse population in the United States has failed to identify any such strains. other reports have noted that not all patients with severe meningococcal infection who have been given adrenocorticotropic hormone have responded to adrenocorticotropic hormone stimulation of cortisol production. a report from Atlanta noted that only of the adult patients with meningococcal infection had meningitis. expanded the closed settings in which meningococcal meningitis originates to include dance clubs and discos. When it occurs. active surveillance among a large. nuchal rigidity. Penicillin or ampicillin. a fulminant complication is acute. Air travelassociated meningococcal disease has also been described and is dened as a patient who meets the case denition of meningococcal disease within days of travel on a ight of at least h duration. with clinical consequences that include amputations and organ failure. In some patients with meningococcal infection. as does the existence of relatively resistant strains. and ACCP Critical Care Medicine Board Review th Edition many steroidtreated patients succumb despite therapy.disco patronage. the CSF analysis may be relatively normal even though the clinical course is hyperacute with fever. Because of the implications of such a complication. or ceftriaxone has been recommended to eradicate the nasal carrier state. posttreatment with rifampin. However. is the association with passive or active cigarette smoking. presumably caused by alterations in the penicillinbinding proteins. endotracheal tube management. Since . a screening test for complement function CH has been suggested for all patients who have invasive meningococcal infections. Prophylaxis is recommended for close contacts. Ciprooxacin generally is not recommended for persons aged yr or for pregnant and lactating women. However. C. In adults without these underlying processes. Chemoprophylaxis administered days has been stated to be of limited or no value. with special efforts to vaccinate young adults. Based on this observation. a search for a CSF leak.to yearolds of . Rifampin is not recommended for pregnant women because the drug is teratogenic in laboratory animals. person with known meningococcal disease. H inuenzae may be isolated from the nasopharynx. Those recommendations are summarized in Table . antimicrobial chemoprophylaxis should be administered as soon as possible ideally within h after the case is identied. which include household members. Because previous studies have demonstrated an incidence as high as in populations of patients with meningococcal infections. kissing. there have been increased numbers of outbreaks of serogroup C meningococcal disease in the United States. In patients with meningitis due to this organism. and C and properdin proteins should be considered. C to C.Table . it was also noted that direct assessment of complement C. daycare center contacts. C. RR. MMWR Recomm Rep . The thirdgeneration cephalosporins cefotaxime and ceftriaxone have had the most successful record of use in this regard. Because the rate of secondary disease for close contacts is highest during the rst few days after the onset of disease in the primary patient. mouthtomouth resuscitation. endotracheal intubation. which may be the basis for the meningitis. at a minimum. C. Rates of infection caused by this pathogen have decreased because of vaccination against H inuenzae. Schedule for Administering Chemoprophylaxis Against Meningococcal Disease Drug Rifampin Age Group Children Children Adults Adults Children Adults yr mo mo Dosage mg/kg qh mg/kg qh mg qh mg mg mg Duration/Route of Administration d d d Single dose Single IM dose Single IM dose Ciprooxacin Ceftriaxone Reprinted from the Centers for Disease Control and Prevention. A predisposing factor for neisserial infections is deciency in the late complement components ie. with a vaccine efcacy among . Meningococcal polysaccharide vaccine has been shown to be effective against serogroup C meningococcal disease in a community outbreak. Like the meningococcus. Even though the secondgeneration cephalosporin Nervous System Infections and Catheter Infections Karam . consideration should be given to using alternative contraceptive measures while rifampin is being administered. ciprooxacin can be used for chemoprophylaxis in children when no acceptable alternative is available. Because the reliability of oral contraceptives may be affected by rifampin therapy. it has been recommended that emphasis be placed on achieving high vaccination coverage in future outbreaks. is necessary. and this may be the immediate source of invading pathogens. Oral administration unless indicated otherwise. because the drug causes cartilage damage in immature laboratory animals. and anyone directly exposed to the patients oral secretions eg. agents that are stable in the presence of these enzymes and that cross the bloodbrain barrier should be used. Because about one third of H inuenzae isolates are lactamase producers. a contiguous focus of infection such as sinusitis or otitis media should be investigated. The Advisory Committee on Immunization Practices and the American Academy of Pediatrics have recommended that healthcare providers and colleges educate freshmen college students especially those who live in dormitories and their parents about the increased risk of meningococcal diseases and the potential benets of immunization so that informed decisions about vaccination can be made. For those patients who are allergic to penicillin. Ampicillin or penicillin is the drug of choice. According to the recent IDSA guidelines for the management of bacterial meningitis. trimethoprimsulfamethoxazole is the agent of choice. Concern about toxicity issues such as aplastic anemia has decreased the use of this agent over the years. Medical conditions. Meningitis due to Gramnegative bacilli occurs most characteristically after neurosurgical procedures. and about of infected adults have no apparent risk. This may lead to hydrocephalus. All of the presently available thirdgeneration agents except for cefoperazone have an indication for meningitis due to susceptible pathogens. cefepime has greater in vitro activity than the thirdgeneration cephalosporins against Enterobacter spp and P aeruginosa.cefuroxime is active against H inuenzae. It may also cause disease in diabetics and elderly persons.. L monocytogenes is an intracellular Grampositive rod that characteristically infects persons with defects in cellmediated immunity. The guidelines summarized these observations by stating that they support cefepime as a useful agent in the treatment of patients with bacterial meningitis. Because of the intracellular location of this pathogen. Listeria meningitis has a predilection for involving the meninges at the base of the brain. unless the CD cell count is cells/ mm and the patient is concomitantly receiving corticosteroids. and HIVinfected patients. and there is no signicant activity by thirdgeneration cephalosporins against this pathogen. Some experts suggest the addition of an aminoglycoside given parenterally because of in vitro synergy. and cheese. recognizing that this ACCP Critical Care Medicine Board Review th Edition latter agent will not cross the bloodbrain barrier in adults but that it might help to eradicate the site of infection outside the CNS that served as the focus for the meningitis. Similar ndings have not been corroborated in adults. it has been shown to result in delayed sterilization of the CSF when compared with ceftriaxone. or with certain skin infections. Thirdgeneration cephalosporins have become the mainstay of therapy for Gramnegative meningitis because of their spectrum and their penetration into the CSF. because of the anthelminthic properties of this rejection agent. including urosepsis. ceftazidime is an efcacious agent. It was noted that hospitalacquired infection occurred as an occasional complication of neurosurgical procedures. one should exclude Strongyloides stercoralis infection as the underlying predisposing cause. it generally . hyperinfection with the resultant predisposition to Gramnegative meningitis is uncommon in two groups of patients with defects in cellmediated immunity transplant recipients who receive cyclosporine. Like fungal and tuberculous meningitis. and it has been used successfully in some patients with meningitis caused by these bacteria. The usual duration of therapy for H inuenzae meningitis is generally days. It is usually administered with a parenteral aminoglycoside. although it still plays an important role in persons with meningitis and type I IgEmediated hypersensitivity to penicillins. Of note. Pharmacologic and microbiologic issues are important for two important pathogens that cause meningitis. with the presence of medical devices. cefepime does not have an FDAapproved indication for the treatment of bacterial meningitis. they need to be administered intrathecally or intraventricularly. For these antibiotics to be useful beyond the neonatal period. A review of Staphylococcus aureus meningitis divided this disease entity into two categories hospitalacquired and communityacquired. Parenterally administered aminoglycosides do not cross the bloodbrain barrier after the th day of life. Acquisition has been associated with consumption of contaminated coleslaw. and it crosses the bloodbrain barrier. account for about of episodes of this infection. This should be taken within the context that as of . For meningitis due to Pseudomonas aeruginosa. A lower incidence of sensorineural hearing loss was demonstrated in children who adjunctively received dexamethasone . the IDSA guidelines list days as the duration of therapy. days of therapy has been recommended. Although the CSF cellular response is usually polymorphonuclear. Chloramphenicol has activity against some Gramnegative bacilli. milk. vs those who did not receive steroids . In certain patient populations in which Gramnegative meningitis develops in the setting of impaired cellmediated immunity. some patients present either with lymphocytes or with a normal glucose. For meningitis due to Gramnegative pathogens. with head trauma being a less likely predisposition. patients may develop meningitis as a systemic manifestation of their herpes infection. the IDSA guidelines suggested vancomycin plus a thirdgeneration cephalosporin as empiric therapy of meningitis when lumbar puncture is delayed or in patients with a nondiagnostic CSF Gram stain. even in the setting of meningeal inammation. and lymphocytic pleocytosis. episode of terrorism in the United States. ampicillin was suggested in a review as a reasonable empiric agent. malaise. septic shock/multiorgan dysfunction syndrome. In contrast. communityacquired S aureus meningitis was associated with valvular heart disease. Of these patients. had received antibiotics prior to lumbar puncture. chloramphenicol was offered in that review as appropriate therapy. With initial episodes or ares of genital herpes simplex virus infection. The index case of bioterrorism anthrax in Florida presented with hemorrhagic meningitis. Enteroviruses. and rapid death with overwhelming bacterial spread. or drug or alcohol abuse. The classic consideration in this differential has been viral meningitis. For patients with a type I IgEmediated penicillin allergy. myalgia. and the pathogens likely to occur in their setting. The activity by ampicillin against Listeria is an important component of the coverage in this regimen. however. some have suggested adding either penicillin or chloramphenicol to the multidrug regimen that would be given for inhalational anthrax. The addition of ampicillin to a broadspectrum cephalosporin plus vancomycin is reasonable empiric therapy for polymorphonuclear meningitis undiagnosed by Gram stain in patient populations with the following underlying conditions advanced age. headache. In . Certain epidemiologic situations may exist that inuence the acquisition of specic pathogens. In this review of patients with communityacquired S aureus meningitis. alcoholism. headache. This process is distinctly different from the lifethreatening entity of herpes encephalitis in that it is selflimited and does not require therapy. which may then cause meningitis. In addition. nonallergic individuals with acute pyogenic communityacquired meningitis in whom little information is available. nonproductive cough. This nding is consistent with the observation that an important presentation of S aureus is in patients with addictassociated infective endocarditis. meningitis without hemorrhage can occur with anthrax. which are recognized causes of pleurodynia and pericarditis. are summarized in Table . Because Nervous System Infections and Catheter Infections Karam . . recommendations suggested a broadspectrum cephalosporin eg. had negative or no CSF culture. most often in the late summer or early fall. and nausea/vomiting followed by a second phase with hemodynamic collapse. which is characteristic of disseminated anthrax. As summarized in Table . the penetration of vancomycin into CSF may be variable. Empiric therapy for meningitis has changed in recent years. and immunocompromised states. For S aureus. This evolution from to in the recommendations for empiric therapy of meningitis is inuenced by penicillin resistance in pneumococci. It is during the stage of bacteremia that there is a strong likelihood of meningitis. Recently. Inhalational anthrax is a biphasic clinical syndrome with initial nonspecic ulike symptoms fatigue. and the response may therefore be less associated with the inability to transport glucose across the meninges. cefotaxime or ceftriaxone as empiric therapy for individuals aged to years who have a nondiagnostic Gram stain. are the most common cause of aseptic meningitis and characteristically cause a selflimited form of meningitis that presents with fever. In previously healthy.had a favorable prognosis and a relatively low mortality rate. which some sources cite as occurring in of cases. In patients in whom infection with Bacillus anthracis is suspected to be the cause of meningitis. Beginning with the September . Those conditions including skull fractures and shuntassociated infections. diabetes mellitus. anthrax is an important consideration in the differential diagnosis of patients with a lifethreatening illness that includes a meningeal component. two other viruses have gained importance in the differential diagnosis of viral meningitis. Those conditions associated with the ndings of lymphocytes and normal glucose in the CSF are listed in Table . nafcillin or oxacillin has better activity against methicillinsensitive strains than does vancomycin. however. and the mortality rate was signicantly higher than for nosocomial infection. Lymphocytic Meningitis With Normal Glucose The meningeal response to infection or inammation may be less marked in certain conditions. In December . patients may present without symptoms of nervous system disease and analysis of their CSF may reveal only a few lymphocytes and a negative VDRLCSF. even though the CSF WBC count and serum rapid plasma reagin reactivity in both populations were likely to normalize. nausea. The classic presentation of neurologic Lyme disease. Leptospirosis. is a recognized cause of asymptomatic infection of the CNS in nonimmunocompromised hosts. both for to days. Treponema pallidum. including those with the acute retroviral syndrome. which is caused by Borrelia burgdorferi. cognitive dysfunction. HIV infection is an important consideration. Because it is highly specic although insensitive. is seventh nerve palsy which may be bilateral in association with a lymphocytic meningitis. will give a normal glucose level in association with lymphocytes. In those individuals who have risk factors for HIV and present with an illness consistent with viral meningitis. is epidemiologically linked to such factors as infected rat urine or exposure to infected dogs.of the propensity for herpes genitalis to recur. Spirochetal infections are an important cause of lymphocytic meningitis with normal glucose level. and symptoms or signs of meningitis should undergo a CSF examination. Because these durations are shorter than the regimen used for late syphilis in the absence of neurosyphilis. often in young patients with a stroke syndrome caused by an endarteritis. caused by Leptospira interrogans. Encephalitis may occur on the basis of both infectious and noninfectious causes. but the high sensitivity of the study has led ACCP Critical Care Medicine Board Review th Edition some experts to believe that a negative CSF uorescent treponemal antibody absorption test excludes neurosyphilis. The most characteristic physical nding during this stage is conjunctival . chills. it may take the form of syphilitic meningitis or a stroke syndrome. When reactive in the absence of substantial contamination of CSF with blood. Because CNS disease can occur during any stage of syphilis. motor or sensory deficits. ophthalmic or auditory symptoms. may present with viral meningitis that may resolve spontaneously. some specialists administer benzathine penicillin . administered as to million U IV qh or continuous infusion. The guidelines now state that a reactive CSFVDRL and a CSF WBC count cells/mm support the diagnosis of neurosyphilis. a patient who has clinical evidence of neurologic involvement with syphilis eg. this form of meningitis may similarly present as a recurrent form of lymphocytic meningitis. herpes encephalitis may result in a low glucose level. According to guidelines. the diagnosis of meningoencephalitis may be made. vomiting. cranial nerve palsies. The septicemic stage occurs after a . An analysis of laboratory measures after treatment for neurosyphilis revealed that HIVinfected patients were less likely than nonHIVinfected patients to normalize their CSFVDRL reactivity with higher baseline titers. If compliance with therapy can be ensured. the recommended regimen for patients with neurosyphilis is to million U/d of aqueous crystalline penicillin G. with syphilitic meningitis. Neurosyphilis can present as cerebrovascular insufciency. million U IM once per week for up to weeks after completion of these neurosyphilis treatment regimens to provide a comparable total duration of therapy. the VDRL test in CSF VDRLCSF is the standard serologic test for CSF. Meningovascular syphilis has been increasingly diagnosed in the era of HIV infection. It presents as two distinct clinical syndromes. new guidelines were published for the management of infections in HIVinfected persons. the etiologic agent of syphilis. The uorescent treponemal antibody absorption test on CSF is less specic for neurosyphilis than the VDRLCSF. However. HIV has a predilection for neural tissue.to day incubation period and is primarily manifested as fever. patients may be treated with procaine penicillin . which progresses through two welldened stages a septicemic stage and an immune stage. The traditional teaching has been that meningoencephalitis. Several important points were made regarding neurosyphilis. When these conditions are associated with WBCs in the CSF. and headache. like viral encephalitis. which most characteristically involves the middle cerebral artery. it is considered diagnostic of neurosyphilis. Anicteric leptospirosis is a selflimiting illness. and patients. million U IM once daily plus probenecid mg orally times a day. The CSF leukocyte count has been stated to be a sensitive measure of the effectiveness of therapy. for to days. As outlined in Table . may cause a lymphocytic pleocytosis with normal glucose that is the result of a vasculitis. Such information underscores a dilemma for the clinician managing a patient with endocarditis who has a CSF pleocytosis Is the pleocytosis due to secondary bacterial seeding of the meninges. it is not surprising that the cellular CSF response would be lymphocytes. it appears that chloramphenicol or tetracycline is the agent most frequently used for this infection. From the limited clinical data available. As previously discussed.to day asymptomatic period. the severity of these manifestations can vary greatly. such as infective endocarditis. the biphasic nature of the disease is somewhat obscured by the persistence of jaundice and azotemia throughout the illness. Lymphocytic Meningitis With Low Glucose With chronic processes. In certain conditions. An important emerging infection in the United States is ehrlichiosis. the diagnosis can be made by demonstrating rising antibody titers. hypotension. the immune stage develops. thrombocytopenia. and subarachnoid hemorrhage. Leptospires can be isolated from blood or CSF during the rst week and from the urine during the second week of illness. carcinomatous meningitis. Low CSF glucose has been described in this syllabus as occurring due to impaired transport based on acute inammation of the meninges. glucose transport may be associated with inltration of the meninges by either granulomatous processes or malignant cells. million U every h has been shown to shorten the duration of fever. In a prospective. certain forms of meningoencephalitis. with of the patients having borderline low CSF glucose concentrations. or Weil syndrome.suffusion. In icteric leptospirosis. Leptospira are present in the urine during this stage and may persist for up to weeks. No positive CSF cultures were reported in any of these patients. Certain infectious diseases. renal involvement. and hospital stay. and renal involvement is not universal. Nervous System Infections and Catheter Infections Karam . ceftriaxone and penicillin G were shown to be equally effective for the treatment of severe leptospirosis. Treatment of leptospirosis involves intense supportive care as well as antibiotic coverage. There was a CSF pleocytosis in and no CSF WBCs in . Following a . and hemorrhage are the hallmarks of this form of leptospirosis. Icteric leptospirosis. A review of a year experience at the Cleveland Clinic included the results of lumbar punctures done on of patients with endocarditis. it is characterized by aseptic meningitis. Jaundice. the etiology was attributed to a stroke in and to encephalopathy in . Four other groups of conditions are important in this setting are tuberculous meningitis. randomized trial. The characteristic CSF abnormalities in patients with ehrlichiosis have been a lymphocytic pleocytosis with elevated protein. The use of IV penicillin . morulae were seen in CSF white cells in only a small minority of the patients. which is caused by Rickettsia rickettsii. is a less common but potentially fatal syndrome that occurs in to of cases. which the infectious process causes in the CNS. In a recent review of the subject. openlabel. Rocky Mountain spotted fever. Over the years. but septicemic and immune stages do occur. and elevated liver enzymes. Viral meningitis due to mumps and lymphocytic choriomeningitis has characteristically been associated with a low CSF glucose. may present in this manner. The clinical illness attributable to this infection is discussed in this syllabus in the section on encephalitis. including that due to herpes simplex virus. or is it due to other events associated with endocarditis that lead to a CNS response that is associated with a secondary cellular response A group of noninfectious causes of lymphocytic meningitis with a normal glucose level are described in Table . the remaining patient only had isolated headaches. in which case there may be a lymphocytic pleocytosis with normal glucose and elevated protein levels. the CSF glucose level was normal in the majority of patients. Partially treated bacterial meningitis and certain chemicalinduced meningitides may have similar ndings. renal dysfunction. Clinical features supporting the diagnosis of ehrlichiosis are leukopenia because of the intracellular location of the organism. has been considered the classic rickettsial infection in the United States. The causative organism can be isolated from blood or CSF at this point. fungal meningitis. Additionally. Such is the situation for several of the conditions summarized in Table that cause lymphocytic meningitis with a low glucose level. In this review. however. Of the patients who had a pleocytosis. Results of CSF analysis are usually normal unless patients have stupor or coma. but in this review it was . several important clinical points can be extracted Ischemic lesions with signs of localization may be present. and therefore ndings may include CSF WBCs/mm and a normal glucose level. the rate has been stated to be to . but falsenegative results have been reported. mg/kg/d in combination with ucytosine mg/kg/d in persons with normal renal function for the initial weeks of therapy followed by uconazole mg/d orally for an additional to weeks. Both organisms gain access to the body via the lungs. The India ink stain. opening pressures mm HO should be treated with largevolume CSF drainage dened in this report as allowing CSF to drain until a satisfactory closing pressure had been achieved. The most recent guidelines of the American Thoracic Society give steroids in the treatment of tuberculous meningitis an A recommendation. pyrazinamide. Overall. When four CSF smears for acidfast bacilli are obtained. Based on the association of elevated intracranial pressure and mortality in patients with cryptococcal meningitis. Enzymelinked immunosorbent assays ELISAs are felt by some to be helpful with this diagnosis. corticosteroids may play a role. Some studies have shown that elevated CSF titers of adenosine deaminase or CSF chloride levels mEq/L in the absence of bacterial infection support the diagnosis of tuberculous meningitis. Although fungal meningitis may be due to several etiologic agents. Polymerase chain reaction PCR for Mycobacterium tuberculosis may be helpful when performed on CSF. Based on data from the Mycoses Study Group of the National Institutes of Health NIH. From the series of patients with tuberculous meningitis admitted to an ICU. Although both of these pathogens have been increasingly diagnosed as a cause of meningitis because of HIV infection. therefore. placebocontrolled trial in Vietnam in patients years of age with tuberculous meningitis showed that adjunctive treatment with dexamethasone improved survival but probably did not prevent severe disability. Included in the recommendations were daily lumbar punctures. it appears that therapy for cryptococcal meningitis in HIVinfected patients should begin with amphotericin B . In lowincidence geographic areas. use of acetazolamide. In addition to antituberculous therapy with agents such as isoniazid. Repeated large volumes to mL of CSF have a higher yield for acidfast bacilli. In the patients with cryptococcal meningitis treated in this doubleblind. and ventriculoperitoneal shunts for asymptomatic patients with intracranial CSF pressure mm HO and for symptomatic patients with pressure mm HO. including lung. and ethambutol. Clinical features and CSF proles did not appear to be modied in the HIVinfected patients. important in the diagnosis. positive ndings may occur in up to of patients with tuberculous meningitis. It also emphasizes the difculty often encountered in establishing the diagnosis. especially in situations of increased intracranial pressure or obstruction resulting from the infection. the two most common ones are Cryptococcus neoformans and Coccidioides immitis. rifampin. clinicians should suspect tuberculous meningitis in members of ACCP Critical Care Medicine Board Review th Edition immigrant groups from highincidence areas. Delay to onset of treatment and the neurologic status at admission were identied as the main clinical prognostic factors. The IDSA guidelines for the management of cryptococcal meningitis in . and blood. latex agglutination test. Potentially helpful in establishing the diagnosis are other sites of involvement. as well as in patients who abuse alcohol or drugs and those with immunosuppression from any cause. it was suggested that measurement of intracranial pressure be included in the management of such patients. it was recommended that in the absence of focal lesions. and fungal culture of the CSF are. commonly mm HO. there may be a lack of inammation in the CSF. More recently. of early deaths and of deaths during weeks through were associated with elevated intracranial pressure. In HIVinfected persons with cryptococcal meningitis. imaging studies of the CNS may reveal an obstructing hydrocephalus. doubleblind. skin.A review of adult patients with tuberculous meningitis who were admitted to an ICU demonstrates the potential for this infectious process to cause serious disease. multicenter trial. Extrameningeal tuberculous infection may support the diagnosis. both caused meningitis in normal hosts prior to the AIDS era. Because of a predilection for tuberculous meningitis to involve the base of the brain. A randomized. Angiostrongylus cantonensis is a nematode that can infect humans who ingest poorly cooked or raw intermediate mollusk hosts. and bone are important in making the diagnosis. and eosinophilic leukemia. and studies have dened uconazole mg/d orally as the agent of choice. complementxing antibodies in the CSF may be an especially important aid to the diagnosis of coccidioidal meningitis. slugs. The diagnosis is conrmed by identifying the organism on CSF wet mount as motile amoeba. the IgG antibody to Toxoplasma is positive in about of these individuals. larvae are usually not found. and pleocytosis. Such a process has been most characteristically described in Asia and the South Pacic. eosinophils are occasionally present. like tuberculous meningitis. In addition to direct examination and culture of CSF. Important noninfectious causes include malignancy eg. such as snails. Although the CSF formula is usually one of lymphocytes with a low glucose level. ciprooxacin. Recent IDSA guidelines noted that oral fluconazole is currently the preferred therapy. From this outbreak. Amphotericin B Nervous System Infections and Catheter Infections Karam . ve deserve special comment. medications eg. and prawns. many RBCs. The most common is due to Toxoplasma gondii and presents most often as multiple ringenhancing lesions in HIVinfected patients. Maintenance therapy is required after completion of primary therapy. In contrast to cryptococcal meningitis. Hodgkin disease. A recent report described an outbreak of meningitis due to A cantonensis that developed in travelers who traveled to the Caribbean and whose clinical illness was strongly associated with the consumption of a Caesar salad at a meal. As with cryptococcal meningitis. Naegleria fowleri is a freeliving amoeba that enters the CNS by invading the nasal mucosa at the level of the cribriform plate. and headache. nonHodgkin lymphoma. may involve the base of the brain and cause obstruction of CSF ow with resulting hydrocephalus. Paragonimus westermani. Regardless of the regimen being used. Gnathostoma spinigerum. and Baylisascaris procyonis. Infection can also occur when fresh vegetables contaminated with infective larvae are eaten. It was acknowledged that some physicians initiate therapy with intrathecal amphotericin B in addition to an azole on the basis of their belief that responses may be more prompt with this approach. but they are less likely to do so. The CSF analysis shows a polymorphonuclear pleocytosis. These lesions may be associated with a CSF pleocytosis. but meningitis is not the most likely presentation of CNS toxoplasmosis. Meningitis Caused by Protozoa or Helminth Of the causes. Because CNS involvement may be clinically recognized in to of cases of progressive disseminated histoplasmosis. the infective larvae penetrate the gut wall and migrate to the small vessels of the meninges to cause a clinical picture of fever. it was suggested that A cantonensis infection should be suspected among travelers at risk who present with headache. with or without eosinophilia. As a general rule. joints. the epidemiologic history and the other body sites of involvement including lung. ibuprofen. with itraconazole being listed as having comparable efcacy. Meningitis due to C immitis commonly presents with headache. meningismus. hydrocephalus may occur. Because this infection usually represents reactivation disease. and hypoglycorrhachia. Toxocara canis. Because Coccidioides has a predilection for the basilar meninges. particularly in association with paresthesias or hyperesthesias. vomiting. management strategies for coccidioidal meningitis may vary from patient to patient. this potential complication nearly always requires a shunt for decompression. CSF analysis reveals an eosinophilic pleocytosis. skin. Taenia solium. Eosinophilic Meningitis The subject of eosinophilic meningitis has been recently reviewed. elevated intracranial pressure. and intraventricular medications or shunts. Therapy is with sulfadiazine and pyrimethamine. or it can be made by biopsy of brain tissue. the diagnosis and management of CNS histoplasmosis has been recently reviewed. Once ingested. The classic presentation is of an acute pyogenic meningitis in a person who recently swam in fresh water. and altered mental status. Other fungi have the capability of causing meningitis.HIVinfected persons with opening CSF pressure of mm HO recommended lumbar drainage sufcient to achieve a closing pressure mm HO or of initial opening pressure. Less classic infectious causes of eosinophilic meningitis include Trichinella spiralis. fungal meningitis. it has been stated that altered mental status indicates bilateral hemispheric or brainstem dysfunction and severely compromises the ability to determine whether the patients neurologic assessment is nonfocal. most of Asia. and perform lumbar puncture immediately after the imaging study if no intracranial mass lesion is present. When imaging is indicated. Over the last several decades. arm drift. As previously noted. nodular. ACCP Critical Care Medicine Board Review th Edition Miscellaneous Issues in the Diagnosis and Management of Meningitis The timing of diagnostic studies in patients with meningitis is of critical importance. because of chronic inammation at the base of the brain. More recently. inability to answer two questions correctly. many have limited the designation of focality to such processes as hemiparesis. Even though seizures are the most common manifestation of neurocysticercosis. Pneumonitis may also be a part of the clinical presentation. hydrocephalus may be present. fever. especially for meningeal infection. history of CNS disease. other symptoms include headache. combined with brain imaging studies and serologies serum enzymelinked immunoelectrotransfer blot or CSF ELISA. when a host inammatory response develops against T solium antigens released after the death of the parasite. Neurocysticercosis. Brain imaging studies may reveal intracranial lesions. and parts of Oceania. visual disturbances. Although not the most classic presentation of neurocysticercosis. the authors concluded that adults with suspected meningitis who have none of the noted baseline features are good candidates for immediate lumbar puncture since they have a low risk of brain herniation as a result of lumbar puncture. headache. or an abnormal focus on an EEG. isolated abnormalities on an imaging study of the brain. dysarthria. focal neurologic decits. inability to follow two commands correctly. especially Latin America. and ataxia. An important issue is focality. Most experts agree that the inammatory response produced by the death of the cyst produces symptomatic neurocysticercosis and that inactive infection ie. gaze palsy.administered systemically and intraventricularly is the drug of choice. observational cohort . aphasia. seizure within week before presentation. immunocompromised state. and extinction. Another amoebic pathogen infecting the nervous system is Acanthamoeba. helps make the diagnosis. is the most common cause of acquired epilepsy in the world and is highly endemic in all parts of the developing world where pigs are raised. Clinical manifestations include mental status abnormalities. institute empiric antibiotic therapy. presence of calcied or ringenhancing lesions does not require anthelminthics. The epidemiologic history. seizures. An important clinical clue may be preexisting skin lesions that have been present for months before CNS disease and may take the form of ulcerative. hemiparesis. which may infect individuals with defects in cellmediated immunity including patients with AIDS or after organ transplantation and result in a granulomatous amoebic encephalitis. Supporting the importance of the timing of antibiotics in patients with meningitis are the ndings of a retrospective. and ataxia. The drug treatment of choice for neurocysticercosis includes albendazole or praziquantel. Thirteen baseline clinical characteristics were used to predict abnormal ndings on head CT age years. abnormal level of consciousness. From the results of the study. Because of the potential for severe neurologic sequelae in individuals with bacterial meningitis who are treated in a suboptimal manner. eosinophilic meningitis may be part of the clinical presentation. which may be cystic or calcied. leg drift. A cantonensis may be a cause of eosinophilic meningitis. and abnormal language ie. attention has been focused in recent years on the appropriate sequencing of diagnostic studies. steroids should be given concomitantly to reduce edema produced by medical treatment. A prospective study of adults with suspected meningitis was conducted to determine whether clinical characteristics present before CT of the head was performed could be used to identify patients who were unlikely to have abnormalities on CT. which is caused by the pork tapeworm T solium. or subcutaneous abscesses. the following sequence of evaluation and management has been suggested obtain blood cultures. subSaharan Africa. meningismus. facial palsy. abnormal visual elds. Symptoms typically begin years after the initial infection. It was acknowledged that such an approach would have resulted in a decrease in the frequency of CT scans performed in the study cohort. it has been stated that of the CNS complications from such infections would be classied as encephalitis. those with one predictor variable. there are indirect mechanisms including induction of autoimmune diseases. In this study. stage II. the involvement in acute viral encephalitis is in the gray matter. rectal. altered mental status. No specic therapy is available for enteroviral encephalitis. Pathologically.study of patients with communityacquired bacterial meningitis. and tissue necrosis.and convalescentphase serology is important because viral shedding from the sites of culture may occur without clinical disease. neuronal destruction. a nding that underscores the need for prompt administration of antibiotics in patients with bacterial meningitis. In addition to infectious agents. In the Medical Knowledge SelfAssessment Program IX of the American College of Physicians. Encephalitis Characteristic of processes involving cortical brain matter are alterations of consciousness and/ or cognitive dysfunction. rapid and accurate diagnostic tests for bacterial meningitis are important. A recent analysis of the causes of death in adults hospitalized with communityacquired bacterial meningitis provides some important insights. is production of neurotoxins as occurs with shigellosis. An additional process. in which the process is referred to as meningoencephalitis. and seizures. Although of the patients had meningitis as the underlying and immediate cause of death. but conrmation using acute. which occurs on the basis of direct infection of neural cells with associated perivascular inammation. A representative clinical entity with such ndings is acute viral encephalitis. cryptococcal meningitis with concomitant HIV infection. Because of implications in both therapy and prophylaxis of meningitis. parameningeal foci. melioidosis. communityacquired bacterial meningitis were stratied into three groups based on the clinical ndings of hypotension. Of all the mechanisms by which an infectious process leads to involvement of the brain. This study was further interpreted as suggesting that the risk for adverse outcome is inuenced more by the severity of illness than the timing of initial antibiotic therapy for patients who arrive in the emergency department at stage III. clinicians have relied on a CSF pleocytosis for diagnosing meningitis. This may be associated with evidence of meningeal irritation and CSF mononuclear pleocytosis. and herpes simplex encephalitis. A recent report describes the potential role for broadrange bacterial PCR in excluding the diagnosis of meningitis and in inuencing the decision to initiate or discontinue antimicrobial therapy. For many years. Diagnostic studies should include viral pharyngeal. Although the most common cause of acute viral meningitis is enteroviral infection notably coxsackie A and B viruses and echoviruses. Patients with none of these three predictor variables were in stage I. It was concluded that such an end point will facilitate greater accuracy of epidemiologic statistics and will assist investigations of the impact of new therapeutic interventions. This process is referred to as postinfectious encephalomyelitis and is characterized by widespread perivenular inammation with demyelination localized to the white matter of the brain. and catscratch disease. it was acknowledged that there are at least four clinical entities in which patients may have fever. and those with two or more predictor variables. of patients had meningitis as the underlying but not immediate cause of death. stage III. which represents the sequelae of an infection. and nuchal ridigity but a normal CSF analysis early bacterial meningitis. The list of infectious and noninfectious processes causing encephalitis is lengthy and is partially summarized in Table . Nervous System Infections and Catheter Infections Karam . direct viral invasion of neural cells is the most classic. coma. and had meningitis as neither the underlying nor immediate cause of death. and urine cultures. Delay in therapy after arrival in the emergency department was associated with adverse clinical outcome when the patients condition advanced from stage I or II to stage III before the initial antibiotic dose was given. which may cause direct brain injury. patients with microbiologically proven. A day survival end point discriminated between deaths attributable to meningitis and those with another cause. PCR analysis of CSF when performed with optimal techniques in an experienced laboratory has been reported to be ACCP Critical Care Medicine Board Review th Edition . to coma. Q fever Parasites Toxoplasma. Patients may progress rapidly from a nonspecic prodrome of fever and malaise. These ndings most characteristically involve the temporal lobes. and the presence of RBCs in the CSF. or EEG. CMV. Subtle clues to focality may include abnormalities such as changes in olfaction. For many years. Cysticercus. leptospirosis Fungal including Cryptococcus. CSF lymphocytosis. Whipple disease. cat scratch disease. nuchal rigidity. infective endocarditis. typhus. EpsteinBarr. Acanthamoeba. to ndings such as behavioral abnormalities and seizures. febrile. Candida Rickettsial RMSF. the most emergent encephalitis to diagnose is that due to herpes simplex virus HSV. physical examination. personality change may be prominent for a few days to as long as a week before other manifestations. including cocaineinduced Drug reactions CMV cytomegalovirus. in its most classic form HSV encephalitis presents as an acute. relapsing fever. brain biopsy with viral culture was considered the goldstandard diagnostic study. focal illness. Actinomyces. Lyme disease. RMSF Rocky Mountain spotted fever. which may be inuenced by the fact that HSV might access the brain via the olfactory tract. Trichinella. Histoplasma. Because of the temporal lobe localization. herpes B simian herpes. Although it may have an insidious onset. Nocardia. Naegleria. such pathologic examination of brain tissue often yielded another treatable diagnosis. there has been attention to noninvasive diagnostic procedures.Table . From the clinical perspective. imaging studies of the brain. and coma. Ehrlichia. Headache is also a prominent early symptom. Encephalitis Postinfectious Encephalomyelitis Vaccinia virus Measles virus Varicellazoster virus Rubella virus EpsteinBarr virus Mumps virus Inuenza virus Nonspecic respiratory disease Noninfectious Diseases Simulating Viral Encephalitis Systemic lupus erythematosus Granulomatous angiitis Behet disease Neoplastic diseases. patients may have hypoglycorrhachia. Characteristic features with lumbar puncture include increased intracranial pressure. echovirus. Echinococcus. Although CSF glucose is characteristically normal. Blastomyces. changes in personality or in olfaction. Listeria. This infection is characteristically caused by HSV type and results in inammation or necrosis localized to the medialtemporal and orbitalfrontal lobes. hepatitis A HIV Bacterial including Brucella. Because of the invasiveness of the procedure and because neurosurgical services are not available at all hospitals. Trypanosoma cruzii Subdural hematoma Subarachnoid hemorrhage Acute multiple sclerosis Toxic encephalopathy. Plasmodium falciparum. A hallmark of the diagnosis is focality. varicellazoster. CSF analysis may initially be unrevealing even in some acutely ill patients who have fever. human herpes Arthropodborne Table Mumps Lymphocytic choriomeningitis Enteroviruses coxsackievirus. including carcinomatous meningitis Sarcoid Reye syndrome Adrenal leukodystrophy Metabolic encephalopathies Cerebrovascular disease Infectious Viral Rabies Herpes viruses HSV and . In suspected cases. which may be demonstrated with history eg. Coccidioides. parameningeal foci M tuberculosis Mycoplasma pneumoniae Spirochetes syphilis. which is transmitted by the tick Ixodes cookei. the virus became much more widespread in its prevalence across the United States. In . nausea. several important points were made. St. making WNV an important diagnostic consideration in patients with an acute viral illness. It was noted that in infected persons had developed a mild febrile illness. including deaths. probable. abnormal EEGs in . In contrast to Eastern equine encephalitis. with seizures in to . NY MMWR Morb Mortal Wkly Rep . Of these. Common laboratory ndings include inappropriate secretion of antidiuretic hormone and pyuria. Of those described in Table . . and death. Noteworthy features in these patients included an asymmetrical weakness without pain or sensory loss in association with Nervous System Infections and Catheter Infections Karam . Louis encephalitis California encephalitis West Nile encephalitis Western equine encephalitis Venezuelan equine encephalitis Powassan encephalitis Mortality Uneventful recovery in most patients. Advanced age was the greatest risk factor for severe neurologic disease. Prompt initiation of IV therapy with acyclovir is critical in management of patients in whom this infection is suspected because prognosis is inuenced by the level of consciousness at the time therapy is begun. a meningitis or encephalitis syndrome was absent. Relapse of HSV encephalitis has been stated to occur in some patients week to months after initial improvement and completion of a full course of acyclovir therapy. Important bases for using this diagnostic study are that IgM antibody does not cross the bloodbrain barrier and that of serum samples obtained within days of symptom onset had been positive for IgM antibody. ArthropodBorne Encephalitis Neurologic Sequelae Rare Encephalitis Eastern equine encephalitis St. It has been stated that one cannot anticipate an accuracy of in the diagnosis of HSV encephalitis in the early course of the infection. which induces clinical disease in about of those infected. the overall mortality related to SLE is about . and this fulminant process results in neurologic sequelae in of survivors. During the outbreak of WNV in the summer of . Eastern equine encephalitis is associated with the highest mortality rate to . . all are mosquitoborne except for Powassan encephalitis. even when one uses physical examination. with the highest mortality rate occurring in elderly persons. Recently reported is the experience with WNV infection in patients. In a decision model comparing a PCRbased approach with empiric therapy. The distinguishing features of these illnesses are summarized in this table. longterm morbidity. or both. spinal uid analysis without PCR. a avivirus that is serologically closely related to SLE virus and that was responsible for human cases. and neuroimaging studies. The outbreak of arboviral encephalitis described in metropolitan New York City in the late summer and fall of was caused by West Nile virus WNV. The limited data available suggest that many patients have substantial morbidity Ann Intern Med . vomiting. disorientation. and stupor. Following a nonspecic pro Table . the PCRbased approach yielded better outcomes with reduced acyclovir use. encephalitis. In the summary of pertinent information on this virus. A feature clinicians need to be familiar with is that related avivirusessuch as those causing SLE or denguemay produce a falsepositive assay for WNV. Emotional disturbances are the most common sequelae. In of these patients with focal decits. Retreatment may be indicated in these patients. and conrmed diagnoses of WNV based on the US national case denitions for WNV encephalitis. The arthropodborne encephalitides are a group of CNS infections in which the viral pathogen is transmitted to humans via a mosquito or tick vector.specic and to sensitive. of whom had a focal neurologic decit at presentation. Based on the outbreak in metropolitan New York. The cited review presents a concise summary of the criteria for making possible. several patients were described who presented with acute accid paralysis syndrome. drome. The most efcient diagnostic method noted in that review was IgM antibodycapture ELISA for IgM antibody to WNV in serum or CSF. patients may experience the abrupt onset of headache. Louis encephalitis SLE is caused by a avivirus. with in developing meningitis. seizures. A recent report acknowledges the potential for rabies to be spread through organ transplantation and provides further support for the contention that rabies should be considered in any patient with unexplained encephalitis. Like SLE virus. and visual disturbances. and it is at this point in the clinical course that paresthesias may begin at the wound site. Several approaches. including interferonb and immunoglobulin with high titer against WNV. transmission. offer promise based on animal models and limited clinical experience. Clinical features may initially include forgetfulness and impaired cognitive function. According to recommendations by the CDC. A review of the topic by the CDC stated that this infection should be considered in the differential diagnosis of persons presenting with unexplained rapidly progressive encephalitis. Supportive measures should focus on cerebral edema. No denitive therapy is presently available for this infection. in contrast to improvement in only of patients who did not receive this therapy p . Treatment for WNV encephalitis is supportive. Although some of these patients were initially thought to have GuillainBarr syndrome.a CSF pleocytosis. and CSF protein elevation in the absence of CSF pleocytosis that are typical of GuillainBarr syndrome. CSF is characteristically acellular. On a chronic basis and occurring later in the course of HIV infection. In this study. HIV has tropism for neural tissue. and cases should be reported promptly to state health departments. After inoculation. patients may develop an acute encephalitis that can include seizures and delirium and from which patients may spontaneously recover with few. Unfortunately. A feature on neuroradiology imaging studies is lack of mass effect. decreases in JC virus DNA to undetectable levels predicted a longer survival. and prevention. paresthesias. Although this infection does not occur very often. Healthcare providers should consider arboviruses in the differential diagnosis of aseptic meningitis and encephalitis cases during the summer months. these may progress to include weakness. the virus replicates in myocytes and then enters the nervous system via unmyelinated sensory and motor nerves. In this primary demyelinating ACCP Critical Care Medicine Board Review th Edition process involving white matter of the cerebral hemispheres. ataxia. and myoclonus. As a part of the acute retroviral syndrome that follows initial infection with HIV. the potential for preventing neurologic progression and improving survival by controlling JC virus replication becomes clinically relevant. Knowledge of these factors allows an understanding of both clinical presentation and prevention. Diagnosis of arbovirus encephalitis may be rapidly facilitated by testing acute serum or spinal uid for virusspecic IgM antibody. serum acute and convalescent and CSF samples should be obtained for serologic testing. and clinical efforts have recently focused on the role of immune reconstitution in modifying the clinical course of the illness. spasticity. neurologic improvement or stability at months after therapy was demonstrated in of patients who received highly active antiretroviral therapy. and a signicant number of patients will develop involvement of the CNS. where it is released into saliva. or ventilation if problems related to any of these occur. In a multicenter analysis of consecutive HIVpositive patients with PML. neurologic sequelae. The virus then moves from the CNS along peripheral nerves to skin and intestine as well as into salivary glands. In the context that untreated PML may be fatal within to months. It spreads until the spinal cord is reached. if any. disorientation. Preliminary interpretation of the ndings of acute accid paralysis in WNVinfected patients is that the pattern is a poliolike syndrome with involvement of the anterior horn cells of the spinal cord and motor axons. clinical presentation. The DNA polyoma virus JC is the etiologic agent in progressive multifocal leukoencephalopathy PML. they did not have the symmetric pattern with sensory changes. which may progress to cortical blindness or ataxia. patients present subacutely with confusion. there have been increasing reports of human rabies in the United States. no effective specic therapy is available for any of these infections. it raises some important points about epidemiology.. WNV is transmitted principally by Culex mosquitoes. Rabies is probably best considered to be an encephalomyelopathy. It is the CNS . In recent months. patients may develop an encephalopathy associated with cerebral atrophy and widened sulci on CT studies of the brain. In those individuals who might be candidates for aggressive management. there is still a strong impetus for postexposure prophylaxis. ear Right shoulder Right wrist Right arm No Right arm Left arm Both legs Right arm Abdominal No Right arm Left arm Findings of CI Yes Yes Yes Yes No No No Yes Yes Yes Yes No Yes Yes Yes Autonomic Instability No Yes No Yes Yes Yes Yes No Yes Yes Yes No No No Yes Myoclonus Yes Yes Yes No Yes Yes No No Yes No No No Yes No Yes Paralysis Total body No Vocal cord. the review stated that corticosteroids should not be used. rabies immunoglobulin. Table . confusion Confusion Hypersalivation Pain and Weakness Left arm Left arm Left face. Noteworthy in Table is that of the patients had pain and/or weakness. the treatment regimen includes local wound cleansing. monoclonal antibodies. Clinical Presentation of Rabies Clinical Feature Case Case Case Case Case Case Case Case Case Case Case Case Case Case Case Encephalitis Symptoms Hallucinations Hypersalivation Confusion Hallucinations Confusion Confusion. Because the rabies virus may in the early stages localize to limbic structures. Nervous System Infections and Catheter Infections Karam . interferon. Only of the cases reported in the recent Morbidity and Mortality Weekly Reports cited in Table were biterelated. ocular No No Dysphagia No Flaccid paralysis Dysphagia No Dysphagia Respiratory dysfunction No No Sixth nerve palsy CI cerebrovascular insufciency. and vaccine. A summary of the potential role of each of these agents was included. the minority is denitively related to an animal bite. ribavirin. human rabies immune globulin. it was acknowledged that the only survivors of the disease had received rabies vaccine before the onset of illness. When the management of rabies in humans was reviewed in . hypersalivation Hallucinations. In . Her case represented the sixth known occurrence of human recovery after rabies infection. Despite this very rare occurrence. including rabies vaccine. which is discussed in the following paragraph.involvement that leads to the cognitive dysfunction characteristic in encephalitis. changes in behavior may result. the most classic presentation is of encephalitis associated with hypertonicity and hypersalivation. The cited review notes that the normal management of patients with rabies should be palliative. Of the cases of batrelated rabies reported in the United States since . In individuals who were not previously vaccinated against rabies but have an indication for rabies postexposure prophylaxis. Although an ascending paralysis simulating the GuillainBarr syndrome has been described. a previously healthy yearold girl developed rabies after being bitten by a bat approximately month before symptom onset. intractable seizures Ataxia. Rabies prophylaxis has been recently reviewed. and ketamine. a combination of specic therapies was listed for consideration. explainable since rabies is a myelopathic infection. Because severe brain edema with herniation has been rare in patients with rabies and because corticosteroids have been associated with increased mortality and shortened incubation period in mouse models of rabies. hypersalivation Disorientation. however. the case was unique because the patient received no rabies prophylaxis either before or after illness onset. hypersalivation No Delirium Agitation Agitation. The pathologic changes have been compared with those occurring in persons in whom acute encephalomyelitis developed following rabies immunization using vaccine prepared in CNS tissue. . case . case . certain viruses may cause a postinfectious encephalomyelitis. . case . which may include involvement of the CNS. which usually occurs during the late summer and early fall. The epidemiology of ehrlichiosis. to minimize potential interference. this form of CNS pathology accounted for about one third of fatal cases of encephalitis with acute viral encephalitis being the major cause of infectious mortality in this category. case . nervous system involvement in ehrlichiosis may include severe headache. . With the elimination of vaccinia virus by vaccination for smallpox. case . In addition to viruses producing direct infection of the brain. and a meningoencephalitis. In addition to causing the characteristic ndings of fever. . . case .The doses of human rabies immune globulin and vaccine have been summarized. and recommendations now are that as much as anatomically feasible of the IU/kg body weight dose should be inltrated into and around the wounds. but tetracycline is considered the usual rstline drug when only RMSF is suspected. Mononucleosis due to EpsteinBarr virus may. Possible percutaneous or mucous membrane exposure to a patients saliva or CSF is an indication for postexposure prophylaxis. which is the most common cause of death resulting from this infection. respectively. Rickettsiae have the ability to produce infection of the CNS. petechial skin lesions involving the palms. the most characteristic is Rocky Mountain spotted fever RMSF. is similar to that of RMSF. and cytomegalovirus. An important consideration is the prevention of rabies infection after exposure of family members or healthcare providers to an index case. . The administration of rabies immune globulin has been modied. case . the following numbers of persons received postexposure prophylaxis case . case . CNS infection is the most signicant extrarespiratory manifestation of infection caused by Mycoplasma pneumoniae. Pathogens within the genus Ehrlichia have the propensity to parasitize either mononuclear or granulocytic leukocytes. . confusion. enteroviruses. but in contrast to RMSF. with the resultant infections referred to as human monocytic ehrlichiosis or human granulocytic ehrlichiosis. . . adenoviruses. case . and case . soles. wrists. . . . For persons in whom preexposure prophylaxis is indicated. thrombocytopenia. ehrlichiosis is associated with rash in only about of cases. At one time. and ankles. on rare occasions. The viruses that have been associated with postinfectious encephalomyelitis are summarized in Table . with the remainder administered IM in the deltoid or quadriceps at a location other than that used for vaccine inoculation. case . Because of the skin lesions and neurologic involvement. . Treatment of patients with such problems is limited to supportive care. the mortality attributable to postinfectious encephalomyelitis is now estimated to be to of cases of acute encephalitis in the United States. . caused by R rickettsii. this intracellular pathogen can produce a constellation of symptoms and signs that includes fever. may cause direct infection that results in encephalitis. cause direct infection of the brain and an encephalitic process. including dengue virus. Even though this organism has been isolated from the CSF. The pathogenesis of this process has not been denitively elucidated. After being transmitted to humans via a tick bite. acute forms of this infection may mimic disease caused by N meningitidis. leukopenia. and abnormal liver enzymes. case . It has been suggested that certain viral infections may cause a disruption of normal immune regulation. . case . lethargy. The emerging rickettsial pathogen identied as a cause of nervous system involvement is Ehrlichia. Chloramphenicol is effective against both of these pathogens. . with resultant release of autoimmune responses. epidemic typhus caused by Rickettsia prowazekii is characterized by central lesions that move distally. the mechanism by which it causes encephalitis is thought to be an autoimmune one. This infection is more likely to occur during the winter months than is RMSF. Of these. including outdoor activity and exposure to ticks. A group of viruses. only vaccine is recommended. In the reports of the patients summarized in Table . In contrast to the distal skin lesions that progress centrally in RMSF. case . ACCP Critical Care Medicine Board Review th Edition Two common infections that usually have benign courses in adolescents and young adults may progress to serious disease. Rarely present as abscesses. certain noninfectious diseases may mimic viral encephalitis. especially in individuals whose CD count falls below cells/ mm. IgG antibody to Toxoplasma is generally present. altered mental status. streptococci including the Streptococcus intermedius milleri group along with anaerobes including B fragilis are the predominant pathogens. morulae were seen in CSF white cells in only a small minority of the patients. Adapted from Clin Infect Dis . Excision or stereotactic aspiration of the abscess is used to identify the etiologic agents and has been recommended for lesions . In a recent review of the subject. or with acute bacterial endocarditis. The characteristic CSF abnormalities have been a lymphocytic pleocytosis with an elevated protein level. On a pathogenetic basis. if such a decision is made. Imaging studies of the brain in AIDS patients with Toxoplasma brain abscess show multiple usually nodular contrastenhancing lesions with mass effect found most commonly in the basal ganglia and at the graywhite matter junction. photophobia. In the clasTable . brain abscess represents a deviation from the classic tenet that Bacteroides fragilis is not a signicant pathogen above the diaphragm. or as a consequence of trauma or neurosurgery. and focal neurologic decits. hyperreexia. with of the patients having borderline low CSF glucose concentrations. and lung abscess. however. the CSF glucose level was normal in the majority of patients. Although the denitive agent for treating this infection has not been established by clinical trials. cranial nerve palsy. with extension from infected cranial structures eg. An alternative to metronidazole in this regimen would be chloramphenicol. Because the disease is due to reactivation of latent infection in about of cases. In the nonimmunocompromised host. they have advised that the patient must be followed meticulously with a brain imaging study such as CT or MRI. and ataxia. penicillin or a thirdgeneration cephalosporin eg. following neurosurgical procedures. Some experts have advocated using empiric antimicrobial therapy without aspiration of the abscess in patients who are neurologically stable and have an abscess cm in diameter that is not encroaching on the ventricular system. Approach to Mass Lesions In HIVInfected Persons Focal Lesions With Mass Effect in HIVInfected Persons Toxoplasmosis Primary lymphoma of the CNS Cerebral cryptococcosis Neurotuberculosis Syphilitic gumma Focal Lesion Without Mass Effect in HIVInfected Persons Progressive multifocal leukoencephalopathy CNS central nervous system. Nervous System Infections and Catheter Infections Karam . new focal or generalized seizures. brain abscess is the second most common. seizures. Radiographic and encephalographic studies did not reveal any lesions that supported a specic diagnosis. A review of neuroimaging studies in patients with AIDS is summarized in Table . The classic presentation may include recent onset of severe headache. blurred vision. T gondii classically presents as fever. Those patients with a presumed otic or sinus origin for their abscess should have coverage against enterobacteriaceae and H inuenzae using a thirdgeneration cephalosporin. As summarized in Table . and enlargement of the abscess during therapy mandates surgery. cyanotic congenital heart disease. and the outcome in patients with nervous system involvement is not well established. . with a key point being whether or not mass effect is present. Brain Abscess Among bacterial infections of the CNS. and clinical evidence of an intracranial mass.broadbased gait. headache. In this review. cm. Because of the lack of consistent efcacy of metronidazole against streptococci and upper airway anaerobic cocci. In the settings of penetrating head trauma. this infection may develop after hematogenous dissemination of organisms during systemic infection which often occurs in the context of such conditions as infective endocarditis. sinuses or middle ear along emissary veins. Rare presentation of neurosyphilis. cefotaxime or ceftriaxone is usually combined with this agent. clonus. nuchal rigidity. The clinical experience with this process has been limited. therapy for S aureus should be included. it appears that chloramphenicol or tetracycline is the agent most frequently used. In HIVinfected persons. In the patient without predisposing factors. Gramnegative bacilli. The most frequent pathogens are S aureus. with otitis another likely predisposing condition. H inuenzae. venous thrombosis. Antibiotics directed against the likely pathogens and surgical interventions are mainstays of therapy. or direct compression of the spinal cord. Septic Intracranial Thrombophlebitis Thrombosis of the cortical vein may occur as a complication of meningitis and is associated with progressive neurologic decits. sensory decit. bilateral weakness. The lesions of toxoplasmosis may be confused with primary CNS lymphoma. Clindamycincontaining regimens may be considered in sulfaallergic patients. face. Gramnegative bacilli. Inferior petrosal sinus thrombosis may produce the syndrome of ipsilateral facial pain and lateral rectus weakness that is referred to as Gradenigos syndrome. which also causes a mass effect due to surrounding edema and which may undergo central necrosis and present as ringenhancing masses. staphylococci. and Gramnegative bacilli. In of cases. trauma. mastoid. Of increasing importance are the reports of this infection occurring as a complication of lumbar puncture and epidural anesthesia. cavernous sinus thrombosis is the most frequently discussed. and focal neurologic decits. Of the forms of venous sinus thrombosis. it is usually a complication of meningitis. Usual pathogens include S aureus. Spinal Epidural Abscess and Subdural Empyema A review of spinal epidural abscess provides the basis for understanding two common threads included in literature published about this infection reports of poor prognosis and appeals for rapid treatment. and anaerobes. The usual pathogens are aerobic streptococci including S pneumoniae. Superior sagittal sinus thrombosis results in bilateral leg weakness or in communicating hydrocephalus. The triad of ndings that supports the diagnosis is fever. Gadoliniumenhanced MRI has replaced myelography as the diagnostic study of choice ACCP Critical Care Medicine Board Review th Edition because it identies not only mass lesions. In young children. urinary tract infections. Brain biopsy is reserved for atypical presentations and for patients who do not respond to initial therapy. The clinical features include fever. or oropharynx. empiric therapy with sulfadiazine and pyrimethamine is recommended. The paranasal sinuses are the source in over half the cases. After acute therapy for toxoplasmic encephalitis. vomiting. streptococci. Lateral sinus thrombosis produces pain over the ear and mastoid. Thrombosis of the intracranial venous sinuses classically follows infections of the paranasal sinuses. headache. Subdural empyema is an infection that occurs between the dura and arachnoid and that results as organisms are spread via emissary veins or by extension of osteomyelitis of the skull. including hemiparesis. The diagnosis is often made using MRI. signs of meningeal irritation. coagulasenegative staphylococci. with possible edema over the mastoid. but CT scan with contrast enhancement may offer the advantage of imaging bone. and focal neurologic decits that progress to focal seizures. or aphasia. Spinal epidural abscess represents a neurosurgical emergency because neurologic decits may become irreversible when there is a delay in evacuating the purulent material. streptococci both aerobic and anaerobic. The predisposing factors to this infection shed light on the likely pathogens. and anaerobes including B fragilis. alteration in mental status. but may be discontinued once CD cells are /L for months. Skin and soft tissue are the most probable source of infection and provide an understanding of why S aureus is the most common pathogen in this infection. middle ear. although the process may be metastatic from lungs or other sites. Within this sinus lie the internal carotid . and respiratory diseases. but also signal abnormalities that are consistent with acute transverse myelopathy and spinal cord ischemia. or temporal lobe seizures. Superior petrosal sinus thrombosis causes ipsilateral pain. mechanisms for the associated spinal cord necrosis include a decrease in arterial blood ow. Five anatomic sites may be involved with varying clinical presentations. prophylaxis to prevent recurrence has been recommended with a regimen like sulfadiazine plus pyrimethamine plus leucovorin. Spinal epidural abscess has been reported to follow surgery. point tenderness over the spine. Although the basis for this irreversibility has not been denitively established.sic setting described above. the source of infection may be unknown. followed by cranial nerve involvement. antibody levels decline over time such that one fth of older children to years of age do not have protective antibody levels. with the sixth cranial nerve usually involved rst. along with the ophthalmic and sometimes maxillary divisions of the trigeminal nerve. periorbital edema. headaches. The toxin of C tetani is transported up axons and binds to presynaptic endings on motor neurons in anterior horn cells of the spinal cord. eyelids. Both C tetani and C botulinum cause indirect nerve involvement on the basis of toxin production. diminished pupillary reactivity. The process. Antitoxin is not available for this disorder. Trigeminal nerve involvement may manifest itself as decreased sensation about the eye. Patients progress to develop proptosis. Clostridium tetani. The issue of anticoagulation in patients with suppurative intracranial thrombophlebitis is controversial. Recent reports of botulism Nervous System Infections and Catheter Infections Karam . but slower fever clearance and a higher incidence of GI side effects were associated with erythromycin. Corynebacterium diphtheriae. The clinical presentation is inuenced by these anatomic considerations. High fever. skin pop. It is the opinion of some experts in the eld that heparin followed by warfarin may be beneficial. Although there is an excellent correlation between vaccination rates and immunity among yearolds. The epidemiology of tetanus has changed somewhat in recent years.artery with its sympathetic plexus and the sixth cranial nerve. Papilledema. usually beginning with the cranial nerves. In a study in Vietnamese children with diphtheria that compared IM benzylpenicillin with erythromycin. HSV type . among those to years of age to . Steroids may be necessary if involvement of the pituitary gland leads to adrenal insufciency and circulatory collapse. and Clostridium botulinum can produce toxins that can injure peripheral nerves. but all were susceptible to penicillin. Such data argue strongly for ongoing tetanus immunization throughout a persons life in an attempt to prevent this potentially fatal disease. and root of the nose. Erythromycin resistance was noted in some of the isolates tested. descending. meningitis. such as Borrelia burgdorferi the etiologic agent of Lyme disease. The disease may be relentless in its progression to alteration in level of consciousness. malaise. and vomiting are the predominant ndings. A populationbased serologic survey of immunity to tetanus in the United States revealed protective levels of tetanus antibodies ranging from . Neuritis Infection of nervous tissue outside of the CNS can take place on the basis of several pathogenetic mechanisms. among those years of age or older. Ophthalmic nerve involvement may present as photophobia and persistent eye pain. cytomegalovirus. Prevention plays a pivotal role in controlling the number of cases of tetanus. In the lateral wall of the sinus are the third and fourth cranial nerves. Joining elderly patients as a patient population at risk for tetanus are injection drug users who inject drugs subcutaneously ie. nausea. Certain pathogens. Ophthalmoplegia may develop. C diphtheriae produces a toxin that directly involves nerves to cause a noninammatory demyelination. and varicellazoster virus. This blocks inhibitory input and results in uncontrolled motor input to skeletal muscle and tetanic spasm. and diminished corneal reexes may also develop. and culminating in involvement of peripheral nerves. Both penicillin and erythromycin have been recommended as treatment of diphtheria by the World Health Organization. and seizures. can produce peripheral neuropathy. but develop clinical evidence of cardiac dysfunction. but heparininduced thrombocytopenia has been noted as a potential complication. The mainstays of therapy include broadspectrum antibiotics and surgical drainage with removal of infected bone or abscess. but tetanus immune globulin and tetanus toxoid are given for clinical disease. The toxin of C botulinum binds to the presynaptic axon terminal of the neuromuscular junction with inhibition of acetylcholine release. and cyanosis of the ipsilateral forehead. chemosis. Direct infection of nerves may occur with Mycobacterium leprae and Trypanosoma spp. accid paralysis of motor and autonomic nerves. HIV. begins unilaterally but usually becomes bilateral within hours. along with antibacterial therapy. This results in a symmetric. both antibiotics were efcacious. Antitoxin is indicated in infected patients. Myocarditis occurs in as many as two thirds of patients. which is considered lifethreatening. Clinical sequelae of such a process initially include local paralysis of the soft palate and posterior pharyngeal wall. As summarized in Table . This constellation of symptoms. or dysarthria in a person who did not have EMG ndings indicating botulism and who did not have C botulinum detected in stool ndings consistent with the diagnosis of suspected case. the mouse inoculation test for toxin using serum. They discovered that the patients at highest risk of dying were ACCP Critical Care Medicine Board Review th Edition those who reported to the hospital with shortness of breath and impaired gag reex but no diarrhea. Patients progress to cranial nerve palsies with common presentations being diplopia. Researchers from the CDC and the Republic of Georgias National Center for Disease Control studied cases of botulism in Georgia. specic EMG ndings normal motor conduction velocities. there are two additional forms of importance. Investigation has shown that some of these cases were caused by colonization of the GI tract by C botulinum or Clostridium baratii with in vivo production of toxin. Along with the traditional forms of botulism. the following criteria were used for making the diagnosis of botulism an electromyographic EMG study showing an increase of in the evoked train of compound muscle action potentials with rapid repetitive stimulation to Hz. These have been referred to as cases of undetermined origin. which occurs most commonly in infants and is rare in children and adults. and standard mouse bioassay positive for toxin from clinical specimens and/or suspect food. dysarthria. stool culture positive for C botulinum. or dysphagia and then to a symmetrical descending accid voluntary muscle weakness that may progress to respiratory compromise. which has the highest reported rate of foodborne botulism of any country. See text. This form of botulism has been referred to as intestinal colonization botulism also termed by some as adulttype infant botulism. the CDC has recorded cases of botulism in which extensive investigation failed to implicate a specic food as the cause. the following were listed normal CSF values. The classic presentation includes neurologic and GI ndings. as is an intact mental status despite a groggy appearance. stool. ToxinMediated Peripheral Neuritis Direct toxin injury Corynebacterium diphtheriae Indirect toxin injury Clostridium tetani Clostridium botulinum Traditional categories Adult botulism Infant intestinal botulism Wound botulism Intestinal colonization botulism New category Inhalational botulism Antitoxin indicated. Since . decreased evoked muscle action potential. Normal body temperature and normal sensory nerve examination ndings are typical. In a recent review of laboratory ndings in foodborne botulism. or food may be positive. which occurs on the Table . . TX. analogous to the pathogenesis of infant botulism. normal sensory nerve amplitudes and latencies.have noted not only foodborne outbreaks associated with consumption of contaminated sh. A large outbreak occurred in in El Paso. antitoxin is indicated for adult botulism. dysphagia. In some cases of botulism strongly suspected to represent intestinal colonization. Of more recent interest is inhalational botulism. would allow doctors to give rst consideration to patients who are at highest risk of dying in a botulism outbreak. and baked potatoes held in aluminum foil for several days at room temperature. In that report. commercial cheese sauce. if validated in the United States and other countries as predictors of death. the patients had a history of GI surgery or illnesses such as inammatory bowel disease. Intestinal botulism. In addition. and by difculty in focusing the eyes that occurs due to interruption of cholinergic autonomic transmission. and blurred vision. and was traced to a dip prepared in a restaurant from potatoes that had been baked in aluminum foil and then left at room temperature for several days. which might have predisposed them to enteric colonization. is the most common form of human botulism in the United States. Role for botulism immune globulin IV human BIGIV. facilitation following rapid repetitive nerve stimulation. but also wound botulism in injection drug users who injected Mexican black tar heroin subcutaneously. Nausea and vomiting may be followed by diminished salivation and extreme dryness of the mouth. which could occur as a component of bioterrorism with intentional release of aerosolized botulinum toxin. With inhalational botulism. simultaneous onset of neurologic symptoms in multiple individuals should suggest a common source for the problem and increase the suspicion of botulism. Paralytic shellsh poisoning is caused by consumption of shellsh most characteristically butter clams. Characteristic neurologic ndings include paresthesias of the mouth and extremities. CatheterRelated Infections Urinary Bladder Catheters A clinical situation frequently associated with injudicious use of antibiotics in the critical care setting is asymptomatic bacteriuria. cardiovascular. Campylobacter infection. the diagnosis of asymptomatic bacteruria was based on results of a culture of a urine specimen collected in a manner that minimizes contamination. often associated with a debilitating hottocold reversal dysesthesia. cerebellar. The classic constellation of ndings involves GI. In adults. infant botulism. or a single catheterized urine specimen with one bacterial species isolated in a quantitative count cfu/mL in women or men. The acute. red snapper. maitotoxin which opens calcium channels. steamer clams. A humanderived human botulism immune globulin has been administered to infants with botulism and has been shown to reduce length of stay with this pattern of disease. and total muscular paralysis. ataxia. mussels. The ascending paralysis that comprises the GuillainBarr syndrome characteristically follows respiratory infection. and neurologic systems. or razor clams or broth from cooked shellsh that contain either concentrated saxitoxin a heatstable alkaloid neurotoxin or related compounds. with resultant sensory. two A recommendations were made regarding treatment of asymptomatic bacteriuria in adults pregnant women. It is important to be aware that skin testing should be performed to assess for sensitivity to serum or antitoxin prior to administration of antitoxin. Ciguatera sh poisoning follows consumption of marine sh most characteristically grouper. muscle paralysis. and men scheduled to undergo transurethral resection of the Nervous System Infections and Catheter Infections Karam . coma. GI infection notably. and palytoxin which causes muscle injury. sea snails. The pathology is segmental inammation with perivascular mononuclear cells and demyelination. cockles. and barracuda that have been contaminated with toxins produced by microalgae known as dinoagellates. Taste sensation is often altered. which occurs when the ingested organism produces toxin within the GI tract. A review of botulism has noted that antitoxin is released from the CDC for cases of intestinal colonization botulism. and for wound botulism. it has been suggested that antitoxin be given as early as possible based on clinical suspicion and should not be delayed while awaiting microbiologic testing. Of note is that pyuria accompanying asymptomatic bacteriuria was not considered to be an indication for antimicrobial therapy. cleancatch voided urine specimen with one bacterial species isolated in a quantitative count cfu/ mL in men.basis of ingestion of preformed toxin. dysphagia. Treatment is supportive. For asymptomatic women. Although this product is not yet commercially available. Asymptomatic bacteriuria was dened as a single. It has been noted with this form of botulism that antitoxin might only prevent progression of disease but not reverse paralysis once it has occurred. Therapy is primarily symptomatic and supportive. it may be obtained for the treatment of infant botulism under a Treatment Investigational New Drug protocol by contacting the California Department of Health Services telephone . Implicated toxins include ciguatoxin which induces membrane depolarization by opening voltagedependent sodium channels. does not respond to antitoxin. in which toxin is produced locally at the infected wound. The characteristic neurologic ndings include paresthesias which may be chronic periorally and in distal extremities. In that document. or immunization. the IDSA published guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Certain toxins produced by sh and shellsh have been associated with neurologic involvement. An exact etiology for this process has not been elucidated. and motor dysfunction. In March . In contrast. bacteriuria was dened as two consecutive voided urine specimens with isolation of the same bacterial strain in quantitative counts cfu/mL. Treatment of Asymptomatic Bacteriuria in Adults Adults in Whom Therapy Is Recommended Pregnant women Men about to undergo transurethral resection of the prostate or other urologic procedures for which mucosal bleeding is anticipated. Table summarizes those situations where therapy for asymptomatic bacteriuria was not recommended and reviews situations where the data are evolving but not conclusive. Although these data represented shortterm eradication of candiduria especially following catheter removal. especially those who are neutropenic or who have undergone renal transplantation see comments in text about renal transplant patients Elderly persons with obstructive uropathy Patients with diabetes mellitus Persons with positive urine cultures both at the time of catheter removal and then again wk after catheter removal Those undergoing certain types of surgery. The organisms most frequently isolated . but one in which there are no denitive data. relates to renal transplant recipients. In of cases.Table . A recent report of the NIHsponsored Mycoses Study Group evaluated the issue of treatment for candiduria that was asymptomatic or minimally symptomatic. Frequent or inappropriate use of antibiotics exerts selective pressures that are responsible for the increasing prevalence of bacterial resistance. An AIII recommendation was given for treatment of asymptomatic bacteriuria before urologic procedures other than transurethral resection of the prostate for which mucosal bleeding is anticipated. it was noted that asymptomatic urinary tract infections in this immunocompromised patient population may be left untreated. The guidelines stated that antimicrobial treatment of asymptomaticwomen with catheteracquired bacteriuria that persists h after indwelling catheter removal may be considered for treatment. it is important to use antibiotics in situations where the clinical ACCP Critical Care Medicine Board Review th Edition benets exceed risks such as adverse effects and the selection of resistant organisms. Patients were randomly assigned to receive uconazole mg/d or placebo for days. A clinically important area. However. Adults in Whom Therapy May Be Considered Women with catheteracquired bacteriuria that persists h after indwelling catheter removal Persons in Whom Denitive Recommendations Are Not Available but for Whom Some Provide Therapy Certain immunocompromised patients. At the end of treatment. urine was cleared in of patients given uconazole vs of those given placebo. Because of this. particularly when prostheses or foreign bodies notably vascular grafts may be left in place Some patients with struvite stones Persons with spinal cord injury Catheterized patients while the catheter remains in situ prostate. Notable in this study were the observations in the placebo group that candiduria resolved in about of chronically catheterized patients when their catheter was only changed and in of untreated patients when the catheter was removed. cure rate was about in both groups at weeks posttreatment. the longterm eradication rates were not associated with clinical benet. It has been acknowledged that urine culture surveillance and periodic renal scan or ultrasound examinations are recommended by some authors. Peritoneal Dialysis Catheters Abdominal pain and/or fever and/or cloudy peritoneal uid are the clinical features usually found in patients who are undergoing either continuous ambulatory peritoneal dialysis or automated peritoneal dialysis and who develop peritonitis. Based on cited references that treatment of asymptomatic urinary tract infections in renal transplant recipients are largely unsuccessful and that such therapy may not have an observable effect on graft function. at least during the rst months after transplantation. the isolate was Candida albicans. with a least one drawn percutaneously. the Society of Critical Care Medicine. but the incidence of Gramnegative pathogens has increased in patients utilizing disconnect systems. Recent trends in the management of this infection have been affected by the emergence of vancomycin resistance. occurring within weeks of completion of the antibiotic course. but subsequently relapses an additional time. it was noted that of the rst patients reported in the United States with this pathogen. the International Society for Peritoneal Dialysis suggested the substitution of ceftazidime for the aminoglycoside.in such processes have been coagulasenegative staphylococci eg. of which at least are polymorphonuclear neutrophils. In their review. The role of empiric therapy with cefazolin has also been reported in potentially infected hemodialysis patients. cefazolin or cephalothin in a loading dose of mg/L and a maintenance dose of mg/L in combination with an aminoglycoside. nosocomial bloodstream infections that occur each year in the United States. A concern about ceftazidime is its risk of selecting resistant Gramnegative organisms. The recommendation regarding blood cultures noted in the preceding statement is different from those recommended in a recent New England Journal of Medicine review. with vancomycin being reserved for conrmed resistant organisms. is supportive of the diagnosis of peritonitis. The committee stated further that modications to this regimen could be made based on the organism isolated or on sensitivity patterns. should be obtained with a new episode of suspected central venous catheter related bloodstream infection. Many episodes of catheterassociated peritonitis may be managed without removal of the catheter. Staphylococcus epidermidis or S aureus. but peritonitis that does not respond to antibiotic therapy and peritonitis associated with tunnel infections may be indications for catheter removal. most are related to different types of intravascular devices. Vascular Catheters Of the . catheter removal and replacement are recommended. the following recommendations were made regarding blood cultures in cases of suspected catheterassociated bacteremia two sets of blood samples for culture. and the Society for Healthcare Epidemiology of America have recently published guidelines for management of intravascular catheterrelated infections. Vancomycin use has inuenced this resistance. Another entity that inuences the decision for catheter removal is relapsing peritonitis. Infection with Pseudomonas. If no clinical response is noted after h of therapy for relapsing peritonitis. even when given for short periods. the Advisory Committee on Peritonitis Management of the International Society for Peritoneal Dialysis recommended that traditional empiric therapy of catheterassociated peritonitis be changed from the regimen of vancomycin and gentamicin to a rstgeneration cephalosporin eg. catheter removal is indicated. a toxic shock like syndrome has been occasionally noted. It is especially noteworthy that use of any aminoglycoside. The IDSA. In a review of vancomycinintermediate S aureus. Residual renal function is an independent predictor of patient survival. if the patient responds clinically. with the resultant potential for recurrent vancomycin use. and paired quantitative blood cultures or paired qualitative blood cultures with a continuously monitored differential time to positivity should be collected for the diagnosis of catheterrelated infection. The nding of WBCs/mm. or mycobacteria often requires catheter removal for cure. especially when the longterm catheter cannot be removed. all but had had exposure to dialysis for renal insufciency. dened as an episode of peritonitis caused by the same genus/species that caused the immediately preceding episode. In recognition of the contribution of injudicious use of vancomycin to the development of vancomycin resistance in Grampositive organisms. including those that produce type I lactamases or extendedspectrum lactamases. When caused by S aureus. both in enterococci as well as in S aureus. and the rate of peritonitis are independent risk factors for the decline of residual renal function in patients using continuous ambulatory peritoneal dialysis. in which it was stated that Two cultures of blood from peripheral sites should be evaluated because it is difcult to determine whether a positive culture Nervous System Infections and Catheter Infections Karam . a fungal pathogen. In its more recent iteration of recommendations for treatment of adult peritoneal dialysisrelated peritonitis. Over the past two decades.of blood from a central venous catheter indicates contamination of the hub. paired quantitative peripheral and IVDdrawn blood cultures. a quantitative culture of blood from the central venous catheter that yields at least cfu/mL may be diagnostic without a companion culture of a peripheral blood sample. the medical literature has proposed several predictors of sepsis from a catheter. each combined with demonstrated concordance with results of concomitant blood cultures. some studies have not supported such a correlation. One study has shown a sensitivity of and a specicity of in determining catheterrelated infection when a blood culture drawn from a central venous catheter became positive at least h earlier than the culture drawn from a peripheral vein. When compared with qualitative cultures. some data have suggested that the semiquantitative culture may not be predictive of clinical outcome. most other methods studied showed acceptable sensitivity and specicity both . Although Gram stain of material from the tip of a catheter may be helpful with diagnosis of local infection. In the IDSA guidelines for the management of catheterrelated infections. An important consideration is whether the infection is intraluminal or extraluminal. followed by serial dilutions and surface plating on blood agarhave greater specicity in the identication of catheterrelated infections. In this analysis. or a catheterrelated bloodstream infection. A new diagnostic method has been made possible by continuous blood culture monitoring systems and compares the time to positive cultures of blood drawn from the catheter and from a peripheral vein. and Candida spp have been most frequently reported. Antibiotic solutions that contain the desired antimicrobial agent in a concentration of to mg/mL are usually mixed with to U of heparin or normal saline and are installed or locked into the catheter lumen during periods when the catheter is not used eg. The volume of installed antibiotic is removed before infusion of the next dose of an antibiotic or IV medication or solution. whereas catheters in place for a longer duration were more likely to have intraluminal infection. S aureus. and the most often used duration of such therapy is weeks. For tunneled catheters. Quantitative blood cultures simultaneously obtained through a central venous catheter and a peripheral vein and demonstrating a ve. catheter colonization. However. A review of Englishlanguage studies published from to July studied the eight diagnostic methods that are most frequently used in clinical practice and for which performance data have been published qualitative catheter segment culture. In the recently published guidelines for management of intravascular catheterrelated infections. . and differential time to positivity of concomitant qualitative IVDdrawn and peripheral blood cultures h. Summarized in this review are some reports of cure of patients with infected tunneled catheters who were treated with both parenteral and lock therapy. to . The most traditionally quoted study regarding predictors of catheterrelated infection suggests that the presence of colonies on a semiquantitative roll culture of the tip of a catheter or needle is most useful. for a h period each night. paired quantitative blood culture was the most accurate test for diagnosis of IVDrelated bloodstream infection. Although such techniques are relied on at present to assist in the determination of an infected catheter. quantitative methodswhich include either ushing the segment with broth or vortexing or sonicating the segment in broth. alternative routes of antibiotic administration were also discussed. or quantitative catheter segment culture. qualitative blood culture drawn through an intravascular device IVD. These data have most applicability to tunneled catheters. . In immunocompromised patients with . semiquantitative catheter segment culture rollplate method. the sensitivities of these three methods were listed as ACCP Critical Care Medicine Board Review th Edition follows sonication. Catheters that have been in place for weeks are most often infected extraluminally.to fold increase in concentration of an organism in catheter blood compared with peripheral blood have been reported to correlate well with catheterrelated infections. coagulasenegative staphylococci. acridine orange leukocyte cytospin testing of IVDdrawn blood. it is signicantly less sensitive than quantitative methods. and ush culture. Of the pathogens most characteristically isolated as a complication of indwelling vascular catheters. and negative predictive value. roll plate method. however. patients with diabetes mellitus may still be at an increased risk for developing S aureus endocarditis. A scoring system based on the presence or absence of four risk factors community acquisition. For patients with vascular catheterassociated coagulasenegative staphylococcal bacteremia. Some have suggested that transesophageal echocardiography TEE may be a costeffective means of stratifying patients with catheterassociated S aureus bacteremia to a specic duration of therapy. if a nontunneled central venous catheter is retained and intraluminal infection is suspected. the bacteremia is demonstrated to promptly resolve with the removal or drainage. the most frequently noted minimum duration of parenteral therapy in such settings is weeks. before one makes the decision to limit parenteral therapy to this short course. metastatic infection was not a signicant problem. Corynebacterium jeikeium and Bacillus spp are important. catheterrelated. Even in such settings. negative surveillance culture of blood obtained to days after beginning appropriate antibiotic therapy and removal of focus. with weeks as the frequently stated duration in these settings. removable focus of infection. there is prompt clinical response. bloodstream infection. all four of the following criteria should probably be met there is removal of the intravascular catheter or drainage of the abscess that was presumed to be the source of the bacteremia. skin examination ndings suggesting acute systemic infection. As a result. It is well accepted that individuals with endocarditis or osteomyelitis occurring as complications of metastatic S aureus infection should receive a prolonged course of parenteral antimicrobial therapy. and if a tunneled central venous catheter or an IVD is retained in patients with uncomplicated. and some experts Nervous System Infections and Catheter Infections Karam . Gramnegative bacilli and atypical mycobacteria are also included as possible pathogens in this setting. the issue of duration of therapy for bacteremia due to this pathogen in catheterassociated bacteremia is exceedingly important. the strongest predictor was a positive followup blood culture at to h. it seems most prudent to remove the catheter when S aureus is isolated from the bloodstream. appropriate systemic antibiotic therapy is recommended for to days. The duration of therapy for patients with S aureus bacteremia that is catheterrelated may be similar to that for S aureus bacteremia due to a drainable focus. With this system. and heart valves are demonstrated to be normal. The medical literature suggests that catheterrelated coagulasenegative staphylococcal bacteremia may be successfully treated without recurrence in up to of patients whose catheters remained in place and who received antibiotics. With infectious disease consultation as one of the six components of the evaluation. it was suggested that a day course of antibiotics may be appropriate for patients with what has been termed simple bacteremia with S aureus if all of the other criteria are met TEE on day to of therapy was negative for both vegetations and predisposing valvular abnormalities. Although some authors have suggested that infections caused by S aureus in the setting of a vascular catheter may respond to treatment with the catheter left in place. Based on the available data. An important and common clinical question is whether a catheterrelated intravascular infection can be cured with a longterm indwelling catheter left in place.longterm indwelling catheters. and no indwelling prosthetic devices. persistent fever at h. Because of the potentially devastating complications that may occur when S aureus seeds heart valves or bone. the following recommendations have been made if a central venous catheter is removed. and notably both have vancomycin as the drug of choice for therapy. In the of patients who remained bacteremic while taking antibiotics with their catheters in place. including resolution of fever. However. patients should be treated with systemic antibiotic therapy for days and with antibiotic lock therapy for days. and positive followup blood culture results at to h has been suggested as a means of clinically identifying complicated S aureus bacteremia. therapy for this clinical problem has not been denitively established by clinical trials. Discussed frequently in the medical literature. there are increasing reports of metastatic sites of infection by this organism when the catheter is not removed. systemic antibiotic therapy for to days and antibiotic lock therapy are recommended. clinical resolution afebrile and no localizing complaints attributable to metastatic staphylococcal infections within h of initiating therapy and removal of focus. Since that study was performed. A clinical trial conducted by the Mycoses Study Group of the NIH compared amphotericin B with uconazole in the treatment of candidemia in nonneutropenic and nonimmunocompromised patients. In the patients who had a single species of Candida isolated. The risk of endocarditis was independent of the type. had denite endocarditis using the modied Duke criteria for the diagnosis of endocarditis. and colonization with Candida spp. uconazole. fungemia. but the following is a representative list from international experts in the eld antibiotics. and some of these strains may not respond to traditional doses of uconazole. In neutropenic patients. Other clinical situations for which catheter removal is necessary for cure of a catheterrelated infection include the following bacteremia due to C jeikeium and Bacillus spp. indwelling catheters. retained and treated with appropriate systemic and antibiotic lock therapy for days. In a trial comparing the echinocandin caspofungin to amphotericin B in patients with Candida infection involving blood or another sterile body site. hospitalization in ICUs. and intravascular lines should be removed. the IDSA presented options for the treatment of candidemia based on the presence or absence of neutropenia. candiduria. For patients who remain febrile and/or have bacteremia for days after catheter removal and/or initiation of antibiotic therapy. caspofungin was shown to be superior with signicantly fewer drugrelated adverse events than in the amphotericin B group. location. cancer therapy. Like S aureus and enterococci. it has been recommended that all patients with a prosthetic valve in whom S aureus bacteremia develops should be aggressively screened and followed for endocarditis. a longer course of therapy and an aggressive workup for septic thrombosis and infective endocarditis should be instituted.have suggested weeks of therapy in this patient population even if heart valves are normal. a lipid preparation of amphotericin B. ACCP Critical Care Medicine Board Review th Edition Risk factors cited for candidemia vary by reports. Candida may seed the retina of the eye to cause retinal abscesses that proliferate into the vitreous and result in the clinical entity of Candida endophthalmitis. of the organisms were C albicans. evidence . Candida spp have a predilection to cause metastatic infection on heart valves and in bone when these organisms are bloodborne. amphotericin B. It is important to reiterate that not all of the recommendations listed in this discussion of S aureus bacteremia have been denitively validated by clinical trials. Because of the high mortality of prosthetic valve endocarditis. or caspofungin were recommended. persistence of fever or bacteremia during therapy. In their guidelines for the treatment of candidemia. with the absence of uconazole in this patient population acknowledging the role of azole exposure as a risk factor for nonalbicans strains of Candida. they are potentially useful in patients who have previously been exposed to azole therapy or in whom empiric therapy is needed for presumed lifethreatening fungal infection. Because echinocandins are more likely to have activity against nonalbicans strains of Candida. In the recommendations just cited. amphotericin B. pocket. Because of the signicant complications associated with candidemia. hyperalimentation. bacteremia with Gramnegative bacilli. The study concluded that uconazole and amphotericin B were not signicantly different in their effectiveness in treating candidemia. and tunneled central vascular catheters or IVDs when there is evidence of tunnel. there are now two basic recommendations for patients with a positive blood culture for Candida the patient should receive a course of antifungal therapy. In a retrospective review of patients with prosthetic heart valves in whom S aureus bacteremia developed. it is not recommended for excluding a diagnosis of catheterrelated endocarditis if TEE can be done. In nonneutropenic patients. immunosuppressive therapy after organ transplantation. Removal is suggested in the following settings of S aureus bacteremia nontunneled central vascular catheters. in selected cases. and caspofungin were offered as options for therapy. or exitsite infection. In addition to the complications of endocarditis and osteomyelitis. or age of the prosthetic valve. there has been an increasing prevalence of nonalbicans strains of Candida in the bloodborne isolates from certain hospitals. it was noted that tunneled central vascular catheters or IVDs with uncomplicated intraluminal infection and S aureus bacteremia should be removed or. Because the sensitivity of transthoracic echocardiography is low. MMWR Morb Mortal Wkly Rep . National Committee for Clinical Laboratory Standards. Rosenstein N. et al. Approach to diagnosis of meningitis cerebrospinal uid evaluation. Robinson K. Hartman BJ. Clin Infect Dis . Treatment of bacterial meningitis. RR . Efcacy and safety of recombinant human activated protein C for severe sepsis. Clin Infect Dis . Rosenstein NE. N Engl J Med . National Committee for Clinical Laboratory Standards. Stephens DS. . European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators. J Infect Dis . 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Management of infections caused by antibioticresistant Streptococcus pneumoniae. Perkins BA. Bernard GR. et al. Infect Dis Clin North Am . . de Gans J. N Engl J Med . Wayne. Dexamethasone in adults with bacterial meningitis. Sporadic meningococcal disease in adults results of a year populationbased study. Crossley KB. no . Taylor JP. Parasitic central nervous system infections in immunocompromised hosts. . Performance standards for antimicrobial susceptibility testing th informational supplement vol . et al. Centers for Disease Control and Prevention CDC. . PA National Committee for Clinical Laboratory Standards. Schaad UB. . Rosenstein NE. New perspectives on bacterial meningitis. Antimicrobial resistance of Neisseria meningitidis in the United States. Walker M. van de Beek D. Overturf GD. N Engl J Med . Currently available data do not support the need for scheduled replacement of shortterm central venous catheters. Corrales JL. 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Zhanel GG. Nicolle LE. Bacterial spinal epidural abscess review of cases and literature survey. Clin Infect Dis . Candiduria a randomized. Blacklow NR. . MMWR Recomm Rep . Kaye D. Harding GK. Philadelphia. et al. Kaitz AL. . . . Keane WF. Perit Dial Int . rd ed. Screening and treatment of asymptomatic bacteriuria in pregnancy prevents pyelonephritis. Bacteriuria in elderly institutionalized men. Peritoneal dialysisrelated peritonitis treatment recommendations. et al. Kneen R. et al. .. Mossey J. Dolin R. Hodder EW. the U. et al. Fridkin SK. . Kiely M. Vila J. Imaging of spinal infection. Keane WF. Clin Infect Dis . Penicillin vs erythromycin in the treatment of diphtheria. Getz J. . Colgan R. Moiscrashvili M. Bjornson J. . Philadelphia. Approach to the patient with urinary tract infection asymptomatic bacteriuria. N Engl J Med . Abrutyn E. Southwick FS. Signs and symptoms predictive of death in patients with foodborne botulismRepublic of Georgia. Torres PJ. Nicolle LE. et al. . 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Nitenberg G. et al. Clin Infect Dis . Editorial response catheters and candidemia. MoraDuarte J. . Rotstein C. et al. Comparison of caspofungin and amphotericin B for invasive candidiasis. . Edwards JE Jr. Levison ME. chronotropic incompetence. It is important to recognize that isolated sinus node dysfunction generally results only in severe symptomatic bradycardia in the setting of concomitant failure of normal subsidiary escape mechanisms usually at the level of the AV junction. Following entry into the AV node. conduction becomes electrocardiographically silent and proceeds to the His bundle through the brous annulus and along the membranous septum before splitting into a leftward Purkinje branch. from the distal circumex artery in of cases. The AV node is also a complex structure with at least three preferential atrial insertions. atrioventricular AV block. and Purkinje system activation does activity emerge from the conduction system and become electrocardiographically apparent with the onset of ventricular muscle activation and the QRS complex. which is a branch of the proximal posterior descending artery that is supplied by the right coronary artery in the majority of patients. Roth. Although it is common to refer to the sinus node as a discrete structure. or acute cardiac damage as might occur with endocarditis or infarction. myocardial infarction. which similarly ramies over the right ventricular endocardium. which arises from the proximal right coronary artery in of cases. resulting in fascicular hemiblock patterns. There are also posterior right and left atrial insertions that have long conduction times and are important in mediating paroxysmal supraventricular tachycardia. Therefore. The anterior atrial insertion has a short conduction time and generally determines the normal AV conduction time in sinus rhythm. Activation then proceeds through the right atrium to the AV node located in the low interatrial septum adjacent to the tricuspid annulus. His bundle. .Bradycardias Diagnosis and Management James A. the use of drugs. sinus node dysfunction Bradycardia Overview All bradycardia is a consequence of the impairment of sinus node function. MD Objectives Understand the mechanisms that govern the normal regulation of heart rate Understand the forms of sinus node dysfunction and indications for pacemaker implantation Understand the forms of atrioventricular block and the indications for pacemaker implantation Understand the signicance of atrioventricular conduction disturbances complicating acute myocardial infarction Key words atrioventricular block. and both in the remainder of cases. Within this complex. resulting in full left bundle branch block or more distally in its anterior or posterior divisions. Blood supply is derived from the sinus node artery. it is in fact a large complex of pacemaker cells extending for several centimeters ACCP Critical Care Medicine Board Review th Edition along the superior lateral right atrium extending downward from the superior vena cava atrial junction within the sulcus terminalis. which ramies over the LV endocardium and rightward branch. Normal Conduction System Anatomy and Physiology Heart rate is normally determined by the intrinsic automaticity of the sinus node. chronic intrinsic conduction system disease. pacemaker. Only following the completion of AV node. the dominant pacemaker activity migrates depending on autonomic tone. occasionally. with faster rates originating in the more superior portions of the complex and slower rates in more inferior portions. or. The leftward branch may be damaged proximally. symptomatic sinus node dysfunction is usually a sign of an extensive process affecting not only the sinus node but subsidiary escape mechanisms as well. Clinically signicant bradycardia or pauses may occur as a consequence of autonomic disturbances. the combination of both processes. bradycardia. The AV node derives its blood supply from the AV nodal artery. Modest persistent bradycardia is often asymptomatic. such as fatigue. Sinus bradycardia may also exacerbate congestive heart failure as well as limit the effective use of blocker therapy. Based on this. it has been proposed that to beats/min is a clinically more accurate working denition of normal heart rate in adults than the traditional to beats/min commonly used by consensus. especially during the hours of sleep. severe symptoms due to sinus node dysfunction always imply both sinus node dysfunction and accompanying simultaneous failure of normal subsidiary escape mechanisms. Therefore. heart rates well below these estimates may be seen in healthy subjects. In athletes.Normal Autonomic Regulation of Heart Rate Normal heart rate is a consequence of tonic and phasic autonomic modulation of intrinsic sinus node automaticity. For these reasons. As a consequence. making the attribution of symptoms to resting bradycardia difcult. the inability to appropriately augment heart rate with exercise. equivalently. pacemaker implantation is reasonable. Sinus node dysfunction is a consequence of the following two distinct processes the failure of intrinsic automaticity. It is important to recognize that the sinus node is at the top of a cascade of automaticity and is normally backed up by a competent AV junctional escape mechanism. and alternate causes of symptoms have been excluded. that increases in prevalence with age. Bradycardias Diagnosis and Management Roth Sinus Node Dysfunction Sick sinus syndrome or. even severe sinus node dysfunction may be completely asymptomatic and clinically well tolerated. nocturnal seconddegree AV block and sinus pauses are common and are related to autonomic adaptations. and it accounts for about half of all pacemaker implantations. or drug effects. Its prevalence is estimated at in patients over the age of years. Sinus node dysfunction presents clinically as one of the following several patterns persistent or episodic sinus bradycardia. if parasympathetic tone is also reduced by autonomic dysfunction. they are commonly nonspecic ones. That the normal heart rate is slower than the intrinsic rate is a consequence of the dominance of parasympathetic tone over adrenergic tone in the resting state. agepredicted maximal heart rates are only observed when both arms of the autonomic nervous system are affected. This is commonly estimated as HRMax age. which is also referred to a sinus exit block. a combination of these patterns. or dyspnea. a resting heart rate below beats/min may be seen. Resting Sinus Bradycardia As noted above. Asymptomatic sinus bradycardia should rarely be treated with pacing unless the need for medical therapy expected to further exacerbate bradycardia is expected. where HRMax is maximum heart rate. or. but it is best dened as signicant bradycardia associated with symptoms that are plausibly attributable to bradycardia. When symptoms are present. and may require no specic therapy. Because exercise entails both sympathetic stimulation and simultaneous parasympathetic withdrawal. dening a cutoff value for pathologic bradycardia in the absence of symptoms is problematic in an otherwise healthy patient. or the failure of the propagation of sinus node impulses to the surrounding atrial tissue. However. In the presence of a competent escape. Based on a review of Holter recordings in a healthy population. which is one of the modern cornerstones of therapy. normal resting heart rate ranges between and beats/min in men and to beats/min in women. The intrinsic heart rate in the absence of autonomic modulation ranges between and beats/min and is somewhat faster than normal resting heart rates. The maximum stressinduced heart rate is related to maximal sympathetic stimulation accompanied by the withdrawal of parasympathetic tone. However. When inappropriate sinus bradycardia is persistent. there is no set rate at which sinus bradycardia can be labeled as pathologic. commonly. listlessness. plausible symptoms are present. physiologic stress. especially when severe. the use of pharmacologic catecholamine stimulation will result in modest tachycardia with the patient at rest. the resultant tachycardia from modest sympathetic stimulation can be more labile and dramatic. sinus node dysfunction is a common clinical syndrome . and sinus pauses. usually referred to as chronotropic incompetence. As sinus node activity is not apparent from a surface ECG. Sinus Pauses or Arrest An abrupt failure of sinus node automaticity will result in a pause in atrial activity. constituting the presence of intermittent pathologic atrial arrhythmias. most commonly intermittent atrial brillation. as well as the need to use potent drugs to decrease ventricular response during atrial brillation. It has also been proposed. Pauses associated with simultaneous symptoms. and. or the documentation of pauses of s in the presence of a history of symptoms plausibly related to bradycardia are indications for pacemaker therapy. This form of bradycardiatachycardia syndrome represents an important form of clinical sinus node dysfunction and is a common indication for pacemaker implantation. with concomitant sinus node dysfunction resulting in long pauses or symptomatic sinus bradycardia when the patients heart is in sinus rhythm. . This form of sinus node dysfunction should be distinguished from a common unrelated form of bradycardiatachycardia syndrome. Except for its intriguing physiology. in this syndrome. Bradycardia in the presence of chronic atrial brillation is a consequence of impaired AV conduction and is unrelated to sinus node dysfunction. Although other patterns may be observed as well. Pauses exceeding s and not occurring during sleep are often pathologic and may result in symptoms.Chronotropic Incompetence Cardiac output during exercise is increased by both an augmentation in stroke volume and an increase in heart rate. This condition is often incorrectly referred to as sick sinus syndrome as well. then exertional symptoms such as fatigue or dyspnea may ensue. the diagnosis is made indirectly by the observation of an abrupt halving in sinus Pwave rate followed by an abrupt return of the baseline sinus rate. Various criteria for this condition have been proposed. As in the case of resting sinus bradycardia. Pwaves will be absent. A common manifestation of this syndrome is a prolonged period of asystole following the termination of atrial brillation due to the slow recovery of sinus node automaticity with resultant presyncope or syncope. the attribution of symptoms to chronotropic incompetence is difcult. This is the presence of chronic atrial brillation. which is a much more conservative denition. Pauses of s are commonly seen in healthy subjects and are rarely symptomatic. If the rise in heart rate with exercise is inadequate. not from the failure of automaticity. that sinus bradycardia itself may promote atrial brillation. which may result in unintended iatrogenic secondary sinus node dysfunction between periods of atrial arrhythmias. Sinoatrial Exit Block Bradycardia due to sinus node dysfunction may also result. with periods of both rapid and slow ventricular response. ranging from the inability to reach of the agepredicted maximum heart rate likely an excessively inclusive denition to the inability to achieve a heart rate of beats/min with exercise. if of adequate duration and not accompanied by a competent escape mechanism. and hence the sinus node has no inuence on heart rate. although it is unproven. will result in abrupt symptoms. as opposed to intermittent atrial brillation. the decision to implant a pacemaker for chronotropic incompetence is a matter of judgement more than criteria. or secondarily related to extrinsic and transient causes of sinus node dysfunction. the atrium chronically brillates. ACCP Critical Care Medicine Board Review th Edition Primary and Secondary Causes of Sinus Node Dysfunction Sinus node dysfunction may be primarily related to intrinsic dysfunction of the sinus node complex. Bradycardia Tachycardia Syndrome as a Consequence of Sinus Node Dysfunction An additional common syndrome is the bradycardiatachycardia syndrome. The common combination of these two seemingly independent processes is in part a consequence of the high prevalence of both atrial brillation and sinus node dysfunction in the elderly. unless severe. As is the case for resting sinus bradycardia. a exit block is the most common. However. but from the failure of propagation from the sinus node complex to the atrium. the symptoms of and therapy for sinoatrial exit block are identical to that of intermittent sinus bradycardia discussed in a previous section. severe bradycardia. or transient asystole associated with syncope or presyncope with otherwise normal sinus node function between episodes is usually related to the syndrome of neurocardiogenic or vasovagal syncope. . it is important to recognize this syndrome. The following are ACC/AHA/NASPE guidelines for pacemaker implantation in sinus node dysfunction. opinion about the usefulness/efcacy of a procedure or treatment. However. recognizing that intrinsic sinus node dysfunction is mostly a disorder of the elderly. The most common factor causing such intermittent sinus node dysfunction is an autonomic disturbance. and . Recommendations for Permanent Pacing in Sinus Node Dysfunction Class I . and . excluding the bradycardia as a primary cause of symptoms. Symptomatic chronotropic incompetence. and are readily documented by monitoring or ambulatory recording even when the patient is asymptomatic.Intrinsic chronic dysfunction of the sinus node is rarely difcult to suspect and diagnose as sinus bradycardia. Sinus node dysfunction in asymptomatic patients. The PR interval encapsulates three distinct phases of AV conduction. with a heart rate of beats/min without association of symptoms with bradycardia. Sinus node dysfunction with symptomatic bradycardia due to nonessential drug therapy. Guidelines for Pacemaker Implantation in Sinus Node Dysfunction Class I conditions for which there is evidence and/or general agreement that a given procedure or treatment is benecial. or intermittent or persistent failure of AV conduction. useful. sinus node function behaves normally with normal resting heart rates and no apparent pauses. and diaphoresis may accompany these episodes. Finally. In the ambulatory patient. Between such episodes. In addition. symptoms may occur in the absence of or be out of proportion to the degree of bradycardia observed. and Class III conditions for which there is evidence and/or general agreement that a procedure/treatment is not useful/effective and in some cases may be harmful. Sinus node dysfunction in patients with symptoms suggestive of bradycardia that are clearly documented as not associated with a slow heart rate. Class IIA . At other times. Class II conditions for which there is conicting evidence and/or a divergence of AV Conduction Disturbances Disturbances of AV conduction result in delay. the diagnosis is suggested by the relatively young age of the patient. and often precede the development of bradycardia. Sinus node dysfunction with documented symptomatic bradycardia. Sinus node dysfunction occurring spontaneously or as a result of necessary drug therapy. if not continuous. Class IIB In minimally symptomatic patients. profound noncardiac autonomic symptoms including dysphoria. and effective. nausea. Syncope of unexplained origin when major abnormalities of sinus node function are discovered or provoked in electrophysiologic studies. the observation of intermittent pauses. symptoms in this syndrome are due to a combination of vasodilation and subsequent bradycardia. the longterm heart rate is beats/min while awake. As this syndrome is common in otherwise healthy patients and has a favorable prognosis in the absence of pacing. suggesting an autonomic process and not primarily an arrhythmic process. Class III . Class IIB usefulness/efcacy is less well established by evidence/opinion. transient sinus pauses and bradycardia are frequently seen in the hospital setting as well as in patients with intermittent symptoms such as syncope. and . pauses are usually frequent. Although the individual components of AV conduction can be readily recorded by a His bundle catheter in an Bradycardias Diagnosis and Management Roth . Often. Class IIA the weight of evidence/opinion is in favor of usefulness/efcacy. The last component of the PR interval is the time for propagation through the His bundle and bundle branches. The development of biventricular pacing has addressed this potential issue and may be appropriate when dualchamber ACCP Critical Care Medicine Board Review th Edition Mobitz I AV Block Also referred to as Wenkebach block. constituting HisPurkinje conduction is short. suggesting that most patients will present with symptoms permitting intervention before progression to sudden death. Because of the profound difference in the natural history of seconddegree AV block at the AV nodal vs infranodal levels. the major clinical task in evaluating patients with seconddegree AV block is to establish the probable level of block. the infranodal conduction system. Although this last portion. The use of conventional AV pacing to rectify this problem has been attempted but has generally been unrewarding. a block in the infranodal conduction system composed of the His bundle and bundle branches can be malignant with a tendency to progress abruptly and unpredictably to higher degrees of AV block accompanied by unstable or absent subsidiary escape mechanisms. which is typically to ms. FirstDegree AV Block Firstdegree AV block is dened as a PR interval exceeding . sudden cardiac death is rarely attributable to complete heart block. and fatigue. and is hence not. This is likely due to the adverse hemodynamic consequences of pacing the right ventricle in a patient with preexisting congestive heart failure. Firstdegree AV block is usually asymptomatic but is a sign of the presence of AV conduction system disease and as such may be a diagnostic clue to the mechanism of intermittent symptoms undocumented by ECG in a patient with unexplained syncope. as it is the time from the onset of His bundle to the time of ventricular activation is commonly referred to as the HV interval. seconddegree AV block at the level of the AV node tends to have a benign prognosis and in the absence of symptoms can be followed up safely without intervention. usually at the level of the AV node or HisPurkinje System ie. which is normally to ms. pacing is undertaken for the purpose of rstdegree AV block in the setting of congestive heart failure. Seconddegree AV block may be asymptomatic or associated with mild symptoms such as palpitations. an indication of the presence of AV conduction system disease. infranodal block may progress to complete heart block and in some cases sudden death. In this regard. Mobitz I AV block is dened as a progressive prolongation in . Seconddegree AV block may be seen commonly in athletes with high parasympathetic tone and resting sinus bradycardia as well as during hours of sleep. rstdegree AV block alone may exacerbate heart failure due to the maladaptive timing of atrial contraction relative to the onset of ventricular systole. Because of stable junctional escape mechanisms that are associated with progression to complete heart block at the level of the AV node. As the atrial conduction time is short and does not change much over time in a given patient. in and of itself. By contrast. Once symptomatic. This last interval. if resulting in protracted pauses or persistent bradycardia. the salient features of AV conduction disturbances can usually be elucidated by the careful interpretation of the surface ECG without the need to resort to invasive recording techniques. The presence of rstdegree AV block implies the presence of conduction delay in one of the components of AV conduction. The second portion of the PR interval is the propagation time through the AV node itself. usually no ms. may result in hemodynamic symptoms including lightheadedness. s or ms in the presence of otherwise preserved AV conduction.electrophysiology laboratory. or. syncope. Despite its malignant nature. The right atrial conduction time from the area of the sinus node where the Pwave begins to the region of the AV node occupies a short rst portion of the PR interval. it can conveniently be ignored when assessing AV conduction. SecondDegree AV Block Seconddegree AV block is dened as the intermittent failure of AV conduction with interspersed periods of intact AV conduction. the surface ECG and pattern of the block are useful in establishing the probable level of block. it is the major prognostic component of AV conduction and hence is very important clinically. AV block at the level of the AV node is usually indolent and gradually progressive. Rarely. As the degree of prolongation of the PR interval is less with each successive beat before block. the ancillary clues described above under Mobitz block remain useful. the denition of Bradycardias Diagnosis and Management Roth . Mobitz II AV Block Mobitz II AV block is dened as the intermittent failure of AV conduction during stable atrial rates without antecedent PR prolongation followed by the recovery of AV conduction. it is generally held that AV block at the level of the AV node never results in true Mobitz II AV block. as two consecutive conducted Pwaves are not available to assess Mobitz pattern. other clues may be helpful. In ambiguous cases. block at the level of the AV node is associated with a junctional escape with a QRS morphology similar to that in conducted sinus rhythm. As a consequence. the RR intervals actually tend to paradoxically shorten in the nal beats before block.PR interval prior to the development of AV block. in practice. when the underlying rhythm is atrial brillation. Although Mobitz II AV block may result from block in either the His bundle or subsidiary bundle branches. For example. the vast preponderance of cases of Mobitz II AV block is due to intermittent conduction failure within the main bundle branches or the hemifascicles of the left bundle. followed by the recovery of conduction with a return to baseline PR interval. Therefore. infranodal block tends to worsen with increasing heart rates associated with exercise or stress. hemodynamically signicant Mobitz II AV block should be addressed with early temporary or permanent pacing. and HighDegree AV Block AV block is dened as conduction of every other P wave. Mobitz II AV block is always a sign of block in the infranodal tissues including the His bundle and bundle branches. Highdegree AV block is dened as seconddegree AV block with conduction failure of two or more consecutive Pwaves. infranodal conduction is commonly normal and is associated with a narrow conducted QRS complex. it may cause a patient to progress to higher degrees of AV block with a consequent decrease in conducted ventricular rate. In the presence of underlying sinus rhythm. However. patients with Mobitz II AV block will generally display a wide conducted QRS complex between episodes of seconddegree AV block. As AV node function is improved with exercise. Although Mobitz periodicity cannot be assigned. the patient must already have a full left bundle branch block present between episodes of block. In ambiguous cases. other clues may be helpful. As the block is at the level of the AV node. Because of its malignant potential. highdegree AV block is neither Mobitz I nor Mobitz II. However. In this case. block. like other forms of seconddegree AV block. Mobitz I block tends to normalizes with activity and return at rest. is dened as the complete failure of AV conduction. Again. complete heart block. As infranodal function improves relatively little with exercise. this is dened as an atrial rate that is faster than the ventricular rate associated with AV dissociation. and. But very rarely this pattern can be seen with advanced infranodal disease in the His and bundle branches. Atropine therapy is not helpful for the treatment of infranodal block. it is also necessary to have xed block in all the remaining branches antecedent to the intermittent failure resulting in ThirdDegree AV Block Thirddegree AV block. block at the level of the His bundle is rare. In order for intermittent failure of conduction in a bundle branch or hemifascicle to result in AV block. If associated with periods of complete heart block. Mobitz I AV block is almost always associated with block at the level of the AV node. AV block is neither Mobitz I nor Mobitz II. Whereas infranodal block may rarely display Mobitz I/Wenkebach periodicity. the level of block may still be established to assess prognosis and guide therapy. or. Seconddegree block at the level of the AV node is improved with the use of atropine and is exacerbated by carotid sinus massage. equivalently. Therapy with catecholamines may be helpful but should not be relied on. This pattern is most commonly seen with infranodal block in the His bundle or bundle branches. the nding of Mobitz II AV block is always reason for concern. for intermittent failure in the right bundle to result in seconddegree AV block. usually for one cycle. and because it may accelerate sinus rates. As is the case for seconddegree AV block. Class III . . especially if cardiomegaly or LV dysfunction is present. AV block expected to resolve and/or unlikely to recur eg. the nding of a regular and a slow ventricular response during atrial brillation implies the presence of associated complete heart block. no matter how seemingly benign and well tolerated. Postoperative AV block that is not expected to resolve after cardiac surgery. the prompt institution of either temporary or permanent ventricular pacing is mandatory. Whereas a junctional escape may be quite reliable and trustworthy. When infranodal complete heart block is suspected. . with or without symptoms. By contrast. Marked rstdegree AV block . . Asymptomatic type II seconddegree AV block with a narrow QRS complex. associated with any one of the following conditions. because there may be an unpredictable progression of AV conduction disease. Asymptomatic type I seconddegree AV block at the supraHis level AV node or not known to be at intraHis or infraHis level. drug toxicity. . infranodal escape rhythms may be absent entirely. Neuromuscular diseases with AV block. should not be relied on. Thirddegree and advanced seconddegree AV block at any anatomic level. and . s or any escape rate of beats/min in awake. . with associated symptomatic bradycardia. regardless of the toleration of the ventricular escape rhythm. leading to the troubling observation of consecutive Pwaves alone with accompanying asystole and loss of consciousness. Complete heart block at the level of the AV node is associated with a generally stable junctional escape with heart rates between and beats/min and usually a narrow QRS complex.complete heart block cannot rely on the demonstration of AV dissociation. . symptomfree patients. As conducted atrial brillation always results in an irregular ventricular response. Lyme disease. Neuromuscular diseases with any degree of AV block including rstdegree AV block. or Recommendations for Permanent Pacing in Acquired AV Block in Adults Class I . When type II seconddegree AV block occurs with a wide QRS complex. a ventricular escape rhythm. ACCP Critical Care Medicine Board Review th Edition . Asymptomatic type I seconddegree AV block at intraHis or infraHis levels found on electrophysiologic study performed for other indications. Firstdegree or seconddegree AV block with symptoms similar to those of pacemaker syndrome. If the patient had an antecedent bundle branch block prior to the development of complete heart block. and . After catheter ablation of the AV junction. Arrhythmias and other medical conditions that require drugs that result in symptomatic bradycardia. Asymptomatic thirddegree AV block at any anatomic site with average awake ventricular rates of beats/min. . Unfortunately. the level of block determines the clinical behavior and prognosis of complete heart block. Documented periods of asystole of . Asymptomatic rstdegree AV block. Class IIB . and . presumably by decreasing left atrial lling pressure. complete heart block at an infranodal level is associated with a wide and slow ventricular escape. s in patients with LV dysfunction and symptoms of congestive heart failure in whom a shorter AV interval results in hemodynamic improvement. often slower than beats/min with a QRS complex that is different from the antecedent conducted morphology. Seconddegree AV block regardless of the type or site of the block. The following are ACC/AHA/NASPE guidelines for pacemaker implantation in acquired AV block. and . . block at the level of the AV node would be associated with a wide QRS escape identical to the conducted QRS complex prior to the development of the block. . Bradycardia with symptoms presumed to be due to AV block. pacing becomes a class I recommendation. Class IIA . Intraventricular conduction delay has been reported in about to of patients with STEMI in past reviews. more proximal occlusion of the right coronary artery or circumex artery in the minority of patients with a leftdominant circulation will involve the AV nodal artery and may result in complete heart block at the level of the AV node. even transient seconddegree or thirddegree infranodal AV block with an associated bundle branch block presents both a shortterm risk as well as a longterm risk of progression to complete heart block. Such block is often well tolerated. it will resolve over time following infarction and not require permanent pacing. the risk of developing heart block has decreased. However. which should be instituted before hospital discharge. the ready availability of transcutaneous pacing has made the need for prophylactic pacing in the absence of seconddegree or thirddegree AV block during the acute phase of infarction less of an issue in such patients. Therefore. Before the era of readily available transcutaneous pacing. With the recovery of AV conduction after the acute phase of infarction. these ndings in the setting of acute anterior wall infarction were indications for prophylactic temporary pacing. Temporary pacing is only required in the presence of hemodynamic compromise related to bradycardia. As myocardial infarction is an acute event where transient changes may occur. especially during infarction involving the inferior and posterior walls of the LV. Heart block may develop in approximately to of patients with STsegment elevation myocardial infarction STEMI. In the current era. Sinus Bradycardia and AV Block Complicating Acute Myocardial Infarction Sinus bradycardia occurs frequently. Block may occur due to infarction or ischemia of the AV node and the infranodal conduction system including the bundle branches. As such. Acute inferior wall infarction may spare the AV node entirely if due to occlusion within the posterior descending artery. Bradycardias Diagnosis and Management Roth . The risk of developing AV block is highest when there is new bilateral bundle branch involvement such as right bundle branch block with an associated left hemiblock. Transient bradycardia may also occur due to hypervagotonia. constituting to of acute myocardial infarction AMIassociated cardiac arrhythmias. Persistent seconddegree AV block in the HisPurkinje system with bilateral bundle branch block or thirddegree AV block within or below the HisPurkinje system after AMI. in the vast majority of patients. New bundle branch block presents a higher risk than the presence of old preexisting bundle branch block. even transient infranodal block complicating anterior infarction is an indication for longterm permanent pacing. the decision regarding the institution of longterm pacing vs simple monitoring with our without shortterm temporary pacing arises. However. AV block predicts an increased risk of inhospital mortality but is less predictive of longterm mortality in those who survive to hospital discharge. In the acute reperfusion era. and my be associated with a stable escape rhythm. unlike the case with block at the level of the AV node complicating inferior wall infarction. Recommendations for Permanent Pacing After the Acute Phase of Myocardial Infarction Class I . may be responsive to atropine therapy. and recurrent AV block does not tend to occur.during hypoxia in sleep apnea syndrome in the absence of symptoms. As is the case with other causes of AV block. The development of AV and intraventricular blocks during STEMI is generally related to the extent of the ischemic/infarcted segment. Acute anterior wall infarction due to occlusion within the left anterior descending coronary artery may result in septal infarction and associated damage to the branches of the infranodal conduction system. the longterm prognosis is excellent. The following are ACC/AHA guidelines for pacemaker implantation following the acute phase of myocardial infarction. AMI may result in transient dysfunction as well as persistent dysfunction of the AV conduction system. prognosis and management are related to the presence of symptoms and the level of the block. Armstrong PW. or both. exit block. et al. J Am Coll Cardiol . ACC/ AHA/NASPE guideline update for implantation of cardiac pacemakers and antiarrhythmia devices a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines ACC/AHA/NASPE Committee on Pacemaker Implantation. and . Available at http//www. if not managed aggressively. is often not accompanied by stable escape mechanisms.org/qualityandscience/clinical/ guidelines/pacemaker/incorporated/index. Acquired left anterior fascicular block in the absence of AV block. seconddegree or thirddegree infranodal block at the level of the bundle branches is potentially malignant. AV conduction disturbances may occur at the AV nodal level or infranodal level. Class IIB Persistent seconddegree or thirddegree AV block at the AV node level. Antman EM. and competent subsidiary escapes usually protect the patient from catastrophic bradycardia. et al. Spodick DH. ACCP Critical Care Medicine Board Review th Edition and. Sinus and AV nodal function are strongly inuenced by autonomic tone. can eventuate in sudden death.. These processes tend to be well tolerated and usually resolve following infarction. . Gregoratos G. Transient advanced seconddegree or thirddegree infranodal AV block and associated bundle branch block. of AV conduction. Accessed March . . anterior infarction may affect the infranodal conduction system at the level of the bundle branches. worsening heart block with tachycardia or exercise. . Sinus bradycardia and heart block occurring in the setting of AMI have a natural history related to the location of the infarction and the natural evolution of acute infarction. Class III . This permits asymptomatic patients to be followed up clinically for the development of symptoms before intervention. Persistent rstdegree AV block in the presence of bundle branch block that is old or age indeterminate. Transient AV block in the absence of intraventricular conduction defects. . associated bundle branch block.htm. Clues to an infranodal level of block are Mobitz II periodicity. Even transient seconddegree or thirddegree block associated with anterior infarction and bundle branch block is associated with a high risk of future progression as well as death. chronotropic incompetence. . Normal sinus heart rate appropriate rate thresholds for sinus tachycardia and bradycardia.acc. including sinus bradycardia. Abrams J. Persistent and symptomatic seconddegree or thirddegree AV block. South Med J . Anbe DT. References . and pacemaker implantation is indicated even if the block appears to have resolved before hospital discharge. and a wide QRS escape rhythm that is different from the conducted QRS in the presence of highdegree or thirddegree AV block. and . and bradycardiatachycardia syndrome due to sinus pauses and bradycardia when concomitant atrial arrhythmias terminate to sinus rhythm. Epstein AE. Block at the level of the AV node tends to be indolent and characterized by gradual progression. especially during sleep or in the setting of athletic training. Inferior infarction commonly results in sinus bradycardia and impairment of AV conduction at the level of the AV node. and signicant bradycardia as well as seconddegree AV block may be observed in healthy subjects due to increased parasympathetic tone. Transient AV block in the presence of isolated left anterior fascicular block. By contrast. Parasympathetic tone dominates at rest. By contrast. Summary and Conclusions All instances of bradycardia are a consequence of the impairment of sinus node function. . ACC/ AHA guidelines for the management of patients with STelevation myocardial infarction executive summary a report of the ACC/AHA Task Force on Practice Guidelines Committee to Revise the Guidelines on the Management of Patients With Acute Myocardial Infarction. Clinical sinus node dysfunction presents as one of several syndromes. Notes Bradycardias Diagnosis and Management Roth . She passed a melenic stool. Two units of pRBCs were infused and a nasogastric NG tube was placed revealing dark blood with clots in the stomach. Surgical consultation should be obtained in the early stages of resuscitation and evaluation. MD Objectives Clinically distinguish upper from lower GI hemorrhage Dene the common etiologies of GI hemorrhage occurring in the ICU Develop strategies for rapid diagnosis and management for both upper and lower GI hemorrhage Discuss prophylactic regimens for prevention of GI hemorrhage Compare therapeutic options for treatment of GI hemorrhage Key words angiography. and faint. hematemesis. a pulse of beats/min. pale. The mortality rate increases with age. is more common in the elderly.Upper and Lower GI Bleeding in the ICU Gregory T. The risk of death increases threefold if the patient is already hospitalized at the time of the initial bleed. melena. GI hemorrhage. and prompt denition and institution of therapy targeted to the underlying etiology. diverticulosis coli. occurs twice as frequently in men. and a temperature of C. The ideal ACCP Critical Care Medicine Board Review th Edition . On arrival at the emergency department. with a BP of /. Immediate measures are focused at restoring intravascular volume and maintaining tissue oxygenation. the patient was admitted to the medical ICU. nonsteroidal antiinammatory drugs. The decrease in hematocrit that occurs with bleeding is due to the reequilibration of body uid and may take to h to manifest. The patient who has sustained a UGI hemorrhage typically exhibits features of hypovolemia or hypovolemic shock. She described the recent use of ibuprofen for headaches but denied alcohol use or any knowledge of underlying liver disease. and examination revealed only a few scattered spider telangiectasias with mild hepatosplenomegaly. evidence of organ dysfunction. volume of transfusion requirement U packed RBCs pRBCs. particularly renal failure. endoscopy. she was alert and oriented. underlying cardiopulmonary disease. to of all admissions to the hospital. The following three principles underline management volume and blood product resuscitation. Hematocrit is not a reliable indicator of the degree of hemorrhage because it does not decrease immediately with acute bleeding. Upper GI Hemorrhage Upper GI UGI hemorrhage accounts for . and underlying liver disease. emergent endoscopy for diagnosis. a respiratory rate of breaths/min. resuscitation. For unknown reasons. and BP should be immediately corrected with a bolus infusion of normal saline solution. hematochezia. She was noted by coworkers to be pale. and remains a signicant cause of ICU morbidity and mortality. Her medical history was unremarkable except for the receipt of a blood transfusion at age years for postpartum hemorrhage. Two largebore indwelling IV catheters should be placed early in the resuscitation effort. varices Case Presentation A yearold woman experienced sudden hematemesis at work while performing her usual secretarial duties. peptic ulcer disease. UGI bleeding from peptic ulcer disease is more common during the winter months. diaphoretic. Resuscitation The initial assessment of severity of bleeding requires a critical evaluation of vital signs. The current mortality rate from transfusionrequiring hemorrhage ranges from to . Emergency medical technicians started peripheral IV lines and administered saline solution. hemodynamic instability. Everson. freshfrozen plasma. The most common etiology is duodenal ulcer disease. history of ulcer disease. Causes of UGI Hemorrhage Site Esophageal Varices Erosive esophagitis MalloryWeiss lesion Medicationinduced ulceration Caustic ingestion Infectious esophagitis Herpes CMV HIV Candida infection Carcinoma Gastric Peptic lesions Gastric ulcer Gastritis NSAID ulcers Dieulafoy lesion Varices Portal hypertensive gastropathy Vascular malformations Neoplastic lesions Carcinoma Lymphoma Leiomyoma Duodenal Peptic ulcer Vascular malformation Aortoenteric stula Hemobilia Hemosuccus pancreatitis of All UGI Bleeds Nonsteroidal Antiinflammatory Drugs and Risk of Bleeding The risk of bleeding with use of nonselective nonsteroidal antiinammatory drugs NSAIDs is approximately . portal hypertensive gastropathy. Management is inuenced signicantly by the presence of underlying chronic liver disease and its etiology. celecoxib and rofecoxib. Calcium infusion may be required in those patients receiving massive units of citratetreated stored blood since citrate may chelate calcium and lower its plasma concentration. Table . by the use of the more selective cyclooxygense inhibitors eg. the maintenance of RBC volume to restore oxygencarrying capacity. the patient should be evaluated for underlying organ dysfunction due to the hemorrhage and examined for the presence of chronic liver disease. However. Endoscopy or radiologic imaging is required to establish the cause of bleeding. Coagulopathic patients may require platelets. Risk increases with age. Bleeding from gastric ulcers is the next most common diagnosis. The coadministration of nonselective NSAIDs to patients receiving steroids or anticoagulation therapy eg.hematocrit guiding the transfusion of blood or pRBCs is somewhat controversial. Upper and Lower GI Bleeding in the ICU Everson . heparin or warfarin increases the relative risk of bleeding up to fold. after months of ongoing treatment. myocardial ischemia and infarction. cerebral ischemia. renal failure. and varices. Oxygen delivery to tissues is ensured by volume replacement to restore BP. UGI hemorrhage in the setting of chronic liver disease is related to portal hypertension in approximately of cases varices or portal hypertensive gastropathy. ICU patients who have experienced UGI hemorrhage may have a higher Etiology The causes of UGI bleeding are given in Table . and is related to the dose of NSAID. or cryoprecipitate to replace brinogen. Helicobacter pylori. The determination of hematocrit/hemoglobin from the sampling if peripheral venous blood is preferable to use of portable bedside hemoglobin monitoring using capillary blood. Risk is reduced. but not eliminated. is not an independent risk factor for UGI bleeding. Lactic acidosis. although proven to increase the risk for ulcer disease. and limb ischemia may all complicate hemorrhagic shock. followed by MalloryWeiss lesions. Because elderly patients ie. a higher target hematocrit may be recommended for these populations. and the administration of nasal oxygen to saturate the carrying capacity of the blood. representing to of all cases of UGI bleeding. bowel ischemia. age gt years and those patients with underlying cardiovascular disease are prone to myocardial infarction during signicant GI hemorrhage. During resuscitative efforts. although most investigators have recommended a target hematocrit of to . a wide array of conditions may present with UGI hemorrhage. and history of cardiovascular disease. A patient passing bright red blood via the rectum with stable vital signs and a benign abdomen is most likely bleeding from a lower. hyperactive bowel sounds. Approximately to of cases. mL. who has a clear NG aspirate. variceal ligation or sclerotherapy. acanthosis nigricans. and physical ndings eg. A recent analysis of ICU mortality Mortality Probability Model.prevalence of H pylori. endoscopy is useful in identifying patients who are at high risk of rebleeding and may benet from early surgical intervention eg. giant ulcer. cherry red spot over a varix and minimal erosive gastritis. Not only is endoscopy diagnostic in gt of cases. has a predicted mortality rate of approximately . had no further bleeding. She was treated with endoscopic ligation of the varices. Mildtomoderate UGI bleeding is characterized by loose. and biopsy for H pylori. is often characterized by hemodynamic instability or shock. diffuse hemorrhagic gastritis. The major role for NG tubes is to allow lavage and the clearance of blood from the stomach for the purpose of performing endoscopy or other diagnostic studies. In addition. but hemoccult testing of aspirates is not useful and not recommended. Massive bleeding from varices or an artery in an ulcer base. A number of studies have demonstrated the effectiveness of proton pump inhibitors PPIs for preventing gastroduodenal ulcers in patients receiving NSAIDs. If the aspirate lacks blood and contains bile. leftsided colonic lesion. jaundice. an abdominal examination. electrocautery. The development of melena requires a minimum bleed of mL and prolonged residence in the gut h. Table . pigmented lip lesions. or miscellaneous lesions Table . a patient admitted to the hospital with hematochezia. A patient admitted ACCP Critical Care Medicine Board Review th Edition to the hospital for melena. a UGI source for ongoing active bleeding is less likely. which revealed esophageal varices with stigmata of a recent hemorrhage ie. Some gastroenterologists also use the NG tube to assess the patient for activity of ongoing bleeding and to determine prognosis. Subsequent . after resuscitation of the patient and the clearance of blood and clots from the stomach. has a predicted mortality rate of . With brisk bleeding from a UGI source . Prediction of Outcome After Upper Gastrointestinal Bleed From Peptic Lesions Increased risk of mortality is associated with Age gt yr Hemodynamic instability with initial bleed Onset of bleeding during hospitalization for unrelated comorbid condition History of cancer Underlying comorbid conditions Endoscopic nding of giant ulcer Endoscopic nding of visible vessel in base of ulcer Endoscopic features predictive of rebleeding Spurting artery actively bleeding Nonbleeding but elevated visible vessel Adherent clot Flat cherry red or black spot with oozing Diagnosis The initial ndings of a physical examination may be useful in providing clues to the location of the bleeding lesion in the GI tract. The evaluation of vital signs. spider telangiectasias. However. hepatosplenomegaly. NG tubes can be helpful diagnostically in some cases. In contrast. Emergent endoscopy. a visible vessel not responding to endoscopic management. which in some cases may lead to antibiotic treatment. it can also be used to provide denitive therapy eg. and palpable purpura. Other clues to a UGI source are the elevation of BUN levels. black bowel movements melena. almost always mixed with darker blood or clots and characterized by hypotension. and the appearance of the bowel movement may localize the bleeding site. of UGI bleeds from duodenal ulcer disease are associated with a clear NG aspirate. A hemodynamically stable patient passing purplish clots and darker blood may be bleeding from the right colon or small bowel. MPMIII indicated that ICU mortality related to GI hemorrhage has diminished in recent years. who has a red NG aspirate. one may observe the passage of red blood via the rectum. and hematemesis. alcohol or sclerosant injection. and was discharged from the hospital h after admission. Case Continued Our patient underwent endoscopy. is indicated for nearly all acute UGI bleeders. initially thought to be bleeding from a lower GI LGI source. are actually bleeding from a UGI source. Transection of the esophagus for bleeding of esophageal varices. Varices . Gastric acid suppression PPIs are favored over Hblockers but are not effective in the setting of active bleeding. After resolution of the acute bleed. The effectiveness of endoscopic therapy is limited by arterial size. . Varices were eradicated by repeated ligation treatments. MurrayLyon IM. a nuclear medicine mTcRBC scan may indicate the site of bleeding. The mortality rate from UGI hemorrhage from varices ranges from to . Grades A points. Prognostic Models for Patients With Cirrhosis ChildPugh Criteria Bilirubin. and coincident gastric varices. and these patients have signicantly worse outcomes if treated empirically for H pylori. Specific Therapeutic Approaches Peptic Lesions Bleeding from peptic lesions of the UGI tract is treated as follows . None None Points . Octreotide. Slight Points . . Arterial bleeders with a diameter of mm usually do not respond to therapy and require surgery. mg/dL Albumin. See Pughs modication of the ChildTurcotte prognostic classication Pugh RN. Surgery is only necessary in approximately of rebleeds.. Br J Surg . and when sequential scans are performed the bleeding site may be localized in to of cases. Barium studies are not recommended in the initial evaluation of UGI bleeding. Angiography can be diagnostic for vascular lesions of the bowel. and she underwent evaluation for liver transplantation. If endoscopic studies are nondiagnostic and bleeding persists. The incidence of nonH pylorirelated duodenal ulcer is increasing. B points. electrocautery and injection of sclerosant. . H pylori status should be determined before initiating triple therapy. Other peptic lesions may also require this therapy if the patient is H pyloripositive. Imaging studies may also be useful in localizing a bleeding source. Rebleeding after initial control with endoscopic treatment is best managed by repeat endoscopic therapy or radiologic intervention. s prolonged Ascites Encephalopathy Point . Angiography is used in patients with higher bleeding rates and may be therapeutic if embolization of the bleeding site is performed. et al. Highdose antisecretory therapy IV PPIs signicantly decrease the risk of rebleeding in patients with bleeding ulcers. Table . After an acute bleed. variceal size and appearance on endoscopy. Although the scan can localize bleeding to a site in the bowel. advanced ChildPugh score Table . . Upper and Lower GI Bleeding in the ICU Everson . A Meckel scan with technetium pertechnetate is usually performed only after all other studies have failed to provide a diagnosis. but some studies have suggested that the rebleeding rate is reduced by to .evaluation revealed cirrhosis due to chronic hepatitis C. all patients with duodenal ulcers should be considered for triple therapy against H pylori. The use of octreotide for this indication is controversial. . Moderate The risk of bleeding from esophageal varices is directly related to portal pressure mm Hg. Dawson JL. Both Hblockers and PPIs are preferable to sucralfate. Therapeutic endoscopy ie. g/dL Prothrombin time. Surgery for those patients who do not respond to endoscopic management. etiology is rarely. C points. a g bolus followed by g/h infusion. dened from this study. if ever. Correction of coagulopathy. This scan is more sensitive than angiography. Ln creatinine . Lower GI Hemorrhage The principles of management for LGI bleeding are similar to those mentioned for UGI bleeding. In addition. and comorbid illness. The treatment of bleeding from esophageal varices is aimed at the control of portal hypertension using pharmacologic agents and the direct application of endoscopic treatment to the bleeding variceal channels. patients with variceal hemorrhage typically have portal pressures of gt mm Hg. Table is a better predictor of survival than either acute physiology and chronic health evaluation APACHE II score or ChildTurcottePugh score.Cirrhotic patients with three or more failing organ systems have a mortality rate. ACCP Critical Care Medicine Board Review th Edition Patients bleeding from gastric varices or those who rebleed from esophageal varices despite endoscopic treatment may require the placement of a SengstakenBlakemore tube and the performance of either transjugular intrahepatic portalsystemic shunt TIPS or surgical shunt Table . but TIPS may thrombose or stenose and require repeated radiologic interventions. these procedures are reserved for patients with thrombosis of the main portal vein or for those patients who are not candidates for TIPS. Still. as Table . Bleeding gastric varices are more difcult to manage endoscopically. Other interventional procedures include balloonoccluded retrograde transvenous obliteration and partial splenic embolization.Ln international normalized ratio . The conditions of the majority of patients bleeding from esophageal varices can be controlled by endoscopic ligation. A number of pharmacologic agents can lower portal hypertension eg. Interestingly. and to of patients undergoing TIPS experience postTIPS encephalopathy. such as combination ligation/ banding with sclerotherapy or a highvolume injection of cyanoacrylate. The mortality rate is gt in Childs class C cirrhotic patients Table .Ln bilirubin . Mortality rates from bleeding varices are directly related to ChildsPugh score. TIPS is costly. The model endstage liver disease or MELD score calculated as . A loading dose of octreotide of g is administered initially and is followed by continuous infusion at g/h. although APACHE II and III scores have been more predictive than the ChildTurcottePugh score. ongoing alcohol use. although preferred over banding as a single modality. nitroglycerin. obtains suboptimal control. and sclerotherapy. and somatostatin. management is compromised by relatively high rates of rebleeding and signicant morbidity and mortality. in one series of patients. renal. welltolerated. We currently favor the use of octreotide or vapreotide since they are effective. and cardiovascular. The most common failing organ systems were hepatic. blockers. Endoscopic ligation treatment banding is associated with fewer complications than endoscopic sclerotherapy and is currently the preferred modality of treatment. TIPS placement is successful in to of cases. and have few side effects. Studies using transjugular hepatic vein pressure measurements indicate that a reduction of portal pressure to lt mm Hg or a reduction in portal pressure controls bleeding and reduces the risk of rebleeding. ligation/banding is associated with a very high risk for rebleeding. Contraindications Absolute Heart failure with elevated CVP Polycystic liver disease Severe hepatic failure Relative Active intrahepatic or systemic infection Portal vein occlusion Hypervascular hepatic neoplasms Poorly controlled hepatic encephalopathy Stenosis of celiac trunk . Indications for and Contraindications to TIPS Indications Accepted Gastroesophageal variceal hemorrhage Refractory acute variceal bleeding Refractory recurrent variceal bleeding Bleeding from intestinal varices Cirrhotic hydrothorax Promising Refractory ascites Hepatorenal syndrome BuddChiari syndrome CVP central venous pressure. fundic varices were eradicated in of patients by balloonoccluded retrograde transvenous obliteration without the recurrence of either varices or bleeding. especially if it is performed with the coadministration of a longacting somatostatin analog. As noted above. Many experienced endoscopists have used combined modalities. vasopressin. However. diverticular disease. although endoscopic treatment is required in less than one third of cases.Table . Schwarz Pharma. mL/min. and other vascular lesions or tumors of the LGI tract Table . transfusion requirement. polypectomy. cautery. Studies comparing colonoscopy to aircontrast barium enema indicate that colonoscopy is far superior. follows resuscitation. Risk of Death From Variceal Hemorrhage According to Severity of Liver Disease ChildPugh Class A B C Table . or sclerotherapy. inammatory bowel disease. One series of ICU patients indicated that bedside Etiology Diverticular Disease Diverticuli are the cause of LGI bleeding in of all cases and in of those patients with active hemorrhage who are undergoing angiography. A study compared angiography to urgent colonoscopy and found that colonoscopy had a higher diagnostic yield. diverticuli are very common. Another advantage of colonoscopy is the ability to provide treatment eg. Causes of Signicant Acute LGI Bleeding Causes Diverticulosis Postpolypectomy Ischemic colitis Colonic ulcerations Neoplasm cancer and polyps Angiodysplasia Radiation proctitis Inammatory bowel disease Miscellaneous lesions Undiagnosed LGI bleeding colonoscopy after purgation was diagnostic in two thirds of cases. but that both were comparable in terms of the control of bleeding. Other Techniques Technetiumlabeled RBC scans are often ordered because of the ease of performance of the test and the perception that valuable information is gained. Angiography is particularly useful in the diagnosis and management of isolated vascular malformation. vasopressin infusion or embolization. However. and patient survival. need for surgery. length of ICU stay. Milwaukee. The usefulness of RBC scans is quite limited. neoplastic lesions. WI. but nearly to of patients who were thought to have LGI bleeding actually receive a diagnosis of an UGI source. The average age of LGI bleeders is years. However. Sigmoidoscopy should be reserved for the evaluation of minor LGI bleeding in relatively young patients years. these scans rarely provide denitive information regarding the cause or localization of bleeding and cannot provide therapy. The causes of LGI bleeding include the following hemorrhoids. rebleeding. A negative result for NG lavage may obviate the need for upper endoscopy. Angiography Angiography can be diagnostic in up to of cases if the rate of bleeding is . One initial consideration in evaluating the LGI bleeder is to exclude a UGI source. and prevalence increases with advancing age. Diagnosis Colonoscopy The primary diagnostic test in LGI bleeding is colonoscopy after purgation of the bowel by use of a bowel evacuant Colyte. Upper and Lower GI Bleeding in the ICU Everson . identifying the source in approximately of cases compared to only approximately for aircontrast barium enema. diagnosis. angiodysplasia. there is a risk of perforation with endoscopic treatments when administered in the setting of acute bleeding. This diagnostic and therapeutic modality is usually restricted to cases in which endoscopy is not possible due to large amounts of blood in the gut lumen or when certain treatments are planned eg. and about are from the small bowel. and planning for specic therapy. Wang KK. NSAID ulcers. Early administration of vapreotide for variceal bleeding in patients with cirrhosis. Review article scoring systems for assessing prognosis in critically ill adult cirrhotics. Gastroenterology . Risk factors. Prevention of peptic ulcer and dyspeptic symptoms with omeprazole in patients receiving continuous nonsteroidal antiinammatory drug therapy a Nordic multicentre study. Grace ND. Senzolo M. Aliment Pharmacol Ther . Cook D. Pharmacotherapy . which may include segmental colonic resection or even subtotal colectomy. only of patients with diverticulosis coli ever experience LGI bleeding. et al. et al.and placebocontrolled study of misoprostol vs lansoprazole. vasculitis. Garnett WR. et al. treatment is directed at the underlying etiology. Cello JP. Sorrenson TA. Assessing contemporary intensive care unit outcome an updated Mortality Probability Admission Model MPMIII. et al. Ciociola AA. N Engl J Med . When bleeding occurs. Pagliaro L. et al. A list of other relatively common causes of LGI bleeding is given in Table . Copes WS. Taniai N. Kaviani MJ. DAmico G. randomized. Higgins TL. Yoshida H. Crit Care Med . Pharmacologic therapy of portal hypertension and variceal hemorrhage. GarciaPagan JC. and prognosisresults from a randomized trial with year followup. Bhattacharya K. Aliment Pharmacol Ther . Dara SI. multicenter. McSorley DJ. painless. and juvenile polyps. Am J Gastroenterol . Mayo Clin Proc . Masliah C. As with other causes of GI bleeding. Carling L. et al. Ekstrom P. Arch Intern Med . Cholongitas E. World J Gastroenterol . Outcome of patients with endstage renal disease admitted to the intensive care unit. Additional rare causes of LGI bleeding include infectious colitis. Ahlquist DA. Octeotide for acute esophageal variceal bleeding a metaanalysis. it is usually sudden. et al. Clin Liver Dis . Afessa B. et al. clinical trial. Patch D. Wetterhus S. Am J Gastroenterol . Grifth L. Heyland D. Helicobacter pylori infection rates in duodenal ulcer patients in the United States may be lower than previously estimated. Campbell DR. Gastroenterology . DAmico G. Acute gastrointestinal bleeding experience of a specialized management team. History of acid suppression focus on the hospital setting.Overall. Bibliography Portal Hypertension Cales P. Hepatic vein pressure gradient reduction and prevention of variceal bleeding in cirrhosis a systemic review. et al. et al. Teglbjaerg PS. Mamada Y. Kazemifar AR. clinical characteristics. Ann Intern Med . sequential organ failure assessment and model for endstage liver disease scores for predicting short term mortality in cirrhotic patients admitted to intensive care unit. Acute bleeding stops spontaneously in of cases. SS Gostout CJ. Bajwa AA. et al. et al. Prevention of rst bleeding in cirrhosis a metaanalysis of ACCP Critical Care Medicine Board Review th Edition . UGI Bleeding Bytzer P. doubleblind. Ulcer prevention in longterm users of nonsteroidal antiinammatory drugs results of a doubleblind. Scand J Gastroenterol . Effect of oral omeprazole in reducing rebleeding in bleeding peptic ulcers a prospective. Diagnosis and treatment of gastrointestinal bleeding secondary to portal hypertension. rectal varices. Senzolo M. Risk factors for clinically important upper gastrointestinal bleeding in patients requiring mechanical ventilation. et al. Aliment Pharmacol Ther . Helicobacter pylorinegative duodenal ulcers prevalence. Am J Gastroenterol . Teres D. The localization of the site of bleeding is essential to plan appropriately for treatment. Hashemi MR. Bernard B. Grace ND. but to of patients rebleed. Crit Care Med . Patch D. randomized. Graham DY. and often from the right colon in up to of cases. J Clin Gastroenterol . Agrawal NM. et al. Adkisson W. Cholongitas E. Turner K. randomized trials of nonsurgical treatment. New methods for the management of gastric varices. Corley DA. active. Luca A. Chu KM. et al. Devlin HB. Lin CC. Am J Gastroenterol . Lam SK. Sloan EP. N Engl J Med . Lau JYW. Rockey DC. et al. Ebel A. BMJ . Cumpston K. Prendergast HM. Zimmerman J. N Engl J Med . Lau JY. An observational study of upper gastrointestinal bleeding in intensive care units is Helicobacter pylori the culprit Crit Care Med . Effectiveness of current technology in the diagnosis and management of lower gastrointestinal hemorrhage. Rockall TA. Endoscopic retreatment compared with surgery in patients with recurrent bleeding after initial endoscopic control of bleeding ulcers. Rockall TA. Relative frequency of upper gastrointestinal and colonic lesions in patients with positive fecal occultblood tests. Lee H. Green BT. Koch J. Selection of patients for early discharge or outpatient care after acute upper gastrointestinal haemorrhage national audit of acute upper gastrointestinal haemorrhage. Portwood G. et al. Upper and Lower GI Bleeding in the ICU Everson . et al. Van de Louw A. et al. Lasserre N. et al. Lansoprazole for the prevention of recurrences of ulcer complications from longterm lowdose aspirin use. J Emerg Med . Logan RFA. Ure T. et al. Intensive Care Med .Lai KC. Incidence and mortality from acute gastrointestinal hemorrhage in the United Kingdom. N Engl J Med . Tsvang E. et al. Lam YH. Rockey DC. et al. Lancet . et al. Gastrointest Endosc . Maury E. Vernava AM. et al. Scand J Gastroenterol . et al. Devlin HB. Lee YC. Sung JJY. Cello JP. Diverticular hemorrhage in the elderly is it welltolerated Dis Colon Rectum . Richter JM. Intensive Care Med . Drouhin F. Christensen MR. Siguencia J. LGI Bleed Bokhari M. Predictors of mortality in patients admitted to hospital for acute gastrointestinal hemorrhage. Lee KK. N Engl J Med . et al. Logan RF. Myocardial infarction and cardiac complications in emergency department patients admitted to the intensive care unit with gastrointestinal hemorrhage. Bedside colonoscopy for critically ill patients with acute lower gastrointestinal bleeding. Urgent colonoscopy for evaluation and management of acute lower gastrointestinal hemorrhage a randomized controlled trial. Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers. Reliability of HemoCue in patients with gastrointestinal bleeding. Sung JJ. Tankovic J. Kaplan LM. atrial utter. atrial utter. to manage that acute illness. this is not necessarily true. MD Objectives Understand the basic mechanisms underlying arrhythmogenesis Recognize and understand the mechanism of the common paroxysmal supraventricular tachycardia syndromes Understand the mechanisms and management of atrial arrhythmias. and reentry. New arrhythmias presenting in the ICU setting are always secondary to either some aspect of the patients critical illness itself. Early afterdepolarizations are promoted by longaction potential durations. However under some conditions. its associated pathophysiology. the working myocardium does not normally exhibit automaticity. occult arrhythmogenic right ventricular cardiomyopathy/dysplasia. remove that cause. Although it is commonly believed that ventricular arrhythmias are more dangerous than atrial arrhythmias. Although cells in the specialized conduction system are normally capable of intrinsic automaticity. being in a position to potentially identify the proximate cause of the arrhythmia and. ventricular tachycardia Tachyarrhythmias Tachycardia presents a different range of clinical problems than bradycardia. tachycardia management is more complex and challenging than the management of bradycardia. long QT syndrome. acute arrhythmias in the ICU often can be traced to a proximate cause related to the acute illness requiring intensive care. Supraventricular arrhythmias are dened as those in which the mechanism depends on the atrium. idiopathic ventricular tachycardia. cells may exhibit abnormal automaticity. the intensivist is at a potential advantage. with good intention. identifying the underlying tachycardia mechanism. and atrial brillation Understand the management of ventricular tachycardia and ventricular brillation in the setting of structural heart disease Understand and recognize the various ventricular tachycardia syndromes that occur in the absence of evident structural heart disease. Roth. including focal atrial tachycardia. Triggered arrhythmias are initiated by afterdepolarizations. the atrioventricular AV node. By contrast. triggered automaticity. which may result in either salvos or continuous rapid activity. The range of tachyarrhythmias is wide and classied broadly into supraventricular arrhythmias and ventricular arrhythmias. Consequently. including idiopathic ventricular tachycardia. Afterdepolarizations occurring before complete repolarization are referred to as early afterdepolarizations. Afterdepolarizations that reach threshold will result in a propagated beat. sudden cardiac death. As a consequence. ventricular brillation. ventricular arrhythmias are dened as those in which the mechanism is not dependent on either the atrium or AV node. and hypomagnesemia. Pathologic tachycardias are attributable to three mechanisms abnormal automaticity. A related phenomenon is triggered automaticity. the management of pathologic tachycardia requires an assessment of mechanism and selection of appropriate management based on this assessment. Although the mechanisms of tachyarrhythmias encountered in critically ill patients are the same as those encountered in other settings. and the cardiac ion channel diseases including long QT syndrome Key words atrial brillation. They can be triggered by pauses that further prolong repolarization and ACCP Critical Care Medicine Board Review th Edition . bradycardia rarely presents an ongoing management conundrum.Tachycardias Diagnosis and Management James A. and exploitation of the likely vulnerabilities of the tachycardia is the key to successful management. hypokalemia. if possible. As such. or alternatively the therapy being used. supraventricular tachycardia. By contrast. Whereas bradycardias may be amenable to pharmacologic palliation. clinically signicant bradycardia can always be addressed denitively by electrical pacing. or both. In the case of tachyarrhythmias. are. However under appropriate conditions. and AT. Afterdepolarizations occurring after full repolarization are referred to as delayed afterdepolarizations DADs. with a few wellunderstood Supraventricular Tachycardias Supraventricular arrhythmias may be broadly classied as the syndrome of paroxysmal Tachycardias Diagnosis and Management Roth . syncope. The requirements for reentry are unidirectional block. as well as later in life. supraventricular tachycardia SVT. Paroxysmal SVT The incidence of SVT is cases per . and either an anatomic or functional obstacle that forms an anchor point for the reentrant wave front to circulate around or through. especially during persistent and rapid tachycardia. longenough refractory periods. diaphoresis. It is important to emphasize that anginal chest pain is frequent. DADs are the cause of ventricular arrhythmias in digitalis toxicity and are likely causal in various calciumchannel blockerresponsive arrhythmias including focal atrial tachycardia AT and some forms of idiopathic ventricular tachycardia VT. Automatic mechanisms are generally selfreinitiating and hence not responsive to electrical cardioversion. The functioning pathway must conduct with adequate delay to permit the previously refractory muscle to recover and be reactivated later in the cardiac cycle. Diagnosis SVT may present in childhood. and often sustained palpitations due to stable SVT. As their mechanism and clinical implications are distinct. reentry can promote continuous and often sustained tachycardia. The syndromes are distinguished both by mechanism and by clinical presentation. atrial utter AFL. and may also be terminated by the same methods. Atrial arrhythmias may be paroxysmal or persistent and are often associated with underlying structural heart disease or atrial enlargement. occasionally. and a distinct group of atrial arrhythmias including atrial brillation AF. and prevalence is approximately . or presyncope. reentry is a macroscopic tissue phenomenon requiring large populations of cells. lightheadedness and. DADs are promoted by intracellular calcium overload and are triggered by tachycardia or rapid pacing. abrupt. especially at tachycardia onset before vascular adaptations to tachycardia. bradycardiadependent. Ischemic STsegment depression is commonly observed on initial ECG and is related to markedly augmented myocardial oxygen demand combined with loss of normal diastolic coronary perfusion time. The syndrome is characterized by recurrent bouts of rapid palpitations often leading to emergency department or physician visits. Reentry is initiated by a premature beat that nds one path refractory or blocked. a region of slowed conduction. Although commonly associated with an otherwise normal heart. may include dyspnea. The term SVT is usually reserved for the common paroxysmal SVT syndrome and atrial arrhythmias are considered separately. They are believed to be causal in the premature beats. persons per year. and smallenough chamber sizes to discourage reentry from occurring. The normal heart is designed to prevent reentry by maintaining adequate propagation velocities. Whereas abnormal automaticity and triggered automaticity are cellular phenomena. Reentrant arrhythmias are inducible by rapid stimulation or ectopic beats. are not a sign of underlying coronary artery disease. They are amenable to electrical cardioversion or debrillation.. certain forms of congenital malformations may predispose to SVT. commonly in adolescence when the heart achieves adult size. and nds a second functioning alternate pathway available. which initiate torsades de pointes in long QT syndrome. in addition to palpitations. Reentry is a distinct arrhythmia mechanism that because of its propensity to cause sustained rapid arrhythmias is the major mechanism of clinically signicant tachyarrhythmias. therefore. and resolve quickly with termination of the tachycardia. Most types of tachycardia have a reentrant mechanism. Paroxysmal SVT is commonly seen in otherwise normal patients with recurrent. Such changes are common in patients with SVT./. atrial arrhythmias will be addressed separately. Symptoms related to unremitting tachycardia. By contrast.conditions accounting for the vast preponderance of episodes. Long before the advent of curative ablation or identication of the anatomic substrate of this arrhythmia. including focal AT and physiologically inappropriate sinus tachycardia. this tachycardia is characterized by a very short RP interval. The posterior insertions needing to traverse the entire compact AV node to activate the His bundle account for the long conduction time. generating a long PR interval and. resulting in a long RP interval. the arrhythmia is classied as a long RP tachycardia. the arrhythmia is classied as a short RP tachycardia. and antegrade conduction time down the slow pathway is long. Under these conditions. it is helpful to develop an approach to such arrhythmias to guide management. If the Pwave is embedded and hence difcult or impossible to perceive during tachycardia or follows close on the heels of the preceding QRS complex. Slower ATs may also give a long RP interval appearance on ECG. and reciprocating AV tachycardia related to WPW. is not evident on ECG. As retrograde conduction time up the fast pathway is short. In patients with normal ECG ndings in sinus rhythm ie. which is related to an accessory AV connection with visible antegrade conduction in sinus rhythm. AV Nodal Reentry Tachycardia Far and away the most common form of paroxysmal SVT. Short RP Tachycardias Tachycardias exhibit a short RP pattern when retrograde VA conduction time is short relative to antegrade AV conduction time. The most convenient strategy is to assess the AV relationship during tachycardia. if delay is adequate. Patients with tachycardia appear to differ from normal subjects by the presence of more robust conduction down the slow pathway than the fast. and the anterior insertion bypassing much of the compact AV node account for a shorter conduction time to the His bundle. In fact RP is so short during typical slowfast AVNRT that the Pwave is entirely ACCP Critical Care Medicine Board Review th Edition . WPW allows for several other more complex arrhythmias and additionally carries a small but real risk of sudden death. if the Pwave follows long after the preceding QRS. This is the case in the two most common paroxysmal forms of SVT typical AV nodal reentry tachycardia. a spontaneous and unrelated premature atrial contraction may block in the fast pathway and conduct exclusively down the slow pathway. The remaining are related to an assortment of mechanisms. is seen frequently in young healthy patients but also commonly presents later in life. Approximately of cases of paroxysmal SVT are related to an accessory AV pathway that. Although the most common arrhythmia seen in WPW is clinically very similar to other forms of paroxysmal SVT. atrioventricular nodal reentry tachycardia AVNRT. The other important group of patients are those with the ECG pattern of WPW. it has become apparent that these pathways actually correspond to the posterior and anterior atrial insertions into the AV node. due to poor antegrade conduction. This condition is usually referred to as concealed Wolff Parkinson White WPW syndrome. With the insights gained with catheter ablation. permitting recovery of fast pathway conduction in time to permit retrograde conduction back to the atrium and initiating reentry down the slow pathway and up the fast pathway. due to a normal short PR during tachycardia. the mechanism was recognized to be related to two distinct pathways at the level of the AV node one with a long conduction time but short refractory period the slow pathway. in particular when the RP is comparable to or longer than the next PR interval during tachycardia. Long RP Tachycardias Tachycardias exhibit a long RP pattern on ECG if retrograde conduction time back to the atrium is long due to a slowly conducting retrograde pathway during tachycardia. the most common cause of paroxysmal SVT is AV nodal reentry. As the underlying mechanism of SVT is rarely known at the time of clinical presentation. and the other with a short conduction time but longer refractory period the fast pathway. accounting for at least of all patients with SVT. with no evidence of a delta wave. in which retrograde conduction is via the slow AV nodal pathway. The existence of these dual pathways is believed to be a normal feature of the AV node. The most common cause of this is atypical AV node reentry. Typical AVNRT is due to conduction down the slow pathway and up the fast. for even a single beat generally results in immediate termination of tachycardia. . Atypical is considerably less common than typical AVNRT and leads to a long RP pattern on ECG with very obvious deeply inverted retrograde Pwaves in leads . When symptoms are problematic or drug therapy not tolerated or desired. EP testing conrmed the mechanism of this tachycardia. the presence of early activation of the ventricle in sinus rhythm. which was cured by slow pathway ablation. It is dependent on the presence of an extranodal AV connection. however. referred to as an accessory pathway or equivalently a Kent bundle. This is a shortRP tachycardia mediated by conduction down the AV node slow pathway and retrograde up the AV node fast pathway. catheter ablation of the slow pathway at the posterior AV node is highly successful in elimination of the arrhythmia with a success rate and a low risk of complications. which is the only reection of the Pwave in the QRS during tachycardia. which normally results in a complete brous annulus throughout the AV groove with the exception of the penetrating His bundle. As might be suspected. and this is referred to as atypical AVNRT. making it entirely unapparent by ECG Fig . results in shortening of the PR interval and slurring of the QRS onset referred to as a delta wave Fig . obscured by the QRS in the majority of patients. obscured by the QRS complex. either spontaneous or druginduced failure of AV nodal conduction. Typical AVNRT. prior to conduction through the normal AV conduction system. if not completely. and aVF. They are a consequence of incomplete development of the AV annulus. If capable of antegrade conduction. it is also possible for patients to have tachycardia mediated by conduction down the fast pathway and up the slow. Sometimes a careful comparison with a sinus rhythm ECG on the same patient will reveal subtle changes in the QRS morphology such as a small pseudo R or S wave. Reciprocating tachycardia is an AV arrhythmia requiring participation of both the atrium and ventricle in the tachycardia. By contrast. As ongoing tachycardia is dependent on AV nodal conduction. It is responsive to similar drugs and interventions as the much more common typical slowfast AVNRT. the patient may still be susceptible to AV tachycardia due to the presence Tachycardias Diagnosis and Management Roth . the Pwave during tachycardia is not apparent because it begins within and is mostly. As is common for this arrhythmia. the ECG in sinus rhythm will lack a delta wave and appear totally normal. Accessory pathways are AV muscle bers with behavior similar to working myocardium. Reciprocating AV Tachycardia The second most common cause of paroxysmal SVT is reciprocating AV tachycardia. Drug therapy of this tachycardia is directed at the AV node.Figure . if the pathway is not capable of antegrade conduction. A sample of this tachycardia is shown in Figure . and an indeterminate/isoelectic delta wave indicates a paraseptal or septal location. This ECG could also be compatible with a focal AT but. Note the absence of delta waves when in tachycardia. at approximately /min. of retrograde conduction up the pathway. in this patients case. At EP testing. It is mediated by antegrade conduction down the fast pathway. The ECG showing SVT in Figure is the same patient in ORT. This is a longRP tachycardia. followed by retrograde conduction back up the slow AV nodal pathway. this pathway was conrmed to be left sided and treated by catheter ablation. WPW pattern on ECG of a patient with recurrent palpitations due to SVT. A positive delta wave in V indicated a leftsided pathway. ACCP Critical Care Medicine Board Review th Edition Whether manifest or concealed WPW. both features which are unexpected with AT. . the most common tachycardia associated with an accessory pathway is mediated by conduction down the AV node to the ventricle followed by retrograde conduction up the accessory pathway to the atrium and back down the AV node. which was cured by ablation of the slow pathway. EP testing conrmed the mechanism of this tachycardia. resulting in a very long RP interval in this patient. This example is relatively slow. resulting in a normal PR interval during tachycardia.Figure . The presence of a functioning pathway capable of good retrograde conduction and hence able to support tachycardia but unapparent on ECG as it lacks antegrade conduction is referred to as concealed WPW. a strongly negative delta wave in V indicates a rightsided pathway. Figure . Note the delta waves most obvious as a positive going slur of the QRS onset in V to V. The Pwave during this tachycardia is characteristically deeply inverted in the inferior leads. Atypical AVNRT. the arrhythmia was readily initiated by PVCs and terminated abruptly with AV block. if the accessory pathway is also capable of antegrade conduction as evidenced by a delta wave on ECG in sinus rhythm. catheter ablation. This is also a shortRP tachycardia like AV nodal reentry. However in WPW. commonly electrophysiology EP testing and. This results in a retrograde Pwave that is usually easily visible in the ST segment following the QRS arrows and not buried within it as is the case in typical AV node reentry. then the ventricular myocardium before arriving at the accessory pathway and propagating back to the atrium. activation must traverse the HisPurkinje system. It is very important to emphasize that this tachycardia is almost identical in appearance and clinical behavior to typical AVNRT. it has become very rare to carry adults with symptomatic WPW on medical therapy and not proceed with ablation. This tachycardia occurred in the patient whose sinus rhythm ECG is shown in Figure . and because the accessory pathway is monopolized serving retrograde conduction during tachycardia. Like AV nodal reentry. Because of the common need to perform EP testing to stratify risk in WPW syndrome and the high efcacy of ablation. special considerations apply. this tachycardia results in a short RP pattern on ECG and is absolutely dependent on AV conduction. such patients may be subjected to electrophysiologic testing and ablation if they participate in activities in which a poorly tolerated arrhythmia would entail undo risk. Tachycardias Diagnosis and Management Roth . However. All patients with WPW and associated symptoms are at potential risk for sudden death and require additional evaluation. Special Considerations in Patients With SVT and Delta Waves on Sinus Rhythm ECG Patients with delta waves on ECG without symptoms are said to have WPW pattern and generally have an excellent prognosis. whereas the most common tachycardia in WPW is clinically similar to typical AVNRT. Also note that the delta waves are absent during the most common form of tachycardia in WPW.Figure . if a competent accessory pathway is identied. This tachycardia is referred to as orthodromic reciprocating AV tachycardia ORT because it conducts in the normal antegrade or orthodromic direction down the normal conduction system. the QRS complex in ORT is usually narrow and the delta wave absent during tachycardia regardless of its presence or absence in sinus rhythm Fig . Both are shortRP tachycardias. Rarely. A single failure to conduct either antegrade via the AV node or retrograde up the accessory pathway will result in immediate termination of the tachycardia. he was subjected to EP testing and underwent ablation that eliminates the clinical tachycardia as well as any risk of sudden death from future rapidly conducted AF. As the patient was symptomatic and had manifest WPW on ECG. Patients with delta waves on ECG and associated SVT or symptoms compatible with tachycardia such as palpitations or syncope are said to have WPW syndrome. Further evaluation and therapy are not generally indicated. ORT related to underlying WPW. is commonly subjected to curative ablation. the presence of competing conduction down the AV node paradoxically moderates conduction down the accessory . when conduction was predominantly down the AV node instead of the accessory pathway. it is important to recognize the ECG signature of AF in the presence of underlying WPW solely from the presenting ECG. if the QRS complex is narrow. there are periods of narrow QRS conduction as well. The clinician will usually be confronted with an unknown rapid and worrisome ECG and need to suspect WPW in the absence of a sinus rhythm ECG showing delta waves. down the Kent bundle RR interval is quite short. This is the arrhythmia that one worries about in any patient with manifest WPW on ECG and symptoms. because of relatively good AV node conduction. This patient underwent ablation and was found to have a left free wall accessory pathway with rapid conduction. then the possibility of AF with rapid conduction down an accessory pathway must be considered. Ablation of the pathway in WPW not only eliminates the risk of sudden death but also usually eliminates the AF as well. special considerations apply to its therapy. The salient features are the presence of a very wide QRS combined with rapid conduction. The key feature of rapidly conducted AF due to underlying WPW is the presence of a wide QRS complex during AF Fig . AV conduction via an accessory pathway results in ventricular activation outside of the normal AV conduction system and results in a wide QRS similar to a ventricular focus. WPW Syndrome and AF The mechanism of sudden death in WPW syndrome has been associated with the degeneration of reciprocating tachycardia into AF. and conventional therapy directed at AV node conduction is safe as in any other patient with AF. when conduction is rapid and the QRS is either intermittently or continuously wide.Figure . Note also that the shortest preexcited eg. As WPW syndrome. it is common for this to be misdiagnosed as VT in the emergency setting. The term preexcited means that the ventricle is activated before activation via the normal conduction system. Also note how wide the QRS is during preexcited AF. Therefore. This is because conduction is directly into the ventricular myocardium bypassing the conduction system entirely like a PVC or VT would activate the ventricle. at approximately ms see the third to last cycle on the ECG. it is uncommon in this era for a patient with known WPW to present with rapidly conducted AF. The risk of sudden death is eliminated by successful catheter ablation of the accessory pathway. followed by rapid antegrade conduction down the accessory pathway and resultant ventricular brillation VF. once symptomatic. No matter how fast AF may conduct. Because of the malignant potential of AF in the setting of WPW. Because the QRS is often so wide with preexcited AF. Preexcited AF with underlying WPW. In most cases. conduction is unrelated to rapid conduction down an accessory pathway. the presence of underlying WPW will not be known at the time of presentation. However. Conduction ms predicts a risk for sudden death if the pathway is not ablated. Therapy for AF in the setting of WPW is ACCP Critical Care Medicine Board Review th Edition quite different from ordinary AF. During AF with underlying WPW. In this patient. indicating that the pathway is capable of very rapid conduction. as is the risk of AF in most patients. this mechanism can also present less commonly as a paroxysmal sustained tachycardia. Automatic arrhythmias tend to be episodic and unsustained. they appear to be automatic and not reentrant in mechanism. digoxin and calciumchannel blockers should be avoided. and tachycardia is unaffected by intermittent AV Tachycardias Diagnosis and Management Roth . As blockers have favorable effects on both AV node and accessory pathway conduction. All describe a characteristic clinical pattern that generally presents as runs of unifocal premature atrial contractions PACs lasting for seconds or minutes. including IV ibutilide. The modern understanding of this arrhythmia involves components of both focal automatic mechanisms and reentry. at times recurring incessantly. usually followed by spontaneous termination and subsequent spontaneous reinitiation of additional salvos of tachycardia. antegrade conduction down the accessory pathway may be facilitated leading to hemodynamic collapse or VF. these arrhythmias are focal in origin. Focal arrhythmias are commonly automatic in mechanism but in some cases may be due to microreentry involving a geographically small portion of the atrium for example around a single pulmonary vein followed by radial spread to the rest of the atrium. If AV nodal conduction is impaired by the use of drugs with selective effects on the AV node. As a consequence. IV amiodarone. The most common of such arrhythmias is typical atrial utter AFL mediated by right atrial reentry around normal anatomic obstacles. Although they may be selfterminating and episodic. the morphology of the rst PAC of the run is identical to the subsequent PACs. As the arrhythmia is focal and automatic. Cycle length tends to vary between and within runs. All such circuits require a central obstacle and a region of slowed atrial conduction related to atrial dilatation or brosis. Focal arrhythmias are dened as arrhythmias originating from a point source within one of the atria with circumferential spread to encompass the rest of the atrium. multiple foci may be active simultaneously leading to a chaotic ECG appearance with multiple distinct Pwaves referred to as multifocal AT. intraatrial arrhythmias will persist despite the development of either spontaneous or pharmacologically induced AV block. Therefore. Cycle length often varies within a run and between runs and with changes in autonomic tone. blockers may be used with caution in this setting but are commonly avoided as well. Atrial Arrhythmias Atrial arrhythmias are dened as arrhythmias that are entirely dependent on the atria and mechanistically independent of AV conduction. procainamide or. or may be chaotic and disorganized as is the case in AF. or automatic AT. reentry may occur around acquired obstacles. and although at times they are triggered by rapid pacing suggesting a triggered automatic mechanism. ectopic AT. The recommended medical therapy is the use of drugs that prolong the refractory period of working myocardium. Major advances have been made in the understanding and management of this common arrhythmia in recent years and will be reviewed below. When mapped in the EP laboratory. in the setting of severe metabolic stress. The ECG features are characteristic and usually permit accurate diagnosis. occasionally. The nal mechanism of atrial arrhythmia is AF. when rapidly conducted AF presents with wide QRS conduction. In addition to typical AFL. Macroreentrant atrial arrhythmias are a consequence of stable reentrant circuits that encompass large portions of either atrium. most commonly scar resulting from prior cardiac surgery involving the atria. Focal Atrial Tachycardia Focal atrial tachycardia AT is commonly referred to by one of several eponyms focal AT. individual episodes tend to be protracted. Such arrhythmias display distinct Pwaves separated by a clear isoelectric segment. Although commonly presenting as above. Although most commonly a single abnormal focus may be active. Reentrant arrhythmias tend to present clinically as paroxysmal sustained or persistent arrhythmias. in the setting of left ventricular dysfunction.pathway by concealed retrograde activation of the accessory pathway. Therapy is directed at either moderating the ventricular response during episodes of tachycardia or suppressing the underlying atrial arrhythmia itself. Tachycardias originating in the atria may be organized and repetitive resulting from either automaticity or intraatrial reentry. The arrhythmia is believed to be due to intracellular calcium overload and resultant triggered automaticity related to DADs making it responsive to calcium and blockers. Amiodarone can also be used in these patients ACCP Critical Care Medicine Board Review th Edition . An example is shown in Figure . The tachycardia occurs in salvos with variable cycle lengths. resulting in frequent atrial ectopy all morphologically identical to the Pwave observed during the runs. accounting for its stereotyped presentation. block that may occur during the runs. A less common reversed typical form of this arrhythmia due to clockwise reentry around the tricuspid demonstrates an ECG exactly opposite to the counterclockwise form with a strongly positive Fwave in . The use of digoxin may exacerbate triggered causes of AT. at times combined with shortened atrial refractory periods due to catecholamine stress in some clinical settings. Electrical cardioversion is useless for this arrhythmia as it is self reinitiating and not dependent on reentry. There are frequent isolated PACs as well. If the unusual Fwave vector is not recognized. When it is frequent and rapid like this. leading to diagnostic confusion. and posteriorly a long ridge in the atrial wall referred to as the crista terminalis forms a function line of block preventing the circuit from collapsing posteriorly. a sharply negative Fwave in V. During conduction. Frequent tachycardia like this is also straightforward to cure by ablation because its frequency makes it easy to map in the EP laboratory. and aVF. However. Atrial Flutter Atrial utter AFL is dened as a persistent atrial arrhythmia with an atrial rate /min. Typical AFL is the most common form of this arrhythmia and is mediated by macroreentry restricted to the right atrium. This arrhythmia tends to respond to nondihydropyridine calciumchannel blockers such as diltiazem or verapamil. The paroxysmal sustained form of this arrhythmia is also adenosine responsive. Focal eg. giving the false impression of dependence on AV conduction. The arrhythmia is readily amenable to catheter ablation if ectopy is frequent enough to permit mapping. as well as the presence of a negative Pwave in the inferior leads. The valve prevents anterior collapse of the circuit. a sharply positive Fwave in V. the utter waves may be very difcult to perceive. Clues to the presence of AFL are persistent unexplained heart rates at approximately beats/ min. . and aVF. and the PAC that initiates each run is the same as all the others during the run indicating a focal mechanism. automatic AT. As the normal AV node cannot conduct at these rates. and positive Fwave in V. with only a few beatsperminute variation over time. or edema.for rhythm control as well. the ability for utter to develop is due to the added presence of abnormal slowed conduction related to atrial enlargement. and a negative Fwave in V. the Fwaves are often difcult to perceive when presenting with conduction. The same focus often res erratically between runs. Class Ia agents such as procainamide and class Ic agents such as ecainide and propafenone may be used in patients without structural heart disease or coronary artery disease. Typical AFL is mediated by counterclockwise reentry around the tricuspid valve as viewed from the ventricle. it can result in tachycardiainduced cardiomyopathy like AF. . the GI side effects of procainamide and its association with druginduced lupus limit its utility. In both cases. brosis. Typical counterclockwise AFL demonstrates a deeply negative Fwave in . An example is shown in Figure . The central obstacles in this circuit consist of normal anatomic structures. this arrhythmia characteristically presents with conduction and a ventricular response of approximately /min. the ECG may be misinterpreted as sinus tachycardia. As the obstacles are already normally present. which would be Figure . AFL is a common transient arrhythmia in acute care hospital settings. The right atrial wall is thin. These two ECGs are as they were recorded rst in the emergency department when the patient presented with conduction and a day later after rate control. On presentation. early restoration of sinus rhythm is preferred for this arrhythmia. In all of these settings. it was not initially suspected that this was AFL. When AFL occurs in the absence of an acute precipitant. Given the difculty achieving rate control in AFL and the need for antiarrhythmic agents with associated potential morbidity to maintain sinus rhythm. This arrhythmia was conrmed to be due to typical AFL mediated by counterclockwise reentry around the tricuspid valve and readily ablated by creating a linear lesion between the tricuspid annulus and the adjacent inferior vena cava that interrupts the typical utter circuit. Although shortterm therapy involves rate control or cardioversion if poorly tolerated. Catheter ablation of typical AFL is a lowrisk procedure with a longterm success rate in experienced centers. catheter ablation has become the primary means of treating this arrhythmia. and aVF and positive F wave in V and negative in V. expected to be positive in sinus rhythm. it is obvious that this is typical counterclockwise AFL with deeply negative Fwaves in . .Figure . Antiarrhythmic therapy for AFL is similar to that for AF and will be discussed below. longterm rate control for this arrhythmia is difcult. and doses that result in exercise rate control often provoke bradycardia at rest. Note that the superimposition of the Twave with the Fwaves makes it quite difcult to discern the presence of utter. This will transiently expose the underlying utter waves but will not terminate the arrhythmia. the presence of atrial disease with associated brosis or more commonly atrial scars created at the time of cardiac surgery for either valvular or congenital heart Tachycardias Diagnosis and Management Roth . Typical AFL. Therefore. longterm therapy is required. Doses of drug that result in acceptable block at rest often fail to control exercise rates. Antiarrhythmic therapy should be reserved for temporary treatment of likely transient utter or for patients who are not suitable candidates for invasive management. Transient therapy for several weeks or a month is appropriate in these settings. Atypical AFL and Reentrant AT In addition to typical AFL circulating around normal anatomic obstacles. Once rate controlled. and pericarditis resulting from cardiac or thoracic surgery results in atrial edema and inammation that may permit adequate slowing and promote transient AFL. endogenous or pharmacologic catecholamine stimulation exacerbates the arrhythmia. The most fruitful method of diagnosis is the provocation of transient AV block either with carotid sinus massage or adenosine infusion. Acute pulmonary decompensation may result in rightheart failure and may also promote transient AFL. Therefore. For uncertain reasons. heart failure. or occasionally one of the other thoracic veins such as the ostium of the superior vena cava or the ostium of the coronary sinus. However. antiarrhythmic therapy is a reasonable rst option and similar to that used for AF. and carefully designed trials exploring the benet of ACCP Critical Care Medicine Board Review th Edition Antithrombotic Therapy in AF The overall risk of stroke in AF is /yr and is associated with one in every six strokes. and death. Therefore. As the circuits are unique. prior thromboembolism or stroke. However. Patients with AF have a higher risk of stroke. and its mechanisms still remain a topic of hot debate. These profound insights have led to highly effective techniques for the cure of AF. atrial rates recorded in and around the pulmonary veins are signicantly higher than other atrial sites. The initiation of spontaneous AF is a consequence of rapid electrical ring from preferential focal sites of origin. and when /min. left ventricular . AF is the characteristic arrhythmia of the left atrium. Stated another way. million people in the United States. and when presenting with conduction may be misdiagnosed as sinus tachycardia if the abnormal Pwave vector and xed heart rate over time is not recognized. Mechanisms of AF Because of its chaotic nature. That ablation restricted to the region of the pulmonary veins and adjacent left atrium is curative in the majority of patients with AF implies that AF is an arrhythmia that. conduction is slow and electrocardiographically silent.disease may create alternative substrates for intraatrial reentry. As the circuit differs from typical AFL. the arrhythmia is arbitrarily classied as atypical AFL. resulting in an isoelectric PP interval. whether AF is merely a marker for increased mortality or a mechanism remains uncertain. Hypertension. it has been difcult to study AF. AF AF is the most common clinically signicant arrhythmia. the Pwave morphology is atypical. affecting . Some form of underlying cardiopulmonary disease or hypertension is present in of patients. Ablation techniques designed to isolate these trigger sites from the atrium have success rates to in the cure of paroxysmal AF and somewhat lower rates in the cure of persistent AF. it is arbitrarily classied as AT. Within the channel. this relative risk is greater in women than in men. The most common site of focal origin is from left atrial muscle sleeves extending along the outer surface of the pulmonary veins. maintenance of sinus rhythm over rate control show no survival benet to sinus rhythm. reaching in those years old. Following initiation. longterm rate control is a difcult strategy to successfully implement. Like typical AFL. ischemic heart disease. is entirely contained within and maintained by the left atrium and connecting veins. Like typical AFL. Therapy and prognosis are otherwise similar to typical AFL. Common to these arrhythmias is the presence of a signicant region of scar with a channel of surviving myocardium either bridging the scar or between the scar and a normal anatomic obstacle. Ablation is used selectively in patients who are good candidates for complex ablative procedures. and diabetes are the most common associated conditions. it has become apparent that in the same way that typical AFL is the characteristic arrhythmia of the right atrium. heart failure. to in the general population and increases with age. Multiple risk factors have been identied that predict a higher risk of stroke. In fact. the role of AF as an independent determinant of mortality is uncertain because it commonly coexists with other potentially important conditions. Its prevalence is from . certain aspects have become clear. mapping and ablation of these arrhythmias are more complex and success rates are lower than for typical AFL. suggesting that activity in the region of the veins is important in perpetuating AF following initiation. heart failure. patients with truly lone AF do not have an increase in mortality. These arrhythmias are also amenable to catheter ablation. these arrhythmias are paroxysmal sustained or persistent arrhythmias. presence of rheumatic mitral disease. including age. When ring does not originate from a pulmonary vein. it is commonly from the left atrial tissue immediately adjacent to one of the veins. When the rate is /min. gender. in most cases. The CHADS Cardiac failure. and diabetes. Epidemiologic data also suggest that patients with intermittent AF have a similar risk of stroke to those with permanent AF./ yr. which is at the middle of the therapeutic range. These studies also documented an average . However. patients with no risk factors should receive aspirin. If the patient was receiving anticoagulation at the time of AF onset or if anticoagulation was started in the rst h. the guideline suggests that these groups be treated similarly. and Stroke score is a useful and wellvalidated clinical means of assessing stroke risk in patients with AF. and the risk of stroke can be accurately estimated with only a subset of weighted factors. To minimize the risk of thromboembolism. as would be the case if the arrhythmia were AF. which overall including all major studies is modest at a reduction. The score assigns point for a history of each of heart failure. However./yr. Diabetes. rate of major hemorrhage during therapy with warfarin. transient ischemic attack or embolism. so it is generally a bad strategy to target low therapeutic INRs in the hope of preventing bleeding. hypertension. left ventricular ejection fraction EF . or if a mechanical heart valve is present a target of . Therefore. a score of implies a risk of ./yr. Hence. cardioversion of AF was associated with a signicant risk of thromboembolism. A score of implies a relatively low risk of . Patients with only one moderate risk factor can be offered either aspirin or adjusteddose warfarin with a target range of . Studies of warfarin in prevention of stroke in AF have demonstrated a signicant reduction the risk of stroke. hypertension. The current recommendations for antithrombotic therapy are contained in the American College of Cardiology/ American Heart Association/European Society of Cardiology AF practice guideline. performance of a transesophageal echocardiography and exclusion of left atrial thrombi permit safe early cardioversion without the need for prior anticoagulation. to . to . and points for a history of prior stroke. Given these considerations. to mg/d. anticoagulation must be continued for at least weeks after conversion if the duration of AF was h Tachycardias Diagnosis and Management Roth .. Age. and diabetes.. or presence of a prosthetic heart valve. dosing should be targeted squarely at . and a score implies an annual stroke risk of . The risk of thromboembolism rises sharply with international normalized ratios INRs . The practice guideline also recommends that patients with AFL be treated with antithrombotic therapy. the decision to continue anticoagulation is based on an assessment of the patients risk for longterm thromboembolism. warfarin has been recommended in patient groups with higher annual risks of stroke and should be avoided in groups at low risk because the risk may outweigh the relatively small benet in these lowrisk groups. then it is safe to proceed with cardioversion without a week run in. there is a time delay between restoration of electrical sinus rhythm and recovery of mechanical atrial function. Moderate risk factors are dened as age years. In addition. left atrial enlargement. In this scheme. and . heart failure. Hypertension.dysfunction. Patients with more than one moderate risk factor or any high risk factor should be placed on adjusteddose warfarin . and attempt to remain in this range as much as possible. to . hypertension. prior to an additional weeks of anticoagulation following successful restoration of sinus rhythm. When using warfarin it is important to target a range of ./yr. It is believed that the delayed presentation of thromboembolism following cardioversion is related to atrial stunning due to the period of prior AF and associated atrial remodeling. it is recommended that patients with AF of h in duration undergo at least weeks of therapeutic anticoagulation with a target INR between . and are similar to the CHADS. age years. High risk factors are dened as previous stroke. and diabetes. these risk factors are not all independent.. in either case. ischemic heart disease. However. Following this. The risk of thromboembolism appears to be independent of the means of cardioversion employed. a score of implies an intermediate risk of . This typically occurred days to weeks after cardioversion and not at the moment of conversion.. mitral stenosis. whether electrical or pharmacologic. larger benets were seen in studies enrolling higherrisk patients and small benets as little as in lowerrisk patients. Management of Anticoagulation Around Cardioversion In the preantithrobotic era.. To avoid this. to . This is the development of tachycardiainduced cardiomyopathy. Finally. any of these agents may be useful. early recourse to cardioversion should be undertaken. Patients who are symptomatic must be controlled promptly. atrial arrhythmias occurring in the ICU setting often are exacerbated by. When pursuing rate control. but for subacute symptoms of progressive congestive heart failure occurring over many weeks or months. However if AF persists for h. A reasonable strategy is to pursue rate control and possibly antiarrhythmic drugs in the rst h. Shortterm Management of AF Rate Control The shortterm management of AF centers on the control of ventricular response. the cardiomyopathy will resolve over several months. and then make the patient nothing by . the timely restoration of sinus rhythm. which represents a true cardiomyopathy that is not simply a consequence of acute hemodynamic consequence of rapid rates. and the identication of potentially reversible factors that may have precipitated the arrhythmia. or even primarily related to. Digoxin is also a useful secondline drug in addition to a blocker or calciumchannel blocker for resting rate control. the fastest way to achieve rate control is the restoration of sinus rhythm.before cardioversion. Although in most clinical settings. and rate control is adjusted with the intent of moderating symptoms of dyspnea and palpitations associated with high exercise rates but not for prognostic reasons. or propranolol or a nondihydropyridine calciumchannel blocker diltiazem or verapamil is preferred. then IV amiodarone is a useful rate control agent. such patients will exhibit a typical dilated cardiomyopathy that is clinically indistinguishable from idiopathic dilated cardiomyopathy. a more subtle but important process occurs when rapid rates persist for weeks to months without control. At least half of AF episodes of new onset will terminate spontaneously in the rst to h. Therefore. When pursuing rate control for acute AF of recent onset. digoxin is a useful agent for resting rate control. the catecholamine stress of acute illness. It should be suspected in a patient presenting with rapidly conducted AF. if well tolerated. If this is suspected. TachycardiaInduced Cardiomyopathy In addition to the acute homodynamic consequences of rapidly conducted AF. Tachycardiainduced cardiomyopathy occurs in the setting of resting rates signicantly beats/min. For this reason. IV administration of a blocker esmolol. In the setting of decompensated heart failure. it is therefore critical to target a resting heart rate well beats/min to prevent the development of cardiomyopathy. then withdrawal of adrenergic pharmacotherapy and the early use of blocker therapy may prove strikingly effective. In this setting. Therefore. especially in the setting of congestive heart failure. the thromboembolic risk is low and anticoagulation is not indicated. If such therapy is ineffective or not tolerated. it may be reasonable to wait until the next day before considering cardioversion. it is strategic to plan for either pharmacologic or electrical cardioversion before the h window expires. not because of the development of palpitations. often with return of normal ventricular function. As noted above. metoprolol. if the duration of AF is known to be h. the risk of thromboembolism is low and cardioversion may be safely performed without anticoagulation either before or after the procedure. By contrast. the use of a calcium blocker may exacerbate heart failure and should be avoided. stress heart rates appear not to be related to the development of ACCP Critical Care Medicine Board Review th Edition cardiomyopathy. newonset AF should be managed with a plan to restore sinus rhythm during this period if possible. On evaluation. and these drugs should be avoided. AF with rapid ventricular response results in acute deterioration in stroke volume and cardiac output as well as increase in myocardial oxygen demand and the potential for coronary ischemia. and additionally may facilitate restoration of sinus rhythm. if rate control or restoration to sinus rhythm are achieved. For the shortterm control of rapidly conducted AF. Shortterm Management of AF Restoration of Sinus Rhythm When sinus rhythm is restored in the rst h of acute AF. rapidly conducted AF related to WPW can be paradoxically accelerated by calciumchannel blockers and digoxin. if rate control proves difcult or not well tolerated. However. Therefore. which included . but occurring late after days of therapy. or heart failure. IV agents with efcacy for early conversion include ibutilide and amiodarone. This risk is even higher in the setting of left ventricular dysfunction. an initial shock energy of at least J for an older monophasic debrillator or a minimum output of J with a newer biphasic device is recommended. IV amiodarone is well tolerated in unstable patients as are commonly seen in the ICU setting. Several antiarrhythmic drugs have been shown to be effective in increasing the rate of early conversion of AF. It may also be a consequence of the relative inefcacy of pharmacologic therapy in the maintenance of sinus rhythm and the difculty establishing if patients believed to be in sinus rhythm are in fact consistently in sinus rhythm in followup. Although lowoutput discharges may be effective in some patients. an anterior posterior patch or paddle position is more effective than the conventional anterior to lateral patch/paddle position used for ventricular debrillation. respectively. The Atrial Fibrillation Followup Investigation of Rhythm Management trial demonstrated no advantage in stroke or mortality with a strategy of maintenance of sinus rhythm over rate control. Cardioversion should also be attempted at least once electively in all cases of newonset AF regardless of toleration. ecainide. sotalol. electrolyte disturbances. Oral agents with efcacy in the early conversion of AF include ecainide. Oral amiodarone and sotalol have been associated with a and conversion rates. If full output shocks are ineffective. at our current state of knowledge. Pharmacologic conversion is generally more successful with AF of recent onset than when chronic. or shock. hypotension. and dofetilide. Pharmacologic Conversion of AF Pharmacologic conversion of AF can be undertaken when restoration of sinus rhythm is not urgent. then cardioversion success can be increased by several maneuvers. either strategy can be offered to patients with an expectation of similar outcomes with regard to hard end points. in selected patients. However. due to low early conversion rates. Antiarrhythmic drugs remain the primary strategy Tachycardias Diagnosis and Management Roth . heart failure. or propafenone may also increase debrillation success as well as decrease the chance of relapse after successful cardioversion. Longterm Maintenance of Sinus Rhythm Despite the association of AF with an increase in stroke and allcause mortality. IV ibutilide signicantly improves conversion success in this setting.mouth and proceed with electrical cardioversion on the following day if sinus rhythm is not restored. most commonly amiodarone. propafenone. approximately of patients will relapse over the rst year following cardioversion of AF. Oral pretreatment with amiodarone. and a strategy of rate control without attempts to maintain sinus rhythm. may be better addressed by maintaining sinus rhythm. In the absence of antiarrhythmic drugs. these drugs are not recommended orally for conversion. patients randomly assigned to a strategy of rhythm control with antiarrhythmic drugs. Following a failed initial shock. When performing electrical cardioversion. Usually the decision to pursue sinus rhythm involves the management of symptoms that. no study to date has established a benet to pharmacologic maintenance of sinus rhythm in terms of stroke risk or survival. The largest and best designed trial addressing this issue was the Atrial Fibrillation Followup Investigation of Rhythm Management trial. Electrical Cardioversion of AF Electrical cardioversion should be performed urgently in the case of severe compromise related to acute AF including angina. Ibutilide is limited by a relatively high rate of druginduced QT prolongation and torsades de pointes VT. Therefore. By contrast. a strategy of starting at higher outputs decreases the number of shocks required and the average cumulative energy delivered. ibutilide should be reserved for the pharmacologic conversion of stable patients with a baseline normal QT interval. and is the preferred pharmacologic agent for conversion in the critically ill. full output should be used for the next attempt. This may be because AF is merely a marker and not a mechanism of stroke and mortality. Administration of an antiarrhythmic drug may also facilitate conversion. Direct anteriorposterier compression over the anterior patch and timing of shock delivery to endexpiration will decrease thoracic impedance and facilitate cardioversion. Therefore. sotalol and amiodarone also provide substantial rate control during relapses of AF. well tolerated. Therefore. With the availability of curative AF ablation. Finally. are safe in the presence of coronary artery disease and in the case of dofetilide with congestive heart failure. and disopyramide may result in signicant myocardial depression and exacerbation of heart failure. Cure of persistent and permanent AF can also be achieved but with lower success rates. Sustained . most persons who experience an outofhospital cardiac arrest do not survive. which work by slowing conduction. Despite substantial advances in the early treatment of cardiac arrest. and coronary artery disease.for maintaining sinus rhythm following cardioversion as well as the prevention of symptomatic episodes in patients with paroxysmal AF. AV node ablation has taken on a secondary role for patients who cannot tolerate a complex ablative procedure or are otherwise not good candidates for curative AF ablation. Sustained VT and VF are the most common causes of cardiac arrest. these drugs may provoke torsades de pointes. including sotalol and dofetilide. Patients with pacemakers and prior AV node ablation will require ongoing anticoagulation because underlying AF is not prevented by simple AV node ablation. obstructive coronary artery disease is present at autopsy. these drugs are exceedingly safe. in this selected group of patients with normal hearts. and must be used with caution. and cardiac arrest remains the most common mechanism of cardiac death. in of cases. However. Ventricular Arrhythmias and Sudden Cardiac Death Cardiac death is the most common cause of death in the United States. Adverse rhythm effects of drugs may include sinus node dysfunction. antiarrhythmic drugs other than sotalol or amiodarone ACCP Critical Care Medicine Board Review th Edition must be combined with a rate control agent such as a blocker or nondihydropyridine calciumchannel blocker during longterm therapy. longterm somatic toxicity limits the use of this drug to older patients or those with limited expected longevity or inability to safely tolerate alternate agents due to advanced cardiac disease or proarrhythmia on alternate agents. which prolong repolarization and refractoriness. but responsiveness to previously ineffective drugs is achieved in a signicant fraction of patients who are not completely cured by ablation. The array of potential adverse effects of antiarrhythmic drugs is beyond the scope of this chapter. rate control with other antiarrhythmic agents is not adequate to prevent rapid conduction with relapse. Amiodarone has a higher longterm efcacy than other drugs and a lower risk of proarrhythmia. left ventricular dysfunction. Catheter ablation of AF is now an important secondary strategy for maintenance of sinus rhythm. In addition. the older technique of AV node ablation can be used to create complete heart block. All antiarrhythmic drugs have the potential for proarrhythmia. It is now routinely available in most centers performing complex ablation procedures. class I drugs such as ecainide. and promotion of potentially lethal ventricular arrhythmias. have a high risk of ventricular proarrhythmia and potential for sudden death in the setting of heart failure. propafenone. promotion of drugslowed AFL permitting rapid conduction. the unintended precipitation of a new arrhythmic problem caused by the drug. The conventional class III drugs. and success rates approaching to can be routinely achieved in patients with paroxysmal AF and relatively preserved cardiac function. which when combined with a pacemaker permits nonpharmacologic rate control but does not prevent ongoing brillation within the atrium. even in patients with normal cardiac function. and often effective. but certain essential concepts are important to recognize. However. The class I drugs such as ecainide and propafenone. and some drugs may actually accelerate response at the time of relapse. however. Ventricular Ectopy and Nonsustained VT VT is dened as three or more consecutive ventricular beats at a rate /min. Use of these drugs is restricted to patients with preserved cardiac function and no evidence of obstructive coronary artery disease. However. Those who do survive may have permanent neurologic impairment. In addition to being useful agents for the prevention of AF. heart block. ICD therapy was associated with a lower risk of arrhythmic and allcause death than antiarrhythmic therapy. Such circuits may be favorably or adversely affected by antiarrhythmic drugs. Therefore. for secondary prevention of cardiac arrest after an episode of sustained VT or VF in the setting of cardiac disease. VT lasting three beats up to s is classied as nonsustained. and nonsustained VT is associated with a higher risk of sudden death in patients with coronary artery disease and left ventricular dysfunction. Implantable Debrillator trial. most commonly chronic ischemic heart disease with prior clinical or subclinical myocardial infarction MI with associated left ventricular dysfunction. however. as well as several smaller similar trials. VT in the chronic phase of ischemic heart disease is mediated by reentry through channels or sheets of surviving myocardium. partially decoupled by interstitial brosis and cell loss. Susceptibility to sustained VT increases with worsening left ventricular dysfunction and associated greater extent of scar. attempts to systematically suppress these arrhythmias with antiarrhythmic drugs in the Cardiac Arrhythmia Suppression Trial proved that the class I drugs in common use at that time. similar in mechanism to that observed in the case of reentrant AT. conduction is abnormally slow due to poor coupling between sparse surviving myocytes. and overall mortality. and a substantial precipitous rise with EFs to . Several trials have examined the utility of antiarrhythmic drugs. for the purposes of clinical classication. Sustained VT and Secondary Prevention of Sudden Death Sustained VT is associated with underlying cardiovascular pathology in of cases. traveling for a time within the channel then reemerging from the initially blocked end to reactivate the ventricle. compared with implantable cardioverter debrillator ICD therapy on survival following an episode of sustained poorly tolerated VT or an episode of sudden arrhythmic death. The mechanism of sustained VT in chronic ischemic heart disease is macroreentry. but enters the other end. which randomized patients with a history of poorly tolerated sustained VT or cardiac arrest between a strategy of empiric amiodarone or ICD implantation. whether such asymptomatic ventricular ectopy and nonsustained arrhythmia is causally linked to death or merely an associated nding not directly linked has been a matter of much debate. These ndings have supported the present concept that nonsustained ventricular arrhythmias are not mechanistically linked to the sustained poorly tolerated arrhythmias that eventuate in sudden death. Nonsustained ventricular arrhythmias including premature ventricular contractions and nonsustained VT are common in the presence of left ventricular dysfunction. VT lasting s is classied as sustained even if spontaneous termination occurs after s. Although there is a statistical association. did not demonstrate an increase in mortality but again failed to show a signicant mortality benet despite substantial suppression of spontaneous nonsustained arrhythmias. a drug may exhibit both favorable effects on one tachycardia while exacerbating alternate tachycardias. In this trial. As multiple functioning circuits may coexist in a single scar with multiple potential VT mechanisms. and that asymptomatic nonsustained arrhythmias and ventricular ectopy should not be pursued as a therapeutic target in the hopes that such therapy will reduce the future risk of death. Tachycardia may be initiated by an ectopic beat that fails to enter one end of the channel due to unidirectional block. especially within the partially spared border zone of a region of scar resulting from prior MI. mostly amiodarone. markedly increased sudden death. The largest trial was the Antiarrhythmics Vs. The chance of cardiac arrest rises progressively with greater degrees of left ventricular dysfunction following MI with very low risks with EFs . ICD implantation has become the rst line of therapy. Subsequent studies in the s testing amiodarone in the European Myocardial Infarct Amiodarone Trial and the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial. Tachycardias Diagnosis and Management Roth . Within these channels. In the s. despite suppression of nonsustained tachycardia.VT is VT that does not end without specic intervention. a drug with much lower proarrhythmic potential. This study demonstrated a substantial mortality reduction with ICD therapy. who had frequent ventricular ectopy and inducible VT at EP testing. a signicant mortality benet was associated with ICD therapy. Finally the recently completed Sudden Cardiac Death in Heart Failure trial enrolled a broader population consisting of patients with both ischemic and nonischemic cardiomyopathy. which enrolled a simplertoidentify population consisting of patients with simply a history of prior MI and EF in the chronic phase. or VF induced at electrophysiologic study when drug therapy is ineffective. However several ICD trials have demonstrated a signicant reduction in mortality. mortality rates in ischemic heart disease are higher than in nonischemic cardiomyopathy. syncope attributable to ventricular tachyarrhythmias in patients awaiting cardiac transplantation. These three major trials combined with generally concordant ndings in other smaller trials form the basis for the current recommendation for prophylactic primary prevention ICD implantation in patients with history of prior MI and EF as well as patients with symptomatic heart failure of any etiology who remain New York Heart Association class II or III on optimized medical therapy and have EFs . or not preferred. suggesting that primary prevention ICD implantation in patients with advanced nonischemic cardiomyopathy and heart failure was also appropriate. Spontaneous sustained VT in patients without structural heart disease not amenable to other treatments. it has been easier to demonstrate mortality benets with primary therapy to prevent sudden death in ischemic than nonischemic cardiomyopathy. Cardiac arrest due to VF or VT not due to a transient or reversible cause. even amiodarone. sudden death predominates as the most common mode of death in advanced cardiac disease states. Therefore. Severe symptoms eg. a survival benet was found in patients treated with ICD when compared with conventional therapy or empiric amiodarone therapy. . Again. . . Primary Prevention of Cardiac Arrest Patients with advanced cardiac disease. Cardiac arrest presumed to be due to VF when electrophysiologic testing is precluded by other medical conditions. symptomatic New York Heart Association class II or III heart failure. Syncope in patients with advanced structural heart disease in whom thorough invasive and noninvasive investigations have failed to dene a cause. not tolerated. The rst such trial was the Multicenter Automatic Debrillator Implantation Trial MADIT. no form of antiarrhythmic drug. The MADIT was followed by MADIT II. Again. . Syncope of undetermined origin with clinically relevant. ACCP Critical Care Medicine Board Review th Edition . and EF . Syncope of unexplained origin or family history of unexplained sudden cardiac death in association with typical or atypical right bundlebranch block and STsegment elevations Brugada syndrome. Recurrent syncope of undetermined origin in the presence of ventricular dysfunction and inducible ventricular arrhythmias at electrophysiologic study when other causes of syncope have been excluded. Except in class IV endstage heart failure with symptoms at rest. and heart failure have a substantial risk of death due to both progressive heart failure and sudden death. . The degree of benet was similar in patients with both ischemic and nonischemic cardiomyopathy. .Indications for ICD Implantation for Secondary Prevention After a First Episode of Documented or Presumed Sustained VT or VF Class I . hemodynamically signicant sustained VT. For any degree of left ventricular dysfunction. Spontaneous sustained VT in association with structural heart disease. left ventricular dysfunction. has resulted in a signicant mortality reduction in this population. . Class IIb . As noted above. which enrolled patients with prior MI. and EF . The occurrence of VT in the absence of structural heart disease represents a heterogenous population of conditions. and some malignant. this syndrome may occasionally present as sustained monomorphic VT. as well as transiently to adenosine infusion. It commonly presents as sustained monomorphic VT. and occasionally sustained VT may be seen in patients without evident underlying structural heart disease. This arrhythmia is focal and automatic in mechanism. Idiopathic Left Ventricular Tachycardia The second idiopathic VT syndrome is clinically distinct and much less common than the outow tract tachycardias. nonsustained VT. and the cardiac ionchannel disorders including the longQT syndrome. but when mapped it originates in the left ventricular outow tract instead. left ventricular dysfunction. Class IIb Familial or inherited conditions with a high risk for lifethreatening ventricular tachyarrhythmias such as longQT syndrome or hypertrophic cardiomyopathy. prior MI. prior MI. This syndrome is referred to as either idiopathic left fascicular tachycardia or simply Tachycardias Diagnosis and Management Roth VT and Fibrillation Without Evident Heart Disease Although most sustained VT is related to underlying advanced structural heart disease. Nonsustained VT with coronary artery disease. It is easiest to classify such patients into three groups idiopathic VT. Several of the malignant conditions are familial. some benign. left ventricular dysfunction. Ventricular ectopy is often quite frequent. and its response to pacing and drugs suggests that the mechanism is likely due to triggered automaticity of the delayed afterdepolarization type. and therefore it is critical that they be identied to protect the welfare of the patient as well as unrecognized affected family members. This arrhythmia originates in the right ventricular outow tract RVOT from a focal origin usually immediately below the pulmonic valve. as the arrhythmia is readily cured by catheter ablation. VT is identied. and inducible VF or sustained VT at electrophysiologic study that is not suppressible by a class I antiarrhythmic drug. ventricular ectopy. right ventricular cardiomyopathy/dysplasia. . However if symptoms are documented. This arrhythmia is responsive to blockers. If documented. and inducible sustained VT or VF at electrophysiologic study. and may be easily documented on lead ECG in many patients. Class IIa Patients with left ventricular EF at least month after MI and months after coronary artery revascularization surgery. This arrhythmia behaves similarly to the RVOT tachycardia. nondihydropyridine calciumchannel blockers such as verapamil or diltiazem. Although both syndromes most frequently present as repetitive bursts of nonsustained monomorphic VT. the QRS morphology has a deeply negative QRS in V and strongly positive in the inferior leads.Indications for ICD Implantation for Primary Prevention in the Absence of Prior Sustained VT/VF Class I Nonsustained VT in patients with coronary disease. at times symptomatic. The most common syndrome occurring in to of cases is repetitive salvos of nonsustained monomorphic VT as well as frequent unifocal premature ventricular contractions PVCs all with the same morphology. giving the beats a left bundlebranch block with inferior axis morphology Fig . Idiopathic VT Right Ventricular Outow Tract Tachycardia Idiopathic VT typically presents in a patient with recurrent palpitations and occasionally syncope. It also responds to antiarrhythmic agents but. patients who fail to respond to calciumchannel or blockers are commonly referred for catheter ablation. The clinical story initially suggests SVT because the ECG is typically normal and cardiac evaluation unrevealing. This clinical syndrome may also at times present with the same clinical pattern but with a right bundlebranch block QRS morphology and inferior axis. This unusual arrhythmia appears to be mediated by reentry within the left posterior . The arrhythmia ACCP Critical Care Medicine Board Review th Edition may easily be misdiagnosed as SVT with aberrancy and if treated with a nondihydropyridine calciumchannel blocker such as diltiazem or verapamil will abruptly terminate. This was a sustained arrhythmia in this patient. most would offer ablation. The arrhythmia is often well tolerated and has an ECG appearance that looks like a typical bifascicular block pattern with a right bundlebranch block and leftaxis deviation Fig . and this is how this patient was treated. This arrhythmia is automatic in mechanism and is likely similar in mechanism to focal AT. the tachycardia was mapped to the posterior apical septum in the region of the left posterior hemifascicle and ablated there. reinforcing the misdiagnosis. Idiopathic RVOT tachycardia. Note the characteristic left bundlebranch morphology and inferior right axis. When frequent and symptomatic like this patient. Idiopathic left fascicular tachycardia. idiopathic left ventricular tachycardia.Figure . idiopathic RVOT tachycardia responds to calciumchannel blockers and also may be helped by blockade. Like focal AT. It is a peculiar arrhythmia with a very stereotyped behavior. This tachycardia terminated abruptly with IV diltiazem but was hard to suppress with oral medication. Note that AV dissociation is absent during this tachycardia because there is retrograde atrial activation arrows. Like the focal AT shown in Figure . Figure . the runs have variable cycle length and occur in salvos. At EP testing. which slowed the rate of the tachycardia somewhat. This ECG was done while the patient was already receiving blocker therapy. although it would tend to terminate after minutes back to sinus rhythm. It is also referred to commonly as arrhythmogenic right ventricular dysplasia. this condition commonly becomes clinically apparent due to the development of ventricular arrhythmias originating in the affected portions of the right ventricle. the left ventricle may also be affected late in some patients. Because the right ventricle is not well imaged by routine cardiac testing. However. As the mechanical consequences of right ventricular dysfunction are often subclinical. its recognition is critical. As the condition is a myopathic process. has an excellent prognosis and may be treated medically. which lies immediately under the right precordial leads Fig . large portions of the right ventricular free wall may become replaced with adipose tissue leading to regional wall motion abnormalities and aneurysm formation. while receiving medication for his index VT. Right ventriculography showed a dilated and aneurismal right ventricle due to fatty replacement. it is a common target for successful catheter ablation. however. and its responsiveness to verapamil or diltiazem is surprising but characteristic. and the family history was unknown. This patient presented with sustained VT.Figure . Both had a left bundlebranch morphology and were poorly tolerated. a late deection at the tail of the right precordial QRS complex called an epsilon wave may be present and is due to late activation caused by slowed conduction in the affected right ventricle. It is an important cause of unexpected sudden death in otherwise healthy persons in parts of Europe although not as frequent in the United States. Note the presence of Twave inversion beyond V and a highfrequency notch in the early STsegment following the QRS complex arrows. ventricular ectopy is often Tachycardias Diagnosis and Management Roth . This patient was orphaned. However. it is now believed to be a progressive cardiomyopathy rather than a dysplastic process and ARVC is the preferred term. This arrhythmia. Arrhythmogenic right ventricular cardiomyopathy. as ARVC carries a potential risk of sudden death and is commonly familial with dominant inheritance. he had another distinct sustained VT. He underwent ICD implantation. this condition may be misdiagnosed as idiopathic RVOT VT. for this reason. as it is often sustained. like idiopathic outow tract tachycardia. fascicle of the leftsided conduction system. which is a more common condition. The ventricular arrhythmias may be nonsustained or sustained and tend to exhibit a left bundlebranch block morphology consistent with a right ventricular origin. Although it predominantly affects the right ventricle. ARVC is associated with Twave inversion in the anterior precordial leads. the presence of right ventricular cardiomyopathy can be easily missed. When advanced. Less commonly. which is an epsilon wave due to late activation of the underlying diseased right ventricle this ECG is shown at double standard to make the epsilon wave easier to see when reproduced. Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia Arrhythmogenic right ventricular cardiomyopathy ARVC is a familial degenerative cardiomyopathy that predominantly affects the free wall of the right ventricle. Due to myocyte death/apoptosis. and the nding of unexplained Twave inversion beyond V is strongly suggestive. Her newborn son was found to have a QTc of . and she was found to have LQT. Asymptomatic patients with a long QT who have no family history of sudden death are usually followed up without treatment. She was resuscitated by bystanders and ultimately shocked out of VF by emergency medical technicians. her brother and nephew remain asymptomatic on blockers years later. a dominantly inherited condition associated with a long QT interval Fig . Cardiac magnetic resonance imaging is the preferred technique to image the fatty inltration and wall motion abnormalities in the right ventricle in ARVC. this patient had a normal pregnancy. The most important set of cardiac ionchannel disorders are the various forms of familial longQT syndrome.Figure . on the day of delivery. and this helps to distinguish it from the idiopathic arrhythmias that are focal with only a single PVC morphology. mild abnormalities may be seen in patients with idiopathic RVOT VT and make interpretation difcult in some patients. Familial longQT syndrome. This yearold woman presented with a cardiac arrest while at work at a manufacturing facility. If symptoms persist despite blocker therapy or the patient presents ACCP Critical Care Medicine Board Review th Edition . In the presence of sustained VT or symptoms such as syncope believed to be due to VT. recurrent syncope. a family history of sudden death in a rstorder relative should raise concern. empiric blocker therapy is helpful in the most common forms but may be harmful in the less common LQT. and LQT. a defect in the HERG gene that encodes a second K channel IKR. received an ICD about a year ago. LQT. a defect in the KVLQT gene that encodes the cardiac slow potassium channel IKS. Cardiac IonChannel Disorders and LongQT Syndrome A number of familial conditions resulting in ventricular arrhythmias have been associated with point mutations in the cardiac ion channels. identifying her brother and her nephew. as both affected but asymptomatic. However. the patient is doing well but has received shocks for torsades. ICD implantation is indicated to prevent future sudden death. multiform. If symptoms of syncope occur or there is a family history of sudden death. Her father also had died suddenly in his s. which is a defect in the SCNA gene that encodes the cardiac sodium channel. who is now years old. With modern genetic techniques. Finally. Her older sister had died suddenly years earlier. and at times sudden death associated with polymorphic VT referred to as torsades de pointes. A year later. She ultimately recovered and underwent ICD implantation. the most common being LQT. RomanoWard syndrome has been found to be a set of longQT syndromes due to one of several channel defects. Her family was screened. These syndromes were historically described as the RomanoWard syndrome. but no investigation was pursued at that time. Her son. These conditions are often colloquially referred to as the cardiac channelopathies. LongQT syndrome often presents with syncope as opposed to palpitations because the VT is very fast and hemodynamically ineffective. the son of her deceased sister. attributed to a heart attack. Genetic testing was done. Boys and girls have a similar rate of onset of symptoms. haloperidol. Table . Unfortunately. The ECG is characteristic but easily missed. is dominantly inherited. However some features differ. pimozide. thioridazine Cisapride. especially following pauses often provoked by a compensatory pause from an antecedent PVC Fig . Acquired LongQT Syndrome Summary and Conclusions Many drugs have been associated with QT prolongation and in susceptible patients with the development of torsades de points VT and at times sudden death. torsades due to druginduced longQT syndrome tends to occur at rest during periods of low heart rates. an effort should be made to avoid future therapy with any drug associated with this syndrome. and syncope is attributable to VT. disopyramide. syndrome is maintained at www. dofetilide. An uptodate database of drugs with an association with acquired longQT Tachyarrhythmias may be broadly classied as supraventricular arrhythmias. Drugs With a Known Risk of Torsades de Pointes Antiarrhythmics Amiodarone. procainamide. quinidine. erythromycin. As the VT is pause dependent at initiation. AV node. Opiates Based on drug lists available from Arizona Center for Education and Research on Therapeutics. In the familial form of longQT syndrome. halofantrine. sparoxicin Chlorpromazine. As this is a dominantly inherited condition. if VT continues to be a problem despite magnesium. the same gene associated with LQT. it is critical to look out for this ECG pattern in patients presenting with unexplained syncope. ibutilide. The disorder is now known to be commonly related to distinct mutations in the sodium channel gene SCNA. By contrast. Of importance. Table gives a list of commonly associated drugs. Treatment involves correcting any electrolyte disturbance. domperidone. clarithromycin. pentamidine. ICD implantation is indicated because of a high risk of sudden death. sotalol Arsenic trioxide Bepridil Chloroquine. VVI pacing at modest rates will prevent pauses and prevent initiation.with resuscitated sudden death.org. Supraventricular Tachycardias Diagnosis and Management Roth . which are exclusively dependent on infranodal tissue. As the syndrome is associated with a high risk of sudden death due to polymorphic VT. methadone Anticancer Antianginal Antibiotics/antiparasitics Antipsychotics Brugada Syndrome GI The Brugada syndrome was described in by Pedro and Josep Brugada when a yearold boy presented with recurrent syncope and an unusual ECG. occurring at times of elevated sinus rates. and ventricular arrhythmias. and many drugs with ability to block the cardiac sodium channel make this condition worse. When the diagnosis is established. and identifying and eliminating any potentially causative agents. VT occurring in the druginduced longQT syndrome is very similar to the familial form.qtdrugs. treatment with IV magnesium sulfate will acutely suppress VT. VT during physical or emotional stress is common. The boys sister died at age years of ventricular arrhythmias and had a similar ECG. the ECG pattern may be inconsistent from one ECG to the next. including the class I antiarrhythmic agents as well as tricyclic antidepressants. ICD is indicated. or in the case of clinical ventricular tachycardia. Until the QT normalizes. or both. but in adulthood women have a higher rate of symptoms likely due to a tendency of women to have longer QT intervals than men. Once torsades has developed from one drug. mesoridazine. and displays otherwise normal cardiac testing and often no apparent arrhythmias between episodes. droperidol Levomethadyl. family screening is mandatory and vastly simplied by the commercial availability of genetic testing for the common forms of longQT syndrome. The Brugada syndrome ECG is characterized by upward coved STsegment elevation in leads V to V with a right bundlebranch block pattern. which are dependent on the atrium. a valuable resource when evaluating a patient with unexplained QT prolongation while being treated with multiple medications. blockers increase the risk of sudden death in Brugada syndrome. which are commonly seen in otherwise normal patients with recurrent paroxysmal sustained palpitations. and was readmitted. the important syndromes are idiopathic VTs. Supraventricular tachycardia.Figure . Antiarrhythmics may have a role for symptomatic arrhythmias in lowrisk patients as well as an adjunct to ICD therapy to prevent frequent ICD shocks. Note that the runs occur after pauses generated by the PVCs. The latter two syndromes are familial and have a potential for malignant arrhythmias and sudden death. and days later the QT interval returned to baseline and the arrhythmias abated. restoration of sinus rhythm in selected patients. in fact structurally normal. Antiarrhythmic therapy is not. Also note the very bizarre Twaves with a mountainous giant U wave rising off the Twaves that initiate polymorphic VT. in which delta waves are absent and the arrhythmia syndrome is similar to the more common AV node reentry. it does occur occasionally. often with frequent atrial ectopy between runs. AT and atypical utters. indicated to reduce the risk of sudden death in patients who are at high risk. the family must also be screened. Failure to do so invites tragedy in followup. Ventricular arrhythmias are most commonly related to underlying structural heart disease. In patients with VT but a structurally normal heart. More than of these are due to either AV node reentry or AV reciprocating tachycardia related to an accessory pathway. felt dizzy and returned to the hospital. Reentrant atrial arrhythmias include typical AFL. The later group includes manifest WPW. ACCP Critical Care Medicine Board Review th Edition . of which the familial longQT syndromes are the most important clinically. Torsades de pointes VT due to acquired longQT syndrome. although an important subset occur in otherwise structurally normal hearts. Once the proband is identied. and nally the ionchannel diseases. The primary issues in atrial arrhythmia management are resting rate control to improve acute cardiac function and prevent the development of tachycardiainduced cardiomyopathy. Amiodarone was stopped. and nally AF. as well as those with symptomatic sustained VT. however. and sudden death is not a concern. Atrial arrhythmias may be focal or reentrant. This patient should never receive any drug associated with acquired QT prolongation and torsades in the future. Delacretaz E. arrhythmias fall into two large groups the paroxysmal SVTs. which circulates around the tricuspid valve around naturally present obstacles. slow or eliminate the tachycardia to restore hemodynamic stability. Focal AT is usually automatic in mechanism and characterized by repeated salvos of tachycardia. Note the frequent PVCs occurring on the descending limb of a very long QT interval. but appears so unless the diagnosis is actively sought. occult ARVC. and assess the likelihood for longterm recurrence and need or lack thereof for longterm management. In managing all arrhythmias. However the only rhythm therapy that has been shown to reduce risk of sudden death in these highrisk populations is ICD implantation. based on current understanding. it is the clinicians role to attempt to identify the tachycardia mechanism and the likely acute precipitants if any so they can be reversed. N Engl J Med . In the setting of heart disease. which circulate around acquired obstacles related to atrial scar tissue and brosis. This patient was started on amiodarone a week earlier for an unrelated arrhythmia. in which the heart is not. in which delta waves are present and there is some potential for sudden death due to rapid conduction of AF resulting in VF and concealed WPW. Amiodarone is the least likely of all class III drugs to cause torsades. ischemic heart disease is most commonly associated with sustained VT and sudden death. which have a generally good prognosis. including those with nonsustained arrhythmias and left ventricular dysfunction. and antithrombotic therapy with aspirin or warfarin based on estimated longterm thromboembolic risk. which is initiated by focal ring involving predominantly the pulmonary veins and likely maintained by chaotic left atrial reentry. References . N Engl J Med . Available at http//www.pdf. Reda DJ. . Epstein AE.. Accessed March . Mortality and morbidity in patients receiving encainide. et al. Available at http//www. et al.org/qualityandscience/clinical/guidelines/ atrialb/pdfs/AFFullText. .htm. Amiodarone or an implantable cardioverter debrillator for congestive heart failure. Arizona Center for Education and Research on Therapeutics. N Engl J Med . Moss AJ. ACC/ AHA/NASPE guideline update for implantation of cardiac pacemakers and antiarrhythmia devices a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines ACC/AHA/NASPE Committee on Pacemaker Implantation. Camm AJ. Randomised trial of effect of amiodarone on mortality in patients with left ventricular dysfunction after recent myocardial infarction EMIAT. Mitchell LB. Improved survival with an implanted debrillator in patients with coronary disease at high risk for ventricular arrhythmia Multicenter Automatic Debrillator Implantation Trial Investigators. et al. Haissaguerre M. N Engl J Med . . N Engl J Med . Frangin G. Bardy MD. et al. Randomised trial of outcome after myocardial infarction in patients with frequent or repetitive ventricular . N Engl J Med . . Hall WJ. Connolly SJ. Gust H.acc. et al. et al. Zareba W. . Fuster V. ecainide. Accessed March . Wyse DG. . Waldo AL. . ACC/ AHA/ESC guidelines for the management of patients with atrial brillation a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines Writing Committee to Revise the Guidelines for the Management of Patients With Atrial Fibrillation. Roberts R. Shah DC. Lancet . Hall WJ. Spontaneous initiation of atrial brillation by ectopic beats originating in the pulmonary veins. J Am Coll Cardiol . Jais P. et al. Rydn LE. Moss AJ. Cannom DS. Julian DG. Tachycardias Diagnosis and Management Roth . Gregoratos G. N Engl J Med . . .org.org/qualityandscience/ clinical/guidelines/pacemaker/incorporated/index. Prophylactic implantation of a debrillator in patients with myocardial infarction and reduced ejection fraction. et al. Cannom DS. . Kerry L. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Investigators. Singh BN. premature depolarisations CAMIAT. Echt DS. DiMarco JP. A comparison of antiarrhythmic drug therapy with implantable debrillators in patients resuscitated from nearfatal ventricular arrhythmias the Antiarrhythmics Versus Implantable Debrillators AVID Investigators. Abrams J. for the Sudden Cardiac Death in Heart Failure Trial Investigators. or placebo the Cardiac Arrhythmia Suppression Trial. et al. et al. Singh SN. et al. A comparison of rate control and rhythm control in patients with atrial brillation. N Engl J Med . Accessed March . Amiodarone versus sotalol for atrial brillation SAFET Trial. Lancet . ee.qtdrugs. Liebson PR.acc. Cairns JA. Available at http// www. . N Engl J Med . . activation of the reninangiotensin system. is becoming more common as a cause of CHF. Heart failure develops in . These stages have been linked to therapeutic approaches. and in patients years of age. The severity of chronic heart failure is most commonly delineated using the classication developed by the New York Heart Association NYHA. both as a primary cause and as a complicating factor of CHF. and etiology of congestive heart failure diagnosis Understand the pathophysiology of the heart failure syndrome Review general treatment goals and medical therapy for heart failure. and systolic vs ACCP Critical Care Medicine Board Review th Edition diastolic dysfunction. The predominant causes. Hollenberg. and CHF results in . More recently. congestive heart failure. Pathophysiology Heart failure is a syndrome caused not only by the low cardiac output resulting from compromised systolic performance. additional compensatory mechanisms come into play. with an emphasis on acute heart failure in the ICU Key words aldosterone antagonism. and vasopressin secretion. and idiopathic cardiomyopathy. It is important for the clinician to distinguish between systolic and diastolic dysfunction. demographics. and to focus on preventive measures and early intervention Table . which is an estimated . All of these . which is dened clinically as cardiogenic pulmonary congestion in the presence of normal systolic performance.Heart Failure and Cardiac Pulmonary Edema Steven M. FCCP Objectives Review the denition. cardiovascular deaths and about . CHF is now the most common reason for hospitalization in the elderly. however. vasodilators Definition and Epidemiology Congestive heart failure CHF can be dened as the inability of the heart to provide an adequate cardiac output without invoking maladaptive compensatory mechanisms. These elevated diastolic lling pressures can compromise subendocardial blood ow and cause or worsen ischemia. leftsided vs rightsided. of the adult population. patients for the rst time every year. including sympathetic nervous system stimulation. remodeling. an elevation in ventricular lling pressure occurs in an attempt to maintain output via the FrankStarling law. diastolic dysfunction. Coronary artery disease is increasing. as both the diagnostic workup and therapeutic sequence differ. stages in the evolution of heart failure have been proposed by an American College of Cardiology/American Heart Association task force to emphasize its progressive nature. MD. This classication divides patients into functional classes depending on the degree of effort needed to elicit symptoms Table . as follows acute vs chronic. CHF affects million patients in the United States. The estimated prevalence of diastolic heart failure is to overall.. Although CHF results most commonly from decreased systolic performance. The incidence of heart failure has been increasing. hypertension. myocarditis. and annual costs are estimated at more than billion. million hospital admissions per year in the United States. angiotensinconverting enzyme inhibition. To compensate for the reduced cardiac output of a failing heart. particularly in the elderly. With continued low cardiac output. Myocardial damage from any cause can produce myocardial failure. angiotensin receptor blockers. cardiogenic shock. The causes of heart failure are protean and are listed in Table . but also by the effects of compensatory mechanisms. are ischemia. alcoholic cardiomyopathy. Heart failure can be broken down into several different classications. due not only to the aging of the population but also because improved treatment of hypertension and coronary disease is allowing patients to avoid early mortality only to have heart failure develop later. hepatomegaly. without structural disease or symptoms Heart disease with asymptomatic LV dysfunction Prior or current symptoms of heart failure Advanced heart disease and severely symptomatic or refractory heart failure Table . Low output produces the symptoms of weakness and fatigue and an ashen appearance. although initially compensatory. involves the left ventricle LV globally and is associated with dilation that increases over time.Table . but late remodeling. distortion of ventricular shape. Similar processes are operative in other sorts of cardiomyopathy as well. along with signs of systemic congestion such as jugular venous distension. Hypotension and evidence of peripheral Heart Failure and Cardiac Pulmonary Edema Hollenberg mechanisms lead to sodium and water retention and venoconstriction. Elevated rightsided preload can lead to symptoms such as anorexia. wheezing can be heard throughout the lung elds. the process by which ventricular size. often. Increased leftsided lling pressures result in symptoms of pulmonary congestion such as dyspnea. a diffuse. Stages of Heart Failure Stage A B C D Description High risk for heart failure. a murmur of tricuspid regurgitation. cough. Crackles and. hypertension. Early local remodeling after MI may expand the infarct zone. as a pathophysiologic mechanism in heart failure. increasing both preload and afterload. lead. with the sudden onset of shortness of breath and tachypnea with use of accessory muscles. can exacerbate the heart failure. Etiologies of CHF Ischemic Hypertensive Idiopathic Valvular Peripartum Familial Toxic Alcoholic Radiation Drugrelated anthracyclines Heavy metals cobalt. or arsenic Metabolic/nutritional Systemic diseases Hypothyroidism Connective tissue disease Diabetes Sarcoidosis Inltrative Amyloidosis Hemochromatosis Tachycardiainduced Autoimmune Table . These increases in preload and afterload. and genetic factors. because elevated preload increases pulmonary congestion. NYHA Functional Classication of Heart Failure Class I II III IV Description Symptoms of heart failure only at levels that would limit normal individuals Symptoms of heart failure with ordinary exertion Symptoms of heart failure on less than ordinary exertion Symptoms of heart failure at rest initiated by hemodynamic stress. cardiomyopathy. and peripheral edema. The failure to normalize increased wall stresses results in progressive dilatation and deterioration in contractile function. Recent attention has focused on cardiac remodeling. and a murmur of mitral regurgitation. a rightsided S gallop. and paroxysmal nocturnal dyspnea as well as signs that may include tachycardia. and laterally displaced point of maximal impulse. and hypertrophy of the walls. Diagnosis The symptoms and signs of CHF relate both to low cardiac output and elevated ventricular lling pressures. nausea. Remodeling may be physiologic and adaptive during normal growth. pulmonary rales. The presentation of acute heart failure and pulmonary edema can be dramatic. ascites. and abdominal pain. or valvular heart disease can be maladaptive. at times obscuring some of the cardiac auscultatory ndings. neurohormonal. an S and S gallop. but excessive remodeling after myocardial infarction MI. enlarged. and elevated afterload impedes cardiac output. sometimes with mottling. Ventricular remodeling can be considered a primary target for treatment and a reliable surrogate for longterm outcomes. which likely involves neurohormonal mechanisms . shape. and function are regulated by mechanical. orthopnea. Such intermediate values may be due to CHF but may also represent preexisting LV dysfunction or rightsided heart failure. the effects of therapy on counterproductive neurohormonal activation have received attention. Doppler echocardiography can be used to evaluate the severity of mitral and tricuspid regurgitation. infection. Different therapies can have disparate effects on these goals. Laboratory evaluation should include baseline measurement of serum electrolytes and creatinine. while levels pg/mL indicated noncardiac dyspnea. increased lling pressures and stretch. Angiotensinconverting enzyme ACE inhibitors. with or without bilateral hazy pulmonary inltrates. reduce . Pleural effusions may be identied but are neither sensitive nor specic. and blood glucose. improve exercise tolerance. classically perihilar. Arterial dilators can also reduce afterload. The measurement of BNP has been used to distinguish between heart failure and pulmonary causes of dyspnea. conduction abnormalities such as AV block and bundle branch block may be diagnosed. Regional wall motion abnormalities are compatible with coronary heart disease but are not specic for ischemia since they are also seen in to of patients with idiopathic dilated cardiomyopathy. The addition of echocardiography in the acute setting may be especially valuable in patients with intermediate BNP levels. The initial evaluation of the patient with pulmonary edema should include an ECG and chest radiograph. liver function tests. aldosterone antagonists. Doppler echocardiography is increasingly used in the diagnosis of diastolic dysfunction. atrial enlargement speaks to the chronicity of elevated lling pressures. toxins. Echocardiography can provide important information about cardiac size and function. and the plasma concentration of BNP has been shown to correlate with NYHA functional class. such as ACE inhibitors. these have been considered in hemodynamic terms.vasoconstriction and hypoperfusion may be present if cardiac output is decreased. correct the underlying cause. and. LV and right ventricular function. The chest radiograph can demonstrate pulmonary vascular redistribution. valvular structure and motion. Plasma BNP levels are increased in patients with heart failure. Inotropic agents can improve cardiac pump function and increase output. Fluid restriction and diuretic and venodilator agents decrease cardiac preload. Therapy Treatment Goals The goals of CHF therapy are to control symptoms. such as pulmonary embolism. a plasma BNP level of pg/mL accurately predicted CHF. The most current approaches. Agents used for therapy that have been shown to have a benecial effect on remodeling. as well as cardiomegaly. or trauma. where possible. More recently. and causes of noncardiac pulmonary edema. Traditionally. and blockers. Fibrotic and thinned akinetic areas. indicate previous infarction. atrial size. values between and pg/mL were less useful. and a CBC count. The ECG may show evidence of myocardial ischemia and can also detect arrhythmias. and aldosterone antagonists counteract the activation of the reninangiotensinaldosterone system and reduce afterload as well. and bronchial asthma. angiotensin receptor blockers ARBs. however. and permits the systemic interrogation of cardiac chamber size. patients presenting to the emergency department with a chief complaint of dyspnea. blockers can counteract sympathetic activation and are being used more commonly in heart failure management. such as aspiration. In the Breathing Not Properly study of . take into account the effects of different therapies on ventricular remodeling. Therapeutic agents can be viewed in the light of the pathophysiologic mechanisms of CHF development. ARBs. BNP is produced by ventricular myocytes in response to increased wall stress ie. Q waves indicative of previous infarction or criteria diagnostic of ventricular hypertrophy may provide clues about the substrate for heart failure. The differential diagnosis of cardiac pulmonary edema includes other causes of acute dyspnea. prolong life. pneumothorax. and ACCP Critical Care Medicine Board Review th Edition should be performed in all patients with newonset heart failure. and pericardial anatomy. In addition. The measurement of plasma Btype natriuretic peptide BNP has been introduced into the diagnostic algorithm for CHF. Echocardiography is simple and safe. and the tricuspid regurgitation velocity can be used to estimate pulmonary artery pressure. however. Table . If intermittent bolus doses of loop diuretics are ineffective or are poorly tolerated due to large uid shifts and consequent hypotension. Alternatively. another diuretic with a different mechanism of action. most of the rapid effect of furosemide is attributable to venodilation. For inpatient treatment of . Nitrates Nitrates are still the rstline agents for the symptomatic relief of angina pectoris and in cases when MI is complicated by CHF. and thus pulmonary and systemic congestion. Bypass surgery or percutaneous intervention for cardiac ischemia can improve both symptoms and ventricular performance. and are administered in IV bolus doses. such as metolazone or chlorothiazide. Given the high incidence of coronary artery disease in patients with CHF. For patients with arrhythmias. the use of nitrates to reduce preload is often desirable. continuous infusion may be preferable. Precipitating Causes of CHF Myocardial ischemia or infarction Excess salt or uid intake Noncompliance or inadequate drug regimen Renal failure Arrhythmias Anemia Infection Fever Thyrotoxicosis Pregnancy Pulmonary embolism Survival Effects Benet Benet ACE better Benet Benet No benet No benet No benet No benet Adverse TNF tumor necrosis factor. decompensated heart failure. the dose is titrated to achieve the desired effect. the most prominent of which are listed in Table . The careful addition of a potassiumsparing diuretic can be considered in some settings. most notably cardiac resynchronization therapy CRT. revascularization confers a survival benet. In patients with severely decompensated CHF. Once the effective dose has been determined. Loop diuretics enter the glomerulus primarily by tubular secretion into the proximal tubule and so exhibit a threshold effect. loop diuretics such as furosemide are usually chosen initially because of their rapid onset. also appear to be effective. Remodeling and Survival by Drug Class Established Therapy ACEI ARB Aldosterone antagonists blocker Diuretic Digoxin Other therapies Endothelin antagonists TNF Inotropes Remodeling Effects Benet Benet ACE better Benet Benet No benet No benet No benet No benet Adverse Table . which can predispose the patient to arrhythmias. Patients with acute heart failure should be put on bed rest which by itself can produce a diuresis. the degree of diuresis is usually adjusted by changing the frequency of diuretic administration. may be added. The use of diuretics can lead to signicant hypokalemia or hypomagnesemia. usually by doubling the dose. mortality and are effective across the whole spectrum of heart failure severity Table . decreasing preload. Registry data consistently support the notion that in the presence of signicant amounts of ischemic yet viable myocardium. Mechanical approaches to remodeling. Attention should be paid to prophylaxis for deep venous thrombosis. with sodium restriction to g per day and uid restriction in severe cases. either cardioversion or rate control can produce marked improvement. If there is no response to a bolus dose of a loop diuretic. therapy with IV nitroglycerin is preferred because of the questionable absorption of oral and transdermal preparations and for the Heart Failure and Cardiac Pulmonary Edema Hollenberg Pharmacologic Therapy Diuretics Diuretics cause renal sodium and water loss. General Measures The rst order of business in the therapy for patients with new or decompensated CHF is to address the precipitating causes. When used for patients who present with pulmonary edema. and increased nitric oxide production may exert direct benecial effects on cardiac myocytes. rst in the VHeft. both intracardiac and intravascular. mg three times daily. and their inhibition by ACE inhibitors may explain part of their benecial effects. The hemodynamic effects of ARBs have been shown in a number of trials to be similar to those of ACE inhibitors. salutary effects on outcome have been demonstrated. ACE inhibitors improve hemodynamics. but the increased inhibition of ventricular remodeling seen with ACE inhibitors compared to that seen with other vasodilators speaks to the potential for involvement of other mechanisms. In the Survival and Ventricular Enlargement Trial or SAVE trial. interestingly. and also decreased hospitalization for heart failure and. ACE inhibitors also improve the outcome in patients with asymptomatic LV dysfunction or overt heart failure after an acute MI. Nonetheless. contribute to myocardial hypertrophy and remodeling. such as cough and angioedema. These trials are described below in the Hydralazine subsection. Moreover. and so therapy with ARBs is usually reserved for patients who cannot tolerate ACE inhibitors. however. hyperkalemia. ARBs An alternative approach to inhibiting the effects of angiotensin II is the use of agents that block the angiotensin II receptor ie. patients with clinical heart failure and showed a reduction in mortality at months. Captopril therapy decreased mortality by at months. Patients should be started on therapy with low doses and titrated upward to the range demonstrated to be benecial in clinical trials ie. the number of heart failure patients treated with ARBs and followed up for mortality is still relatively small compared to those treated with ACE inhibitors.ease of titration. the incidence of some side effects. is greatly reduced. and angioedema. captopril. and more recently in the AHeFT trial. the latter through bradykinininduced nitric oxide production. therapy with ACE inhibitors also prevented the development of CHF in patients ACCP Critical Care Medicine Board Review th Edition with asymptomatic LV dysfunction in the SOLVD prevention trial. Longterm therapy with oral nitrates alone does not impact ventricular remodeling and. enalapril. The latter effect may have been due to an improvement in endothelial function. IV nitroglycerin should be started at g/min and increased in increments of g/ min every to min as needed for symptomatic relief. . The Acute Infarction Ramipril Efcacy or AIRE trial compared therapy with ramipril to placebo in . ACE inhibitors also modulate sympathetic nervous system activity. in the absence of ongoing ischemia. The CONSENSUS group compared therapy with enalapril to placebo in patients with advanced heart failure NYHA class III or IV and showed a reduction in month mortality. mg once daily. recurrent MI. functional capacity. When combined with hydralazine. mg twice daily. or lisinopril. with a risk reduction averaged over the year duration of the trial of . Since these agents do not increase bradykinin levels. asymptomatic patients with an ejection fraction EF of were randomly assigned to receive either captopril or placebo. ARBs are a good alternative. and survival in patients across the spectrum of severity of chronic CHF and also after MI. Both of these actions produce vasodilation. The major adverse effects of nitrates are hypotension and headache. however. The side effects of ACE inhibitors include cough. . this benet was sustained. ACE Inhibitors ACE inhibitors inhibit the conversion of angiotensin I to angiotensin II and also inhibit the breakdown of bradykinin. Local reninangiotensin systems. patients with symptomatic heart failure NYHA class II to III and showed a mortality reduction. thus. renal failure usually occurring in the setting of renal artery stenosis. Trials comparing ACE inhibitors to ARBs in patients with heart failure have suggested similar mortality reductions. ARBs. The SOLVD treatment trial compared therapy with enalapril to placebo in . The survival benet was maintained in the long term in both trials. is not usually a rstline choice. This collective experience indicates that longterm treatment with blockers can relieve symptoms... . including the sympathetic nervous system. potentially leading to programmed cell death. and found a reduction in the month mortality rate from to relative risk. decreasing afterload.. and also those receiving blockers but not ACE inhibitors. patients with LV dysfunction after MI to receive eplerenone or placebo. p . blockers also reduce the circulating level of vasoconstrictors and mitigate their effects. ACE inhibitors. which is a process that is counteracted by blockers. which initially support the performance of the failing heart. Perhaps most importantly. captopril.. when valsartan was added as triple therapy on top of both ACE inhibitors and blockers mortality was increased. in which valsartan or placebo was added to usual therapy in patients with heart failure. its neurohumoral effects are gaining increasing recognition. interestingly. condence interval. The longterm stimulation of receptors reduces the responsiveness to adrenergic agonists due to the downregulation and desensitization of the receptor and its coupled signaling pathways. Longterm activation of the sympathetic nervous system. Thus. In the VALIANT trial.. although it is perhaps counterintuitive on hemodynamic grounds. the incidence of hypokalemia was reduced from . improve ventricular performance. but. patients with class III and IV heart failure to receive spironolactone or placebo. Other trials. careful attention to serum potassium levels is warranted when using these agents for any indication. . exerts deleterious effects. and can also provoke arrhythmias. p . however. patients with heart failure and systolic dysfunction. a combined end point of mortality and hospital admission for CHF was reduced with valsartan therapy. Blockers Symptomatic heart failure results in the activation of neurohumoral mechanisms. and blockers was not seen. hyperkalemia was noted in . This approach was tested in the VHeft. Nonetheless. Catecholamines induce oxidative stress in cardiac myocytes. to . blockers have now been evaluated in . have not shown adverse effects of triple combination therapy. Although mortality was unchanged. In this trial. to . and the main side effect was gynecomastia. The RALES trial randomized . The recently reported EPHESUS triala randomized .. The following three different agents have been shown to decrease mortality in patients with Heart Failure and Cardiac Pulmonary Edema Hollenberg Aldosterone Antagonists Although aldosterone is predominantly known for its role in the regulation of renal sodium and potassium excretion. It should be noted that the doses of aldosterone antagonists used in these heart failure trials were well below those used for diuresis. there is now compelling evidence that blockers are benecial not only for patients with acute MI complicated by heart failure but also with chronic heart failure from all causes. A subset analysis of this trial yielded the provocative nding that although valsartan therapy improved mortality in patients who were receiving ACE inhibitors but not blockers. Increased mortality was also not observed when the ARB candesartan was added to therapy with ACE inhibitors and blockers in heart failure patients in the CHARMAdded trial. however. . and the combination of the two agents in patients with acute MI and CHF. of the placebo group p . . restoring inotropic and chronotropic responsiveness. of the eplerenone group compared to . which compared therapy with valsartan. and reduce both mortality and the need for hospitalization.The recognition that angiotensin II is produced by pathways other than ACEs has provided a rationale for using ACE inhibitors and ARBs in combination therapy. Circulating catecholamine levels correlate with survival in these patients. Sympathetic activation can increase ventricular volumes and pressure by causing peripheral vasoconstriction and impairing sodium excretion by the kidneys. and blockers can decrease LV endsystolic and enddiastolic volume. blockade can upregulate adrenergic receptor density. and found a reduction in mortality relative risk. catecholamines promote deleterious ventricular remodeling. Aldosterone inhibition impacts ventricular remodeling as well. Hyperkalemia was uncommon. an adverse effect of the combination of ARBs. Symptoms of dyspnea were decreased and global clinical status was improved with nesiritide therapy compared with placebo. Assays of circulating BNP levels have been used in the diagnosis of heart failure and have some prognostic value. patients. In patients with heart failure. nesiritide is a balanced arterial and venous vasodilator that may also have a modest natriuretic effect. the placebotreated patients were randomly reassigned to receive either nesiritide or IV nitroglycerin. and all patients were observed for h ie. and quality of life. Discontinuing therapy with blockers. After this initial placebocontrolled period. In addition. mm Hg. the activetreatment phase. and carvedilol. reducing mortality in patients with class III and IV heart failure in the ACCP Critical Care Medicine Board Review th Edition . may expose myocardial receptors to endogenous catecholamines and may result in a brief increase in contractility. Enalapril was shown to be superior to this combination. Therapy with hydralazine and nitrates improved mortality. Hydralazine therapy is effective in increasing cardiac output in patients with heart failure. present a previously rare dilemma that is becoming more common. IV nesiritide has been shown to increase stroke volume and cardiac output and to decrease right atrial and pulmonary capillary wedge pressure. Studies with carvedilol have suggested that the benets extend to patients with class IV heart failure. or placebo for h. hospitalization for heart failure. mm Hg. blockers should be introduced when the patient is in a wellcompensated and euvolemic state. in patients with acute heart failure were tested in the randomized VMAC trial. vs .NYHA class II and III heart failure metoprolol XL. When administered for the treatment of heart failure indications per se. The initiation of therapy with blockers. IV nitroglycerin. Its effects. including who underwent pulmonary artery catheterization. vs . VHeft trial. No controlled observations are available to guide therapy. but there was no signicant difference Hydralazine Hydralazine reduces afterload by directly relaxing smooth muscle. On the other hand. In . These benets of blockers are seen in patients with or without coronary artery disease and in patients with or without diabetes. Its effects are almost exclusively conned to the arterial bed. compared to those of IV nitroglycerin. respectively. When infused IV. and to halve the dose if heart failure persists. and prolonged administration is attended by the development of a lupuslike syndrome in up to of patients. but the therapeutic use of BNP differs. oral hydralazine must be administered four times a day. so hydralazine has usually been reserved for ACEintolerant patients. can be problematic during the acute phase of heart failure. Patients who experience an exacerbation of heart failure while receiving maintenance blocker therapy. the hypotensive actions of hydralazine provoke a marked reex tachycardia. or decreasing their dose. Therapy with hydralazine in combination with oral nitrates was the rst therapy shown to improve mortality in CHF patients. were randomly assigned to receive nesiritide. a xed dose of both isosorbide dinitrate and hydralazine administered twice daily was tested in black patients with class III and IV heart failure. typically in the ambulatory setting and at low doses. the slow titration of blockers will need to begin anew after the resolution of acute CHF. so current practice remains largely at the discretion of individual clinicians. and are also observed in patients who are already receiving ACE inhibitors. In this trial. respectively and signicantly more than therapy with nitroglycerin at h . particularly at a higher dose. but this response is often blunted in patients with heart failure. Nesiritide Nesiritide is a recombinant form of human BNP. It is usually best to attempt to resolve acute episodes of heart failure by diuresis and the adjustment of other medications while holding blocker doses constant. Therapy with nesiritide decreased the mean PCWP signicantly more than therapy with either IV nitroglycerin or placebo at h . a subgroup that was previously noted to have a favorable response to this therapy and that may not respond as well to ACE inhibition. however. In healthy subjects. and . bisoprolol. as they can depress contractility. There was no signicant difference in day rehospitalization rate or the month mortality rate. a study of . ACE inhibitors. but survival did signicantly decrease during hospitalization for heart failure patients. controversy has arisen regarding the use of inotropic agents other than digoxin as outpatient maintenance therapy for chronic heart failure. In addition. Therefore. which has been used to treat heart failure for years. Because milrinone does not stimulate adrenergic receptors directly. inotropic support may be initiated. the dose can be increased every h by . phosphodiesterase inhibitors have fewer chronotropic and arrhythmogenic effects. Compared to catecholamines. Dobutamine is a selective adrenergic receptor agonist that can improve myocardial contractility and increase cardiac output. The proof that these agents have benecial effects on hard clinical end points remains elusive. followed by a continuous infusion of . causing intracellular sodium accumulation and increasing intracellular calcium via the sodiumcalcium exchange system. Hypotension is the most common side effect. but the potential adverse effect on longterm outcome is a signicant concern. it may be effective when added to therapy with catecholamines or when adrenergic receptors have been downregulated. metaanalyses of data from the VMAC trial and other trials have suggested that nesiritide may worsen renal function and decrease survival at days compared to conventional therapies. possibly due to the downregulation of adrenergic receptors. Tolerance of the effects of dobutamine may develop after to h. apart from its use as an antiarrhythmic agent. it has not been shown to improve either the glomerular ltration rate or renal plasma ow.in these parameters when compared to therapy with IV nitroglycerin. infusion is usually initiated at g/kg/min and then titrated. either by induction of myocardial ischemia or by independent pathways. Dobutamine is the initial inotropic agent of choice in patients with decompensated acute heart failure and adequate systolic BP. Although they clearly are useful in improving hemodynamics in the acute setting. but its inotropic effects are mild in comparison to those of catecholamines. thereby biasing the enrollment toward a less severely aficted cohort. Although these observations did not demonstrate any advantage for patients who were treated with milrinone. Digoxin improves myocardial contractility and increases cardiac output. Concerns have included exacerbation of arrhythmic complications. Inotropic Agents In severe decompensated heart failure. the utilization of such agents today remains at the discretion of the clinician. g/kg/min up to a maximum of . Nesiritide is given as an initial IV bolus of g/kg. Milrinone has been examined in a prospective manner in the OPTIMECHF trial in order to determine whether its use could reduce hospitalization time following an exacerbation of acute heart failure. patients with symptomatic CHF and systolic dysfunction. Dobutamine has the potential to exacerbate hypotension in some patients and can precipitate tachyarrhythmias. and the perpetuation of neurohumoral activation that might accelerate the progression of myocardial damage. but Heart Failure and Cardiac Pulmonary Edema Hollenberg Digoxin Digitalis. and blockers. The degree to which these issues are applicable for use in patients with acute heart failure and hemodynamic decompensation is controversial. patients whom the investigators felt needed acute inotropic support were not included in the trial. g/kg/min. Milrinone is a phosphodiesterase inhibitor with both positive inotropic and vasodilatory actions. g/kg/min. the resolution of which awaits the completion of appropriately powered prospective clinical trials. Dobutamine has a rapid onset of action and a plasma halflife of to min. There was no difference in survival between the digoxin and placebo groups. . Thus. The effect of digoxin on patient survival was denitively addressed in the Digoxin Investigators Group or DIG trial. works by inhibiting NaKdependent adenosine triphosphatase activity. Although nesiritide has natriuretic properties. digoxin is recommended for therapy in patients with systolic dysfunction and symptomatic heart failure despite therapy with diuretics. and so attention has focused on identifying patients who would benet from the placement of an implantable cardiac debrillator ICD. a signicant reduction in mitral regurgitation jet area. with decreased pulmonary capillary wedge pressures. The optimization of lling pressures and serial measurements of cardiac output and other parameters. More recently. Studies of outcomes after CRT are beginning to emerge. such as mixed venous oxygen saturation allow for the titration of inotropes and vasopressors to the minimum dosage required to achieve the chosen therapeutic goals. Nonsustained ventricular tachycardia may occur in as many as of patients. Cardiac Resynchronization Left bundle branch block or other conduction system abnormalities can cause dyssynchronous ventricular contraction. CRT. functional class.. may be attributable in part to antiarrhythmic properties. The MADIT II trial showed a mortality benet with ICD therapy in a trial in which the entry criterion was simply an EF of . and quality of life in this trial. The goal of CRT is to pace the LV and right ventricle to restore physiologic atrioventricular timing and contraction synchrony. with ICD therapy in patients with LV dysfunction EF. the SCDHeFT compared ICD implantation to amiodarone therapy in patients with heart failure due either to ischemic or nonischemic cardiomyopathy EF. This is accomplished by placing the standard leads in the right atrium and right ventricle and also by placing a special lead through the coronary sinus to enable pacing of the lateral aspect of the LV. ICDs are effective as primary prevention in selected heart failure patients as well. however. The MADIT I trial and MUSST showed a mortality benet ACCP Critical Care Medicine Board Review th Edition . have not proven to be very effective for the prevention of sudden death in patients with heart failure. and can increase the duration and degree of mitral regurgitation. all of which are signs of reverse remodeling. Specic antiarrhythmic agents. and found a mortality benet with ICD in both groups. and a reduction in LV mass. Forty to of deaths are sudden. In the MIRACLE trial. and because changes in myocardial performance and compliance and therapeutic interventions can change cardiac output and lling pressures precipitously. Inotropic infusions need to be titrated carefully in patients with ischemic heart disease to maximize coronary perfusion pressure with the least possible increase in myocardial oxygen demand. Virtually all of the patients enrolled in the study had LV dysfunction. particularly blockers. reduces diastolic lling times. Cardiac resynchronization also improved exercise capacity. decreasing contractile performance and myocardial efciency. biventricular pacing is associated with reverse ventricular remodeling. by optimizing the coordination of contraction. and about half had clinical heart failure. thus increasing myocardial efciency. biventricular pacing produced signicant decreases in LV endsystolic and enddiastolic dimensions. Such dyssynchrony causes abnormal septal motion. to and nonsustained VT in whom sustained VT was inducible in an electrophysiologic study. and complex ventricular depolarizations in as many as . Most of the patients in these trials had ischemic cardiomyopathy. stroke volume. The mortality benets of some of the standard therapies for heart failure.their hemodynamic effects are attractive for treating decompensated patients. and cardiac output. because clinical estimates of lling pressure can be unreliable. and many of these deaths are attributable to arrhythmias. Invasive hemodynamic monitoring can be extremely useful for the optimization of therapy in these unstable patients. improves LV contractile function. thus minimizing the increases in myocardial oxygen demand and arrhythmogenic potential. This improved performance is associated with either no increase in myocardial oxygen consumption or a decrease. Most importantly. The insertion of ICDs as secondary prevention in survivors of sudden cardiac death or patients with hemodynamically signicant sustained ventricular tachycardias has been well demonstrated to improve survival in clinical trials. The COMPANION trial compared optimal medical therapy to CRT with and without Arrhythmias Arrhythmias are common in patients with heart failure. prognosis. et al. N Engl J Med . Nowak RM. Friday G. a combination of allcause mortality and hospitalization. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction results of the Survival and Ventricular Enlargement Trial. Oh JK. cardiac resynchronization reduced the interventricular mechanical delay. . et al. Effects of enalapril on mortality in severe congestive heart failure results of the Cooperative North Scandanavian Enalapril Survival Study CONSENSUS. New concepts in diastolic dysfunction and diastolic heart failure part II. N Engl J Med . N Engl J Med . . Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure.an ICD in . N Engl J Med . et al. et al. Circulation . Rapid measurement of Btype natriuretic peptide in the emergency diagnosis of heart failure. ventricular volume. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. SOLVD Investigators. Part II causal mechanisms and treatment. Yancy C. Cohn JN. . Moye LA. et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. Heart disease and stroke statistics update. Pfeffer MA. Williamson DR. Archibald DG. Braunwald E. . N Engl J Med . van Meyel JJ. . . Sutton MG. Zile MR. Acute Infarction Ramipril Efcacy AIRE Study Investigators. Tajik AJ. et al. and reduced both death and the combined end point of death and hospitalization compared to medical therapy. CASS Principal Investigators. The relevance of tissue angiotensinconverting enzyme manifestations in mechanistic and endpoint data. ee . Maisel AS. . Sharpe N. . . LL . Circulation . patients with NYHA class III to IV heart failure and an LV EF of . References . Dzau VJ. The reduction in the secondary end point of allcause mortality alone was signicant only in the CRTplusICD arm compared to medical therapy. Heart Failure and Cardiac Pulmonary Edema Hollenberg . and measurements of diastolic function. Flegal K. Diagnosis. Hatle L. a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. New concepts in diastolic dysfunction and diastolic heart failure part I. de Denus S. . Bernstein K. Logeart D. Rosamond W. N Engl J Med . Brutsaert DL. J Am Coll Cardiol . A randomized trial of coronary artery bypass surgery survival of patients with a low ejection fraction. et al. Zile MR. Gerlag PG. Ziesche S. Celermajer D. Chest . . . and mitral regurgitation. Taylor AL. Circulation . Ziesche S. Effect of vasodilator therapy on mortality in chronic congestive heart failure results of a Veterans Administration cooperative study. Diuretic efcacy of high dose furosemide in severe heart failure bolus injection versus continuous infusion. J Am Coll Cardiol . et al. In the recently reported Cardiac ResynchronizationHeart Failure or CAREHF trial. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. CONSENSUS Trial Study Group. Saudubray C. Comparative value of Doppler echocardiography and Btype natriuretic peptide assay in the etiologic diagnosis of acute dyspnea. was reduced in both the CRTalone arm and the CRTplusICD arm compared to medical therapy. Diastolic heart failure can be diagnosed by comprehensive twodimensional and Doppler echocardiography. et al. Causal mechanisms and treatment. Lancet . increased EF. improved symptoms and quality of life. . Dormans TP. N Engl J Med . Circulation . Krishnaswamy P. Brutsaert DL. J Am Coll Cardiol . Brain natriuretic peptide in the management of heart failure the versatile neurohormone. . Am J Cardiol . Beyne P. . . SOLVD Investigators. Left ventricular remodeling after myocardial infarction pathophysiology and therapy. N Engl J Med . Pharand C. The primary end point. or both in myocardial infarction complicated by heart failure. Cuffe MS. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. Valsartan. Moss AJ. Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure.Pitt B. Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure Investigators. Johnson G. VMAC Investigators. N Engl J Med . Lee KL.. N Engl J Med . JAMA . N Engl J Med . et al. a natriuretic peptide. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Buxton AE. . . Eplerenone. Olivari MT. Coats AJ. Circulation . et al. What is the role of adrenergic signaling in heart failure Circ Res . Swedberg K. Circulation . Cannom DS. . Effects of initiating carvedilol in patients with severe chronic heart failure results from the COPERNICUS Study. Packer M. JAMA . et al. Remme WJ. . N Engl J Med . et al. Hunt SA. ACC/ AHA guideline update for the diagnosis and management of chronic heart failure in the adult summary article. et al. The effect of digoxin on mortality and morbidity in patients with heart failure. Fowler MB. Lancet . PooleWilson PA. A comparison of antiarrhythmicdrug therapy with implantable debrillators in patients resuscitated from nearfatal ventricular arrhythmias the Antiarrhythmics Versus Implantable Debrillators AVID Investigators. et al. . . Tognoni G. N Engl J Med . Effect of carvedilol on survival in severe chronic heart failure. A randomized trial of the angiotensinreceptor blocker valsartan in chronic heart failure. et al. Lancet . the Losartan Heart Failure Survival Study ELITE II. Fox M. Engelhardt S. Digitalis Investigation Group. et al. captopril. Krum H. SacknerBernstein JD. Adams KF Jr. Segal R. Velazquez EJ. N Engl J Med . . . . Mohacsi P. Lancet . et al. N Engl J Med . Cohn JN. A randomized study of the prevention of sudden death in ACCP Critical Care Medicine Board Review th Edition . . Levine TB. Cohn JN. Dowling TC. et al. Pfeffer MA. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure randomised trial. or both. Kowalski M. JAMA . . J Am Coll Cardiol . et al. . Zannad F. A comparison of enalapril with hydralazineisosorbide dinitrate in the treatment of chronic congestive heart failure. left ventricular dysfunction. Improved survival with an implanted debrillator in patients with coronary disease at high risk for ventricular arrhythmia. et al. JAMA . Zannad F. . N Engl J Med . Antiarrhythmics Versus Implantable Debrillators AVID Investigators. Lohse MJ. Chin MH. McMurray JJ. CIBISII Investigators. Pitt B. Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure a randomized controlled trial. The Cardiac Insufciency Bisoprolol Study II CIBISII a randomised trial. Shortterm intravenous milrinone for acute exacerbation of chronic heart failure a randomized controlled trial. in the treatment of decompensated congestive heart failure Nesiritide Study Group. Elkayam U. Roecker EB. Ziesche S. Wang DJ. . et al. Aaronson KD. a selective aldosterone blocker. . a. et al. Eschenhagen T. Hall WJ. Colucci WS. et al. in patients with left ventricular dysfunction after myocardial infarction. Horton DP. Effects of candesartan in patients with chronic heart failure and reduced leftventricular systolic function taking angiotensinconvertingenzyme inhibitors the CHARMAdded trial. Fisher JD. Abraham WT. . Nesiritide does not improve renal function in patients with chronic heart failure and worsening serum creatinine. Effect of metoprolol CR/XL in chronic heart failure Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure MERITHF. Meadows D. . McMurray JJ. . . . . . Lancet . Shortterm risk of death after treatment with nesiritide for decompensated heart failure a pooled analysis of randomized controlled trials. Pitt B. Intravenous nesiritide. SacknerBernstein JD. Cohn JN. N Engl J Med . Skopicki HA. Remme W. Califf RM. N Engl J Med . Ostergren J. N Engl J Med . et al. N Engl J Med . . N Engl J Med . Erdmann E. . Cardiac resynchronization in chronic heart failure. et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. Hall WJ. Cleland JG. Abraham WT. et al. . N Engl J Med . Cardiacresynchronization therapy with or without an implantable debrillator in advanced chronic heart failure. N Engl J Med . Heart Failure and Cardiac Pulmonary Edema Hollenberg . Daubert JC. . Moss AJ. N Engl J Med . et al.patients with coronary artery disease Multicenter Unsustained Tachycardia Trial Investigators. Bardy GH. Saxon LA. Amiodarone or an implantable cardioverterdebrillator for congestive heart failure. Lee KL. N Engl J Med . Smith AL. et al. Zareba W. Mark DB. Boehmer J. . Prophylactic implantation of a debrillator in patients with myocardial infarction and reduced ejection fraction. Bristow MR. et al. Fisher WG. syncope. ACSs have traditionally been classied into Qwave myocardial infarction MI. nonQwave MI NQMI. vasoconstriction. but previously quiescent. and microembolization dictates the clinical manifestations of the syndrome. Classication according to the ACCP Critical Care Medicine Board Review th Edition Diagnosis Signs and Symptoms Patients with myocardial ischemia can present with chest pain or pressure.Acute Coronary Syndromes Steven M. coronary atherosclerotic plaque. which is usually precipitated by increased myocardial oxygen demand eg. exertion. or sudden death. since patients presenting with ST elevation benet from immediate reperfusion and should be treated with thrombolytic therapy or urgent revascularization. The exposure of plaque contents to the circulating blood pool triggers the release of vasoactive amines. myocardial infarction. with emphasis on diagnostic pitfalls Understand indications. thrombosis. and the activation of platelets and the coagulation cascade. angioplasty. and patients with unstable angina. constant. limitation of the oxygen supply. Acute Coronary Syndromes Terminology Acute coronary syndromes ACSs describe the spectrum of disease in patients who present with any constellation of clinical symptoms that are compatible with acute myocardial ischemia. or tachycardia with background coronary artery narrowing ie. patients without ST elevation but with enzyme evidence of myocardial damage ie. they differ from stable angina. Hollenberg. In this sense. with unstable angina/NSTEMI more often associated with plateletrich lesions and STEMI more often associated with brinrich clots. and surgical revascularization Review adjunctive medical therapy of acute myocardial infarction Review complications of acute myocardial infarction Key words antiplatelet agents. shortness of breath. The relative brin and platelet contents of these lesions vary. the classication has shifted and is now based on the initial ECG ndings. although it should be noted that all lesions contain some degree of both components. FCCP Objectives Review the diagnosis of myocardial infarction. Patients are divided into the following three groups patients with STelevation MI STEMI. brinolytic therapy. and retrosternal. percutaneous coronary intervention. antithrombotic agents. These syndromes are caused by recent thrombus formation on preexisting coronary artery plaque leading to impaired myocardial oxygen supply. The discussion in this chapter will follow this schematization. Pathophysiology The common link among the various ACSs is the rupture of a vulnerable. . and use of thrombolytic therapy Understand the role of cardiac catheterization. contraindications. complications. These observations form the scientic rationale for the use of brinolytic agents in the treatment of STEMI and the use of platelet inhibitors in the treatment of unstable angina/NSTEMI. nonSTEMI NSTEMI. ACSs comprise a family of disorders that share similar pathogenic mechanisms and represent different points along a common continuum. fever. Its duration is most often min. whereas brinolytic agents are not effective treatment in patients with other acute coronary syndromes. ST elevation presenting ECG ndings coincides with current treatment strategies. or down the arms. Diaphoresis. MD. nonST elevation. and unstable angina. The extent of the resultant platelet aggregation. More recently. The pain commonly spreads across the chest and may radiate to the throat or jaw. The pain of MI is typically severe. palpitations. Prodromal symptoms of myocardial ischemia occur in to of patients in the days preceding the infarction. Right ventricle infarction may be detected by ST elevation in recordings from the right precordial leads. The number of leads involved broadly reects the extent of myocardium involved. A systolic murmur of mitral regurgitation may be present due to papillary muscle dysfunction or left ventricular dilation. it is important to recognize that the pain of MI may sometimes be atypical in terms of location or perception. and an S gallop. III. which include pericarditis. As total occlusion continues. tachycardia. both cardiovascular such as aortic dissection or pericarditis and noncardiac. V Tall R wave in V VV I. which usually indicates a large infarction with extensive muscle damage. Although these are the classic signs of infarction. VV II. although it is often milder. V VR. conned to the jaw. Localization of MI by ECG Area of Infarction Inferior Anterior Lateral True posterior Septal Anterolateral Inferolateral Right ventricular ECG Leads II. and the morphology of the ST segments in patients with pericarditis tends to be concave upward while that of ischemia is convex. aVL. Distended jugular veins signal right ventricular diastolic pressure elevation. arms. or perceived as burning or pressure. aVF V. Cx circumex coronary artery. I. In patients with pericarditis. aVL. or interscapular region. III. and anxiety are often present. Q waves. With continued occlusion. there is an evolution of ECG abnormalities.nausea. Jpoint elevation. The clinician must also be careful not to be fooled by ECG imposters of acute infarction. The pain of unstable angina may be similar. which represent unopposed initial depolarization forces away from the mass of the infarcted myocardium. aVL. With total acute occlusion of a coronary artery. LAD left anterior descending coronary artery. VR InfarctRelated Artery RCA or posterolateral branch of Cx LAD or diagonal branch of LAD Cx Posterolateral branch of Cx or posterior descending branch of RCA LAD or diagonal branch of LAD Proximal LAD Proximal Cx or large RCA in right dominant system RCA RCA right coronary artery. Pericarditis may also be distinguished from infarction by the presence of PRsegment depression in the inferior leads and also by PRsegment elevation in lead aVR. with biphasic and then inverted T waves. particularly the VR. A pansystolic murmur may also result from an acute ventricular septal defect due to septal rupture. If enough myocardium is infarcted. pallor. V. ST segments may be elevated. but is useful in diagnosing specic complications and in excluding alternative diagnoses. It may be epigastric. Acute Coronary Syndromes Hollenberg . The physical examination can be insensitive and nonspecic. and the appearance of pulmonary crackles in the absence of pulmonary disease indicates elevated left ventricular lling pressures. V. wrists. aVF. may appear. but the elevation will be diffuse. and tachypnea. there is elevation of the ST segments in the same leads. WolffParkinsonWhite syndrome. but the pattern of ECG changes generally gives a guide to the area and extent of the infarction Table . Cardiac Biomarkers Measurement of enzymes released into the serum from necrotic myocardial cells after Table . V. reecting the anatomic area of the myocardium that is in jeopardy. The ECG The ECG abnormalities in myocardial ischemia depend on the extent and nature of coronary stenosis and the presence of collateral ow. the rst demonstrable ECG changes are peaked Twave changes in the leads. V I. At times. Left ventricular failure is suggested by the presence of basal crackles. the diminution of Rwave voltage in the affected area may be the only ECG evidence for the presence of permanent myocardial damage. and hypertrophic cardiomyopathy. peaks at to h after the onset of infarction. and diaphoresis may be prominent features. To be diagnostic for MI. Once elevated. but a third heart sound is usually indicative of more extensive damage. but nonetheless signicant. Nonetheless. which have become available in the past few years. and so critical therapeutic interventions should not be delayed pending assay results. Compromised left ventricular function may result in pulmonary edema with the development of pulmonary bibasilar crackles and jugular venous distention. brinolytic agents have shown no benet when used for the treatment of unstable angina/NSTEMI. Rapid pointofcare troponin assays. without elevation of CPKMB identies a subpopulation of patients who are at increased risk for complications. It is also important to provide reassurance to the patient. to mg orally. vomiting. Some patients may be better treated with emergent coronary angiography with percutaneous coronary intervention PCI as clinically indicated. adequate analgesia. A lead ECG should be performed and interpreted expeditiously. The classic biochemical marker of acute MI is the elevation of the CPKMB isoenzyme. recent data suggest that patients with STEMI and new LBBB may stand to gain greater benet from reperfusion strategies than those patients with ST elevation and preserved ventricular conduction. Nausea. and there is currently no role for their use in treating these latter syndromes. and troponin elevation in patients without ST elevation or in fact. the selection of patients with acute MI for the administration of a brinolytic agent should be undertaken with prudence and caution. and the patient should be considered for immediate reperfusion therapy. Indications and contraindications for brinolytic therapy are listed in Table . Their use is becoming more widespread and has superceded the use of CPKMB assays in most settings. most notably intracranial hemorrhage. which begins to appear in the plasma to h after the onset of infarction. The diagnosis of STEMI can be limited in the presence of preexisting left bundlebranch block LBBB or a permanent pacemaker. should be used to relieve pain and also to reduce anxiety. and should be treated with oxygen. Troponin T and troponin I are constituents of the contractile protein apparatus of the cardiac muscle. A newer serologic test for the detection of myocardial damage employs the measurement of cardiac troponins. preserve left ventricular function. the total plasma CPK value must exceed the upper limit of normal. STEMI Symptoms suggestive of MI are usually similar to those of ordinary angina but are greater in intensity and duration. the salutary effects of which have been known for decades and must not be underestimated. Indeed. and reduce shortterm and longterm mortality. In contrast to the treatment of STEMI. troponin levels can remain high for days to weeks.. Overwhelming evidence from multiple clinical trials has demonstrated the ability of brinolytic agents administered early in the course of an acute MI to reduce infarct size. and returns to baseline at to days after the onset of infarction. a new LBBB with a compatible clinical presentation should be treated as acute MI and treated accordingly. have further extended the clinical utility of this marker. Troponins are also more sensitive for the detection of myocardial damage. Patients treated early derive the most benet. and the MB fraction must exceed a certain value usually . ACCP Critical Care Medicine Board Review th Edition .infarction can aid in the diagnosis of MI. Because of the small. Patients presenting with suspected myocardial ischemia should undergo a rapid evaluation. Narcotics. Troponins may not be elevated until h after an acute event. risk of a bleeding complication. STsegment elevation of at least mV in two or more contiguous ECG leads provides strong evidence of thrombotic coronary occlusion. but it depends on the CPKMB assay used. limiting their utility to detect late reinfarction. a fourth heart sound can be present with small infarctions or even mild ischemia. and aspirin. and are more specic than the conventional CPKMB assays for the detection of myocardial damage. sublingual nitroglycerin unless systolic pressure is mm Hg. and stupor and malaise attributable to low cardiac output may occur. Fibrinolytic Therapy Early reperfusion of an occluded coronary artery is indicated for all eligible candidates. Why enhanced patency attained with rPA therapy did not translate into lower mortality is uncertain. with equivalent day mortality and bleeding rates. but subsequent trials showed similar day mortality rates. Based on these results. slower clearance from the circulation. Hypotension with infusion usually responds to the administration of uids and a decreased infusion rate. SK is given as a .Table . mg/ kg up to mg IV over the initial min. in general. The GUSTO angiographic substudy showed that the difference in patency rates explains the difference in clinical efcacy between these two agents. tPA demonstrated a small but signicant survival benet compared to SK in patients with STEMI absolute reduction. which demonstrated improved coronary ow at min compared to tPA. TNKtPA is given as a single bolus. with a rate of intracranial hemorrhage of approximately . Hemorrhagic complications are the most feared side effect. but allergic reactions are possible. currently have no additional cost compared to tPA. and is given as two mg boluses min apart. In the large . tPA is usually given in an accelerated regimen consisting of a mg bolus. they have gained popularity. and are simpler to administer. aneurysm. resistance to plasminogenactivator inhibitor. or AV malformation Stroke or neurosurgery within wk Trauma or major surgery within wk that could be a potential source of serious rebleeding Aortic dissection Relative Prolonged min or clearly traumatic cardiopulmonary resuscitation Noncompressible vascular punctures Severe uncontrolled hypertension / mm Hg Trauma or major surgery within wk but wk Preexisting coagulopathy or current use of anticoagulants with INR Active peptic ulcer Infective endocarditis Pregnancy Chronic severe hypertension Could be an absolute contraindication in lowrisk patients with MI... Allergic reactions do not occur because tPA is not antigenic. . but the rate of intracranial hemorrhage may be slightly higher than that with SK approximately . Indications for and Contraindications to Thrombolytic Therapy in Patients With Acute MI Indications Symptoms consistent with acute MI ECG showing mm . which produces a systemic lytic state for about h. and . SK produces coronary arterial patency approximately to of the time and has been shown to decrease mortality by compared to placebo. relative reduction. and increased brin specicity. adjusted for weight. Because these newer agents. mV ST elevation in at least two contiguous leads or new left bundlebranch block Presentation within h of symptom onset Absence of contraindications Contraindications Absolute Active internal bleeding Intracranial neoplasm. therapy with singlebolus TNKtPA is an acceptable alternative to tPA that can be given as a single bolus. millionunit IV infusion over h.. Tenecteplase TNKtPA is a genetically engineered tPA mutant with amino acid substitutions that result in prolonged halflife. . and more resistance to plasma protease inhibitors are being studied. patients Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries GUSTO trial. The ideal thrombolytic agent has not yet been developed. Reteplase rPA is a deletion mutant of tPA with an extended halflife. Fibrinolytic Agents Streptokinase SK is a singlechain protein produced by hemolytic streptococci. The major Acute Coronary Syndromes Hollenberg . have equivalent efcacy and sideeffect proles. Tissue plasminogen activator tPA is a recombinant protein that is more brinselective than SK and produces a higher early coronary patency rate to . and these patients should be considered for primary PCI. Newer recombinant agents with greater brin specicity. rPA was originally evaluated in angiographic trials. A single bolus of TNKtPA has been shown to produce coronary ow rates identical to those seen with accelerated tPA. . mg/kg up to mg over the next min. Primary PCI in Acute MI As many as one half to two thirds of patients presenting with acute MI may be ineligible for thrombolytic therapy. While emerging data suggest that this practice is not only feasible but also safe. In patients who do not respond to thrombolytic therapy. there was a clinical benet in the combined primary end points of death. which revealed coronary occlusion Situations in which PTCA may be preferable to thrombolytic agents Elderly patients yr Hemodynamic instability Patients with prior CABG Large anterior infarction Patients with a prior MI CABG coronary artery bypass grafting. further largescale investigations will be necessary to clarify this issue.advantages of therapy with primary PCI over thrombolytic therapy include a higher rate of normal ow thrombolysis in myocardial infarction TIMI grade . transfer for PCI conferred a signicant mortality benet despite adding to the time to treatment. or stroke. There is no convincing evidence to support empirical delayed PTCA in patients without evidence of recurrent or provocable ischemia after thrombolytic therapy. The TIMI IIB trial and . In the PRAGUE study. it has been thought that when the performance of PCI requires a substantial time delay. however. More important than the method of revascularization is the time to revascularization. a lower risk of intracranial hemorrhage. Data from several randomized trials have suggested that PCI is preferable to thrombolytic therapy for acute MI patients at higher risk. A metaanalysis. including those patients who are years old. Emergent cardiac catheterization is also preferred in patients with cardiogenic shock. There are certain subpopulations in which primary PCI is preferred. salvage PTCA is indicated. Recently reported studies comparing inhouse thrombolysis to hospital transfer for PCI have challenged this notion. Procedural volume is important as well. if performed in a timely manner ideally within min by highly experienced personnel. Thus. nonfatal reinfarction. reocclusion is more common. Interestingly. from comparing direct PTCA therapy with thrombolytic therapy found lower rates of mortality and reinfarction among those patients receiving direct PTCA. Other indications are listed in Table . patients. and nonfatal disabling stroke in the patients treated with percutaneous coronary angioplasty PTCA compared to those treated with tPA. with standby surgical backup. and that this is achieved in the most efcient and expeditious manner possible. Situations in Which Primary Angioplasty Is Preferred in Acute MI Situations in which PTCA is clearly preferable to therapy with thrombolytic agents Contraindications to thrombolytic therapy Cardiogenic shock Patients in whom uncertain diagnosis prompted cardiac catheterization. those with anterior infarctions. At days. direct angioplasty. may be the preferred method of revascularization since it offers more complete revascularization with improved restoration of normal coronary blood ow and detailed information about coronary anatomy. Historically. While these data are intriguing. which randomized . in which referral for primary PCI reduced the occurrence of a composite end point of death. and those with hemodynamic instability. More controversial is the issue of performing PCI at centers without onsite surgical backup. The largest of these trials is the GUSTOIIb Angioplasty Substudy. Similar results were found in the DANAMI study. It should be noted that these trials were performed in institutions in which a team skilled in primary angioplasty for acute MI was immediately available. reinfarction. but there was no difference in the hard end points of death and MI at days. the importance of procedural volume and experience has been underscored by retrospective studies suggesting that in the community setting as opposed to PCI performed as part of a controlled clinical trial. and mortality is higher. thrombolytic therapy may be preferable. PCI. although the initial success rate is lower than that of primary angioplasty. mortality rates after MI with routine primary PCI and thrombolytic therapy are currently equivalent. in patients treated between and h. allowing for prompt reperfusion of the infarctrelated artery. and the ability to stratify risk based on the severity and distribution of coronary artery disease. compared with thrombolysis using tPA. there was no difference in mortality between patients treated within h with either thrombolysis using SK or offsite ACCP Critical Care Medicine Board Review th Edition Table . using death or MI at days as the primary end point. These ndings were conrmed in a very large .. Therapy with heparin should be continued for to h. nitrates are still rstline agents for the symptomatic relief of angina pectoris and when MI is complicated by congestive heart failure. with a bolus of U/kg up to a maximum of . there was no signicant excess risk of bleeding in this study. reinfarction. Therapy with enoxaparin was compared to therapy with unfractionated heparin in the EXTRACTTIMI trial. Further analysis showed that an excess of cardiogenic shock in the metoprolol group. nitrates also reduce platelet aggregation. Although the risk of reinfarction or ventricular brillation was signicantly decreased. This combined end point was signicantly reduced with therapy with enoxaparin although mortality was unchanged at the cost of a small but signicant increase in major bleeding. Nonetheless. patient trial randomizing patients with STEMI to metoprolol IV and then oral or placebo n . immediate blockade with metoprolol resulted in a signicant reduction in recurrent ischemia and reinfarction. Adjunctive Therapies in STEMI Nitrates Antiplatelet Agents Aspirin has been shown to reduce mortality in patients with acute infarction to the same degree as thrombolytic therapy. patients with STEMI for treatment with brinolytic therapy. Despite these benets. U/h. and death. mortality was unchanged. They reduce myocardial oxygen demand by decreasing preload and afterload. which randomized . aspirin reduces the risk of reinfarction. In addition. or nonfatal intracranial hemorrhage termed the blockers are benecial both in the early management of MI and as longterm therapy. STEMI patients half of whom received brinolytic therapy. although mortality was not decreased. In addition to their hemodynamic effects. early therapy with IV atenolol was shown to signicantly reduce reinfarction. The composite of death. Unless contraindicated. The efcacy of the addition of clopidogrel to aspirin for therapy in STEMI patients was recently shown in the Clopidogrel and Metoprolol Myocardial Infarction Trial or COMMIT trial. the Gruppo Italiano per lo Studio Della Streptochinasi NellInfarto Miocardico or GISSI trial and the International Study of Infarct Survival or ISIS trial failed to show a signicant reduction in mortality from routine shortterm and longterm nitrate therapy. Heparin Blockers The administration of fulldose heparin after thrombolytic therapy with tPA is essential to diminish reocclusion after successful reperfusion. with adjustment to keep the partial thromboplastin time between and s. net clinical benet was also reduced with enoxaparin therapy. suggesting that lowmolecularweight heparin LMWH is an attractive agent for therapy in patients receiving brinolysis for STEMI. Acute Coronary Syndromes Hollenberg . the addition of clopidogrel to the treatment regimen reduced both total mortality and the composite end point of death. In the prethrombolytic era. particularly in patients presenting with Killip class III heart failure as heart failure on presentation was not an exclusion criterion. reinfarction. cardiac arrest. In conjunction with thrombolytic therapy with tPA. NSTEMI.. cardiac rupture. and may also improve the myocardial oxygen supply by increasing subendocardial perfusion and collateral blood ow to the ischemic region. all patients with a suspected ACS ie. and its effects are additive to thrombolytic agents.other studies have suggested that a strategy of watchful waiting allows for the identication of patients who will benet from revascularization. STEMI. Dosing should be adjusted to weight. U and an initial infusion rate of U/kg/h up to a maximum of . In . patients with ST elevation due to occlusive coronary artery spasm may have dramatic resolution of ischemia with the use of nitrates. or stroke. or unstable angina should be given aspirin as soon as possible. Nitrates have a number of benecial effects in the treatment of acute MI. Occasionally. . The PROVEIT trial showed that the reduction of lowdensity lipoprotein LDL cholesterol to a mean concentration of mg/dL with atorvastatin was associated with improved outcomes compared to therapy with pravastatin at a dose that achieved a mean LDL concentration of mg/dL. because these agents not only reduce myocardial oxygen demand but inhibit coronary vasoconstriction. longacting dihydropyridine agents without prominent negative inotropic effects. lisinopril. The adverse effects of calciumchannel blockers include bradycardia. particularly those with hypertension. A smaller but still signicant reduction in mortality was seen when all patients were treated with captopril in the ISIS study.These ndings suggest that IV blockade should be considered for all patients with STEMI who have continued ischemic discomfort.. and clinical evidence links cholesterol and coronary artery disease. Although current guidelines suggest an LDL concentration goal of to mg/dL. perhaps as a result of the antiinammatory effects of statins. nicardipine. or the AngiotensinConverting Enzyme Inhibitors Therapy with angiotensinconverting enzyme ACE inhibitors is clearly benecial in patients with congestive heart failure. elevated triglycerides and low highdensity lipoprotein cholesterol concentrations and the treatment of other atherogenic risk factors. but a reduction in ischemic events was seen as well. More recent studies have suggested that therapy with statins should be started in the hospital. diltiazem can be given orally. but should be avoided in patients with moderate or severe heart failure. The mechanisms responsible for the benets of therapy with ACE inhibitors probably include limitation in the progressive left ventricular dysfunction and enlargement remodeling that often occur after infarction. to mg once daily. even if they have not been treated with IV blockers. and exacerbation of heart failure For hemodynamically stable patients. as well as in the CARE study and the LongTerm Intervention with Pravastatin in Ischaemic Disease or LIPID trial. atrioventricular block. Diltiazem is the only calcium channel blocker that has been proven to have tangible benets. In patients with severe left ventricular dysfunction. Calcium channel blockers may be useful in the treatment of patients whose postinfarction course is complicated by recurrent angina. in ACCP Critical Care Medicine Board Review th Edition . starting at to mg every to h. Maximum benet may require the management of other lipid abnormalities ie. and also in patients after MI. mg three times daily. laboratory. enalapril. Oral blockade has been clearly demonstrated to decrease mortality after acute MI. as the benets can be demonstrated early. or ramipril. Patients should be started on low doses of oral agents captopril. and severe bronchospastic disease. ACE inhibitors were shown to decrease mortality in the SAVE trial. which patients with left ventricular dysfunction ejection fraction. and should be initiated in all patients who can tolerate it. such as amlodipine. newer recommendations are likely to be even more aggressive. Immediate IV ACE inhibition with enalaprilat has not been shown to be benecial. Therapy with ACE inhibitors should be started early. In fact. Diabetes mellitus is not a contraindication. after an MI had a improvement in survival after treatment with the ACE inhibitor captopril. to mg twice daily. reducing reinfarction and recurrent ischemia in patients with NQMIs who do not have evidence of congestive heart failure. preferably within the rst h after the MI. metaanalyses have suggested that high doses of the shortacting dihydropyridine nifedipine increase mortality in patients with MI. mg once daily. hypotension. LipidLowering Agents Extensive epidemiologic. mg three times daily and rapidly increased to the dosage range that has been demonstrated to be benecial in clinical trials captopril. Calcium Channel Blockers Randomized clinical trials have not demonstrated that the routine use of calcium channel blockers improves survival after MI. Impressive results have been achieved using hydroxymethylglutarylcoenzyme A HMGCoA reductase inhibitors statins in patients with documented coronary artery disease in the S trial. severe bradycardia or heart block. but the empiric IV administration of g of magnesium in patients with early ventricular ectopy is probably a good idea. Nonetheless. and seizures Therapy with IV amiodarone is an alternative to therapy with lidocaine for ventricular arrhythmias. NSTEMI The key to the initial management of patients with ACSs who present without ST elevation is Acute Coronary Syndromes Hollenberg . The incidence of sustained ventricular tachycardia or brillation is highest in the rst to h. Toxic manifestations primarily involve the CNS. the routine prophylactic administration of lidocaine is no longer recommended. even within normal limits. A potential treatment algorithm for treating patients with STEMI is shown in Figure . and can include confusion. but these arrhythmias may occur at any time. metaanalyses of pooled data have demonstrated increased mortality from the routine use of lidocaine. may not reect myocardial concentrations. Amiodarone is given as a mg IV bolus infused over min. and serum magnesium levels. The routine administration of magnesium has not been shown to reduce mortality after acute MI. Perhaps the most important point in the prevention and management of arrhythmias after acute MI is correcting hypoxemia. particularly after diuretic therapy. and maintaining normal serum potassium and magnesium levels. mg/min for h. Magnesium depletion is also a frequently overlooked cause of persistent ectopy. followed by infusion of mg/min for h. may be preferable. then . Antiarrhythmic Therapy A major purpose for admitting MI patients to the ICU is to monitor for and prevent malignant arrhythmias. longacting preparation of nifedipine. Therefore. Possible treatment algorithm for patients presenting with STEMI. and could be considered in patients with nonsustained ventricular tachycardia. increased mortality with these agents has not been demonstrated. Although lidocaine increases the frequency of premature ventricular contractions and of early ventricular brillation. slurred speech. The serum levels of electrolytes should be monitored closely. Ventricular extrasystoles are common after MI and are a manifestation of electrical instability of periinfarct areas. Malignant ventricular arrhythmias may be heralded by frequent complex ectopy but may occur suddenly without these preceding warning arrhythmias. lethargy. lidocaine infusion may be useful after an episode of sustained ventricular tachycardia or ventricular brillation.Treatment of ST elevation myocardial infarction ST elevation Aspirin Beta blocker lt hr gt hr Eligible for thrombolytic therapy Thrombolytic therapy contraindicated Not a candidate for reperfusion therapy no Persistent Symptoms yes Consider reperfusion therapy Thrombolytic therapy PCI or CABG Other medical therapy ACE inhibitors Nitrates Secondary prevention Figure . In fact. overall mortality is not decreased. Conversely. and a metaanalysis of the available data has indicated that the addition of heparin to therapy reduces the composite end point of death or MI. LMWHs. have several advantages. LMWHs have longer halflives and can be given by subcutaneous injection. It should be noted that this benet came with a absolute increase in major. In the SYNERGY trial. The potential for heparinassociated thrombocytopenia is also a safety concern. to endothelial cells and other cells. Aspirin also reduces the number of events after the resolution of an ACS and should be continued indenitely. most of whom were treated invasively.risk stratication. MI. in particular elevated levels of troponin. low levels are associated with low event rates. Conversely. stroke. ACCP Critical Care Medicine Board Review th Edition . and heparin inhibition by several factors released by activated platelets. The risk of progression to acute MI or death in patients with ACSs is dependent on clinical factors such as age. Both the Veterans Administration Cooperative Study Group and the Canadian Multicenter Trial showed that aspirin reduces the risk of death or MI by approximately in patients with unstable angina or NQMI. Clopidogrel is used in combination with aspirin when intracoronary stents are placed. or cardiovascular death in . most of the patients were managed conservatively. The overall risk of a patient is related to both the severity of the preexisting heart disease and the degree of plaque instability. there is less variability in the anticoagulant response and a more predictable doseresponse curve. Clopidogrel added to aspirin signicantly reduced the risk of MI. which was performed in highrisk patients. this is due to heparin binding to heparinbinding proteins. Biochemical markers of cardiac injury. Heparin. and STsegment depression seen on the ECG. Finally. Specic considerations with the use of LMWH include decreased clearance Antiplatelet Therapy As previously noted. In these early trials. can be difcult to administer. is more potent than aspirin and can be used in its place if necessary. and patients with heparininduced thrombocytopenia with antiheparin antibodies cannot be switched to LMWH. which begins with hospital admission and continues through hospital discharge. When added to therapy with aspirin. heparin has been shown to reduce refractory angina and the development of MI. The benecial effects of LMWH therapy in patients with unstable coronary syndromes were documented in the ESSENCE trial and the TIMI IIB trial. with a slightly higher major bleeding rate with enoxaparin. Therefore. The incidence of thrombocytopenia is lower but not absent. aspirin is a mainstay of therapy for ACSs. a normal ECG nding confers an excellent shortterm prognosis. Because they bind less avidly to heparinbinding proteins. although the absence of troponin elevation does not guarantee a good prognosis and is not a substitute for good clinical judgment. the activated partial thromboplastin time must be monitored closely. Clopidogrel. obviating the need to monitor activated partial thromboplastin time. absolute increase in major/lifethreatening bleeds associated with coronary artery bypass grafting CABG within days. patients with unstable angina in the randomized CURE trial. or recurrent ischemia compared to unfractionated heparin. presentation with heart failure. however. which are obtained by the depolymerization of standard heparin and the selection of fractions with lower molecular weight. are associated with an increased risk of cardiac events and a higher day mortality rate. no difference was found in efcacy between enoxaparin and unfractionated heparin. These data have raised concerns about administering clopidogrel prior to having information about the coronary anatomy. a thienopyridine that inhibits adenosine diphosphateinduced platelet activation. because the anticoagulant effect is unpredictable in individual patients. both in patients managed invasively with stents and those managed medically. which showed that the LMWH enoxaparin reduced the combined end point of death. nonlifethreatening bleeds as well as a . Risk stratication is an ongoing process. Anticoagulant Therapy Heparin is an important component of primary therapy for patients with unstable coronary syndromes without ST elevation. Abciximab has been most extensively studied. but Glycoprotein IIb/IIIa Antagonists Given the central role of platelet activation and aggregation in the pathophysiology of unstable coronary syndromes. The benets of therapy with glycoprotein IIb/IIIa inhibitors as adjunctive treatment in patients undergoing PCI have been substantial and consistently observed. with refractory ischemia in some patients. or refractory ischemia at days as the primary outcome. These studies suggest that alternatives to therapy with unfractionated heparin are safe and effective. the TACTICS TIMI study. This outcome was equivalent. Interventional Management Cardiac catheterization may be undertaken in patients presenting with symptoms suggestive of unstable coronary syndromes for one of the following reasons to assist with risk stratication. the TIMI IIIb study and the VANQWISH trial. found no difference in a composite end point of death. An initial strategy of medical management with attempts at stabilization is warranted in patients with lower risk. both of which were performed before use of coronary stenting and platelet glycoprotein IIb/IIIa inhibitors was widespread. was signicantly reduced with fondaparinux therapy. with death. and major bleeding was lower in the fondaparinux group. was tested in patients with nonSTelevation ACSs. a smallmolecule. The most recent comparison. and to exclude signicant epicardial coronary stenosis as a cause of symptoms when the diagnosis is uncertain. improved adjunctive antiplatelet. this trial likely argues not so much against an early invasive strategy as for the selection of those patients who are most likely to benet. Alternatively or in parallel. nonpeptide agent. a chimeric murinehuman monoclonal antibody Fab fragment. or recurrent angina with invasive management. A secondary end point. were negative. MI.in renal insufciency and the lack of a readily available test to measure the anticoagulant effect. Recently. satisfying noninferiority for fondaparinux. The results of two earlier trials. which inhibit the nal common pathway of platelet aggregation. a smallmolecule cyclic heptapeptide. synthetic. The benets appear to accrue primarily to patients undergoing PCI. Risk stratication is the key to managing patients with NSTEMI ACSs. and lipidlowering therapy may have narrowed the difference between strategies. The following three agents are currently available abciximab. Taken together. antithrombin. mortality at days. More recently. One possible algorithm for managing patients with NSTEMI is shown in Figure . as a prelude to revascularization. As of patients in the selectively invasive group were revascularized in the rst month. death and MI. the major trials show a small but signicant reduction in composite end points ie. eptibatide. Further testing of their effects when combined with an invasive strategy will clarify their appropriate role. which may not be entirely surprising. MI. ECG changes or elevated troponin levels. and tiroban. In patients with ACSs. several trials. the ICTUS study. The OASIS trial compared fondaparinux to enoxaparin in . Additional analysis suggests that glycoprotein IIb/IIIa inhibition is most effective in highrisk patients. patients with ACSs most of whom were treated conservatively. and the RITA study found a signicant reduction in the combined end point of death. including a substudy of the FRagmin and Fast Revascularisation during InStability in Coronary artery disease or FRISC II study. those with either Acute Coronary Syndromes Hollenberg . or rehospitalization for angina at year between a group assigned to early invasive management and another assigned to selectively invasive management. An early invasive approach has now been compared to a conservative approach in several prospective studies. a pentasaccharide that inhibits factor Xa. MI. attention has focused on platelet glycoprotein IIb/IIIa antagonists. but a benet for eptibatide has also been demonstrated. the evidence supporting the efcacy of therapy with glycoprotein IIb/IIIa inhibitors is somewhat less impressive. fondaparinux. an intraaortic balloon pump should be inserted. pericardiocentesis to relieve acute tamponade. Immediate management includes therapy with aspirin. PTCA can be performed if the culprit lesion is suitable. patients at higher risk should be considered for cardiac catheterization. anemia. CABG should be considered for patients with left main artery disease and threevessel disease. blocker Angiography Yes Refractory angina No Noninvasive evaluation at h or consider aggressive strategy with catheterization Figure . Ventricular freewall rupture typically occurs during the rst week after MI. Hep heparin. and diagnostic coronary angiography. LV function High Admit High IV Hep.Treatment algorithm for nonST elevation acute coronary syndromes Clinical presentation Hemodynamic instability Ongoing ischemia/rest pain Initial risk stratification Electrocardiogram Serum markers Pre existing factors age. female. ACCP Critical Care Medicine Board Review th Edition . and thoracotomy for repair. but late use may actually increase the risk. ASA aspirin. hypotension. early coronary angiography in selected patients with ACSs can lead to better management and lower morbidity and mortality. ASA. such as hypertension. blocker Early IIb/IIIa blockade Medium Low Medium Tn Discharge ASA. If the angina cannot be controlled medically or is accompanied by hemodynamic instability. Possible treatment algorithm for patients with nonSTelevation ACSs. and in those patients who are unsuitable to undergo PTCA. Tn troponin. The early use of thrombolytic therapy reduces the incidence of cardiac rupture. When good clinical judgment is employed. blockers. Emergent echocardiography or pulmonary artery catheterization can help to make the diagnosis. Pharmacologic and mechanical strategies are intertwined because the selection of patients for early revascularization will inuence the choice of antiplatelet and anticoagulant medication. IV nitroglycerin. CAD. Ventricular FreeWall Rupture Complications of Acute MI Postinfarction Ischemia Ischemia after MI can be due to mechanical problems that increase myocardial oxygen demand and to extracardiac factors. ASA. The classic patient is elderly. and hypertensive. but it usually results from decreased myocardial oxygen supply due to coronary reocclusion or spasm. Salvage is possible with prompt recognition. Freewall rupture presents as a catastrophic event with shock and electromechanical dissociation. Postinfarction angina is an indication for revascularization. blocker Tn IV Hep. the consideration of calciumchannel blockers. or hypermetabolic states. heparin. VR to VR or by characteristic hemodynamic ndings on right heart catheterization ie. Echocardiography is extremely useful in the differential diagnosis.. Right Ventricular Infarction Right ventricular infarction occurs in up to of patients with inferior infarction and is clinically signicant in of patients. hypotension. Papillary muscle rupture typically occurs to days after an acute MI. Inotropic or vasopressor therapy may also be needed to support cardiac output and BP. and cardiogenic shock. The diagnosis is substantiated by the demonstration of ST segment elevation in the right precordial leads ie. elevated right atrial and right ventricular enddiastolic pressures with normal to low pulmonary artery occlusion pressure and low cardiac output.Ventricular Septal Rupture Septal rupture presents as severe heart failure or cardiogenic shock. The maintenance of atrioventricular synchrony is also important in these patients to optimize right ventricular lling. and overdilation of the right ventricle can compromise left ventricular lling and cardiac output. however. The rapid institution of intraaortic balloon pumping and supportive pharmacologic measures is necessary. intraaortic balloon pumping may be useful. but most authorities now suggest. within h of the rupture. In some cases. with a pansystolic murmur and parasternal thrill. which should be undertaken as soon as possible since clinical deterioration can be sudden. which includes freewall rupture. Acute Coronary Syndromes Hollenberg . that repair should be undertaken early. is surgical valve repair or replacement. and infarct extension with pump failure. whereas unsuccessful reperfusion was associated with persistent hemodynamic compromise and a mortality rate of . Denitive therapy. a stepup in oxygen saturation from the right atrium to the right ventricle. Acute Mitral Regurgitation Ischemic mitral regurgitation is usually associated with inferior MI and ischemia or with infarction of the posterior papillary muscle. however. A study using direct angioplasty demonstrated that the restoration of normal ow resulted in dramatic recovery of right ventricular function and a mortality rate of only . and presents dramatically with pulmonary edema. the murmur of acute mitral regurgitation may be limited to early systole because of the rapid equalization of pressures in the left atrium and left ventricle. This may be due in part to the fact that right ventricular function tends to return to normal over time with supportive therapy. In patients with right ventricular infarction. ventricular septal rupture. although anterior papillary muscle rupture can also occur. Reperfusion of the occluded coronary artery is also crucial. Patients with cardiogenic shock due to right ventricular infarction have a better prognosis than those with leftsided pump failure. Hemodynamic monitoring with pulmonary artery catheterization may also be helpful. Operative repair is the only viable option for longterm survival. More importantly. The hallmark nding is a lefttoright intracardiac shunt ie. The combination of a clear chest radiograph with jugular venous distention in a patient with an inferior wall MI should lead to the suspicion of a coexisting right ventricular infarction. particularly because elevated right ventricular pressures and volumes increase wall stress and oxygen consumption. although such therapy may need to be prolonged. Echocardiography can demonstrate depressed right ventricular contractility. right ventricular preload should be maintained with uid administration. Inotropic therapy with dobutamine may be more effective in increasing cardiac output in some patients. Management includes afterload reduction with nitroprusside and intraaortic balloon pumping as temporizing measures. When a papillary muscle ruptures. For patients with continued hemodynamic instability. and decrease right coronary perfusion pressure. exacerbating right ventricular ischemia. but the diagnosis is most easily made with echocardiography. The timing of surgery has been controversial. the murmur may be soft or inaudible. uid resuscitation may increase pulmonary capillary occlusion pressure but may not increase cardiac output. and monitoring with serial echocardiograms may also be useful to detect right ventricular overdistention. especially when cardiac output is low. et al. Global Use of Strategies to Open Occluded Coronary Arteries GUSTO III Investigators. or both on coronaryartery patency. A new paradigm for plaque stabilization. et al. . . Circulation . International Study Group. Biomarkers in acute cardiac disease the present and the future. . Anbe DT. Circulation . Canto JG. N Engl J Med . patients with suspected acute myocardial infarction randomised between alteplase and streptokinase with or without heparin. Lancet . Lancet . An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. Widimsky P. N Engl J Med . et al. . The effects of tissue plasminogen activator. 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Platelet Receptor Inhibition in Ischemic Syndrome Management PRISM Study Investigators. events in unstable angina/nonQwave myocardial infarction results of the Thrombolysis in Myocardial Infarction TIMI B trial. et al. N Engl J Med . Ferguson JJ. N Engl J Med . . Circulation .. A critical appraisal of platelet glycoprotein IIb/IIIa inhibition. et al. McCans J. Comparison of fondaparinux and enoxaparin in acute coronary syndromes. Theroux P. N Engl J Med . . . Gurnkel EP. Simoons ML. Beasley JW. Adding heparin to aspirin reduces the incidence of myocardial infarction and death in patients with unstable angina a metaanalysis.. Zhao F. Circulation . et al. Enoxaparin prevents death and cardiac ischemic . . N Engl J Med . . Christenson RH. Armstrong PW. ORourke RA. . . N Engl J Med . . Yusuf S. et al. controlled trials. McCabe CH. . Cardiac troponin T levels for risk stratication in acute myocardial ischemia. N Engl J Med . N Engl J Med . Mehta SR. or both to treat acute unstable angina. 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Right ventricular infarction as an independent predictor of prognosis after acute inferior myocardial infarction. . . Windhausen F. Emergency cardiac procedures in patients in cardiogenic shock due to complications of coronary artery disease. et al. Circulation . Postinfarction ventricular septal defect. Blanche C. Cardiol Clin . DellItalia LJ. Gray RJ. Nedeljkovic ZS. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tiroban. et al. et al. PerezDavid E. Bowers TR. N Engl J Med . Bates ER. Circulation . Matloff JM. . Semin Thorac Cardiovasc Surg . . Ischemic left ventricular free wall rupture prediction. . MartinezSelles M. Weintraub WS. N Engl J Med . Lancet . Eur Heart J . de Winter RJ. and nitroprusside in patients with predominant right ventricular infarction. MD. Accordingly. and crackles on lung auscultation. warm extremities with bounding pulses and rapid capillary rell. FCCP Objectives Describe the clinical evaluation of patients with shock Describe the different types of shock Describe resuscitation of shock Describe new therapies for septic shock Describe vasoactive drugs used for treatment of shock Key words left ventricular failure. The end result of multiorgan hypoperfusion is tissue hypoxia. The jugular venous pulse is often reduced in such a patient. Since the mean BP is the product of the cardiac output CO and the systemic vascular resistance SVR. A hypotensive patient with decreased intravascular and cardiac volume status may have a history suggesting hemorrhage or other volume losses eg. Kerley B lines. cells/L or bands. The most common cause of highCO hypotension is sepsis. anaphylaxis. reductions in BP can be categorized by decreased CO and/or decreased SVR. burns and other trauma that elicit SIRS. which include abnormalities in temperature C or C. Signs of increased CO include ACCP Critical Care Medicine Board Review th Edition a widened pulse pressure particularly with a reduced diastolic pressure. congestion of the vascular pedicle. followed by recommendations for the diagnosis and treatment of each category of shock. hypovolemic. Clinical Evaluation of Patients in Shock Most patients who present with shock are hypotensive. or . extremity edema. In hypotensive patients with clinical evidence of reduced CO. Accordingly. and pulmonary edema. heart rate beats/min. increased jugular venous pressure JVP. and oliguria. acute altered mental status. right ventricular failure. Shock Defined Shock is dened by the presence of multisystem endorgan hypoperfusion.Shock John P. a search for the causes of decreased SVR is appropriate. these . the initial evaluation of a hypotensive patient should evaluate the adequacy of the CO. an assessment of intravascular and cardiac volume status is appropriate. shock. and polyuria. severe pancreatitis. vasopressors Shock is a common condition necessitating admission of the patient to the ICU or occurring in the course of critical care. vomiting. Chest pain and ECG changes consistent with ischemia may also be noted. If a hypotensive patient has clinical signs of increased CO. though not always. one can infer that the reduced BP is a result of decreased SVR. the three most common categories of shock include cardiogenic. In summary. present. respiratory rate breaths/min. sepsis. and peripheral arteriovenous shunts. and WBC count . thyrotoxicosis. In hypotensive patients with clinical evidence of increased CO. Clinical indicators include reduced mean BP. The chest radiograph may show cardiomegaly. cool skin and extremities. which is often clinically seen as lactic acidosis. one should search for signs of the systemic inammatory response syndrome SIRS. Last. Kress. A hypotensive patient with an increased intravascular and cardiac volume status may have S and/or S gallops. A person with SIRS and a presumed or conrmed infectious process fullls the criteria for sepsis. Hypotension is usually. diarrhea. This chapter discusses the pathophysiology of various shock states. A person with sepsis and one or more organ failures fullls the criteria for severe sepsis. Clinical evidence of diminished CO includes a narrow pulse pressure a surrogate marker for stroke volume and cool extremities with delayed capillary rell. Other causes of highCO hypotension include the following liver failure. a brief review of commonly used vasoactive agents is presented. tachypnea. tachycardia. Certainly. and high CO with decreased SVR. The reasons for the institution of endotracheal intubation and mechanical ventilation include acute hypoxemic respiratory failure as well as ventilatory failure. some data have suggested that. an early assessment of the patients airway is mandatory during resuscitation from shock. and. the respiratory muscles receive a very small percentage of the CO. Though one study reported improved outcomes in trauma patients whose volume resuscitation was delayed until denite surgical repair average time to operation. as long as hemoglobin levels remain g/dL. Inadequate perfusion to respiratory muscles in the setting of shock may be another reason for early intubation and mechanical ventilation. this practice may not improve outcomes and perhaps may even worsen outcomes in select subgroups of patients. who can undergo surgical repair quickly. in patients who are in shock with respiratory distress for the reasons listed above. extreme tachypnea breaths/min. Ventilatory failure often occurs as a result of an increased load on the respiratory system. paradoxical abdominal muscle activity. This practice may impair the assessment of the patients circulatory status and potentially delay denitive treatment. muscle paralysis will decrease oxygen demand of the respiratory muscles allowing improved oxygen delivery to other hypoperfused tissue beds. During the initial resuscitation of patients in shock. However. Certainly. Since patients in shock may be obtunded and unable to protect the airway. approximately h. the oxygencarrying capacity of the blood. it is important to remember that oxygen delivery is the product of CO. The goal of early resuscitation is to reestablish adequate perfusion to prevent or minimize endorgan injury.categories may overlap and occur simultaneously eg. or septic and cardiogenic shock. the principles of advanced cardiac life support should be followed. early resuscitation is instituted based on the initial assessment. Blood products should be administered through a blood warmer to minimize hypothermia and subsequent disturbances in coagulation. The transfusion of packed RBCs to anemic patients in order to improve oxygen delivery is physiologically rational. Resuscitation Resuscitation should focus on improving endorgan perfusion. although data from suggest that colloid albumin is not better than crystalloid. including the following inability to speak full sentences. a patient with a reduced CO by clinical assessment with a decreased intravascular and cardiac volume status should receive aggressive IV resuscitation. Patients in shock should be intubated before other procedures are performed. since attention to the airway and breathing may wane during such procedures. a conservative transfusion strategy does not apply to hemorrhaging hypovolemic patients who are in shock. In summary. Acute hypoxemic respiratory failure may occur in cardiogenic shock pulmonary edema as well as septic shock pneumonia or ARDS. aggressive volume resuscitation in patients with reduced intravascular and cardiac volume status is merited in virtually all patients except for torso trauma patients. The question of which type of IV uid to use is controversial. the percentage of CO dedicated to respiratory muscles may increase fold. and indeed may be associated with increased morbidity and mortality. The early administration of vasoactive drugs in hypovolemic patients in order to increase BP is not recommended. however. not simply raising the BP. Endotracheal intubation and mechanical ventilation with sedation. more objective assessments such as echocardiography and/or central venous or pulmonary artery catheterization may be useful. Normally. and decreasing respiratory rate despite an increasing drive to breathe. Shock Kress . This load may present in the form of acute metabolic acidosis often lactic acidosis or decreased compliance of the lungs as a result of pulmonary edema. Early intubation and mechanical ventilation are often required. Mechanical ventilation may relieve the patient of the work of breathing and permit the redistribution of a limited CO to other vital organs... accessory respiratory muscle use. particularly since there are data suggesting that the early resuscitation of shock both septic and cardiogenic may improve survival. If the initial bedside assessment yields equivocal or confounding data.. Such patients often demonstrate signs of respiratory muscle fatigue. if necessary. hypovolemic and septic shock. Accordingly. It is important that aggressive. The initial assessment of a patient in shock as outlined above should take only a few minutes. mental status. impaired diastolic relaxation. If evidence of hypoperfusion persists. impaired CO. When LV systolic function is impaired. This strategy is only rarely necessary and should only be instituted temporarily until volume resuscitation is accomplished. a good study can exclude or conrm tamponade. LV Failure Systolic Dysfunction This is the classic example of cardiogenic shock. Patients present with reduced CO and a resulting increased oxygen extraction ratio by the peripheral tissues. inadequate hemoglobin concentration. patients who remain in shock may benet from therapy with vasoactive drugs. and mental status should be sought. As mentioned above. pulmonary hypertension. increases in afterload. Accordingly. central venous pressure. pulmonary artery catheterization. vasoactive drugs must be started prematurely when volume resuscitation needs are large. or abnormal heart rate and rhythm. A survival benet was seen in patients subjected to this strategy compared to the medical management of cardiogenic shock. Careful and repeated searches for signs of volume overload ie. The specic cause of decreased pump function must be considered. urine output. rather than to an arbitrary BP value. These topics are covered separately in another chapter in the syllabus. and venous oxygen saturation are reasonable end points to target in these patients. Concrete end points such as increased BP and pulse pressure. improved capillary rell. lactic acidosis. and/or inadequate oxygen saturation as likely explanations. valvular dysfunction. By denition. or signicant valve dysfunction. urine output. The absence of a response suggests that the volume challenge may not be adequate. all of which inuence therapy and may supplement or replace the more invasive right heart catheterization. and pulmonary edema should be performed while the resuscitation is ongoing. or echocardiography may be useful. If the objective information obtained by physical examination is unclear or ambiguous. The result is a reduction of CO relative to the increases in preload. one should consider inadequate volume resuscitation. capillary rell and skin temperature. pump failure is seen when CO is inappropriately low despite adequate input in the form of venous return determined by right atrial pressure. Some evidence supports the use of early aggressive revascularization using angioplasty or coronary artery bypass grafting in patients with cardiogenic shock. Echocardiography is a useful adjunct or even replacement to invasive pressure measurements and can be used to distinguish poor ventricular pumping function ACCP Critical Care Medicine Board Review th Edition from hypovolemia. Once intravascular volume has been restored. If the patient remains in shock despite adequate volume resuscitation. Cardiogenic Shock The model of the heart as a pump is useful in considering cardiogenic shock. additional information obtained via invasive monitoring ie. . These drugs should be titrated to endorgan perfusion. the most common reason is acute coronary ischemia. When severe hypotension and hypovolemia are present. It is important to remember that vasoactive drugs may obscure hypovolemic shock by raising BP despite a low CO state. Occasionally. support with vasoactive drugs is appropriate.and arterial oxygen saturation. increased JVP. acute myocardial infarction or ischemia is the most common cause of LV failure leading to shock. Early reassessment of the patient with purported hypovolemic shock after the initial resuscitation is extremely important. Cardiogenic shock is reported to complicate up to of acute myocardial infarctions. this approach is occasionally needed to buy time while volume resuscitation is ongoing. Left ventricular LV and/or right ventricular RV dysfunction may occur due to decreased systolic contractility. Each of these components must be considered and optimized when addressing the resuscitation of patients who are in shock. Attempted compensation for this impaired pump function occurs via the FrankStarling mechanism as well as by uid retention by the kidneys and by increased venous tone mediated by the sympathetic nervous system. The low mixed venous oxygen saturation may exacerbate hypoxemia. especially in patients with pulmonary edema and intrapulmonary shunt physiology. new gallop or extra heart sounds. The maintenance of a normal sinus rhythm is important to maximize ventricular lling. Intraaortic balloon counterpulsation may be used to support the circulation as a bridge to coronary artery revascularization. Medical management includes the use of chronotropic agents to decrease regurgitant lling time and afterloadreducing agents to facilitate forward ow. the careful titration of chronotropic agents to achieve the optimal heart rate that maximizes CO is necessary. usually accompanied by inferior myocardial infarction. Preload should be maintained. Often. A more precise characterization of the circulation can be obtained with the use of pulmonary artery catheterization and/or echocardiography. Medical management includes attempts to establish and maintain sinus rhythm. These conditions generally require acute surgical interventions. Diastolic Dysfunction Increased LV diastolic chamber stiffness and impaired LV lling occur most commonly as a result of myocardial ischemia. sinus bradycardia may be detrimental. this condition may be difcult to treat. Surgical evaluation or palliative valvuloplasty are other important considerations in patients with cardiogenic shock complicated by aortic stenosis. Valvular Dysfunction The management of valvular disease contributing to cardiogenic shock is guided by interventions to counter the specic pathophysiology. which may not tolerate further reductions in afterload via arteriolar dilation. since there is a xed afterload imposed by the aortic stenosis. topics that are discussed in more detail in another chapter of the syllabus. Inotropic support includes the use of agents such as dobutamine. which serve to decrease the obstruction of the LV outow tract during systole. aortic stenosis is managed by efforts to decrease heart rate while maintaining sinus rhythm.including those patients to whom thrombolytic therapy was administered. and afterload must not be reduced. as documented by echocardiography usually best seen in the shortaxis view at the level of the papillary muscles. Elevated JVP in the presence of clear lungs is the classic physical nding seen Shock Kress . and the reader is referred to other chapters of the syllabus for further discussion of this topic. but many times there are only further increases in diastolic pressure with little change in diastolic volume. Although the most common reason for RV failure is concomitant LV failure. which seek to maximize diastolic lling time across the stenotic valve. a very low heart rate eg. this section will discuss the management of isolated RV failure. A detailed discussion on the management of dysrhythmias is beyond the scope of this chapter. RV Failure RV failure resulting in cardiogenic shock is typically associated with increased right atrial pressure and reduced CO. This lesion is managed by the maintenance of preload with volume administration and therapy with negative inotropic and chronotropic agents. Volume administration can be tried. Rarely. This may be accomplished with medications such as nitroprusside or intraaortic balloon counterpulsation as a bridge to mitral valve repair or replacement. Therapy with inotropic agents are usually ineffective. acute obstruction of the mitral valve by left atrial thrombus or myxoma may also result in cardiogenic shock. Last. The aggressive management of tachycardia with volume administration and the cautious use of negative chronotropic agents is a rational approach to therapy. Cardiac Arrhythmias Dysrhythmias may exacerbate shock in critically ill patients. milrinone. Accordingly. Cardiogenic shock due to aortic insufciency may present acutely and may require urgent surgical repair. Mitral regurgitation may occur acutely as a result of ischemic injury to papillary muscles. although LV hypertrophy and restrictive myocardial diseases may also contribute. Mitral stenosis contributing to cardiogenic shock is managed by negative chronotropic agents. Since very little ventricular lling occurs late in diastole in these patients. hypertrophic cardiomyopathy may contribute to cardiogenic shock. RV infarction may result in RV failure. Patients usually present with increased cardiac lling pressures despite a small LV enddiastolic volume. or levosimendan. Aside from the management of acute ischemia. The treatment of cardiogenic shock due to systolic dysfunction includes the judicious administration of intravenous crystalloid if hypovolemia is present. as well as afterload reduction to decrease the percentage of regurgitant blood ow. Other causes of external cardiac compression include tension pneumothorax. blind drainage of the pericardial sac with a needle may be necessary. however. elevated intraabdominal pressure eg. and RV dilation may increase tricuspid regurgitation. inhaled nitric oxide and prostaglandin E may be considered. hypercapnia. socalled abdominal tamponade. some investigators have found volume administration to result in favorable hemodynamics in patients with acute RV failure due to increased RV afterload. This is particularly relevant if resuscitation is delayed and underscores the importance of early aggressive resuscitation in patients with hypovolemic shock. Pulmonary vasodilator therapy eg. with circulatory support again centered around inotropic agents as well as norepinephrine. However. left atrial ie. Medical management of the circulatory pathophysiology of tamponade includes the use of aggressive volume administration as well as inotropic and chronotropic support to increase heart rate and thus maintain forward ow. Echocardiography may be helpful in making this distinction. In patients with hypovolemic shock. Echocardiography reveals pericardial uid with diastolic collapse of the atria and RV.in patients with acute RV infarction. venoconstriction driven by the sympathetic nervous system can no longer maintain mean arterial BP. Recently. although outcome benets in the acute setting are largely lacking. resulting in shock. Decreased Venous Return Hypovolemia is the most common cause of shock due to decreased venous return. large pleural effusions.. The phenomenon of systemic inammation as it . Norepinephrine is more effective at improving RV function and RV coronary perfusion pressure than phenylephrine. pulmonary capillary wedge pressure. The diagnosis is established by the presence of elevated jugular venous pulse with Kussmaul sign and pulsus paradoxus. ACCP Critical Care Medicine Board Review th Edition Pericardial Tamponade and Other Syndromes Causing External Compression of the Heart Cardiac tamponade impairs diastolic lling. Levosimendan is discussed in more detail in the section on Vasoactive Agents. Orthostatic changes in BP and heart rate may be seen early in patients in hypovolemic shock. It is important to distinguish RV infarction from cardiac tamponade. and pneumopericardium. In unstable patients. The treatment of RV failure is complicated. leading to worsening hepatic and renal congestion. ARDS. Hypoxic pulmonary vasoconstriction may be reduced by improving alveolar and mixed venous oxygenation with the administration of supplemental oxygen. Management is focused on treating the underlying physiologic derangement. volume overload is common with RV failure. At a level of approximately loss of intravascular volume. Therapy with dobutamine may be used to increase RV inotropy. and other causes of alveolar hypoxia. and righttoleft septal shift during inspiration. tense ascites. and venoconstriction in response to hypovolemia can compensate for the initial decreases in intravascular volume. and RV diastolic pressures. RV failure as a result of increases in right heart afterload may be due to pulmonary embolism. More aggressive correction of hypercapnia and acidemia may be necessary in patients with acute right heart syndromes. and therapy with norepinephrine may improve RV endocardial perfusion. and metabolic acidosis. Thrombolytic therapy for acute pulmonary embolism complicated by cardiogenic shock has been shown to improve survival and is currently accepted as a recommended strategy. Pulmonary artery catheterization may reveal a decreased CO with equalization of right atrial. Therapy includes careful volume administration to maintain preload. Optimal management is often facilitated by echocardiographic or pulmonary artery catheterdirected therapy. The venous circuit has tremendous capacitance potential. tissue injury especially gut ischemia and the resulting systemic inammation may lead to ongoing shock despite the replacement of volume losses. Treatment is focused at the underlying cause and includes pericardial drainage with a catheter or surgical window in the case of pericardial tamponade. levosimendan the rst of a new class of drugs known as calcium sensitizers has become available. since volume administration may result in worsening RV function by causing mechanical overstretch and/or by reex mechanisms that depress contractility. Sepsis is dened by the presence of SIRS in the presence of known or suspected infection. or tumor invasion increases the resistance to venous return and may occasionally result in shock. A subgroup of patients with septic shock may present with depressed cardiac function. As noted above. Circulating myocardial depressant factors have been identied in some septic patients. A survival benet has been reported in patients with severe sepsis who were treated with recombinant activated protein C. For many years. and a reduced diastolic and mean BP. and corrected with platelet and plasma product transfusions. warm extremities. Septic shock is seen in patients with severe sepsis who manifest shock. viruses. Sepsis is a signicant problem in the care of critically ill patients. Severe sepsis occurs when patients with sepsis accrue one or more organ failures. as described above. Currently. Current estimates suggest that gt . the pathophysiology behind severe sepsis has become better understood. and these numbers are expected to increase in the coming years as the population continues to age and a greater percentage of people who are vulnerable to infection seek medical care. More recently. All of these processes result in decreased venous tone and impaired venous return. sought out. The principal therapy of hypovolemic shock and other forms of shock due to decreased venous return is aggressive volume resuscitation while attempting to reverse the underlying problem driving the pathophysiology. thrombus formation. dilutional thrombocytopenia and reduction in clotting factors should be anticipated. including all bacteria. The obstruction of veins due to compression eg. Septic shock is a common cause of shock due to decreased venous tone and is discussed separately in the next section. Any infectious organism may result in sepsis and septic shock. The prototypical example of loss of venous tone due to drug exposure is anaphylaxis. The optimal hemoglobin concentration is controversial. It is the leading cause of death in noncoronary ICUs in the United States. but the reason that only a small subgroup of patients manifest cardiac depression is not well understood. pregnancy or intraabdominal tumor. as directed by the ndings of a platelet count and coagulation assays. brisk capillary rell. Decades of research have focused on modifying the pathophysiologic responses of the body to severe infection. In patients with hemorrhagic shock. This study was the rst ever to demonstrate a survival benet from a therapy directed at modifying the underlying pathophysiology of Shock Kress . Numerous trials attempting to block a particular inammatory pathway were conducted without any survival benets noted. resulting in decreased CO and BP. After largevolume RBC transfusions. These patients have a widened pulse pressure. and transfusion should be paced by the extent of ongoing blood loss. This has been described in more detail above. and parasites. This unregulated immunologically mediated release of histamine can result in profound shock requiring aggressive catecholamine support epinephrine is the drug of choice. resuscitation with packed RBCs should be performed through a blood warmer. fungi. Such unregulated microvascular coagulation is thought to lead to impaired tissue perfusion and to predispose patients to the multiple organ dysfunction syndrome that is commonly observed in patients with severe sepsis. patients typically present with evidence of high CO assuming hypovolemia has been resuscitated. Other causes of shock due to decreased venous return include severe neurologic damage or drug exposure resulting in hypotension due to a loss of venous tone. patients are affected each year.pertains to shock will be discussed in more detail in the section on Septic Shock. the pathophysiology of severe sepsis is thought to be driven by unregulated inammation via cytokines such as interleukin and tumor necrosis factor coupled to a hypercoagulable state favoring microvascular coagulation and impaired brinolysis. HighCO Hypotension Septic Shock Septic shock is the most extreme presentation of a spectrum of pathophysiologic responses to an infectious insult. Therapy with activated protein C has a salutary impact on all three pathophysiologic derangements noted in patients with severe sepsis. an unregulated proinammatory state was thought to be the driving force behind severe sepsis and septic shock. The mainstays of therapy include volume repletion and vasoactive support with drugs that have venoconstricting properties. This includes early identication of the source of infection with eradication by surgical or percutaneous drainage. if possible. The optimal extent of volume resuscitation is controversial. and further studies are needed before it can be recommended for widespread use. A level of gt g/dL is viewed as an appropriate response. nevertheless. Vasoactive support is directed by the underlying circulatory derangement. The use of lowdose dopamine as a renal protective strategy has been found to be of no benet in preventing acute tubular necrosis in patients with SIRS and acute renal insufciency. More than of patients with severe sepsis will require ventilatory support for respiratory failure. Acute renal failure in patients with septic shock carries a poor prognosis. Some clinicians favor aggressive volume administration. However. The early institution of broadspectrum antibiotic therapy focused on potential pathogens has been shown to improve survival. Some more recent studies in the literature supports the use of an aggressive approach to renal replacement therapy. uid resuscitation. Circulatory failure is supported with aggressive volume administration to correct any component of hypovolemia. Other therapeutic interventions in patients with severe sepsis await further evaluation. Early trials evaluating the utility of highdose corticosteroids in patients with septic shock have failed to demonstrate a survival benet. and the identication of the precipitating cause. pulmonary artery catheterization. this test is performed in the morning with a baseline cortisol level drawn and then g of ACTH administered IV. Myxedema presenting as shock should be treated with the administration of IV thyroid hormone. Furthermore. which may complicate aggressive thyroid replacement. It is reasonable to consider testing all patients who present with septic or other occult reasons for shock with an ACTH stimulation test. a multicenter trial found that a combination of lowdose hydrocortisone and udrocortisone ACCP Critical Care Medicine Board Review th Edition improved survival in patients with septic shock who had relative adrenal insufciency. dexamethasone which does not crossreact with the cortisol laboratory assay should be administered while the ACTH stimulation test is being performed. with a survival benet demonstrated with daily hemodialysis compared to alternateday hemodialysis. Some data suggest that the response to an adrenocorticotropic hormone ACTH stimulation test may have important prognostic implications. Other Types of Shock Adrenal insufciency is often viewed as a rare occurrence in critically patients. which should be instituted early for the reasons outlined earlier in this chapter. Treatment includes aggressive .severe sepsis. Severe hypothyroidism or hyperthyroidism may result in shock. Pheochromocytoma often presents with a paradoxical hypertension despite a state of shock and impaired tissue perfusion. Neurogenic shock typically occurs as a result of severe injury to the CNS. Corticosteroid therapy remains controversial. One should watch carefully for myocardial ischemia and/or infarction. while others favor the earlier use of vasoactive drugs ie. The increase in afterload caused by endogenous catecholamines may also precipitate a shocklike state. Because of its anticoagulant properties. and echocardiography should be used early to guide therapy. keeping patients dry. propranolol. adrenal insufciency may not be as rare as previously thought. Thyroid storm requires urgent therapy with Lugol solution. one study has reported a incidence of blunted adrenal response to ACTH in patients with septic shock. Conventionally.. there was a small but signicant increase in bleeding complications associated with activated protein C. This number may be a generous estimate since the parameters for dening adrenal insufciency have not been universally agreed on. propylthiouracil. Trials are ongoing to attempt to better answer this difcult question. Thirtyminute and min cortisol levels are then drawn. If adrenal insufciency is suspected. Objective monitoring using central venous catheterization.. The loss of sympathetic tone results in venodilation and venous blood pooling. steroids. Intravascular volume depletion is masked by extreme venoconstriction from therapy with endogenous catecholamines in patients with pheochromocytoma. The mainstay of therapy for septic shock is aggressive supportive care. . It appears to enhance CO without increasing myocardial oxygen consumption.. Classically. hypotension and new atrial arrhythmias were found to occur more frequently in patients who received milrinone compared to placebo. the day mortality rate. which increases the force and rate of contraction. Levosimendan Levosimendan is the rst clinically available agent from a new class of drugs known as calcium sensitizers. the inhospital mortality rate. These drugs may improve diastolic relaxation or at least are neutral with regard to diastolic function. Because data are accumulating that report the ill effects of dopamine in patients with shock. however. Preliminary studies have suggested that levosimendan may improve RV mechanical efciency. It has potent vasodilating properties that decrease both systemic and pulmonary vascular resistance. with other agents such as norepinephrine being more widely used see next section. A prospective observational cohort study found a signicant reduction in mortality when compared to therapy with dopamine and/ or epinephrine in patients with septic shock. there is evidence that dopamine may impair mesenteric perfusion to a greater degree than norepinephrine. Norepinephrine Norepinephrine stimulates receptors as well as receptors. this agent has fallen out of favor in the view of many clinicians. This notion has been disproven. This reduction in afterload may benet patients with LV systolic dysfunction. Indeed. The end result is typically an increase in CO with diminished SVR.volume replacement as well as adrenergic and adrenergic blockades. One study of patients with acute exacerbations of congestive heart failure did not demonstrate a benet with regard to the number of days hospitalized for cardiovascular causes. and coronary arteries. Vasoactive Agents The choice of vasoactive medications should be based on the underlying pathophysiology of the circulation as gleaned by the physical examination and supplemented by more sophisticated measurements. Levosimendan causes the dilation of systemic. Calcium sensitizers improve myocardial contractility without signicantly increasing intracellular calcium levels. The role of levosimendan in the management of shock or RV failure has not been studied extensively. Levosimendan increases the sensitivity of the cardiac Phenylephrine Phenylephrine is a pure agonist. Dopamine is purported to have varying physiologic effects at different doses. lowdose dopamine to g/kg/min is thought to stimulate dopaminergic receptors and to increase renal and mesenteric blood ow. Dopamine Dobutamine Dobutamine is a powerful inotrope.. which results in venous and arteriolar constriction. Milrinone Milrinone is an inotropic agent that induces a positive inotropic state via phosphodiesterase inhibition. Data are now accumulating that suggest that norepinephrine may be a preferred drug in the treatment of septic shock and other vasodilatory types of shock.. Studies have shown levosimendan to be superior to placebo and dobutamine in patients with chronic congestive heart failure. A search for the location of the pheochromocytoma with subsequent surgical removal is indicated. myolaments to calcium during systole. or the composite incidence of death or hospital readmission. It Shock Kress . there are no outcome studies to guide clinicians with regard to the use of a particular agent in the management of shock. which stimulates both and receptors. It appears to have a lesser propensity to cause renal injury and provides a more reliable increase in BP compared to dopamine. Rather. pulmonary. It is sobering to realize that despite the widespread use of these agents for many decades. often elicits a reex bradycardia that is mediated via baroreceptors. This may prove useful in patients with tachydysrhythmias accompanied by hypotension. In a prospective observational study of patients with septic shock, phenylephrine was found to increase BP, SVR, and cardiac index when added to lowdose dopamine or dobutamine after volume resuscitation. There is a theoretical concern that agonism may precipitate myocardial ischemia, though there are few objective data to support or refute this concern. Epinephrine Epinephrine has both agonist as well as agonist properties. It has potent inotropic as well as vasoconstricting properties. It appears to have a higher propensity toward precipitating mesenteric ischemia, a property that limits its utility as a rstline agent for the management of shock, regardless of the underlying etiology. Vasopressin The use of vasopressin as a vasoactive agent has increased tremendously in the last few years. Patients who present with septic shock or latephase hemorrhagic shock have been shown to have a relative deciency of vasopressin. A study found that patients with septic shock demonstrate an increase in BP and urine output without evidence of impaired cardiac, mesenteric, or skin perfusion when treated with lowdose ie, mU/min vasopressin. The exact role of vasopressin in the treatment of patients who are in various shock states requires further investigation. References . Ely EW, Smith AC, Chiles C, et al. Radiologic determination of intravascular volume status using portable, digital chest radiography a prospective investigation in patients. Crit Care Med . Bone RC, Balk RA, Cerra FB, et al. Denitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis the ACCP/SCCM Consensus Conference Committee American College of Chest Physicians/Society of Critical Care Medicine. Chest . Rivers E, Nguyen B, Havstad S, et al. Early goal directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med . Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization in acute myocardial infarction complicated by cardiogenic shock SHOCK Investigators should we emergently revascularize occluded coronaries for cardiogenic shock. N Engl J Med . Rochester DF, PradelGuena M. Measurement of diaphragmatic blood ow in dogs from xenon clearance. J Appl Physiol . Hussain SNA, Roussos C. Distribution of respiratory muscle and organ blood ow during endotoxic shock in dogs. J Appl Physiol . Robertson CH Jr, Foster GH, Johnson RL Jr. The relationship of respiratory failure to the oxygen consumption of, lactate production by, and distribution of blood ow among respiratory muscles during increasing inspiratory resistance. J Clin Invest . Hall JB, Wood LDH. Liberation of the patient from mechanical ventilation. JAMA . Cochrane Injuries Group Albumin Reviewers. Human albumin administration in critically ill patients systematic review of randomised controlled trials. BMJ . Finfer S, Bellomo R, Boyce N, et al. A comparison of albumin and saline for uid resuscitation in the intensive care unit. N Engl J Med . Bickell WH, Wall MJ Jr, Pepe PE, et al. Immediate versus delayed uid resuscitation for hypotensive patients with penetrating torso injuries. N Engl J Med . Hebert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med . Goldberg RJ, Gore JM, Alpert JS, et al. Cardiogenic shock after acute myocardial infarction incidence and mortality from a communitywide perspective, to . N Engl J Med . Mebazaa A, Karpati P, Renaud E, et al. Acute right ventricular failure from pathophysiology to new treatments. Intensive Care Med ACCP Critical Care Medicine Board Review th Edition . DellItalia LJ, Starling MR, Blumhardt R, et al. Comparative effects of volume loading, dobutamine and nitroprusside in patients with predominant right ventricular infarction. Circulation . Hirsch LJ, Rooney MW, Wat SS, et al. Norepinephrine and phenylephrine effects on right ventricular function in experimental canine pulmonary embolism. Chest . Layish DT, Tapson VF. Pharmacologic hemodynamic support in massive pulmonary embolism. Chest . Hirsch LJ, Rooney MW, Wat SS, et al. Norepinephrine and phenylephrine effects on right ventricular function in experimental canine pulmonary embolism. Chest . Ghignone M, Girling L, Prewitt RM. Volume expansion versus norepinephrine in treatment of a low cardiac output complicating an acute increase in right ventricular afterload in dogs. Anesthesiology . Mathru M, Venus B, Smith R, et al. Treatment of low cardiac output complicating acute pulmonary hypertension in normovolemic goats. Crit Care Med . JerjesSanchez C, RamirezRivera A, Gareia M de L, et al. Streptokinase and heparin versus heparin alone in massive pulmonary embolism a randomized controlled trial. J Thromb Thrombolysis . Arcasoy SM, Kreit JW. Thrombolytic therapy of pulmonary embolism a comprehensive review of current evidence. Chest . Parker MM, Shelhamer JH, Bacharach SL, et al. Profound but reversible myocardial depression in patients with septic shock. Ann Intern Med . Schremmer B, Dhainault J. Heart failure in septic shock effects of inotropic support. Crit Care Med SS . Parrillo JE, Burch C, Shelhamer JH, et al. A circulating myocardial depressant substance in humans with septic shock. J Clin Invest . Sands KE, Bates DW, Lanken PN, et al. Epidemiology of sepsis syndrome in eight academic medical centers. JAMA . Angus DC, LindeZwirble WT, Lidicker J, et al. Epidemiology of severe sepsis in the United States analysis of incidence, outcome, and associated costs of care. Crit Care Med . Bone RC. Why sepsis trials fail. JAMA . Kidokoro A, Iba T, Fukunaga M, et al. Alterations in coagulation and brinolysis during sepsis. Shock . Bernard GR, Vincent JL, Laterre PF. Recombinant human protein C Worldwide Evaluation in Severe Sepsis PROWESS study group efcacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med . Ibrahim EH, Sherman G, Ward S, et al. The inuence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. Chest . Kollef MH, Sherman G, Ward S, et al. Inadequate antimicrobial treatment of infections a risk factor for hospital mortality among critically ill patients. Chest . Schif H, Lang SM, Fischer R. Daily hemodialysis and the outcome of acute renal failure. N Engl J Med . Bellomo R, Chapman M, Finfer S, et al. Lowdose dopamine in patients with early renal dysfunction a placebocontrolled randomised trial Australian and New Zealand Intensive Care Society ANZICS Clinical Trials Group. Lancet . Bone RC, Fisher CJ, Clemmer TP, et al. A controlled clinical trial of highdose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med . Veterans Administration Systemic Sepsis Cooperative Study Group. Effect of highdose glucocorticoid therapy on mortality in patients with clinical signs of systemic sepsis. N Engl J Med . Annane D, Sebille V, Troche G, et al. A level prognostic classication in septic shock based on cortisol levels and cortisol response to corticotropin. JAMA . Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and udrocortisone on mortality in patients with septic shock. JAMA . Zaloga GP. Sepsisinduced adrenal deciency syndrome. Crit Care Med . Cuffe MS, Califf RM, Adams KF, et al. Shortterm intravenous milrinone for acute exacerbation of chronic heart failure a randomized controlled trial. JAMA Shock Kress . Haikala H, Nissinen E, Etemadzadeh E, et al. Troponin Cmediated calcium sensitization induced by levosimendan does not impair relaxation. J Cardiovasc Pharmacol . Ukkonen H, Saraste M, Akkila J, et al. Myocardial efciency during levosimendan infusion in congestive heart failure. Clin Pharmacol Ther . Yokoshiki H, Katsube Y, Sunagawa M, et al. Levosimendan, a novel calcium sensitizer, activates the glibenclamidesensitive K channel in rat arterial myocytes. Eur J Pharmacol . Slawsky MT, Colucci WS, Gottlieb SS. Acute hemodynamic and clinical effects of levosimendan in patients with severe heart failure. Circulation . Follath F, Cleland JG, Just H, et al. Efcacy and safety of intravenous levosimendan compared with dobutamine in severe lowoutput heart failure the LIDO study a randomised doubleblind trial. Lancet . Moiseyev VS, Poder P, Andrejevs N, et al. Safety and efcacy of a novel calcium sensitizer, levosimendan, in patients with left ventricular failure due to an acute myocardial infarction a randomized, placebocontrolled, doubleblind study RUSSLAN. Eur Heart J . Hannemann L, Reinhart K, Grenzer O, et al. Comparison of dopamine to dobutamine and norepinephrine for oxygen delivery and uptake in septic shock. Crit Care Med . Marik PE, Mohedin M. The contrasting effects of dopamine and norepinephrine on systemic and splanchnic oxygen utilization in hyperdynamic sepsis. JAMA . Nasraway SA. Norepinephrine no more leave em dead Crit Care Med . Desjars P, Pinaud M, Bugnon D, et al. Norepinephrine therapy has no deleterious renal effects in human septic shock. Crit Care Med . Martin C, Papazian L, Perrin G, et al. Norepinephrine or dopamine for the treatment of hyperdynamic septic shock Chest . Martin C, Viviand X, Leone M, Thirion X. Effect of norepinephrine on the outcome of septic shock. Crit Care Med . Gregory JS, Bonglio MF, Dasta JF, et al. Experience with phenylephrine as a component of the pharmacologic support of septic shock. Crit Care Med . Levy B, Bollaert PE, Charpentier C, et al. Comparison of norepinephrine and dobutamine to epinephrine for hemodynamics, lactate metabolism, and gastric tonometric variables in septic shock a prospective, randomized study. Intensive Care Med . Tsuneyoshi I, Yamada H, Kakihana Y, et al. Hemodynamic and metabolic effects of lowdose vasopressin infusions in vasodilatory septic shock. Crit Care Med ACCP Critical Care Medicine Board Review th Edition Notes Shock Kress Mechanical Ventilation Gregory A. Schmidt, MD, FCCP Objectives Provide a rationale for distinguishing two aspects of mechanical ventilation oxygen and ventilation Review new evidence regarding the role of positive endexpiratory pressure in the treatment of patients with acute lung injury ALI/ARDS Describe the role of pressure and ow waveforms in determining respiratory mechanics Recommend diseasespecic ventilator strategies aimed at reducing the adverse consequences of mechanical ventilation Review new information regarding lungprotective ventilation and effective strategies in patients with ALI and ARDS Address the role of noninvasive ventilation Discuss the complications of mechanical ventilation Key words acute lung injury ARDS assistcontrol ventilation COPD inverse ratio ventilation lungprotective ventilation mechanical ventilation noninvasive ventilation pressure control pressure support status asthmaticus synchronized intermittent mandatory ventilation tidal volume ventilatorinduced lung injury This chapter offers an approach in which two aspects of mechanical ventilation, oxygenation largely determined by fraction of inspired oxygen Fio and positive endexpiratory pressure PEEP and ventilation depending mostly on mode, rate, and tidal volume Vt or set inspiratory pressure Pinsp are considered separately. Then, the ventilator is used as a probe of the patients respiratory system mechanical derangements, and ventilator settings are tailored to the patients mechanical and gas exchange abnormalities. This facilitates early stabilization of the patient on the ventilator in such a way as to optimize carbon dioxide removal and oxygen delivery within the limits of abnormal neuromuscular function, lung mechanics, and gas exchange. The impact of new information regarding ventilatorinduced lung injury VILI on current practice will be covered, as well as the potential roles of highfrequency ventilation HFV, prone positioning, and recruitment maneuvers. The fundamental purpose of mechanical ventilation is to assist in the elimination of carbon dioxide and the uptake of adequate oxygen while the patient is unable to do so or should not be allowed to do so. Such patients fall into the following two main groups patients in whom full rest of the respiratory muscles is indicated eg, during shock severe, acute pulmonary derangement or deep sedation or anesthesia and patients in whom some degree of respiratory muscle use is desired eg, to strengthen or improve the coordination of the respiratory muscles, to assess the ability of the patient to sustain the work of breathing, or to begin spontaneous ventilation. It is important for the intensivist to be explicit about whether the respiratory muscles should be rested or exercised because the details of ventilation ie, mode and settings usually follow logically from this fundamental point. For example, in a patient who is in profound shock, the ventilator should be set to fully take over the work of breathing eg, using volume assistcontrol ventilation ACV mode while the ow and pressure waveforms are examined to determine whether this goal has been met. Using the Ventilator To Control Oxygenation The ventilator settings most concerned with oxygenation are the Fio and PEEP. Generally, mode, Vt, rate, and other settings have only very modest effects on Pao. For example, in the ARDS Network Vt trial, use of the vs mL/kg predicted body weight was associated with a small but real decrement in the Pao/Fio ratio vs , respectively. Oxygen is clearly toxic in high concentrations, likely due to the effects of reactive oxygen species on many biological systems. The threshold for toxicity is uncertain, especially in the injured lung. Generally, an Fio of . is considered nontoxic, while higher fractions are avoided when possible. There is some experimental evidence ACCP Critical Care Medicine Board Review th Edition that the injured lung may be more resistant to oxygeninduced injury. Given the uncertainties in this area, most clinicians strive to limit exposure to concentrations in excess of . to less than h, using PEEP, diuresis, positional maneuvers, or inhaled vasodilators. Evidence arose years ago that PEEP could protect the injured lung. Repeated recruitment and derecruitment was postulated to amplify lung injury. By keeping some portion of the lung open at endexpiration, PEEP was postulated to reduce this aspect of VILI. In a clinical study performed more than a decade ago, Amato and colleagues used a higher than usual level of PEEP set cm HO above the Pinsp at which the slope of the volumepressure relationship steepened, combined with low Vts, in an openlung approach, which improved outcomes in ARDS patients. The two individual components of this ventilatory approach ie, lower Vt and higher PEEP were investigated subsequently by the ARDS Network in separate trials. The benecial effect of low Vt was conrmed in the ARMA trial. The role of PEEP was claried subsequently in the ALVEOLI study. In this study, various combinations of Fio and PEEP were allowed, so that in one group the PEEP was set higher than in the other . vs . cm HO on average, respectively. There was no signicant difference in outcome, suggesting that the lower PEEP was sufcient to adequately protect the lung or that PEEP is simply not important in the treatment of VILI. Given these ndings, PEEP should be set using the ARDS Network table of Fio and PEEP, or, similarly, the least PEEP approach, in which PEEP is set at the lowest value that allows adequate saturation of hemoglobin arterial oxygen saturation, . on a nontoxic Fio, should be used. Some lung lesions are not responsive to PEEP some lesions may even be worsened by increasing PEEP, so the effect of PEEP should always be judged before further adjustments are made. When PEEP is ineffective and oxyhemoglobin saturation is unacceptable, additional approaches such as prone positioning may be useful. By recruiting lung, PEEP raises the pleural pressure, a feature that could have hemodynamic consequences. Most often, however, the effects are modest, probably because if the lung gets very much bigger with PEEP lots of recruitment, not much PEEP is needed. Another concern regarding PEEP has been the potential to cause pneumothorax. However, Palv is determined largely by Vt, not PEEP. The current use of lungprotective Vts, combined with the regular assessment of plateau airway pressure Pplat see section on Modes of Mechanical Ventilation, makes this effect of PEEP of little consequence. Using the Ventilator To Effect Carbon Dioxide Elimination The Paco depends on total body carbon dioxide production and alveolar ventilation. The ventilator can be used to set minute ventilation, the sum of alveolar ventilation and dead space ventilation. Various ventilatory modes control minute ventilation by delivering a Vt either directly, as in volumepreset modes, or indirectly, as in pressurepreset modes. Modes of Mechanical Ventilation Technologic innovations have provided a plethora of differing modes by which a patient can be mechanically ventilated. Various modes have been developed with the hope of improving gas exchange, patient comfort, or speed of return to spontaneous ventilation. Aside from minor subtleties, however, nearly all modes allow full rest of the patient, on the one hand, or substantial exercise on the other. Thus, in the great majority of patients, the choice of mode is merely a matter of patient or physician preference. Noninvasive ventilation NIV should be considered before intubation and ventilation in many patients who are hemodynamically stable and do not require an articial airway, especially those with acuteonchronic respiratory failure, postoperative respiratory failure, cardiogenic pulmonary edema, or acute respiratory failure complicating severe immunosuppression. During volumepreset ventilation and assuming a passive patient, the Pplat is determined by the Vt and the static compliance of the respiratory system Crs Pplat Vt/Crs PEEP where PEEP also includes autoPEEP. Mechanical Ventilation Schmidt On the other hand, in pressurepreset modes a xed Pinsp is applied to the respiratory system, whatever the resulting Vt. However, the Vt is predictable again, assuming a passive patient when the Crs is known Vt Pinsp PEEP Crs assuming time for equilibration between Pinsp and Palv. Thus, a patient with a Crs of mL/cm HO ventilated on ACV at a Vt of mL with no PEEP or autoPEEP will have a Pplat of about cm HO, while the same patient ventilated on pressurecontrol ventilation PCV mode at cm HO will have a Vt of about mL. Thus, while physicians comfort level with volumepreset and pressurepreset modes may be very different, the modes can be similar as they are tied to each other through the patients Crs. A potential advantage of pressurepreset ventilation is greater physician control over the peak airway opening pressure Ppeak since Ppeak Pinsp and the peak Palv, which could lessen the incidence of VILI. However, this same reduction in volutrauma risk should be attainable during volumepreset ventilation if a Vt appropriate to the lung derangement is chosen. Indeed, the ARDS Network ARMA trial, which demonstrated a mortality reduction in the lowVt group, used ACV and a Vt of mL/kg predicted body weight. Pressurepreset modes could make such a lungprotection strategy easier to carry out by dispensing with the need to repeatedly determine Pplat and periodically adjust the Vt. During the use of pressurepreset modes, the patient also has greater control over inspiratory ow rate, and therefore potentially increased comfort. Several features of pressurepreset modes have raised concern that lung protection cannot be assured. Most importantly, a safe level of maximal Palv is not known. Moreover, unless the patient is fully passive, the transpulmonary pressure cannot be controlled using pressurepreset modes and is not even known. A nal limitation is that pressurepreset modes do not allow ready determination of the respiratory system mechanical properties. In the following descriptions, each mode is rst illustrated for a passive patient, such as following muscle paralysis, then for the more common situation in which the patient plays an active role in ventilation. On some ventilators, Vt can be ACCP Critical Care Medicine Board Review th Edition selected by the physician or respiratory therapist, while on others a minute ventilation and respiratory rate f are chosen, secondarily determining the Vt. Similarly, on some machines an inspiratory ow rate is selected, while on others ow depends on the ratio of inspiratory time Ti to total respiratory cycle time and f, or an inspiratory/expiratory IE ratio and f. Conventional Modes of Ventilation Volume ACV Volume ACV was found to be the most commonly used mode in an international survey of mechanical ventilation. Among its advantages are that it was the mode used in the ARMA trial demonstrating reduced mortality in patients with acute lung injury ALI and ARDS, and that respiratory mechanics can be measured readily. Passive Patient The set parameters of the ACV mode are the inspiratory ow rate, f, and Vt. The ventilator delivers f equal breaths per minute, each of the set Vt. Vt and ow determine the Ti, expiratory time Te, and the IE ratio. Pplat is related to Vt, the compliance of the respiratory system, and PEEP, while the difference between Ppeak and Pplat includes contributions from ow and inspiratory resistance. Active Patient The patient has the ability to trigger extra breaths by exerting an inspiratory effort exceeding the preset trigger sensitivity, each at the set Vt and ow, and to thereby change Ti, Te, and IE ratio, and to potentially create or increase autoPEEP. Typically, each patient will display a preferred rate for a given Vt and will trigger all breaths when the controlled ventilator f is set a few breaths per minute below the patients rate in this way, the control rate serves as an adequate support should the patient stop initiating breaths. When high inspiratory effort continues during the ventilatordelivered breath, the patient may trigger a second, superimposed stacked breath rarely a third as well. Patient effort can be increased if the goal is to exercise the patient by increasing the magnitude of the trigger or by lowering Vt which increases the rate of assisting. Lowering f at the same Vt generally has no effect on work of breathing when the patient is initiating all breaths. Synchronized Intermittent Mandatory Ventilation In the passive patient, synchronized intermittent mandatory ventilation SIMV cannot be distinguished from controlled ventilation in the ACV mode. Ventilation is determined by the mandatory f and Vt. However, if the patient is not truly passive, he may perform respiratory work during the mandatory breaths. More to the point of the SIMV mode, the patient can trigger additional breaths by lowering the airway opening pressure Pao below the trigger threshold. If this triggering effort comes in a brief, dened interval before the next mandatory breath is due, the ventilator will deliver the mandatory breath ahead of schedule in order to synchronize with the patients inspiratory effort. If a breath is initiated outside of the synchronization window, Vt, ow, and IE ratio are determined by patient effort and respiratory system mechanics, not by ventilator settings. The spontaneous breaths tend to be of small volume and are highly variable from breath to breath. The SIMV mode has historically been used to gradually augment the patients work of breathing by lowering the mandatory breath f, but SIMV has been shown to prolong weaning., Although this mode continues to be used widely, there is little rationale for it, and the use of SIMV is falling out of favor. Thus, the maximal inspiratory Palv is generally less than the set Pinsp on the ventilator and the endexpiratory pressure exceeds the set expiratory pressure ie, there is autoPEEP. The active patient can trigger additional breaths by reducing the Pao below the triggering threshold, raising the IE ratio. The inspiratory reduction in pleural pressure combines with the ventilator Pinsp to augment the transpulmonary pressure and the Vt. This point has led many intensivists to be skeptical regarding the ability of PCV to assure lungprotective Vts in patients with ALI and ARDS. Because Ti is generally set by the physician, care must be taken to discern the patients neural Ti from the waveform display and adjust the ventilator accordingly otherwise, additional sedation might be necessary. PressureSupport Ventilation The patient must trigger the ventilator in order to activate this mode, so pressure support is not applied to passive patients. Ventilation is determined by Pinsp, patientdetermined f, patient effort, and the respiratory mechanics. Once a breath is triggered, the ventilator attempts to maintain Pao at the physiciandetermined Pinsp, using whatever ow is necessary to achieve this. Eventually, ow begins to fall as a result of either the cessation of the patients inspiratory effort or the increasing elastic recoil of the respiratory system as Vt rises. The ventilator will maintain a constant Pinsp until inspiratory ow falls by an arbitrary amount eg, to of initial ow or below an absolute ow rate. Since patients respiratory system time constants vary widely so that the time for ow to fall to varies widely, many patients have to work actively to turn off the Pinsp, raising the work of breathing. Some ventilators allow the intensivist to adjust the threshold for turning off the expiratory ow, allowing the ventilator to be tailored to the respiratory mechanics. Especially in patients with exacerbations of COPD, a threshold well is often necessary to minimize this unintended expiratory work. During pressuresupport ventilation PSV, the work of breathing can be increased by lowering Pinsp or making the trigger less sensitive, and can inadvertently increase if respiratory system mechanics change, despite no change in ventilator settings. Respiratory system mechanical Mechanical Ventilation Schmidt PCV In the passive patient, ventilation is determined by f, the Pinsp increment ie, Pinsp PEEP, IE ratio, and the time constant of the patients respiratory system. In patients without severe obstruction ie, the time constant not elevated given a sufciently long Ti, there is equilibration between the ventilatordetermined Pinsp and alveolar pressure Palv so that inspiratory ow ceases. In this situation, Vt is highly predictable, based on Pinsp Palv, and the mechanical properties of the respiratory system Crs. In the presence of severe obstruction or if the Ti is too short to allow equilibration between ventilator and alveoli, Vt will fall below that predicted based on Pinsp and Crs. It is typically the case during PCV that alveolar and ventilator pressures do not equilibrate either at endinspiration or at endexpiration. parameters cannot be determined readily on this mode because the ventilator and patient contributions to Vt and ow are not represented by Pao accordingly, these important measurements of Pplat, Ppeak Pplat, and autoPEEP are measured during a brief, daily switch from PSV to volumepreset ventilation. A potential advantage of PSV is improved patient comfort and, for patients with very high drive, reduced work of breathing compared with volumepreset modes. the Vt with a physicianset Vt and automatically and gradually adjusts the Pinsp of subsequent breaths in order to deliver the desired Vt. A downside of PRVC is that as patient effort increases, the ventilator reduces support. Proponents of PRVC argue that this mode provides the benets of pressurepreset modes, while at the same time guaranteeing Vt. Whether this guarantee makes the mode better or worse for the patient is debated. VSV Mixed Modes Some ventilators allow combinations of modes, most commonly SIMV plus PSV. There is little reason to use such a hybrid mode, although some physicians use the SIMV as a means to add sighs to PSV, an option that is not otherwise generally available. Because SIMV plus PSV guarantees some backup minute ventilation which PSV does not, this mode combination may have value in occasional patients who are at high risk for abrupt deterioration in central drive. VSV is a pressurepreset mode in which Pinsp is automatically varied to gradually bring Vt in line with the desired Vt over several breaths it differs from PRVC in that the Ti is not set but, rather, depends on patient effort, as in PSV. It is unknown whether this mode speeds or impedes weaning. VolumeAssured Pressure Support This mode begins as PSV, but, if a desired Vt is not met, the ventilator switches to ACV within the same breath in order to guarantee Vt. As with many dualcontrol modes, the physician delegates decision making to the ventilator. Complex adjustments and their potentially detrimental effects on the patient may come into play at any time of day or night, depending on changes in the mechanical properties of the respiratory system or changes in the patients level of consciousness, comfort, or neuromuscular competence. DualControl Modes The sophisticated microprocessors included with modern ventilators allow remarkably complex modes of ventilation. These modes typically try to meld the best features of the volumepreset and pressurepreset modes. Some cause a switch of modes between breaths eg, pressureregulated volume control PRVC volume support ventilation VSV or within a breath eg, volumeassured pressure support. In general, these modes are complex, and their effects may vary greatly depending on the details of the patients effort. None have been shown to be safer or more useful than more conventional modes. The greatest problem with such newer modes is that they are very complex, the algorithm describing their function is not usually understood by practitioners, and they change during a breath, or from breath to breath, depending on patient effort, sometimes in ways that can provoke unanticipated effects. Choosing Mode and Settings If full rest of the respiratory muscles is desired, it is incumbent on the physician to assure that this is indeed achieved. Although some patients are fully passive while being ventilated eg, patients with deep sedation or therapeutic paralysis, some forms of coma, metabolic alkalosis, or sleepdisordered breathing, most patients will make active respiratory efforts, even on volume ACV, at times performing extraordinary amounts of work. Unintended patient effort can be difcult to recognize but, aside from obvious patient effort, may be signaled by an inspiratory fall in intrathoracic pressure as noted on a central venous or pulmonary artery pressure tracing, or with an PRVC This is a pressurepreset mode with a set Ti ie, it is time cycled in which the ventilator compares ACCP Critical Care Medicine Board Review th Edition esophageal balloon or by triggering of the ventilator. Recognizing patient effort has been greatly aided by the provision of realtime displays of ow and pressure waveforms. Using waveforms, it is easiest to gather information regarding the patientventilator interaction when patients are ventilated with a volumepreset mode ie, ACV or SIMV. Still, some useful information can be gleaned from waveforms during pressurepreset ventilation ie, PSV and PCV. The rst step is to seek signs of inspiratory effort in the pressure tracing. In volumepreset modes, the signs of persistent effort include the presence of triggering, concavity during inspiration, and a variable Ppeak. When the goal of ventilation is to rest the respiratory muscles, ventilator adjustments, psychological measures, and pharmacologic sedation all may be effective. Ventilator strategies to reduce the patients work of breathing include increasing the minute ventilation to reduce Pco although this may run counter to other goals of ventilation, especially in patients with ARDS or severe obstruction, increasing the inspiratory ow rate, and changing the mode to pressurepreset ventilation ie, PSV or PCV. Only rarely is therapeutic paralysis required to achieve ventilatory goals. The next step is to determine whether the patient has signicant airow obstruction. This can be inferred by inserting a brief endinspiratory pause, then determining the difference between Ppeak and Pplat. Alternatively, one can examine the expiratory ow waveform, seeking lowow and prolonged expiration, signs that are present regardless of the mode of ventilation eg, ACV, SIMV, PSV, or PCV. Bronchodilator therapy can be assessed by noting whether expiratory ow increases, the Te shortens, or there is a reduction in Ppeak, Pplat, or autoPEEP. Finally, one should ensure that the patient and ventilator are synchronized ie, that each attempt by the patient to trigger the ventilator generates a breath. The most common situation in which the patient fails to trigger breaths occurs in patients with severe obstruction when autoPEEP is present. This is recognized at the bedside when the patient makes obvious efforts that fail to produce a breath. Using waveforms, these ineffective efforts cause a temporary slowing of expiratory ow, sometimes halting it completely. Triggered Sensitivity In the ACV, SIMV, and pressuresupport modes, the patient must lower the Pao below a preset threshold in order to trigger the ventilator. In most situations, this is straightforward. The more negative the sensitivity, the greater the effort demanded of the patient. This can be used intentionally to increase the work of breathing when the goal is to strengthen the inspiratory muscles. When autoPEEP is present, however, the patient must lower Palv by the autoPEEP amount in order to have any impact on Pao, then lower it further by the trigger amount to initiate a breath. This can dramatically increase the required effort for breath initiation. Flowtriggering systems or owby systems have been used to further reduce the work of triggering the ventilator. In contrast to the usual approach in which the patient must open a demand valve in order to receive ventilatory assistance, continuousow systems maintain a continuous high ow, then further augment ow when the patient initiates a breath. These systems can reduce the work of breathing slightly below that present when using conventional demand valves, but do not solve the problem of triggering when autoPEEP is present. Unconventional Ventilatory Modes InverseRatio Ventilation Inverseratio ventilation IRV is dened as a mode in which the IE ratio is . There are two general ways to apply IRV, as follows pressurecontrolled IRV PCIRV, in which a preset airway pressure is delivered for a xed period of time at an IE ratio or volumecontrolled IRV VCIRV, in which a Vt is delivered at a slow or decelerating inspiratory ow rate or an endinspiratory pause is inserted to yield an IE . For PCIRV, the physician must specify the inspiratory airway pressure, f, and IE ratio, while Vt and ow prole are determined by respiratory system impedance, as discussed for PCV above. Commonly, the initial Pinsp is to cm HO or to cm HO above the PEEP, f is breaths/min, and the IE is to . For VCIRV, the operator selects a Vt, f, ow typically a low value, ow prole, and, possibly, an Mechanical Ventilation Schmidt endinspiratory pause. The chosen values result in an IE ratio and as high as . Compared with conventional modes of ventilation, lung oxygen exchange is often improved with IRV, owing to increased mean Palv and volume consequent to the longer time above functional residual capacity, or due to the creation of autoPEEP. It is remotely possible that IRV causes better ventilation of lung units with long time constants, but these are so short in healthy lungs and shorter in patients with acute hypoxemic respiratory failure that such redistribution is unlikely to occur with slower ow, and could not reduce shunt even if it did. Because autoPEEP is a common consequence of IRV, serial determination of its magnitude is essential for the safe use of this mode. Both PCIRV and VCIRV generally require heavy sedation of the patient with or without muscle paralysis. where V is volume, and f and f are selectable functions of volume elastic assist and ow resistive assist, values that can be estimated from the patients respiratory mechanics. The potential advantages of this method are greater patient comfort, lower Ppeak, and enhancement of the patients reex and behavioral respiratory control mechanisms. HFV Several modes of ventilation have in common the use of Vt smaller than the dead space volume. Gas exchange does not occur through convection as during conventional ventilation, but through bulk ow, Taylor diffusion, molecular diffusion, nonconvective mixing, and possibly other mechanisms. These modes include highfrequency oscillatory ventilation and highfrequency jet ventilation. The theoretical benets of HFV include a lower risk of barotrauma as a result of smaller tidal excursions, improved gas exchange through a more uniform distribution of ventilation, and improved healing of bronchopleural stulas. HFV is attractive as a lungprotective mode, since the lung is kept open, yet barely tidally distended. A substantial risk is that dynamic hyperination is the rule and Palv is greatly underestimated by monitoring pressure at the airway opening. HFV holds promise as the natural extension of lowering the Vt as a means to prevent volutrauma, and there is renewed interest in this old technique. In a controlled trial in patients with ARDS, HFV showed no advantage in terms of gas exchange or of shortterm or longterm mortality, but did appear to be safe, at least during the performance of a clinical trial. A nonsignicant trend toward a shortterm mortality benet for HFV has been interpreted as a reason to pursue additional clinical studies. It is worth mentioning, however, that the control arm ventilation strategy was not lungprotective, potentially biasing the study in favor of HFV. Airway PressureRelease Ventilation Airway pressurerelease ventilation consists of continuous positive airway pressure, which is intermittently released to allow a brief expiratory interval. Conceptually, this mode is PCIRV during which the patient is allowed to initiate spontaneous breaths. An advantage over IRV is that patients are more comfortable, requiring less sedation. It is not known whether airway pressurerelease ventilation can deliver lungprotective ventilation, so this mode is not a good choice in patients with ALI or ARDS. Whether this mode provides any benet over modern lowVt ventilation remains to be shown. ProportionalAssist Ventilation Proportionalassist ventilation is intended only for spontaneously breathing patients. The goal of this novel mode is to attempt to normalize the relationship between patient effort and the resulting ventilatory consequences. The ventilator adjusts Pinsp in proportion to patient effort both throughout any given breath and from breath to breath. This allows the patient to modulate his breathing pattern and total ventilation. This is implemented by monitoring the instantaneous ow and volume of gas from the ventilator to the patient and varying the Pinsp as follows Pinsp f V f Flow NIV Mechanical ventilation for acute respiratory failure carries a high morbidity and mortality due, in part, to violation of the glottis by ACCP Critical Care Medicine Board Review th Edition the Vt is sufcient. ACV or pressurepreset ventilation is superior for NIV remains under debate. The limitations of portable pressuretargeted ventilators include the lack of waveform displays. Nasal. Mechanical Ventilation Schmidt . achieving a better t. reassurance. inadequate airway protective reexes. I believe the following points will minimize the chances that NIV will fail . Either conventional ICU ventilators or one of many portable bilevel pressuretargeted ventilators. Increase the PEEP to ease the work of triggering with a goal of typically to cm HO. can minimize this problem. so the ventilator fails to switch off the Pinsp even while the patient is making active expiratory efforts. such as a PEEP of cm HO. such as timecycled PSV or volume ACV. and full facial masks. This serves to increase patient discomfort and the work of breathing. but nearly all practitioners now use a pressuresupport mode. reduces the work of breathing. and the potential for the rebreathing of exhaled gas. During NIV. and the most sensitive trigger. removing nasogastric tubes gastric decompression is not recommended during NIV. . oronasal. Inatable cuffs. and the availability of a range of mask sizes to ensure proper t can minimize mask complications. . Using other methods for terminating inspiration. two mechanisms of PVA are common. the inability to deliver a high Fio greater than approximately . The rst is the failure of the patient to sufciently lower the proximal airway pressure ie. . Use the pressuresupport mode. as well as fullhead helmets have been used successfully. Education. Have available a selection of masks to increase the probability of a good t. changing the type of mask. and modest sedation when required may improve tolerance to the mask and ventilator. shortens the ICU length of stay. . nasal bridge protection. The second common mechanism for PVA is the failure of the ventilator to detect endinspiration because the patients subsiding effort is cloaked by a mask leak. counterbalancing the autoPEEP with externally applied PEEP provides a means by which to lower the work of triggering. Both modes have been used successfully. beginning with modest settings. Most pressuresupport ventilators terminate inspiration when inspiratory ow falls to a preset threshold. lessens complications. improves gas exchange. In patients with acuteonchronic respiratory failure. or little prospect of improvement within the next several days. with a goal of to cm HO. can be used. Select patients carefully. Careful attention to mask leaks and adjusting air ow and pressuresupport levels are important considerations. which were initially designed for home ventilation. numerous studies have demonstrated that NIV effectively relieves symptoms. As during invasive ventilation. mask pressure due to the presence of autoPEEP.. excluding those with hemodynamic instability. but carry some risk of respiratory depression and aspiration. rather than rst strapping the mask on and then initiating ventilatory assistance.. but direct comparisons between modes are few. Detect and correct mask leaks by repositioning. Mask leaks prevent the ow from falling to this threshold. and improves survival. or adjusting the ventilator to reduce peak airway pressure. . . a PSV of cm HO. raise the level of PSV until the patients breathing subjectively improves. Ventilators designed for NIV are very leak tolerant as are some newer ICU ventilators that have been redesigned with NIV in mind. Whether volumepreset ventilation eg. . and the rate begins to fall. using waveform displays as a guide. Nasal masks are especially difcult to use in edentulous patients who are unable to control mouth leak. Develop an individual and institutional commitment to NIV. Sedative medications are occasionally appropriate and can improve tolerance of NIV. I nd it useful to initiate ventilation by briey holding the mask already connected to the ventilator onto the patients face. Patientventilator asynchrony PVA describes patient breathing efforts that are not coupled to machine output. periodically removing the mask to allow the patient to sense its effect. Pay particular attention in the rst hour to patientventilator synchrony. often at an arbitrary low value of ow or at a xed percentage of the peak inspiratory ow. some new machines allow an Fio as high as .the endotracheal tube. supplemented in some patients by therapeutic paralysis. but most will require invasive ventilation. If the goal of ventilation is full rest. such as a tumor or a foreign body. airway malposition. The level of pressure support is adjusted usually to the range of to cm HO above PEEP to bring the f down into the low breaths/min. of course. decreased sympathetic tone from sedating drugs. Positivepressure ventilation may reduce venous return and so cardiac output. cm HO is used to prevent atelectasis.. or Vt. drug overdose or structural injury to the brainstem. airway pressure and ow waveforms should be inspected for evidence of patientventilator dyssynchrony or undesired patient effort. If gas exchange is entirely normal. In the rst minutes following the institution of mechanical ventilation. In patients who do not have acute lung injury but are at risk of it developing. especially in patients with a low mean systemic pressure eg. Some of these patients may benet from NIV. f. the physician should remain alert for several common problems. to . Alternatively. it may be prudent to use a low Vt since there is some evidence that mechanical ventilation at Vts of roughly mL/kg predicted body weight can induce lung injury. hypovolemia. the Fio can likely be lowered further based on pulse oximetry or arterial blood gas determinations. or obstruction causing autoPEEP. the patients respiratory drive can often be suppressed by increasing the inspiratory ow rate. If such adjustments do not diminish breathing effort despite normal blood gas levels to an undetectable level. applying PEEP. or neuromuscular disease or a very high ventilationrelated pleural pressure eg. in the treatment of elevated intracranial pressure following head trauma. the patients respiratory system mechanics. Although each critically ill patient presents myriad challenges. that are not bypassed with the endotracheal tube.Management of the Patient Initial Ventilator Settings Initial ventilator settings depend on the goals of ventilation eg. initial ventilator orders should be an Fio of . sedation may be necessary. These interventions help to reduce The Patient With Normal Respiratory Mechanics and Gas Exchange Patients with normal lung mechanics and gas exchange can require mechanical ventilation for several of the following reasons because of the loss of central drive to breathe eg. aspiration. full respiratory muscle rest vs partial exercise. because of neuromuscular weakness eg. Deep sedation should be provided in such instances. intravascular volume should be rapidly expanded while steps are taken to lower the pleural pressure eg. These include. the patient with acuteonchronic respiratory failure. it is possible to identify the following ve subsets of ventilated patients the patient with normal lung mechanics and gas exchange. but also rarely in those with inhalation injury or central airway lesions. Patients With Severe Airflow Obstruction Severe obstruction is seen most commonly in patients with status asthmaticus. large amounts of PEEP. These patients are usually extremely anxious and distressed. the initial Fio should usually be . although it can usually be lowered within minutes when guided by pulse oximetry and. as an adjunctive therapy in ACCP Critical Care Medicine Board Review th Edition . If this does not abolish inspiratory efforts and full rest is essential as in patients who in shock. PSV can be used. and an inspiratory ow rate of to L/min. most notably. or myasthenia gravis. or in order to achieve hyperventilation eg. the patient with severe airow obstruction. usually corresponding to a Vt of approximately mL. in the appropriate setting. A small amount of PEEP to . Soon after the initiation of ventilation. if the patient has sufcient drive and is not profoundly weak. and minute ventilation needs. venodilating drugs. chest wall restriction. to . and hypotension. In all patients. smaller Vt or less minute ventilation. a respiratory rate of to breaths/min. and the patient with restrictive lung or chest wall disease. high cervical cord injury. a Vt of to mL/kg. If hypotension occurs. the patient with acute hypoxemic respiratory failure. the latter two changes may induce respiratory alkalemia. muscle paralysis should be considered. to assure adequate oxygenation. the treatment of shock. Following intubation. acute idiopathic myelitis. the goal is to rest the patient and respiratory muscles for to h. Unlike patients with status asthmaticus. Two days of such rest presumably will restore biochemical and functional changes associated with muscle fatigue. yet autoPEEP and its consequences are common. bicarbonate wasting by the kidney. and perhaps in those with ventricular dysfunction or critical pulmonary hypertension. in the patient with COPD and minimally reversible airway disease. Reducing minute ventilation to achieve these goals generally causes the Pco to rise to mm Hg. the Vt should be small to mL/kg. excessive ventilation risks severe respiratory alkalosis and. an Fio of . potentially compromising cardiac output. A peak ow of L/min is recommended. Because gas exchange abnormalities are primarily those of ventilationperfusion mismatch. often requiring ICU admission. The majority of patients with COPD will appear exhausted at the time when mechanical support is instituted and will sleep with minimal sedation.. as described above. hypoperfusion is common. higher ow rates do little to increase Te. Finally. Many such patients can be ventilated effectively with NIV. Some patients who remain agitated during ACV can be made more comfortable by using PSV mode or PCV mode with a total Pinsp of approximately cm HO. if the patient is triggering the ventilator. continuing to demonstrate a high work of breathing. patients in this population tend to have relatively smaller increases in inspiratory resistance. This example serves to emphasize not only the relative lack of benet of raising the ow rate but also the importance of minimizing minute ventilation when the goal is to reduce autoPEEP. Ventilation should be initiated using the ACV mode or SIMV mode. usually autoPEEP increases little as long as PEEP is not set higher than about of the autoPEEP. For those patients who require intubation. if the Vt is mL/kg. s. usually occurring in patients with COPD. supplemental oxygenation with Fio in the range of . In many patients. Adding extrinsic PEEP to Mechanical Ventilation Schmidt . s. and the f should be to breaths/min. Also. and often to mm Hg. Although this occasionally compounds the dynamic hyperination. should achieve saturation of arterial hemoglobin. The goals are to minimize alveolar overdistention Pplat. In contrast.oxygen consumption and hence carbon dioxide production to lower airway pressures and to reduce the risk of selfextubation. As a consequence. rest and sleep are desirable. and typically responds to briey ceasing ventilation combined with uid loading. the Te is . Raising ow dramatically to L/min increases the Te to only . a strategy that largely prevents barotrauma. Because the gas exchange abnormalities of airow obstruction are largely limited to ventilationperfusion mismatch. such permissive hypercapnia is tolerated quite well. mL/kg. Patients With AcuteonChronic Respiratory Failure Acuteonchronic respiratory failure is a term that is used to describe the exacerbations of chronic ventilatory failure. except in patients with increased intracranial pressure. some PEEP should be added to reduce the work of triggering. the goals of rest and appropriate hypoventilation can usually be achieved with initial ventilator settings of a Vt of to mL/kg and an f of to breaths/min. and the ow is L/min. cm HO and to minimize dynamic hyperination autoPEEP. as manifested by tachycardia and relative hypotension. because the patient typically has an underlying compensated respiratory acidosis. which is a trivial improvement. An examination of airway pressure and ow waveforms can be very helpful in identifying this extra work of breathing and in suggesting strategies for improving the ventilator settings. Although this requires sedation. with ACV mode set on minimal sensitivity. For example. Because the majority of these patients receive ventilation after days to weeks of progressive deterioration. over time. Small numbers of patients will have difculty resting while receiving ventilation. peak airway pressures on the ventilator tend not to be extraordinarily high. At the time of intubation. this is the result of autoPEEPinduced triggering difculty. the f is breaths/min. sufces in the vast majority of patients. or endinspiratory lung volume. s. their expiratory ow limitation arising largely from the loss of elastic recoil. but h may not be sufcient. a small reduction in f to breaths/min increases the Te to . To the extent that muscle fatigue has played a role in a patients functional decline. cm HO. Ventilatory strategies have evolved markedly in the past decade. The goals of ventilation are to reduce shunt. continuous positive airway pressure of cm HO for s has often been chosen.. a higher Vt is associated with higher mortality. reexpanded. or inspected independently. and progressive shock is begun. the leastPEEP approach. A number of different devices have been used to obstruct a bronchus. the end results of which are impaired lung mechanics and gas exchange. The Fio is usually determined by the degree of alveolar lling or collapse. rather than a stiff lung. Large bronchopleural stulas . by lowering minute ventilation or correcting hypovolemia. An occasional consequence of lungprotective ventilation is hypercapnia. but experience is greatest with the Fogarty embolectomy catheter. the large ventilationinduced rise in pleural pressure has the potential to compromise cardiac output. Although these maneuvers have shown some ability to transiently raise the Po. Patients With Acute Hypoxemic Respiratory Failure Acute hypoxemic respiratory failure is caused by alveolar lling with blood. The Patient With Restriction of the Lungs or Chest Wall A small Vt to mL/kg and rapid breathing rate to breaths/min are especially important in order to minimize the hemodynamic consequences of positivepressure ventilation and to reduce the likelihood of barotrauma. or edema. The lung of the ARDS patient should be viewed as a small lung. if any. but occasionally its benets are dramatic. DLTs carry the advantages of allowing each lung to be ventilated. the f should be set at to breaths/min. PCV could be used as well. The Vt should be mL/kg while receiving ACV. This in turn will lower the mixed venous Po and. If the physician responds to this falling Pao by augmenting PEEP or increasing the minute ventilation. The Airway During SplitLung Ventilation The lungs may be separated for purposes of differential ventilation in two major ways blocking the bronchus of a lobe or whole lung while ventilating with a standard endotracheal tube. Recruitment maneuvers have generally applied a sustained ination pressure while the patient is therapeutically paralyzed. then rapidly adjusted to the lowest PEEP necessary to produce an arterial saturation of on an Fio no higher than . In ARDS.nearly counterbalance the autoPEEP dramatically improves the patients comfort. such as occurs with lobar pneumonia. Potentially. A potentially catastrophic cycle of worsening gas exchange. collapsed. This circumstance must be recognized because the treatment is to reduce dead space eg. further circulatory compromise ensues. or passing a doublelumen tube DLT. changing clinical practice and generating tremendous excitement. however. in view of the typically extreme hypoxemia. avoid toxic concentrations of oxygen. but the parameters that assure lungprotective ACCP Critical Care Medicine Board Review th Edition ventilation are not known. termed permissive hypercapnia. In either mode. When the restrictive abnormality involves the chest wall including the abdomen. This approach of preferring hypercapnia to alveolar overdistention. pus. in the setting of ventilationperfusion mismatch or shunt. The gas exchange impairment results from intrapulmonary shunt that is largely refractory to oxygen therapy. is very well tolerated. the Pao as well. it is now clearly established that excessive distention of the lung of the ARDS patient compounds lung injury and may induce systemic inammation. In patients with ARDS. The initial Fio should be . For example. PEEP therapy is indicated in patients with diffuse lung lesions but may not be helpful in patients with focal inltrates. increasing ventilator settings. ie. they have not been shown to change clinically meaningful outcomes. Splitlung ventilation is only rarely useful in the critical care unit. PEEP should be instituted immediately. the signicantly reduced functional residual capacity arising from alveolar ooding and collapse leaves many fewer alveoli to accept the Vt. In line with this current conception of ARDS. making the lung appear stiff and dramatically increasing the work of breathing. and choose ventilator settings that do not amplify lung damage. N Engl J Med . Slutsky AS. . Amato MBP. nd ed. Meharg J. et al. Mehta S. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. This study sought to compare higher versus lower PEEP in subjects with acute lung injury who were receiving a lungprotective tidal volume of mL/kg predicted body weight. and tamponading the bleeding site while awaiting denitive therapy. et al. Am J Respir Crit Care Med . . The rst trial to show convincingly the benets of NIV. . In Hall JB. New York.severely compromise ventilation and may not respond to HFV. . Benito S. . Kramer N. Lung. N Engl J Med . Rauss A. Mancebo J. patients with focal causes of acute hypoxemic respiratory failure. Finally. Physiol Rev . The protective approach improved day survival. Description of ventilation using VTs less than the dead space volume. A comprehensive review of many aspects of mechanical ventilation. Schmidt GA. Management of the ventilated patient. Annotated References . The other major weaning trial. Gordo F. One of two large multicenter trials comparing weaning modes. et al. Wood LDH. Principles of critical care. . may benet from differential ventilation and the application of PEEP. Barbas CSV. Am J Respir Crit Care Med . Stewart TE. controlled trial. N Engl J Med . A mode that adjusts pressure to meet patient demand. Hall JB. Outcomes were similar regardless of the level of PEEP. Slutsky A. Comparison of three methods of gradual withdrawal from ventilatory support during weaning from mechanical ventilation. weaning from ventilation. . Proportional assist ventilation results of an initial clinical trial. . Highfrequency oscillatory ventilation for acute respiratory distress syndrome in adults a randomized. such as lobar pneumonia or acute total atelectasis. This key study indicated that the details of ventilating acute lung injury patients affected outcome but raised questions as to which component or components of the protective strategy led to the benet. Am J Respir Crit Care Med . . Highfrequency ventilation. where the lungprotective strategy involved both lower tidal volumes and higher PEEPs than the conventional approach. Extubation outcome after spontaneous breathing trials with Ttube or pressure support ventilation. eds. maintaining airway patency. Drazen JM. Mechanical ventilation. Randomized. and the incidence of barotrauma. et al. but failing to demonstrate any signicant clinical benets compared with PCV in patients with ARDS. Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. Am Rev Respir Dis . Fiftythree subjects with early acute lung injury were ventilated with a conventional versus lungprotective approach. Ala I. Meyer TJ. Higher versus lower positive endexpiratory pressures in patients with the acute respiratory distress syndrome. Esteban A. et al. Roberts D. et al. Brochard L. Chest . A DLT will maintain ventilation of the healthy lung while facilitating closure of the bronchopleural stula. . et al. Randomized trial showing that HFV can be performed safely. Puddy A. Medeiros DM. Kamm RD. prospective trial of noninvasive positive pressure ventilation in acute respiratory failure. and Blood Institute ARDS Clinical Trials Network. Signal study establishing that VT is an important determinant of outcome in patients with acute lung injury and ARDS. Mechanical Ventilation Schmidt . N Engl J Med . The Acute Respiratory Distress Syndrome Network. Brochard L. SIMV was clearly shown to be inferior. Derdak S. Younes M. Wysocki M. Am J Respir Crit Care Med . lung separation may be lifesaving by minimizing blood aspiration. Schmidt GA. This trial conrmed the trial of Brochard et al. Describes ventilation based on individual patient physiology. During massive hemoptysis. et al. Effect of a protectiveventilation strategy on mortality in the acute respiratory distress syndrome. The National Heart. . NY McGrawHill. . Ranieri VM. Williams TJ. Giuliani R. such as barotraumas and hypotension. Ventilatorassociated lung injury in patients without acute lung injury at the onset of mechanical ventilation. et al. Demonstrated that large VTs elaborate potentially damaging cytokine levels in patients. et al. Demonstrated improved outcome by limiting minute ventilation. The effects of ventilatory pattern on hyperination. ACCP Critical Care Medicine Board Review th Edition . Gajic O. Demonstrates the impact of externally applied PEEP in patients receiving autoPEEP. Tuxen DV. Permissive hypercapnia how permissive should we be Am J Respir Crit Care Med . Ranieri VM. and circulation in mechanical ventilation of patients with severe airow obstruction. Tuxen DV. Effects of mechanical ventilation on inammatory mediators in patients with acute respiratory distress syndrome a randomized controlled trial. Suter PM. Crit Care Med . Tortoella C. Feihl F. . Perret C. Physiologic effects of positive endexpiratory pressure in patients with chronic obstructive pulmonary disease during acute ventilatory failure and controlled mechanical ventilation. . Scheinkestel CD. . Lane S. et al. Cinnella G. airway pressures. . et al. This key article demonstrated the link between minute ventilation and potentially detrimental consequences. Am Rev Respir Dis . This retrospective study found an association between the initial VT and subsequent development of acute lung injury.. Am Rev Respir Dis . showing reduced work of breathing. Dara SI. JAMA . Use of a measurement of pulmonary hyperination to control the level of mechanical ventilation in patients with acute severe asthma. Mendez JL. A comprehensive review of the risks and benets of hypercapnic ventilation. suggesting that VTs of mL/kg may be injurious even before lung injury is established. Am Rev Respir Dis . Notes Mechanical Ventilation Schmidt . the lowering of BP needs to be immediate or may be accomplished over hours based on the assessment of risk. or seizures may indicate hypertensive encephalopathy. and uncontrolled hypertension may complicate ICU stay for those patients admitted for other reasons. A differential diagnosis of hypertensive encephalopathy includes severe hypertension in association with subarachnoid hemorrhage or stroke. however. Headache. Dening hypertensive emergency based on acute endorgan damage is more appropriate than using specied numbers for systolic or diastolic BP. or extremity pulse decits related to aortic dissection. MD. Hypertensive urgencies identify patients who are at risk for organ dysfunction due to hypertension. The organ systems that are most frequently involved include the CNS. Both the absolute level of BP and the time to reach that level are important in the development of organ injury. based on clinical assessment. hypotensive urgency. and a chest radiograph may offer clues to aortic dissection eg. confusion. Pertinent laboratory tests performed in the evaluation of patients with known or suspected hypertensive emergencies or urgencies include a urine analysis in search of glomerulonephritis as a secondary cause of hypertension or creatinine measurement as a marker of hypertensioninduced acute renal dysfunction when the baseline value is known. and coma. lethargy. A CT scan may be required to assure the absence of these entities. generalized seizures. The patient received lorazepam IV with the cessation of seizures. and invasive monitoring and ICU admission are typical. acute endorgan injury may occur at different blood values in different patients. Secondary hypertension eg. renal artery stenosis should. vomiting. nausea. He was intubated and mechanically ventilated. confusion. Therefore. be considered. the cardiovascular system. Clinical manifestations of a hypertensive encephalopathyinduced increase in intracranial pressure include headache. a murmur of aortic insufciency associated with proximal aortic dissection. These conditions require immediate control of BP to ameliorate organ injury. Chest pain may signify aortic dissection or myocardial ischemia. widened mediastinum or hypertensioninduced pulmonary edema. A physical examination of the chest may reveal rales associated with hypertensioninduced pulmonary edema. postoperative hypertension Severe hypertension with acute organ dysfunction is a reason for admission to the ICU. Phillip Dellinger. FCCP Objectives Identify acute endorgan dysfunction due to hypertension Recognize the importance of lowering BP in a timely but nite manner Match appropriate drugs for the treatment of hypertensive emergencies/urgencies based on patient characteristics Appreciate the potential toxicities and side effects of the drug chosen Key words hypertensive emergency. hypertension. hypertensive encephalopathy. An ECG may reveal myocardial ischemia exacerbated by hypertension. supporting the diagnosis of hypertensive encephalopathy. Symptoms and physical examination ndings are important clues to trigger a search for acute organ dysfunction in hypertensive patients. A fundus examination revealed papilledema. Hypertensive emergency is dened as a severe elevation in BP that is associated with acute endorgan damage. and the kidneys. IV medications are required.Hypertensive Emergencies and Urgencies R. Identification of EndOrgan Damage Most patients with hypertensive emergencies will have a history of poorly controlled essential ACCP Critical Care Medicine Board Review th Edition . Hypertensive Encephalopathy A yearold man presented with generalized seizures and a BP of / mm Hg. In patients with hypertensive encephalopathy. The onset of action of labetalol is to min with peak hypotensive effect occurring at to min and an effect lasting up to h. cerebral blood ow is autoregulated such that cerebral blood ow remains constant between mean arterial pressures of and mm Hg Fig . depending on the response. Cyanide and thiocyanate toxicity are potential problems with nitroprusside infusion. Nitroprusside is nonenzymatically converted to cyanide in the blood. Drugs that offer these traits include nitroprusside. Unlike nitroprusside. this autoregulation shifts to the right. Unlike other calciumchannel blockers. nicardipine. In chronically hypertensive patients. thiocyanate levels can be followed as a marker for the risk of cyanide and thiocyanate toxicity. mg/h every min to a maximum rate of mg/h. Infusion is begun at mg/h and is increased by . therapy with nitroprusside. labetalol may be utilized in most patients without arterial line placement. and the regulation of cerebral blood ow occurs at a much higher pressure range. it is unlikely to produce negative inotropic effects. In patients with chronic hypertension. Overzealous lowering of the mean arterial pressure in patients with severe hypertension to even high normal BPs may drop the BP to a level that is below the lower range of autoregulation and decrease cerebral blood ow. Figure . Its combined / effect typically produces a signi cant lowering of peripheral vascular resistance with a minimal decrease in heart rate and a minimal change in cardiac output. IV nicardipine is an effective. is begun with an initial infusion of . the initial BP therapeutic target is to decrease the mean arterial pressure by to . Although maintenance continuous infusions Hypertensive Emergencies and Urgencies Dellinger . Patients with liver disease are at an increased risk of cyanide toxicity. the cerebral blood ow autoregulation curve is shifted to the right. g/kg/min with a maximum dosage of g/kg/min for min or a maximum sustained dose of g/kg/min. and nitroglycerin. IV labetalol is a reliable drug for the treatment of hypertensive encephalopathy as well as other etiologies of hypertensive emergencies. to . and patients with kidney disease are at an increased risk of thiocyanate and cyanide toxicity. In the normotensive patient. fenoldopam. Even in patients with anuric renal failure. even when the value is within normal range. Loading by continuous infusion at . as in those with other causes of hypertensive emergencies. An arterial line is advised for the administration of nitroprusside due to the sudden drops in BP that may occur with the titration of nitroprusside. and is an arterial vasodilator that is associated with increased cardiac index. used at recommended doses during the initial stabilization of BP. is safe. titratable continuousinfusion calciumchannel blocker that is used for the treatment of hypertensive emergencies/urgencies. Therapy with sodium nitroprusside. In patients without renal dysfunction. Thiocyanate is excreted by the kidney. the ideal drug is an IV vasodilator with quick onset of action and quick offset of action. Cerebral autoregulation maintains constant blood ow in the absence of acute brain injury between approximately and mm Hg mean arterial pressure.General Principles of IV Drug Therapy for Hypertensive Emergencies In hypertensive encephalopathy. long a staple drug in the treatment of hypertensive emergencies. producing iatrogenic strokes. With chronic sustained elevations in blood pressure the autoregulation curve shifts to the right and puts the patient at risk for cerebral hypoperfusion and stroke when blood pressure is aggressively lowered. as well as in most hypertensive emergencies and urgencies. to mg/min is also possible. This rarely occurs with recommended infusion rates occurring over h of therapy. It has a rapid onset and intermediate halflife. and cyanide is converted to thiocyanate in the liver. Drug loading is accomplished with incremental dosing an IV bolus of to mg every to min. This may be particularly problematic in patients with underlying cerebral vascular disease. diastolic function and normal or increased ejection fraction. it has been demonstrated to increase renal blood ow. CO retention. This includes an increase in venous capacitance. postcoronary artery bypass surgery. labetalol was primarily developed for the initial control of BP through loading followed by conversion to labetalol administered orally or other alternative antihypertension therapies. It may be chosen to treat mildtomoderate hypertension in patients with congestive heart failure due to systolic dysfunction or in patients with an activation of the reninangiotensin system such as scleroderma kidney. to mg administered as a single bolus every h. pink frothy sputum. may leave the patients intravascular volume depleted with prerenal azotemia. The dose is . and increasing compliance softening of the LV. to . g/kg/min and titrated in increments of . patients with asthma. or increased left ventricular LV lling pressures. and pulmonary edema as a cause of weaning failure. a decrease in arteriolar resistance. The use of fenoldopam is safer than nitroprusside in patients with moderatetosevere renal dysfunction fenoldopam carries no risk for cyanide toxicity but is more expensive. Primary consideration for the use of nitroglycerin should be in hypertensive emergencies/urgencies associated with congestive heart failure. Administration is begun at . since lower ranges of BP elevation may be present with a contribution of myocardial ischemiainduced wall stiffness playing a prominent role in the rise in pulmonary capillary pressure. although clinical studies have not been able to demonstrate a renal clinical outcome benet compared to that with nitroprusside. Initial therapy targets any intervention that lowers the LV enddiastolic pressure. and also may produce an increase in BP. associated with hypertension. and pulmonary edema seen on a chest radiograph. Hypertension and Systolic Dysfunction Enalaprilat is an IV drug with a potential to treat hypertension and to improve cardiac function. Labetalol may also be useful as a combination /blocker. and mildtomoderate hypertension. which is a balanced arteriolar IV acting drug. vasodilatation is the most effective therapy. It is not usually a goto drug to treat severe lifethreatening hypertension. may occur during weaning from mechanical ventilation. unlike nitroprusside. The use of diuretics. therapy with blockers is also very effective. It is an afterload reducer with an onset of action of min and a duration of action of h. creatinine levels should be followed and therapy should be discontinued if the Hypertension Associated With Cardiac Dysfunction Hypertensive Crisis With HighPressure Pulmonary Edema Clinical features of a severe hypertensioninduced rise in LV enddiastolic pressure with associated high pulmonary capillary pressure and pulmonary edema include severe hypoxemia.have been successfully utilized. It is particularly useful in patients with active myocardial ischemia. Diuresis is an effective therapy. Fenoldopam is a drug with a very similar pharmacodynamic prole as nitroprusside. to . or patients with signi cant systolic cardiac dysfunction. an associated rise in LV enddiastolic pressure. although studies have demonstrated that most patients with this diagnosis do not have increased intravascular blood volume. The typical patient will have chronic LV hypertrophy with ACCP Critical Care Medicine Board Review th Edition . It should not be used in patients with bilateral renovascular disease or in pregnant women in the second or third trimester. This presentation is likely to be more insidious than the presentation of the patient presenting to the emergency department with acute hypertensioninduced pulmonary edema. high LV lling pressures. It also has the potential to redistribute coronary artery blood ow to benet the ischemic myocardium. Labetalol should not be used in patients with seconddegree heart block or greater. Since diastolic function is often present. When used on an ongoing basis in the ICU. As a selective dopamine receptor agonist. The potential disadvantages of enalaprilat include idiopathic angioedema. g/kg no more frequently than every min. therefore. has predominately venous capacitance effects. although effective in abating pulmonary edema. Acute ischemia. Nitroglycerin is a directacting vasodilator and. coronary artery disease. mg/h every min to maximun of mg/h If blood pressure not controlled. which might benet from higher BPinduced collateral ow. mg/h. and once the aneurysm is clipped that very high BPs may be tolerated as there is no signicant risk Table . titrate up by . Hypertensive Emergencies and Urgencies Dellinger . may repeat every min. hemorrhagic stroke. extreme elevations in BP are associated with poor outcomes after both ischemic and hemorrhagic cerebrovascular accidents and are thought to play a role in this bad outcome. Concerns of severe elevations in BP after stroke include reinfarction. and at least some component of the rise is thought to be a bodycompensatory mechanism. when desired blood pressure attained. maximum dose of mg. Stroke . including bland stroke. or arbitrary selected limits for systolic BP are present. et al. consider sodium nitroprusside Reprinted with permission from Adams H. and then every hour for h Blood pressure level Systolic mm Hg or diastolic mm Hg Labetalol mg IV over min. Although increased BP is considered to put the patient at risk for increased edema in areas of injury as well as to increase the chance of bleeding or rebleeding. cerebral edema. del Zoppo G. be instituted in patients with stable elevated creatinine levels. maximum dose of mg. Hypertension With Acute CNS Events An increase in BP is thought to be a normal physiologic response to acute CNS strokes. then every min for h. mg/h. or Nicardipine infusion. However. as neurologic deterioration may occur in this circumstance with aggressive pharmacologic lowering of BP. reduce to mg/h If blood pressure does not decline and remains / mm Hg. intracranial hemorrhage. Alberts MJ. The optimum method to be used for the management of BP following cerebral vascular accidents remains controversial. and hemorrhagic transformation. acute endorgan damage is occurring. equally important in these patients are watershed areas of brain penumbra that are at risk for further ischemic injury. Approach to Arterial Hypertension in Acute Ischemic Stroke Indication that patient is eligible for treatment with intravenous rtPA or other acute reperfusion intervention Blood pressure level Systolic mm Hg or diastolic mm Hg Labetalol mg IV over min. There is general agreement that in an unclipped subarachnoid hemorrhage BP should be normalized. or Nitropaste inches. and subarachnoid hemorrhage. withholding therapy for hypertension in the acute phase of ischemic strokes is the recommendation. In general.to min intervals. It is a doubleedged sword. or Labetalol mg IV followed by an infusion at mg/min. however. or Labetalol mg IV followed by an infusion at mg/min Systolic mm Hg or diastolic mm Hg Labetalol mg IV over min. may repeat every min. Hypertension is common after both ischemic and hemorrhagic strokes. do not administer rtPA Management of blood pressure during and after treatment with rtPA or other acute reperfusion intervention Monitor blood pressure every min during treatment and then for another h. maximum dose mg/h. Cerebral edema is problematic in light of a dysfunctional ability to autoregulate cerebral blood ow following a stroke.creatinine level begins to rise. Therapy with enalaprilat can. titrate up to desired effect by increasing . may repreat . increased hemorrhage size. mg/h at . or Nicardipine infusion. however. unless thrombolysis is planned. and good systolic function. Table contrasts esmolol with two other choices of IV antihypertensive agents. and the classic chest radiographic nding is a widened mediastinum. where a greater preservation of renal blood ow may occur. Esmolol may be administered by IV bolus or by continuous infusion. Severe HypertensionInduced Renal Dysfunction A patient may present with severe hypertension and acute deterioration in renal function. stroke. Maintaining systolic pressure seems reasonable. hypertension. and wound hemorrhage. and aortic coarctation. heart rate. Esmolol is a cardioselective adrenergic blocker with quick onset of action peak effects within to min and a short halflife to min. and nitroprusside. myocardial ischemia/ infarction. hydralazine. The aortic pulse wave. nicardipine. A wide variety of drugs may by used to manage postoperative hypertension depending on particular patient characteristics. In patients who experience intracerebral hemorrhage. and BP. hypercarbia. These drugs should be used with caution in patients with obstructive airways disease and avoided in patients with asthma. When a blocker is used in the treatment of patients with potential side effects of blockade. Recommended drugs include labetalol. hypoxemia. Either esmolol or intermittent bolus metoprolol may offer an advantage to postoperative patients with hypertension. primarily driven by volume overload. or shearing force. Dissecting thoracic aortic aneurysms involving the arch and descending aorta that do not interfere with major vessel outow are typically managed medically with BP control. and good systolic function. or urinary retention. dyelled true aortic channel. Dissections involving the area proximal to the left subclavian artery are considered to be type A. A history of hypertension. Diagnosis is made either with a contrastenhanced CT scan or transesophageal echocardiography. Indications for the treatment of postoperative hypertension have been arbitrarily dened as a systolic BP of mm Hg or a diastolic BP of mg on two consecutive readings. the penumbra issues are very important. esmolol is preferred over intermittent metoprolol. Dialysis is the treatment of choice for severe hypertension and associated hypoxemia. labetalol. Drugs that may be particularly suited to the treatment of this group of patients include labetalol and hydralazine. Aortic Dissection Aortic dissection is caused by a tear in the intima of the aorta that is propagated by the aortic pulse wave. The current recommendation is to administer thrombolytic therapy with a systolic BP of mm Hg and a diastolic BP of mm Hg Table . involving the descending aorta only. Postoperative Hypertension Hypertensioninduced postoperative complications include arrhythmias. Chest pain is the typical presenting symptom. Esmolol is rapidly metabolized by RBCs and does not depend on renal or hepatic function. and fenoldopam. tachycardia. The degree of BP rise likely is associated with a risk for rebleeding. Dissection is usually diagnosed utilizing CT scanning with and without contrast enhancement. connective tissue diseases. and the grade of the surgical stress are risk factors for postoperative hypertension. depends on a combination of myocardial contractility. The risk factors for aortic dissection include advanced atherosclerosis. and hypertension may be protective against a postbleed vasospasm. Less hypertension is tolerated when thrombolysis is planned.of rebleeding. but it is also likely that a higher BP better maintains perfusion of the risk area surrounding the stroke. esmolol. which demonstrates a grayish/whitish false lumen predominately lled with a clot alongside a brightwhite. Continuous infusion is usually initiated following a loading dose. These include nitroprusside. Aneurysms involving the ascending aorta or are comprimizing organ blood ow are typically surgically treated. It is a good t for patients with tachycardia. age. high body mass index. It is important to evaluate for possible causes of hypertension that are secondary to pain. ACCP Critical Care Medicine Board Review th Edition . nicardipine. and when this area is not involved are considered to be type B ie. The lowering of BP by likely does not put the penumbra at risk after intracerebral hemorrhage and may decrease the risk of bleeding. reinitiation of the drug may be sufcient to treat the elevated BP. systemic vascular resistance. and Labetalol Nicardipine Administration Onset Offset HR SVR Cardiac output Myocardial O balance Continuous infusion Rapid Rapid Minimal increase Decreased Increased Positive Esmolol Continuous infusion Rapid Rapid Decreased Decreased Positive Labetalol Bolus continuous infusion Rapid Slower Minimal decrease Decreased No change Positive HR. The treatment of severe preeclampsia and eclampsia includes delivery of the fetus combined with therapy with magnesium sulfate for the prevention and treatment of seizures and BP control. nausea. SVR. Dissection of the aorta is another circumstance unclipped aneurysm was discussed earlier in which the immediate normalization of BP is indicated. heart rate. In addition to magnesium. Aneurysms of the ascending aorta may dissect proximally. and decreasing inotropy. Hypertensive Emergencies and Urgencies Dellinger Severe Hypertension in Pregnancy Hypertension is responsible for of maternal deaths in the United States. which is diagnosed in time to allow lifesaving surgery. vomiting.Table . and anxiety. abdominal pain. The propagating force for a dissection is the change in blood pressure over the shearing force. to min and a duration of effect of to h. Distal migration may produce an obstruction of the major vascular outow vessels or a rupture into the thorax. is a rare tumor producing a catecholamineexcess state with the potential for severe hypertension accompanied by headache. Contrasting Effects of Nicardipine. diaphoresis. Although hydralazine has historically been recommended as the antihypertensive agent of choice. Esmolol. Excessive hypotension can be dangerous to both mother and fetus. Hypertension of pregnancy is dened as a systolic BP of mm Hg or a diastolic BP of mm Hg. hydralazine has traditionally been the drug of choice in the treatment of these patients. the use of blocker therapy alone as the initial therapy should be avoided because of the possibility of the loss of adrenergically mediated vasodilation leading to an unopposed effect. Preeclampsia is dened by newonset hypertension accompanied by proteinuria and edema. A rapid surge in catecholamines resulting in hypertension may also accompany withdrawal from blocker or blocker agents. In this circumstance. and anxiety. Pheochromocytoma. Eclampsia is dened as the development of seizures or coma in a preeclamptic patient. or certain diet pills. autonomic dysfunction GuillainBarr syndrome. headaches. decongestants such as ephedrine and other agents alkaloids. This shearing force is minimized by a combination therapy of keeping the heart rate normal. It is associated with reex tachycardia. The drug of choice for therapy is phentolamine. which is more likely to be encountered on board examinations as opposed to in real life. In general. The typical recommendation is to reduce diastolic BP to mm Hg or mean arterial pressure by . Potential problems include tachycardia and side effects that mimic the symptoms of eclampsia eg. palpitations. and tyramine ingestion in the presence of monoamine oxidase inhibitor therapy. It is also advocated as a drug of particular benet in patients with eclampsia. Rare causes of catecholamineassociated hypertensive crisis include pheochromocytoma. Occasionally. and its use should be avoided in patients with dissecting aortic aneurysm and acute myocardial ischemia. producing a murmur of aortic insufciency or acute pericardial tamponade. a leak may occur into the thorax. Hydralazine is a direct arteriolar vasodilator with an onset of action in . recent data have suggested that labetalol and nifedipine may be more viable options. normalizing BP. CatecholamineAssociated Hypertensive Crisis Catecholamineinduced hypertensive crisis may be associated with consumption of sympathomimetic agents such as amphetamines. Another good general review. Treatment of hypertensive urgencies and emergencies. Nienaber CA. Renew presenting a logical approach to specic organ dysfunctions and causes of hypertensive crises. et al. This review includes perioperative and operative management. Aggarwal M. Perez MI. Hypertensive emergency and severe hypertension What to treat. Acute hypertensive emergencies in pregnancy. This article discusses issues related to autoregulation of cerebral blood ow. Covers issues related to intravenous option only and comorbidities to prevent operation specic complications wound hemorrhage and not operation specic complications. Feldmann E. Feldstein C. Khan IA. Salvetti M. Ramin SM. Med Clin North Am . Autoregulation of cerebral blood ow surrounding cute to hours intracerebral hemorrhage. Vidaeff AC. Zazulia AR. Neurology . et al. supplSS McCoy S. This is a concise but informative review of both pathophysiology and treatment of aortic dissection. Am J Health Syst Pharm . LeBlanc JM. Haas CE. Hypertensive crisis hypertensive emergencies and urgencies.Annotated Bibliography Adams HP. . Pharmacological interventions for hypertensive emergencies a Cochrane systematic review. Farsang C. Cardiol Clin . Elliott WJ. Review and update targets selected endorgan dysfunction scenarios. Rosei EA. and how to treat. Strategies for managing perioperative hypertension. Prog Cardiovasc Dis . Drugs . Concise managementbased format. Guidelines for the early management of adults with ischemic stroke. Connolly S. Pharmacotherapeutic options for the treatment of preeclampsia. Am J Ther . A cardiologists perspective on hypertensive emergencies. General review of hypertensive emergencies and urgencies. Curr Opin Cardiol . Videen TO. Musini VM. General review of hypotensive urgencies and emergencies across all settings. Haas AR. Clinical features in the management of selected hypertensive emergencies. Salvetti M. Elliott WJ. J Hum Hypertens . Modeliar SS. Covers both diagnostic approach as well as medical intervention. Varon J. et al. Heart . Varon J. Current AHA American Stroke ASA Association recommendations. Prog Cardiovasc Dis . Current recommendations for management in intracerebral hemorrhage. Vitberg D. Review specically targeting ICU presentations and treatment. Am J Health Syst Pharm . Clinical review the management of hypertensive crises. Marik PE. Managing emergency hypertension in aortic dissection and aortic aneurysm surgery. Ince H. Alberts MJ. Plestis KA. Broderick J. Up to date review of the changes that have occurred over the last years about this important topic. Treatment of hypertensive urgencies and emergencies. Flanigan JS. Baldwin K. Carroll MA. who to treat. Goldberg ME. Good general view of both established and more recent agents for treatment of severe hypertension. This article reviews the initial therapeutic approach to hypertensive emergencies and the most commonly used medical therapies. Slama M. Crit Care . Blood Press . Acute postoperative hypertension a review of therapeutic options. Powers WJ. Management of hypertensive crises. Treatment of acute severe hypertension current and newer agents. Blood Press . Marik PE. ACCP Critical Care Medicine Board Review th Edition Khoynezhad A. J Card Surg . Weaver FA. Semin Dial . Current diagnosis and management of hypertensive emergency. The Cochrane methodology applied to interventions to control blood pressure in the presence of organ dysfunction. and how that inuences perihemorrhagic blood ow in smallsized to mediumsized acute intracranial hemorrhages. Stroke . Clinical features in the management of selected hypertensive emergencies. Farsang C. This is a clinical pharmacologyrelated review that includes both narrative and tabular summaries of drug treatment options for postoperative hypertension. its preservation or lack of preservation. Crit Care Med . del Zoppo G. Guidelines for the management of spontaneous intracerebral hemorrhage in adults. Diagnosis and management of patients with aortic dissection. Rosei EA. Hypertension in the intensive care unit. Stroke . supplSS Covers predisposition and management. Crit Care Clin . Notes Hypertensive Emergencies and Urgencies Dellinger . Strek. In the United States.. This chapter will review the normal physiology of pregnancy as well as the diagnosis and treatment of disorders of the respiratory and circulatory systems that account for the vast majority of admissions to the ICU during pregnancy. Critical illnesses in pregnancy may result from worsening of an underlying cardiac or pulmonary disease or the onset of a unique pregnancyrelated illness. Assessment. and preeclampsia are especially important topics that will be covered in detail. The need for intensive care in pregnancy ranges from to in . preeclampsia. deaths per . and treatment of cardiovascular disorders of pregnancy including preeclampsia Key words critical illness. venous thromboembolism VTE. The development of critical illness during pregnancy is a rare but potentially devastating occurrence because two lives are affected. in the range of .. Renal compensation results in a maternal pH that is only slightly alkalemic. the overall pregnancyrelated mortality from to was . MD. with serum bicarbonate decreasing to to mEq/L Table . and Pco falls to to mm Hg throughout pregnancy. diagnosis.. but this increase does not signicantly increase oxygen delivery. live births. Adaptation of the Respiratory System Oxygen consumption increases to in normal pregnancy. This results from ventilationperfusion mismatch from airway narrowing or closure in gravid ACCP Critical Care Medicine Board Review th Edition . Awareness of the determinants of oxygen delivery to the fetoplacental unit is important to maintain fetal viability. Mild hypoxemia and an increased alveolartoarterial oxygen gradient may occur in the supine position as pregnancy progresses. and treatment of the gravid patient in the ICU must take into account both maternal and fetal wellbeing and require a multidisciplinary approach to care. The augmented alveolar ventilation is attributed to respiratory stimulation due to increased levels of progesterone and results from a to increase in tidal volume from to mL while respiratory rate is unchanged to mildly increased Table .Critical Illness in Pregnancy Mary E. during labor. Maternal Pao is increased throughout pregnancy by virtue of augmented minute ventilation. Understanding the normal maternal physiologic adaptation to pregnancy is essential to the accurate diagnosis and treatment of critical illness in the gravid patient. the leading causes of death were embolism. and kidneys to meet the increased metabolic demands of the mother. The increased oxygen consumption and associated increase in carbon dioxide production requires an increase in minute ventilation that begins in the rst trimester and peaks at to above baseline at term. This occurs to meet fetal and placental needs as well as maternal increases in cardiac output and work of breathing. Alveolar ventilation is increased above the level needed to eliminate carbon dioxide. hemorrhage. and placenta. pregnancy. fetus. monitoring. and pregnancyinduced hypertension. circulation. venous thromboembolism Physiology of Pregnancy Adaptive changes occur in the maternal respiratory system. to . Asthma. Knowledge of the normal changes in these organ systems is essential to distinguish between expected adaptive and pathologic ndings so that early recognition and treatment of critical illness during pregnancy is possible. FCCP Objectives Understand the normal physiologic changes of pregnancy Review the causes and management of respiratory disorders in pregnancy Understand the diagnosis and treatment of venous thromboembolism in pregnancy Review the causes. there is a further increase. gastrointestinal system. gestations with a mortality of to . During this period. Adaptation of the Circulation During pregnancy. Typical Arterial Blood Gas Values Variables Nonpregnant Term pregnancy. with a decrease in hematocrit of approximately . makes the pregnant woman and fetus more vulnerable to hypoxia in the event of hypoventilation or apnea. AlveolarArterial Pressure Gradient. individuals during normal tidal breathing Table . Critical Illness in Pregnancy Strek . numerous circulatory adjustments occur that ensure adequate oxygen delivery to the fetus. Diffusing capacity is unchanged or mildly increased early in pregnancy and then decreases to normal or just below normal after the rst trimester. arterial blood gas samples should be obtained in the seated position to avoid the mild positional hypoxemia of pregnancy. g/dL occur.Table . Functional residual capacity decreases progressively to at term as a result of increased abdominal pressure from the enlarged uterus. The decreased functional residual capacity. . reaching a level above baseline by the th week. The increase in maternal blood volume contributes to a to increase in cardiac output. mm Hg To convert millimeters of mercury to kilopascals. The augmented cardiac output results from an increase in heart rate and stroke volume. Direction Increases Unchanged Increases Unchanged Decreases Unchanged Unchanged pregnancy. There is no increase in ejection fraction as calculated from echocardiography. to . Total lung capacity decreases minimally because the function of the diaphragm and thoracic muscles is unimpaired. Respiratory Changes in Pregnancy Parameters Oxygen consumption Respiratory rate Vt Total lung capacity FRC FVC FEV FRC functional residual capacity. The increase in blood volume is greater with multiple births. The increase in stroke volume is due to an increase in preload caused by augmented blood volume and a decrease in afterload from a to fall in systemic vascular resistance SVR. and widening of the thoracic cage results in an increased inspiratory capacity. Maternal blood volume increases early. most of which occurs in the rst trimester and continues throughout gestation Table . with heart rate reaching a maximum of to beats/min above resting nonpregnant levels by weeks to .. FEV. The fall in SVR is attributed both to arteriovenous shunting through the lowresistance uteroplacental bed and hormonally mediated vasodilation. Mild peripheral edema is noted in to of normal pregnancies.. Lung compliance also is unchanged. the ratio of FEV to FVC. Despite increases in levels of many hormones known to affect smooth muscle. When possible. FVC remains unchanged during pregnancy. Expiratory reserve volume and residual volume are decreased during the second half of pregnancy. Parallel decreases in colloid osmotic pressure and serum albumin concentration from . and specic airways conductance are unchanged during pregnancy. . multiply the value by . seated Term pregnancy. supine Pao. mm Hg pH . This is an important consideration during endotracheal intubation. but left ventricular wall thickness and mass increase. Left ventricular enddiastolic pressure remains normal. mm Hg Paco. The fact that owvolume loops are also unaffected by pregnancy is further evidence of normal airway function. which results in diaphragmatic elevation and decreased chest wall compliance Table . the function of large airways does not appear to be altered in Table . The increased number of erythrocytes and even greater increase in plasma volume result in a mild dilutional anemia. when combined with the increased oxygen consumption in pregnancy. with both left Renal and GI Adaptation Renal blood ow increases greatly during pregnancy. Fetal Oxygen Delivery Oxygen delivery to the fetal tissues depends on the oxygen content of uterine artery blood. somewhat lower than baseline . and uterine artery blood ow. The glomerular ltration rate rises early in pregnancy to above baseline at to weeks and remains increased throughout pregnancy. Right ventricular. Exogenous or endogenous sympathetic stimulation and maternal hypotension elicit uterine artery vasoconstriction. Peak decreases in systolic and diastolic pressures average to mm Hg and to mm Hg. In addition. the critically ill gravid patient is more dependent than the nonpregnant individual on cardiac output to maintain oxygen delivery. signicantly increasing the risk of aspiration. and occur at to weeks. Blood pressure then increases gradually. fetal hemoglobin has a higher afnity for oxygen than maternal hemoglobin. The anemia of pregnancy reduces the oxygen content signicantly. returning to baseline shortly after delivery. Lower esophageal sphincter tone decreases during the rst trimester of pregnancy and remains low until near term. This effect on cardiac output. respectively. hemoglobin concentration and saturation. Blood pressure decreases early in pregnancy from peripheral vasodilation. During labor.Table . At all levels of Po. therefore. uterine contraction can increase cardiac output to over resting pregnant levels by increasing blood return from the contracting uterus. uterine artery blood ow and fetal oxygen delivery decrease. to . Circulatory Changes in Pregnancy Parameters Heart rate BP Cardiac output Stroke volume SVR Pulmonary vascular resistance Direction Increases Decreases Increases Increases Decreases Decreases Percentage Time Course Peak at wk Nadir at wk Peak at wk First trimester During the course of pregnancy. This effect is most notable in the third trimester. Should maternal cardiac output fall. pulmonary artery. Numerous factors affect uterine artery blood ow. The gravid uterus displaces the stomach. therefore. serum creatinine is ACCP Critical Care Medicine Board Review th Edition . The chest radiograph reveals an enlarged cardiac silhouette. further reducing the effectiveness of the gastroesophageal sphincter. mg/dL. Basal gastric acid secretion and pH remain unchanged during pregnancy. and pulmonary capillary wedge pressures PCWPs are unchanged from prepartum values in the healthy pregnant woman. as determined by maternal Po. the fetus has a high hemoglobin concentration g/dL and a high systemic cardiac output. In addition. Vena caval obstruction is maximal in the supine position and much less pronounced in the left lateral decubitus position. creatinine levels that would be normal in a nonpregnant patient can indicate renal dysfunction in pregnancy. Labor and narcotic analgesics given during labor delay gastricemptying time. however. maternal alkalosis may cause uteroplacental vasoconstriction with decreased uteroplacental perfusion and fetal hypoxia. may be tempered by blood loss during delivery. compensatory mechanisms maintain fetal oxygen delivery. During pregnancy. cardiac output becomes more dependent on body position because the gravid uterus can cause signicant obstruction of the inferior vena cava with reduced venous return. Despite a low umbilical vein Po of to mm Hg and fetal Pao of to mm Hg at baseline. Diastolic pressures of mm Hg in the second trimester and mm Hg in the third trimester should be considered the upper limits of normal. being to saturated at a Po of to mm Hg. perhaps as a result of increased plasma progesterone levels. Normal adaptation of the circulatory system to pregnancy results in a physiologic third heart sound in the majority of pregnant patients. Fetal oxygen delivery can be decreased by uterine artery vasoconstriction. The uterine vasculature is maximally dilated under normal conditions and therefore unable to adapt to stress by increasing ow through local vascular adjustment. Category X includes drugs contraindicated in pregnancy. Obstetrical consultation and assessment of fetal wellbeing by monitoring fetal heart rate is essential. in onethird it improves. it is important to be aware of the US Food and Drug Administration safety ratings for medication use in pregnancy. redirection of the fetal cardiac output to the brain. The fetoplacental unit is unable to increase oxygen delivery by local vascular adjustment. is protected from hypoxic insult by the avidity of fetal hemoglobin for oxygen relative to maternal hemoglobin. In an individual patient.and right ventricles delivering blood to the systemic circulation. oxygen delivery to maternal and fetoplacental tissue beds is highly dependent on adequate blood ow and maternal oxygen content. In approximately onethird of pregnant asthmatic women. Category A drugs are those in which adequate. including preterm labor. Adverse maternal outcomes in pregnant woman with asthma have been noted. Category B drugs are those with no evidence of fetal risk in humans if animal studies demonstrate risk. Asthma Acute asthma requiring a visit to the emergency department or hospitalization may occur in about of pregnant women cared for by an asthma specialist. Tocolyticinduced pulmonary edema has a much better outcome. asthma does not change. and supplemental oxygen Early elective intubation and mechanical ventilation for respiratory failure Continuous monitoring of fetal heart rate to assess fetal wellbeing Delivery of the fetus may be in the best interest of mother and fetus if the fetus is beyond the age of viability Critical Illness in Pregnancy Strek . affecting to of all gravidas. and decreased oxygen consumption. The institution of mechanical ventilation in the pregnant patient requires careful attention to the special needs of both mother and fetus. An understanding of these physiologic concepts suggests some general principles for management of the critically ill gravid patient Table . In summary. animal ndings are negative. heart. preeclampsia. Protective responses to hypoxic stress include a shift to anaerobic metabolism. Respiratory Disorders of Pregnancy This section focuses on the diagnosis and management of respiratory disorders in the gravid patient. Maternal oxygen consumption increases progressively during gestation and rises further in labor. potential benets may outweigh risks. and the autoregulatory responses of the fetal circulation to hypoxic insult.. and US Food and Drug Administration Drug Classification When prescribing medications for pregnant patients with critical illness. ARDS is infrequent but has a high mortality. the high fetal hemoglobin content and cardiac output. The fetus. Category C agents are those in which risk cannot Table . during pregnancy. Venous thromboembolic disease is the major cause of maternal mortality in the United States. and adrenal glands. and in onethird it worsens. Patients with more severe asthma are more likely to experience worsening asthma during pregnancy. General Principles of Management in Critical Illness in Pregnancy Echocardiogram to assess maternal cardiac function due to high ow state of pregnancy Oxygen delivery to fetus is maximized by adequate maternal circulation. left lateral decubitus position. however. wellcontrolled studies in pregnant women have not demonstrated a risk to the fetus. Asthma is the most common disease to complicate pregnancy. Category D includes agents with evidence of fetal risk by virtue of investigation or postmarketing human data in critical illness. Asthma typically worsens during the second and third trimesters. the course of asthma during pregnancy is variable. human ndings do not. with improvement during the last month of pregnancy. or if human studies are not adequate. be ruled out but potential benets may outweigh risk human studies are lacking and animal studies are either positive for fetal risk or lacking. tachycardia. More cases of DVT in pregnancy are ileofemoral and more likely to embolize than in the nonpregnant individual. Negative ddimer result helpful . black race. Because epinephrine causes vasoconstriction of the uteroplacental circulation in animal studies. heart disease. may decrease the work of breathing and preclude intubation and mechanical ventilation when administered to patients in status asthmaticus. VTE Pulmonary embolism PE is the leading cause of pregnancyrelated death in the United States. obesity. Thrombolytic therapy an option Inferior vena cava lter below renal veins Partial thromboplastin time monitoring Warfarin long term Pregnant .cesarean delivery. An arterial blood gas with a Paco of mm Hg during status asthmaticus may be a sign of impending ventilatory failure. Indications for mechanical ventilation include hypercapnia. Challenging Problems in Management of Pregnant Patients vs Nonpregnant Patients With VTE Nonpregnant . Compression ultrasonography of legs helpful . thought to be due to stasis in the left iliac vein caused by increased compression where it is crossed by the right iliac artery as the gravid uterus enlarges. Adverse fetal outcomes include preterm birth and infants small for gestational age. Crosses placenta and contraindicated ACCP Critical Care Medicine Board Review th Edition . Known risk factors include age years. and mild lowerextremity edema are often noted in normal pregnancy. a lowdensity mixture of helium and oxygen. CT angiography safe for fetus. Most asthma medications are safe for use during pregnancy. . Inferior vena cava lter placed suprarenally . Hypercoagulable states less common . altered consciousness. Heliox. maternal exhaustion. parenteral terbutaline is preferred but may inhibit labor and cause pulmonary edema if administered near term. Pregnant women occasionally Table . sickle cell disease. diabetes. Inhaled albuterol should be administered every min or continuously and may be mixed with ipratropium bromide. There is a to incidence of left leg DVT. The management of the pregnant patient with status asthmaticus is similar to that of the nonpregnant patient. Antifactor Xa heparin level may be preferable . Thrombophilia increases the risk even further and is noted in approximately of woman with VTE during pregnancy. Less accurate for isolated calf and iliac vein thrombosis . The diagnosis of VTE requires a high index of suspicion because dyspnea. Hypercoagulability. with a few exceptions. all pregnant women are at increased risk of VTE. The specics of mechanical ventilation will be discussed later. Use of parenteral agonists is limited to the rare situations in which inhaled agents have been ineffective. venous stasis. Deep venous thrombosis DVT and subsequent PE occurs in all three trimesters and the postpartum period. Underlie of cases of VTE in pregnancy . Guidelines for managing asthma in pregnancy have been updated and are readily available online. Diagnosis and treatment of both DVT and PE are more complicated in pregnancy Table . Mild hypoxemia should be treated aggressively because it may be detrimental to the fetus. and endothelial damage to pelvic vessels during delivery or cesarean section all occur in normal pregnancy. increases future risk maternal breast cancer . lupus. Systemic corticosteroids are given for acute asthma exacerbations.. and fetal distress. smoking. Riskier and contraindicated at term . . thus. cesarean section. An IV infusion of magnesium sulfate can be considered for its potential bronchodilator effect in refractory cases as long as the patient is monitored carefully for respiratory depression. and multiple pregnancies. CT angiography safe . Helpful if compression ultrasonography ndings are normal . . given the baseline respiratory alkalosis in normal pregnancy. Studies show that active treatment of the gravid patient to control asthma improves both maternal and fetal outcomes. Cesarean section in refractory cases has been successful and should be considered when fetal viability is likely. The risk of VTE is increased fourfold during pregnancy. Amniotic Fluid Embolism Amniotic uid embolism is a rare occurrence but is estimated to account for of maternal deaths. Although most cases occur during labor and delivery or immediately postpartum. Risk factors may include advanced maternal age. a normal perfusion lung scan rules out PE and avoids the extra radiation exposure from the ventilation scan. treatment with lowmolecularweight heparin LMWH should be begun while diagnostic testing is pursued. a negative ddimer test result with a highly specic assay in the rst and second trimester makes DVT unlikely. Because the ddimer increases as pregnancy progresses. with the advantage of providing additional imaging of the chest. Radiation exposure to the fetus from either test is low and within the amount considered safe in pregnancy. The current guidelines suggest that the decision to make dose adjustments and monitor heparin levels should be based on the clinicians judgment and experience. so the dose may be adjusted based on increased weight or periodic antifactor Xa LMWH levels performed to h after injection with dose adjustments to achieve an antifactor Xa level of . a ventilation scan is performed and anticoagulation is begun for a highprobability study. which has a high sensitivity for iliac vein thrombosis and is not harmful to the fetus. especially during the initial treatment phase. CT pulmonary angiography is performed rather than a ventilationperfusion lung scan. For patients with heparininduced thrombocytopenia. a positive ddimer test requires further imaging with magnetic resonance direct thrombus imaging. Compression ultrasonography is the diagnostic test of choice. amniotic Critical Illness in Pregnancy Strek . In a pregnant woman with suspected PE. compared with CT angiography. Echocardiography may be useful to document rightsided clot or rightheart strain. anticoagulation with heparin is begun. and the clinical presentation alone cannot be relied on to diagnose or exclude VTE. Current guidelines favor LMWH because of the decreased risk of bleeding and heparinrelated thrombocytopenia and osteoporosis with these agents. multiparity. It is important to make a denitive diagnosis.. with anticoagulation continued for at least weeks postpartum. the potential volume of distribution for LMWH changes. fever. and trauma. and anticoagulation is begun. It is important to remember that patients may be without symptoms and have a normal physical examination. Adjusteddose subcutaneous LMWH or IV adjusteddose unfractionated heparin is recommended for treatment of acute VTE. slightly increases the risk of childhood cancer in the offspring but has a lower risk of maternal breast cancer. danaparoid a lowmolecularweight heparinoid or fondaparinux a synthetic pentasaccharide and direct inhibitor of factor Xa may be given. Thrombolysis can be performed safely in pregnancy. In patients suspected of having DVT who have negative compression ultrasonography results.. U/mL. and possible fetal hemorrhage. In patients with asthma or an abnormal chest radiograph. Recombinant tissue plasminogen activator does not cross the placenta and is the preferred thrombolytic agent. Subcutaneous heparin should be continued throughout the duration of pregnancy. or repeat compression ultrasonography in to days. Once a diagnosis of either DVT or PE is made. Previously the mortality rate has been reported to be to . This is the treatment of choice because heparin does not cross the placenta. Ventilationperfusion lung scanning. A positive study is considered sufcient to justify treatment. although there is the potential risk of maternal or fetal hemorrhage and fetal loss. so a high clinical suspicion must be maintained. to .present with lower abdominal pain. small incidence of fetal central nervous system abnormalities throughout pregnancy. If DVT or PE is suspected. with negativecompression ultrasonography of the legs. but more recent series suggest it is much lower . As the pregnancy progresses. Lifethreatening VTE should prompt consideration of thrombolytic therapy. although it is less accurate for isolated calf and iliac vein thrombosis. The halflife of LMWH is shorter in pregnancy so twicedaily dosing may be preferable. Warfarin crosses the placenta and is absolutely contraindicated category X because of the high incidence of embryopathy in the rst trimester. If the lung scan nding is abnormal. Most survivors develop permanent neurologic decits from cerebral hypoxia. and an elevated WBC count mimicking acute appendicitis. turbulent labor. dizziness. Cytologic examination of pulmonary artery catheter blood may show fetal squamous cells and lanugo hairs but is not sufcient to make the diagnosis because small numbers of fetal squamous cells have been observed in patients without clinical evidence of amniotic uid embolism. acid aspiration. The history and clinical ndings should help in distinguishing this disorder from acute thromboembolic disease. and inhaled nitric oxide are some of the treatments described to be of benet in small case reports. especially cesarean delivery. Entry of amniotic uid and fetal products into the maternal circulation may result in an inammatory cascade or anaphylactoid syndrome of pregnancy. Most patients complain of chest discomfort and dyspnea. and controlling bleeding. After administration of oxygen. and positive endexpiratory pressure PEEP often are required. Most of the reported cases have resulted from use of IV mimetics such as ritodrine. and diaphoresis. and surgical procedures. continuous hemoltration. IV corticosteroid therapy. relaxation of . tachycardia. and invasive hemodynamic monitoring is usually not required. and diuresis. plasma exchange transfusion. they manifest tachypnea and tachycardia with crackles on lung auscultation. central venous access. mechanical ventilation. orogenital sex. Venous Air Embolism Venous air embolism may occur during normal labor or delivery. factor replacement and freshfrozen plasma are given based on laboratory ndings and bleeding. Vasoconstriction of the pulmonary vasculature is thought to cause hypoxia and rightheart failure followed by leftheart failure with shock and pulmonary edema. Most women have intact membranes at the time of presentation. Symptoms include chest pain. tachypnea. The classic presentation is the abrupt onset of severe dyspnea. tachypnea. When pulmonary edema develops postpartum. the vast majority of cases are encountered within h of delivery. isoxuprine.and secondtrimester abortions. Hyperbaric therapy may benet patients with paradoxic cerebral embolism. Fluid resuscitation and vasopressors may reverse hypotension. terbutaline.uid embolism occurs up to h after delivery and during rst. Sudden hypotension is usually followed by respiratory arrest. concurrent infection. abortions. A millwheel murmur or bubbling sound is occasionally heard over the precordium. Response is usually rapid. The course of this disease is usually benign. and arrhythmias have been noted on the ECG. The patient should be given oxygen in an effort to decrease the size of the embolus by removing nitrogen. and salbutamol. Factors that increase the risk of aspiration in the pregnant woman include the increased intragastric pressure that results from external compression by the enlarged uterus. and have pulmonary edema on chest radiography. and those receiving corticosteroid therapy. Once DIC is established. Tocolytic Therapy Pulmonary edema associated with adrenergic agents that are administered to inhibit preterm labor is seen in up to of women receiving these drugs. the patient should be placed immediately in the left ACCP Critical Care Medicine Board Review th Edition Aspiration Aspiration is an uncommon but welldescribed and ominous complication of the peripartum period. lateral decubitus position and Trendelenburg to direct the air embolus away from the right ventricular outow tract. A positive uid balance is often noted in the hours to days preceding the onset of symptoms. There is an increased incidence in women with multiple gestations. ARDS may develop in patients who survive the initial cardiopulmonary collapse. oxygen administration. When venous air embolism is suspected. with resolution of tachypnea and hypoxemia often occurring within hours. Pulmonary edema typically develops during tocolytic therapy or within h after the discontinuation of these drugs.. intubation. Treatment consists of discontinuation of tocolytic therapy. stabilizing the circulation. The third phase involves neurologic impairment with seizures and coma. ischemia. dyspnea. Disseminated intravascular coagulation DIC is common. and hypoxemia in association with cardiovascular collapse and altered mental status. Treatment is supportive and aimed at ensuring adequate oxygenation. and amniotic uid embolism. Rightheart strain. Amphotericin B should be used to treat disseminated coccidioidal infections in pregnancy. zanamivir. In the pregnant woman. cephalosporins. It is the most common cause of AIDSrelated death in pregnant women in the United States. and opportunistic infection. and sulfacontaining regimens should be avoided near term except for the treatment of PCP.. The early injury is a chemical pneumonitis followed by the development of ARDS. Active tuberculosis during pregnancy is treated with isoniazid. and fetal mortality. Favorable results have been obtained using acyclovir to treat pregnant women with varicella pneumonia. A late complication of aspiration is the evolution to bacterial pneumonia. Injury due to aspiration of gastric contents is related to the volume of aspirated material. Prevention of this dread complication should be the primary goal of all physicians assessing and managing the patients airway. Pneumonia Pneumonia during pregnancy most often occurs from communityacquired bacterial organisms. and should not be used in pregnancy. and rimantadine are category C. Recommendations have been made to use them in patients who contract inuenza in the third trimester and in patients with cardiopulmonary disease. These medications cross the placenta. Coccidioidomycosis is the fungal infection associated with increased risk of dissemination during pregnancy. Corticosteroids are added if clinically indicated. Critical Illness in Pregnancy Strek . the presence of particulate material. Testing for HIV infection and antiretroviral therapy to prevent vertical transmission are standard of care in the pregnant patient. No teratogenic effects have been noted in animal studies of acyclovir. Primary infection with varicellazoster virus progresses to pneumonia more often in adults than in children. and ethambutol plus pyridoxine until drug susceptibility testing is complete. rifampin. as is usually the case in the nonpregnant population. especially when used early. Obstetric complications of pneumonia include preterm labor. and azithromycin are safe. Penicillins. Antibiotics should be given only if bacterial pneumonia develops.the lower esophageal sphincter resulting from use of progesterone. with respiratory failure requiring mechanical ventilation occurring in of patients and a mortality rate of . HIV infection is complicated by the risk of perinatal transmission to the fetus. Its use near term can increase the risk of fetal kernicterus. Drugs used to treat inuenza oseltamivir. Some azole antifungal agents are category D and are known teratogens in animals. Pregnant women may have more frequent inuenzarelated morbidity. especially if it is contracted in the third trimester. Tetracycline and chloramphenicol are contraindicated. preterm delivery. treatment is supportive and is similar to that for the nonpregnant individual. but are not teratogenic. especially pneumonia. preterm delivery. its acidity. Fetal mortality is also high and may be worse if PCP occurs during the rst or second trimester. No adverse effects on the fetus have been reported for amphotericin. amantadine. They should not be used in pregnancy. as for the nonpregnant patient. and depressed mental status and vocal cord closure from analgesia. with asthma and anemia increasing the risk. An increased incidence of inuenza pneumonia was noted among pregnant patients during the and inuenza pandemics. with death from fulminant inuenza pneumonia. rather than secondary bacterial infection. Pneumocystis pneumonia PCP may complicate pregnancy and be especially virulent. PCP is treated with trimethoprimsulfamethoxazole. With appropriate chemotherapy. The choice of antibacterial agents should take into account potential fetal toxicity. Once aspiration has occurred. and host resistance to subsequent infection. which results in an improved outcome compared with other therapies. the prognosis for pregnant women with tuberculosis is excellent. the bacterial burden of the aspirated material. delayed gastric emptying during labor. Respiratory failure requiring mechanical ventilation and maternal mortality also occur. Streptomycin is the only antituberculosis drug with documented harmful effects on the human fetus. The clinical presentation is not altered by pregnancy. continuous fetal heart rate monitoring. Control of the airway should be achieved by a skilled individual. increased intraabdominal pressure from compression by the gravid uterus. sufcient PEEP should be used to correct arterial hypoxemia at a nontoxic fraction of inspired oxygen . and nasotracheal intubation is best avoided.ARDS Many of the respiratory disorders previously discussed can cause acute lung injury and ARDS during pregnancy Table . no adverse effects were noted when Pco was maintained at mm Hg. The patient with ARDS should be ventilated with a small Vt to mL/kg and a high respiratory rate to breaths/min to avoid ventilatorinduced lung injury. values higher than that used ACCP Critical Care Medicine Board Review th Edition . Problems With Airway Management Upper airway edema Diminished airway caliber Propensity for bleeding Increased risk of aspiration may be necessary. In the awake patient needing temporary ventilatory assistance. chorioamnionitis. and the highly vascular upper airway may bleed from even minor intubationrelated trauma. supportive care. the aim is to keep the Pao mm Hg or oxygen saturation . a low Vt ventilation strategy.. In the pregnant patient. laryngeal. endometritis. In summary. Pharyngeal. and close monitoring of the fetus. the use of a lower tidal volume Vt and respiratory rate minimizes the adverse effects of intrinsic PEEP. In the asthmatic patient. There is an increased risk of aspiration during pregnancy because of delayed gastric emptying. chest wall stiffness from the gravid uterus may cause high airway pressures unrelated to lung stiffness or overdistention. Intubation and mechanical ventilation are usually necessary. Ventilatory changes associated with fetal distress by fetal heart rate monitoring should be avoided. The management of ARDS is directed at treatment of the underlying cause. septic abortion Pneumonia Aspiration Trauma Preeclampsia Obstetric hemorrhage Amniotic uid embolism Venous air embolism Obstetric hemorrhage and transfusions Table . endometritis. although it is important that intubation occur in an early and elective fashion. transfusion. septic abortion. and allowing plateau airway pressures to be slightly higher than normal are recommended in these patients. avoiding rapid rises in Paco. Respiratory alkalosis should be avoided because animal models suggest that hyperventilation can reduce fetal oxygenation by decreasing uteroplacental blood ow. Fetal distress and premature labor are common. noninvasive positive pressure ventilation is a reasonable rst step but the patient must be monitored closely. and vocal cord edema are common. Noninvasive mask ventilation for acute respiratory failure has not been studied in pregnancy. Initial ventilator settings should aim for eucapnia Pco of to mm Hg. and diminished competence of the gastroesophageal sphincter. Theoretical limitations include pregnancyrelated upper airway edema and increased risk of aspiration. During the third trimester of pregnancy. and eclampsia as well as the more typical causes of ARDS such as sepsis. pregnancyspecic causes such as placental abruption. In addition. Several difculties in airway management should be anticipated Table . and trauma may occur. Acute lung injury is more likely to result in pulmonary edema given the increased plasma volume and decreased plasma oncotic pressure noted in pregnancy.. The safety of permissive hypercapnia in pregnancy has not been studied but in the few case reports of lungprotective ventilation in pregnancy. Use of cricoid pressure to minimize the risk of pulmonary aspiration is recommended. Relatively small endotracheal tubes to mm in diameter Table . Mechanical Ventilation The indications for intubation and mechanical ventilation are not signicantly changed by pregnancy. Causes of ARDS in Pregnancy Sepsis chorioamnionitis. When ARDS is present requiring high levels of oxygen. in the nonpregnant patient. disruption of an abnormal placental attachment placenta previa. Circulatory Disorders of Pregnancy In pregnancy. When this procedure is necessary. and previous abruption. Antepartum hemorrhage is most often caused by premature separation of the normal placental attachment site placental abruption. cardiac dysfunction. To prevent the gravid uterus from limiting the effectiveness of chest compressions. Rightheart catheterization has not been shown to improve mortality in nonobstetric critical illness. In the healthy pregnant woman. a subclavian or internal jugular approach is recommended. and sepsis. and spontaneous uterine rupture. Cardiac output is increased. Most often the state of perfusion can be determined by bedside assessment. necessitating immediate intervention. produce no adverse fetal effects with shortterm use. the best survival rate for infants occurs when delivery is no more than min after the mothers heart stops beating. The initial approach to the critically ill hypoperfused gravida is to distinguish between lowow states. Should resuscitation be unsuccessful. Femoral vein catheterization is relatively contraindicated because of obstruction of the vena cava by the uterus and the possible need for emergent delivery. The femoral vein should not be used for venous access because drugs administered through these sites may not reach the maternal heart. therefore. it is important that the pregnant patient be managed in a lateral position whenever possible. caused by inadequate circulating volume. pulmonary artery. An emergency hysterotomy may save the life of both the mother and the fetus if gestational age is weeks. Nondepolarizing neuromuscular blocking agents. high parity. Of these. and in patients with hemodynamic instability. To minimize the decrease in venous return that occurs with positive pressure ventilation. the patient should be placed to from the left lateral position by use of a wedge under the right hip or by pulling the gravid uterus manually to the side. It is the second most common cause of maternal death and a common reason for admission to the ICU.. right ventricular. and much of this may remain concealed within the uterus. The severity of maternal blood loss is correlated with the extent and duration of abruption and fetal demise. Hemorrhage in pregnancy can be massive and swift. Common causes of hypoperfusion include hemorrhage. Placental abruption occurs in patients with hypertension. and SVR and pulmonary vascular resistance are decreased during pregnancy. including cisatracurium. suggest echocardiography may be an alternative to invasive monitoring. or trauma. cardiac dysfunction. Narcotic analgesics such as morphine sulfate and fentanyl may be used safely during pregnancy. certain modications to resuscitation algorithms are required. Left and right ventricular hemodynamics assessed by echocardiography correlated with pulmonary artery catheter pressures in a heterogenous group of critically ill obstetric patients. In patients with ARDS requiring high levels of PEEP. vecuronium. Hemorrhagic Shock The common causes of hemorrhagic shock in pregnancy are listed in Table . while keeping in mind the physiologic alterations of pregnancy. Fetal or uterine monitors should be removed prior to delivering shocks. and highow states such as septic shock. cisatracurium is preferred because it does not depend on renal or hepatic function for elimination. Should cardiac arrest occur. Maternal complications include Critical Illness in Pregnancy Strek . to prevent fetal distress. and atracurium. circulatory impairment may be lifethreatening because mother and fetus depend on cardiac output for oxygen delivery.. These agents all cross the placenta. and PCWPs are unchanged from prepartum values. The best hope of fetal survival is maternal survival. Benzodiazepines may increase the risk of cleft palate when used early in pregnancy. if administered near the time of delivery. immediate intubation of the neonate may be required. trauma. cigarette or cocaine use. Blood loss averages to L when abruption results in fetal death. Preeclampsia is a vascular disorder unique to pregnancy that is associated with maternal hypertension. muscle relaxation and sedation may decrease oxygen consumption. Chest compressions should be performed higher on the sternum to adjust for the elevation of the diaphragm and abdominal contents caused by the gravid uterus. pancuronium. Placenta previa infrequently causes massive hemorrhage because ultrasound examination during pregnancy leads to identication prior to delivery. Fetal monitoring is important because fetal distress in the setting of obstetric hemorrhage indicates hemodynamic compromise. or cesarean section. peritoneal signs may be observed. Some injuries are unique to pregnancy. and assaults. Patients may initially present with painful vaginal bleeding and be misdiagnosed as having premature labor. surgical obstetric trauma. The cephalad displacement of abdominal contents in pregnancy increases the risk of visceral injury from penetrating trauma of the upper abdomen. retained placental tissue. Because critical illness in pregnancy is frequently associated with DIC. Substantial blood loss can occur in the absence of signicant physical ndings. uterine rupture. along with supplemental oxygen. Massive obstetric hemorrhage is a setting in which initial resuscitation may require the use of unmatched typespecic blood until more complete crossmatching can be accomplished. or as a result of retained intrauterine contents or chorioamnionitis. operative assisted vaginal delivery. The gravid woman is at greater risk of hemorrhage after trauma. The diagnosis is made using clinical information and ultrasound. Borderline tachycardia and supine hypotension may be caused by pregnancy itself. The urinary bladder is a target for injury because it is displaced into the abdominal cavity beyond weeks of gestation. or if trophoblastic tissue invades the myometrium placenta previa et accreta. Immediate volume replacement with crystalloid is instituted until blood is available. In most cases. the patient is at risk for massive hemorrhage at delivery. uterine inversion. If shock is not immediately reversed by volume resuscitation or is accompanied by respiratory dysfunction. if vaginal examination results in disruption of the placenta over the cervical os. falls.Table . The initial management of the patient is similar to that of the nonpregnant patient. and thus vital signs may not indicate signicant blood loss. as blood ow to the entire pelvis is increased. overdistention of the uterus from multiple gestation or hydramnios. Etiology of Hemorrhagic Shock in Pregnancy Early Trauma Ectopic or abdominal pregnancy Abortion DIC Hydatidiform mole Late Third Trimester Trauma Placenta previa or abruption Uterine rupture DIC Marginal sinus rupture Postpartum Uterine atony Surgical trauma Uterine inversion DIC Retained placenta acute renal failure and DIC. oxytocin administration. Common causes of postpartum hemorrhage include uterine atony. Other risk factors include prior cesarean section. In overt rupture. . placental abruption. premature labor. Uterine rupture typically occurs spontaneously in the multipara with protracted labor. abruptio placentae. massive bleeding should prompt an evaluation for a coagulopathy. elective intubation and mechanical ventilation are indicated. Rapid deceleration injury can cause placental abruption as a result of deformation of the elastic uterus around the less elastic placenta. Blood replacement with packed red blood cells should begin immediately. including splenic rupture. and two or three largebore gauge venous catheters should be inserted. it signies enormous blood loss because of the expanded blood volume associated with pregnancy. Hypoperfusion and shock may occur as a result of injury from motor vehicle ACCP Critical Care Medicine Board Review th Edition accidents. Fetal mortality is low. and coagulopathies due to DIC. Nonetheless. The patient should be placed in the left lateral decubitus position. The physiologic changes of pregnancy make evaluation and treatment of the gravid patient more difcult. including amniotic membrane rupture. and fetal trauma. Hemorrhage from surgical obstetric trauma may be due to cervical or vaginal lacerations or uterine incision for cesarean section. Trauma is a leading cause of nonobstetric maternal mortality. vaginal bleeding will be present when abruption has occurred. and use of uterotonic agents. When hypovolemia is clinically evident in gravid patients. Uterine atony occurs after prolonged labor. Patients at increased risk of bleeding should be identied early so that IV access and blood typing can be done. smoking. mediastinal widening is often noted in patients with aortic dissection. The chest radiograph may suggest the diagnosis. or remove the uterus may be necessary when these measures fail. Ergot preparations such as methylergonovine have been associated with cerebral hemorrhage and are contraindicated if the patient is hypertensive. to . the initial management should focus on volume status. When cardiogenic shock persists despite inotropic drug support. Balloon tamponade. Oxytocin can cause hyponatremia by virtue of its antidiuretic effect. afterload reduction with nicardipine should be considered.Measurement of factor VIII levels is inexpensive and can be accomplished more quickly than a full DIC screen. IV sodium nitroprusside or nitroglycerin is a secondline agent. and hypovolemia should be excluded. Massive blood loss can result in a dilutional coagulopathy with secondary thrombocytopenia. New York Heart Association class III or IV or cyanosis. Myocardial infarction is uncommon but should be considered in the hypoperfused patient with chest pain. It is essential to identify the exact cause of the underlying cardiac dysfunction and hypoperfusion. draining the bladder. Alternatively. Predictors of maternal cardiac complications include prior cardiac events. Ultrasonography is used to diagnose retained intrauterine products of conception that require curettage. Thrombotic complications are a rarely reported side effect of this medication. Uterine atony is treated with uterine massage. should be substituted as soon as possible to avoid nitroprusside toxicity. Aortic dissection presents most commonly during the third trimester. prostaglandin analogs such as carboprost tromethamine can be used to improve uterine contraction and decrease bleeding. or pulmonary hypertension have a mortality rate of up to during pregnancy. Echocardiography can help determine the volume status and detect valvular abnormalities. and the dose and duration of therapy should be minimized. Surgical exploration to repair lacerations. and IV oxytocin. and uterine artery embolization may control hemorrhage in many cases. Pulse asymmetry or aortic insufciency may be noted on examination. leftheart obstruction. myocardial dysfunction. deliveries. perhaps related to the increased shear stress on the aorta associated with pregnancy. cyanotic congenital heart disease. Bacterial endocarditis has been reported. compression sutures. twin gestations. or ischemia. and postpartum hypertension. Oral agents. Prior subclinical heart disease may manifest itself for the rst time during pregnancy owing to the physiologic changes of pregnancy previously described. Recombinant factor VIIa has been used successfully in the management of severe obstetric hemorrhage and is thought to be most effective when used early. Once the cause of cardiac dysfunction is determined. Vasoactive drugs are reserved for situations in which hypovolemia has been corrected and maternal perfusion remains inadequate. Transesophageal echocardiography and MRI are the most sensitive and specic tests for detecting aortic dissection. When cardiogenic shock is complicated by pulmonary edema. peripartum cardiomyopathy presents in the last month of pregnancy or the rst months after parturition. preeclampsia. Heart disease during pregnancy is uncommon but increases the likelihood of maternal and fetal morbidity and mortality. particularly in patients with a history of IV drug use. Risk factors include race. parenteral furosemide should be given. In of every . which needs to be corrected. Side effects include hypertension. Neonatal complications are associated with poor functional class or cyanosis. anticoagulation. aortic or mitral stenosis. although CT scan of the chest is often done rst given its ready availability. older age. dobutamine is the drug of choice. and multiple gestations. There is an increased incidence of aortic dissection during pregnancy. If cardiogenic shock persists despite an adequate preload. ligate the uterine artery. multiparity. and left ventricular systolic dysfunction. such as hydralazine or labetalol. anemia. often as a tearing interscapular pain. Cardiogenic Shock Shock from cardiac dysfunction is most often caused by congestive heart failure due to preexisting myocardial or valvular heart disease or to a cardiomyopathy arising de novo. bronchoconstriction. and intrapulmonary shunt with arterial oxygen desaturation. Angiotensinconverting enzyme inhibitors are absolutely contraindicated during pregnancy because they Critical Illness in Pregnancy Strek . Patients with Eisenmenger syndrome. uterine tenderness. increased cardiac output. Bacterial Infections Associated With Sepsis in Pregnancy and Postpartum Obstetric Postpartum endometritis Chorioamnionitis intraamniotic infection Septic abortion Septic pelvic thrombophlebitis Antepartum pyelonephritis Nonobstetric Appendicitis Cholecystitis Pyelonephritis Pneumonia Invasive procedures Abdominal wall or perineal incisions necrotizing fasciitis Amniocentesis/chorionic villus sampling septic abortion Infected cerclage chorioamnionitis Reprinted with permission from Fein AM. abdominal pain and tenderness. chorioamnionitis. Patients with endometritis may present with fever. and its vasodilatory actions may be of benet in patients with congestive heart failure. Although evidence of myocardial depression is . antepartum pyelonephritis. and anuric renal failure in human neonates exposed in utero. Rarely. pregnant patients have an increased susceptibility to infection with Listeria monocytogenes and disseminated herpesvirus and coccidioidomycosis infections. oligohydramnios. An awareness of the usual settings and patients at risk will increase the chance of recognizing this lifethreatening state. with recent reports of this occurring after medical abortion with oral agents. or pulmonary hypertension. Labor and delivery is an especially dangerous time for women with cardiac disease. Because decreased SVR may lead to further decompensation in patients with aortic stenosis. Animal data suggest that pregnancy may cause increased vulnerability to the systemic effects of bacteremia and endotoxemia. but occasionally reects hematogenous spread from maternal bacteremia. The common causes of sepsis in pregnancy include septic abortions. Toxic shock syndrome may also result from infection with Clostridium sordellii. cesarean sections are safer than in the past. Sepsis in obstetric patients occurs postpartum following cesarean section. decreased SVR. Sepsis in pregnancy. Septic Shock The diagnosis of sepsis in the febrile gravid patient can be obscured by the normal hemodynamic changes of pregnancy ie. congenital malformations. Epidural anesthesia will ameliorate tachycardia in response to pain. as well as neonatal death. Episiotomy sites and cesarean section incisions are less common sources of postpartum infection. Patients present with fever.cause fetal growth retardation. although with improved surgical techniques and close hemodynamic monitoring. hypertrophic cardiomyopathy. Cesarean section should be reserved for patients with obstetric complications or fetal distress. A wide range of Grampositive. perhaps owing to a decreased cellmediated immune response during pregnancy. and Clostridium spp may cause gas gangrene of the uterus. and purulent lochia. Infection at the placental site results in endometritis. and anaerobic organisms must be considered. In addition. general anesthesia may be preferred in these patients.. Table . Clin Chest Med . prolonged rupture of membranes. Gramnegative. toxic streptococcal syndrome may occur as a result of infection with pyrogenic exotoxin Aproducing group A streptococci in patients with necrotizing fasciitis or may unexpectedly follow an uncomplicated pregnancy and delivery. and postpartum infections Table . Lifethreatening wound infection with group A streptococci results in necrotizing fasciitis. The optimal method of delivery is an assisted vaginal delivery in the left lateral decubitus position. or prior instrumentation of the genitourinary tract. Duvivier R. Chorioamnionitis or intraamniotic infection occurs most commonly after prolonged rupture of membranes or prolonged labor or after invasive procedures such as amniocentesis ACCP Critical Care Medicine Board Review th Edition or cervical cerclage. The hemodynamic prole in septic shock is similar to that of the nonpregnant septic patient. maternal and fetal tachycardia. and foulsmelling amniotic uid. Invasive monitoring or echocardiography may be required to follow shifts in volume status that occur from the tremendous autotransfusions produced by each uterine contraction during labor and the blood loss that occurs with delivery. known as soluble fmslike tyrosine kinase . The role of vasopressin in the pregnant patient with septic shock remains undened. however. or high. Mechanical ventilatory support should be instituted if needed. the predominant abnormality is highoutput hypotension with a decreased SVR. It occurs most often in nulliparous women after the th week of gestation. It complicates to of all pregnancies. An increased ratio of serum soluble fmslike tyrosine kinase to placental growth factor is thought to show promise as a biomarker for preeclampsia. preeclampsia is characterized by hypertension. diabetes mellitus. causing to of maternal deaths.. norepinephrine may be used. and packed RBCs and inotropes to increase central venous oxygen saturation of . Early goaldirected therapy improves survival in the nonpregnant population. with possible hysterectomy. and SVR is increased. The septic gravid patient requires thorough culturing and evaluation of pelvic sites. Recommended vasoactive drugs are ephedrine and dopamine. maternal or paternal family history of preeclampsia. proteinuria. but epinephrine should be avoided.often present. Ultimately. and meticulous supportive care. making the diagnosis of early disease difcult in many cases. and generalized edema. leading to maternal endothelial dysfunction. and it is impossible to make informed commentary on its risk/benet prole in this setting. Complications of sepsis in pregnancy include ARDS and DIC. endothelial damage. identication and control of the source of infection with surgical treatment if necessary. Clinically. Although the exact pathogenesis is not known. and anaerobic organisms is administered until specic cultures are available. As in the nonpregnant septic patient. Close fetal monitoring is required as dopamine and norepinephrine can decrease uterine blood ow. Postpartum deterioration in septic patients receiving antibiotics suggests a localized abscess. these features may be mild and may not occur simultaneously. Goals include uid to achieve a central venous pressure to mm Hg. neutralizes the proangiogenic actions of vascular endothelial growth factor and placental growth factor. Rightheart catheterization reveals low normal right atrial pressure and PCWP. typically near term. Empiric antibiotic therapy to cover polymicrobial infection involving Grampositive. besides the primigravid state. in certain patients. include preexisting and gestational hypertension. a resistant organism. The essentials of treatment are early appropriate antibiotics. maternal age years. When necessary. vasoconstriction. an aminoglycoside. it may begin with placental hypoperfusion from abnormally formed uteroplacental spiral arteries. and microthrombi affect multiple organ systems. Chorioamnionitis associated with sepsis requires delivery of the fetus. or another broadspectrum agent. Preeclampsia may progress without Critical Illness in Pregnancy Strek . Gramnegative. an exaggerated inammatory response. multiple gestation. Cardiac output and plasma volume are decreased. it is necessary to expand the initial regimen to a semisynthetic penicillin. Recombinant protein C has not been systematically evaluated in pregnant patients. but institution of an infusion at to milliunits per hour is reasonable in refractory shock. and antiphospholipid antibody syndrome. and may even occur postpartum. corticosteroids are given if adrenal insufciency is documented. the use of vasoactive agents to achieve a mean arterial pressure to mm Hg. may be required. body mass index . preexisting renal disease. or septic pelvic thrombophlebitis. particularly in patients with myometrial microabscesses or gas gangrene from clostridial species. Cardiac output may be low. Excess production of placentaderived vascular endothelial growth factor receptor. It is best to avoid aminoglycosides in patients with sepsis antepartum because these agents can be ototoxic and nephrotoxic to the fetus. Surgical drainage of appropriate pelvic and abdominal sources. Reasonable regimens include clindamycin and a thirdgeneration cephalosporin. Risk factors for the development of preeclampsia. normal. The corticotropin stimulation test may be difcult to interpret in the pregnant woman because baseline cortisol may be elevated in pregnancy and stimulation tests have not been studied in this population. with dobutamine the inotrope of choice. Preeclampsia Preeclampsia is a disorder unique to pregnancy that accounts for a substantial proportion of obstetric ICU admissions. the most common being ACCP Critical Care Medicine Board Review th Edition malaise. ARDS. and idiopathic postpartum renal failure. Intrahepatic hemorrhage or subcapsular hematoma occurs in of patients and may progress to hepatic rupture. antepartum pulmonary edema may develop. Patients less frequently present with jaundice. or rupture. The differential diagnosis of preeclampsia includes thrombotic thrombocytopenic purpura TTP. epigastric or right upper quadrant pain. Immediate delivery is appropriate when there are signs of impending eclampsia. Maternal complications of severe preeclampsia include seizures eclampsia. GI bleeding. elevated liver enzymes. Delivery is curative in most cases. multiorgan involvement. in one large clinical series of eclamptic patients had a diastolic BP mm Hg or no proteinuria prior to experiencing convulsions. The HELLP syndrome is characterized by multiorgan dysfunction arising from dysfunction with secondary brin deposition and organ hypoperfusion./L. Laboratory values that suggest the HELLP syndrome include hemolysis on peripheral smear. Although hydralazine has been the traditional treatment. and glomerular disease characterized by swollen glomerular endothelial cells known as glomeruloendotheliosis. there is no clear benet to antihypertensive drug treatment in women with mild gestational hypertension or preeclampsia. pulmonary edema. A microangiopathic hemolytic anemia and consumptive coagulopathy develop. Renal dysfunction may result from intravascular volume depletion. Based on a number of clinical trials. and a platelet count of . close medical observation. the HELLP syndrome. and hepatic infarction. nausea. vomiting. Maternal and fetal morbidity and mortality are signicant if eclampsia or the HELLP syndrome develops or if preeclampsia develops prior to weeks of gestation. acute fatty liver of pregnancy. Early in gestation. mg/dL or lactate dehydrogenase U/L. and timely delivery.warning to a convulsive and potentially lethal phase. In up to of patients. Once the diagnosis is made. Complications include acute renal failure. Maternal mortality ranges from to . hypoglycemia. IV labetalol is now favored in the . In patients who have mild preeclampsia at term and have a favorable cervix. or fetal distress. Presenting symptoms are usually nonspecic. and nephrogenic diabetes insipidus. Although the risks of eclampsia are higher when these markers of disease severity are present. An especially fulminant complication of preeclampsia is the HELLP hemolysis. and edema. labor should be induced. In a subgroup of patients who are obese and chronically hypertensive with secondary left ventricular hypertrophy. conservative management with close monitoring to improve neonatal survival and morbidity may be appropriate in selected cases at tertiary perinatal centers. further management is based on an evaluation of the mother and fetus. increased liver enzyme levels. termed eclampsia. placental abruption with DIC. bilirubin . A sustained diastolic BP mm Hg should be treated to keep the mean arterial pressure from to mm Hg and the diastolic pressure from to mm Hg. it has been reported up to days postpartum. with higher perinatal mortality to . and in patients who are weeks pregnant. hemolytic uremic syndrome HUS. Acute renal failure is rare and most often seen in patients with the HELLP syndrome. The presence of symptoms and proteinuria increases the risk of placental abruption and eclampsia. These patients and those with disease progression should be hospitalized and observed closely. renal dysfunction. Pulmonary edema most commonly occurs after parturition. renal ischemia. The increased intravascular volume of pregnancy and the hemodynamic derangements of preeclampsia cause diastolic dysfunction with an elevated PCWP and pulmonary edema in these patients. The HELLP syndrome occurs in to of patients with preeclampsia. or hematuria. subcapsular hemorrhage. Isolated thrombocytopenia that progresses may be one of the rst clues to the diagnosis. hemorrhage. cerebral hemorrhage or edema. Patients are more often preterm than those with uncomplicated eclampsia. The objective of antihypertensive therapy is to prevent cerebral complications such as encephalopathy and hemorrhage. low platelets syndrome. the HELLP syndrome develops after parturition. The principles of management of preeclampsia include early diagnosis. failure. hyponatremia. The liver involvement is characterized by periportal or focal parenchymal necrosis with elevated liver function tests. followed by either repeated incremental doses of to mg at .to min intervals or an infusion starting at to mg/min and titrated up until the target BP is achieved. and renal biopsy can conrm the diagnosis. but evacuation of the hematoma and packing of the liver may be required. Antihypertensive therapy has no effect on the progression of preeclampsia and does not prevent complications such as HELLP. Aspirin has no role in the treatment of preeclampsia. Nitroprusside is relatively contraindicated. and acute fatty liver of pregnancy. hemorrhage. Other Disorders of Pregnancy Acute Renal Failure The incidence of acute renal failure associated with pregnancy is from . Acute cortical necrosis is associated with placental abruption.. A loading dose of labetalol. Nicardipine may be an acceptable alternative. hemolysis. mg. Embolization of the hepatic artery is often successful. The disorder may be a variant of HUS or TTP because it is clinically and pathologically Renal Insufciency. Creatinine . Because calciumchannel blockers may be potentiated by magnesium infusion. The preeclamptic patient with oliguria may benet from judicious volume loading. No signicant effect in delaying delivery was noted.ICU. septic abortion. administration of corticosteroids resulted in improved maternal platelet counts and liver function test results and in a trend toward better fetal outcome. mg/dL Patellar reex present Respiratory rate breaths/min Urine output mL / h Hypotension/asystole Respiratory depression Calciumchannel blockers may enhance adverse/toxic effects g IV over min g/h infusion Monitor every h Patellar reex present Respiratory rate breaths/min Urine output mL / h Hypotension/asystole Respiratory depression Calciumchannel blockers may enhance adverse/ toxic effects Critical Illness in Pregnancy Strek . Magnesium Dosing in Severe Preeclampsia/Eclampsia Variables Initial Maintenance Serum levels Monitor Normal Renal Function which can be difcult to distinguish from the HELLP syndrome. These patients may actually have TTP or HUS. Acute nicardipine infusion can induce severe maternal tachycardia. or organ dysfunction may benet from plasmapheresis with freshfrozen plasma. Acute tubular necrosis may occur from hemorrhage or sepsis. to . phenytoin. Management of intrahepatic hemorrhage with subcapsular hematoma includes administration of blood products. Arteriography may demonstrate loss of the cortical circulation. and amniotic uid embolism. or nimodipine in the prevention of eclampsia. magnesium sulfate was superior to both phenytoin and diazepam for the treatment and prevention of recurrent convulsions in women with eclampsia. In two studies.. Magnesium sulfate should be administered to all women with either preeclampsia or eclampsia and for a minimum of h postpartum Table . Acute oliguric renal failure necessitating dialysis typically results. Although renal function often improves. prolonged intrauterine retention of a dead fetus. and control of liver hemorrhage. care should be taken to avoid hypotension when the two medications are used together. endstage renal failure is the eventual outcome. Table . the HELLP syndrome. Magnesium sulfate prophylaxis has been shown to be better than placebo. is recommended. Diuretics should be used with caution because they may aggravate the reduction in intravascular volume that is often seen in preeclampsia. Patients with delayed postpartum resolution of the HELLP syndrome with persistent thrombocytopenia. and angiotensinconverting enzyme inhibitors are absolutely contraindicated in pregnancy. In a recent large study. Idiopathic postpartum acute renal failure is an unusual complication of pregnancy and may occur days to weeks after a normal pregnancy and delivery. delivery. The etiology is unknown. mL/dL Adverse effects Drug interactions g IV over min g/h infusion . Acute renal failure may complicate preeclampsia. New York. Marik PE and Plante LA. antithrombotic therapy. and DIC may worsen for a few days after delivery but then should improve. Jaundice. Am J Respir Crit Care Med . Slutsky AS. deliveries. and anorexia. N Engl J Med . Critical care in the pregnant patient. Liver failure rarely complicates preeclampsia and the HELLP syndrome. Lapinsky SE. The onset of acute fatty liver of pregnancy may be similar to the onset of preeclampsia with peripheral edema. and proteinuria. with supportive care and dialysis as necessary. Acute asthma in pregnancy. Kreiger BP. Because deterioration may occur rapidly. Hall JB. Bethesda. . Acute fatty liver of pregnancy progresses to ACCP Critical Care Medicine Board Review th Edition fulminant hepatic failure complicated by encephalopathy. Because longchain hydroxyacylcoenzyme dehydrogenase deciency in the fetus has been reported to be associated with acute fatty liver of pregnancy in women in a recent study. Renal dysfunction associated with preeclampsia and the HELLP syndrome should respond to delivery of the fetus. The biopsy is characterized by microvesicular fatty inltration detected only on frozen sections. . MMWR Surveill Summ . DIC. Full maternal recovery is to be expected. MD National Institutes of Health. ElamEvans LD. Olson MM. subcapsular hematoma and rupture are more common complications. Gilligan T. . Pereira A. Chang J. Patients present with headache. Risk factors include male fetus. renal failure. Jaundice may follow to weeks later. Kalassian KG. . expectant management is generally not advised. Levels of serum aminotransferases and bilirubin are unchanged in normal pregnancy. liver dysfunction. . NY McGrawHill. infants may have hypoglycemia. nausea and vomiting. Chest . although without hemolysis or thrombocytopenia.similar to these entities. and a rst pregnancy. malaise. In general. while TTP and HUS require plasmapheresis with freshfrozen plasma. de novo liver function test abnormalities are uncommon and occur in of pregnancies in the United States. Bates SM. Kruczynski K. acute or chronic skeletal and cardiac muscle dysfunction. Naylor DF. Chest . seizures. the treatment of acute renal failure in pregnancy is similar to that in the nonpregnant patient. Working Group Report on managing asthma during pregnancy recommendations for pharmacologic treatment. . References . Ultrasound may show increased echogenicity. The treatment is delivery of the fetus. and many patients respond to treatment with prednisone administration and plasmapheresis. SS . Liver biopsy is sometimes necessary to make the diagnosis but must be undertaken with caution because these patients often have a coagulopathy. Berg CJ. Acute fatty liver of pregnancy is estimated to occur in of . publication . Cholestasis with mildtomoderate elevations in serum aminotransferases is the rule. Critical illness in pregnancy. Hanania NA. et al. Critical care obstetrics and gynecology. In JB Hall. In pregnancy. SS . hypertension. Pabinger I. peaking at two to four times normal at term. although the disorder can be seen as early as weeks and postpartum. although this imaging exposes the fetus to signicant radiation. hypotonia. Venouos thromboembolic disease and pregnancy. Maternal and fetal mortality has improved with early delivery and is . LD Wood. and sudden infant death syndrome. multiple gestations. . Serum albumin concentrations decrease in pregnancy. Clin Chest Med . Pregnancyrelated mortality surveillanceUnited States. Crit Care Med . . Mean onset is at weeks of gestation. . . Obstetric complications in pulmonary and critical care medicine. and pregnancy. and death. et al. et al. pancreatitis. rd ed. Strek ME. National Asthma Education and Prevention Program. GA Schmidt. Serum alkaline phosphatase increases during the rst months of pregnancy. Venous thromboembolism. Pulmonary complications of pregnancy. eds. OConnor M. CT abdominal scans are more sensitive and may demonstrate decreased attenuation. Crit Care Clin . Rizk NW. hemorrhage. et al. Belfort MA. thrombophilia. Greer IA. right upper quadrant or epigastric pain. coma. Acute Liver Failure Acute liver failure is an uncommon complication of pregnancy. Principles of critical care. . Crit Care Med . Obstet Gynecol Clin North Am . Clin Chest Med . Early goal directed therapy for sepsis during pregnancy. Carty DM. . . Guntupalli SK. Gammill HS. . et al. Ruiz E. Mazur JE. Which anticonvulsant for women with eclampsia evidence from the Collaborative Eclampsia Trial. . Murali S. Lancet . SS . Izquierdo L. Guinn DA. Duvivier R. Pendem S. Bandi VD. et al. SS . SS . Steingrub J. Harrington D. . with an emphasis on pharmacotherapy. SS . Franchini M. . Fein AM. Ramsey PS. Pregnancyassociated hemolysis. Cardiac arrest associated with pregnancy. . VigilDeGracia P. . A critical review on the use of recombinant factor VIIa in lifethreatening obstetric postpartum hemorrhage. Roberts WE. Cole DE. Raoof S. Obstet Gynecol Clin North Am . Severe hypertension in pregnancy hydralazine or labetalol a randomized clinical trial. FernandezPerez ER. Cardiac arrest in pregnancy and somatic support after brain death. The Magpie Trial Collaborative Group. Tomlinson MW. Acute renal failure in pregnancy. Taylor TL McCullough DM. Risk factors for preeclampsia at antenatal booking systematic review of controlled studies. Peripartum cardiomy opathy. Hepatic disease and pregnancy an overview of diagnosis and management. et al. Lancet .. Eclampsia Trial Collaborative Group. Do women with preeclampsia. Matthay MA. elevated liver functions. Novel biomarkers for predicting preeclampsia. Sepsis in pregnancy. . J Intensive Care Med . Soper DE. Lasso M. Sepsis during pregnancy. Amniotic uid embolism. Moore J. Common problems in critically ill obstetric patients. Bergamini V. . Crit Care Med . Crit Care Med . Guy E. Salman S. Crit Care Med . Jeyabalan A. Am J Med Sci . Acute respiratory distress syndrome in pregnancy. Ko R. Trends Cardiovasc Med . Abel DE. SS . et al. and their babies. Obstet Gyncol Clin North Am . Circulation . Golden P. Hypertension . Pastis NJ. Baldisseri MR. Acute lung injury and acute respiratory distress syndrome in pregnancy. Crit Care Clin . Delles C. Crit Care Med . Pneumonia in pregnancy. . Crit Care Med . Preeclampsia. Eur J Obstet Gynecol Reprod Biol . Goodnight WH. et al. Baldisseri MR. . BMJ . . Duckitt K. Roberts JM. Crit Care Med . . George L. low platelets HELLP syndrome an obstetric disease in the intensive care unit. Amniotic uid embolism. Pneumonia in pregnancy. Gammill HS. Mallampalli A. Crit Care Clin . SS . Dominiczak AF. Franchini M. Semin Thromb Hemost . benet from magnesium sulphate The Magpie Trial a randomized placebocontrolled trial. . Ramin KD. SS Critical Illness in Pregnancy Strek . Munnur U. et al. Emergent obstetric management of postpartum hemorrhage. Gilson G. . Crit Care Med . Aurangzeb I. . inferior vena cava lter placement. therefore making acute thromboembolism one of the more important risk factors for VTE. perfusion lung scanning Risk Factors Major risk factors for pulmonary thromboemboli are processes that predispose a patient to the development of deepvein thrombosis DVT ie. The frequency of VTE increases exponentially between the ages of and years. surgery for malignant disease results in a twofold to threefold increase in thromboembolism compared with surgery for nonmalignant conditions. Patients with a history of VTE who undergo major surgery. increasing age increases risk beginning with adulthood and continues to increase after the age of years. such as venous valvular insufciency. FCCP Objectives Recognize the risk factors for pulmonary embolism PE Appreciate the typical clinical presentations of PE Choose rationally among perfusion lung scanning. the postpartum state. thromboembolism. thrombolytic therapy. or immobilization Table . and. any cause of venous stasis. The incidence in women was higher in individuals years old but not in those years old Stein et al. MD. DVT develops in of patients who do not receive prophylactic therapy while undergoing elective total hip replacement and knee replacement surgery. pregnancy. Longdistance air travel has also been linked to PE. the postoperative period. or protein S. and thrombolytic therapy in the management of PE Key words anticoagulation. deepvein thrombosis. One study demonstrated a incidence of PE in . Orthopedic surgery of the lower extremity has long been recognized as one of the greatest risk factors for VTE. as well as the presence of anticardiolipin antibody. Phillip Dellinger. or who are hospitalized for serious medical illnesses must be aggressively targeted for prophylaxis therapy. to a lesser degree. pulmonary embolism. tertiarycare hospital admissions with linear relation to age. and prolonged bed rest. advanced cancer is associated with a high risk of VTE. In patients with a history of thromboembolic disease who undergo hospitalization. compression ultrasound. nearly doubling with each decade. . patients with fractures of the pelvis. periods of immobility. hip. rightsided heart failure. Trauma to the extremities. leg ultrasound. The period of greatest risk is during the rst weeks after the initial injury. advanced malignancy increasingly recognized as a major risk factor.Venous Thromboembolic Disease R. Although an age of years has often been used as a break point for agerelated increase in VTE. there is nearly an eightfold increase in acute thromboembolism compared with patients without such a history. and ddimer assay in the diagnostic approach to PE Understand the place of anticoagulation. Since the rst controlled trials demonstrating a reduced rate of pulmonary embolism PE mortality with anticoagulant prophylaxis were performed in this highrisk group. or femur are of signicant historical relevance. With other risk factors considered equal. birth control pills current ACCP Critical Care Medicine Board Review th Edition formulations have lower estrogen content are signicant risk factors. Hypercoagulable states secondary to deciencies of antithrombin. Over of proximal thrombi occur in hip replacement patients on the operated side. Although precise estimates of risk increase in malignancy are difcult to ascertain. protein C. There is an estimated risk of VTE and a incidence of PE in patients with traumatic spinal cord injury and associated paralysis of lower extremities. Abdominal operations requiring general anesthesia min place the patient at risk for venous thromboembolism VTE. prothrombin GA mutation. . or factor V Leiden mutation are predisposing factors for thromboembolic disease. lupus anticoagulant. death occurs rarely in PE patients after months. CT scanning. Pulmonary infarction is the classic presentation of PE and is characterized by a pulmonary inltrate that is often peripheral and wedge shaped Hampton hump.Table . decreased pulmonary vascularity. with or without chest pain often pleuritic when present. murmur of tricuspid regurgitation. enlarged right descending pulmonary artery. protein C. Pulmonary infarction is more likely to occur in the face of preexisting compromise of nutrient or oxygen supply. These ndings represent the textbook version of PE that is taught to medical students but seen in only of pulmonary emboli. as well as femoral vein thrombosis. Inltrates are usually absent in massive PE unless the embolus has fragmented and moved peripherally. In addition. Radiographic inltrates may or may not be present. wedgeshaped inltrate. tachypnea. widely splitsecond heart sound. Chest pain may be present and is probably due to right ventricular RV or left ventricular LV myocardial ischemia. Nevertheless. the inferior vena cava IVC. protein S. and deciencies antithrombin. is acute massive PE characterized by a large thromboembolus lodging in the proximal pulmonary circulation resulting in hypotension and possible syncope. The physical examination is not typically helpful in considering PE. Clinical Findings The clinical diagnosis of PE is difcult. prothrombin GA mutation. Clinical acumen falters due to both sensitivity and specicity problems. backperfusion from the pulmonary venous system may also be a potential source of oxygen and nutrient supply. and hyperhomocysteinemia may benet from treatment with B vitamins. anticardiolipin antibody or lupus anticoagulant dictates more aggressive warfarin therapy. This screening is most appropriate for the three coagulopathies that can be easily accurately measured accurately in the presence of acute clot burden/ anticoagulation and have therapeutic implications factor V Leiden most common hypercoagulable state and would warrant more aggressive prophylaxis. anticardiolipin antibody. not infrequently. factor V mutation. Tachypnea and tachycardia may be transient. A more frequent presentation of PE is acute onset of shortness of breath or hypoxemia in the absence of pulmonary infarction. The most common symptoms/signs of dyspnea. particularly unilateral leg swelling in the setting of pulmonary symptoms compatible with thromboembolism. Risk Factors for Pulmonary Emboli Rightsided heart failure Postoperative period Prolonged bed rest Travel economy class syndrome Trauma Advanced malignancy Pregnancy Postpartum state Birth control pills Previous DVT Hypercoagulable states Hypercoagulable states include the following antiphospholipid syndrome lupus anticoagulant. Acute pulmonary hypertension with Venous Thromboembolic Disease Dellinger . Pulmonary infarction is rare due to three sources of oxygen and two sources of nutrient supply to the lung the bronchial and pulmonary arteries and the airways. such as in intrinsic lung disease or in the presence of reduced cardiac output. or an accentuated pulmonary closure sound. Central venous catheters are risk factors for superior vena cava/axillary/subclavian vein thrombosis. pleuritic chest pain. a bloody pleural effusion. but more lethal. pelvic veins and. Examination of the lower extremity is unreliable for predicting the presence or absence of DVT. new ndings supportive of acute deepvein obstruction. Although most pulmonary emboli come from deep veins of the lower extremities. and may be normal up to Less frequent. cardiomegaly. Chest radiographic ndings of PE include the following atelectasis and parenchymal densities. and tachycardia are seen with a myriad of other disorders. with the exception of the presence of ndings to support acute increases of rightsided pressure such as a new rightaxis deviation or new right bundlebranch block. hyperhomocysteinemia. less frequently. Screening for select hypercoagulable states is appropriate in patients with no obvious risk factors who acquire PE. clinically signicant emboli also occur from other sites of venous thrombosis including the iliac veins. should strengthen the possibility of PE. hemoptysis and. a clot may be visualized in the right heart and thus allows a specic diagnosis. sepsis. Analysis of pleural uid in a patient suspected of having PE is useful only to conrm other diagnoses. The traditional ELISA assay typically requires h for results. Echocardiography may be helpful in delineating other etiologies of clinical ndings.. tricuspid regurgitation. F . Recent nonlatex agglutination assays are clinically useful in the evaluation for possible PE since a nonelevated ddimer makes PE unlikely. advanced age. although hypotension is usually the primary clinical concern.. ndings such as acute RV dilation and hypokinesis. elevated hemidiaphragm. Patients who acquire PE in the ICU typically have abnormal chest radiographic ndings due to preexisting pulmonary disease. No. Chest . secondgeneration tests. such as asthma or exacerbation of COPD. One study found cardiomegaly to be the most common chest radiographic abnormality. An unremarkable chest radiograph with signicant hypoxemia and no obvious cause. With massive pulmonary embolus. may be seen in many circumstances other than PE recent surgery. In massive PE. Other potential etiologies of bloody pleural effusions include malignancy and trauma. McConnell. ACCP Critical Care Medicine Board Review th Edition However. total bilirubin mg/dL. Am J Cardiol Clinically signicant PE may also occur in the absence of any abnormal RV ndings on echocardiography. and reduced diastolicshaped LV size may support the diagnosis of PE but are not specic enough to establish the diagnosis. . trauma. such as myocardial ischemia or pericardial tamponade. and atelectasis. F has been demonstrated to be present in of angiographically documented PE with no other cause of fever Stein et al. A fall in endtidal CO may also be useful in raising the clinical suspicion of PE. An elevated ddimer. the effusion may be a transudate or exudate. neither can be relied on to exclude PE. late pregnancy. in low pretest clinical suspicion scenarios. A distinct radiograph pattern has recently been noted in patients with large PE in which regional RV dysfunction is noted but the apex is spared. Respiratory alkalosis is a common nding in the tachypneic patient with PE. rightheart strain may be indicated by Pwave pulmonale. . pleural effusion. Patients with PE may have a normal alveolararterial gradient. . Although a room air Pao mm Hg . This nding is more likely to occur in the presence of previous normal cardiopulmonary status. . Tachycardia and nonspecic STT changes are the most common ECG ndings in PE. The ddimer assay may be particularly important in the emergency department.. Leukocytosis may or may not be present. malignancy. it may or may not be bloody. and in combination with other studies in the inpatient population. There are no pathognomonic pleural effusion ndings with PE. may offer reliable and rapid bedside testing. interventricular septum bulge into the left ventricle. respiratory acidosis may be present due to increased dead space. or right bundlebranch block. however. SQT pattern. F Table . pulmonary artery dilation. Hypoxemia and an increase in alveolararterial gradient may also be transient. Distribution of Temperature in PE Temperature.. Hypoxemia is almost always present. while a decrease in Paco may be a marker of success of thrombolytic therapy in patients with PE. Chest radiographic abnormalities due to PE include pulmonary inltrate. Fever temperature . should also raise the concern for PE. Rarely. central dilated pulmonary arteries may also be present Westermark sign. A ddimer measured by enzymelinked immunosorbent assay ELISA was noted to be normal in of angiographically documented PE in one study Quinn et al. Only of patients had temperatures . .Table . including rapid ELISA. wedgeshaped inltrate called a Hampton hump may be seen in some cases of pulmonary infarction. Newer. rightaxis deviation. pulmonary hypertension estimated from tricuspid regurgitation jet. kPa or a normal alveolararterial gradient makes the diagnosis of PE less likely. A pleuralbased. . A bloody pleural effusion that accompanies PE usually implies pulmonary infarction. loss of respiratory variation in IVC diameter. leg ultrasound. had PE. It must also be remembered that a CTA may allow identi cation of other pulmonary processes as the cause of clinical ndings.Fortytwo patients in the Prospective Investigation of Pulmonary Embolism Diagnosis PIOPED trial had suspected PE. this righttoleft shunt produces hypoxemia unresponsive to oxygen therapy and also places the patient at risk for embolic cerebral vascular events. and in patients with no prior history of cardiopulmonary disease. especially in patients with selflimited risk factors. as well as the potential for opening of a probepatent foramen ovale due to high rightsided pressures. with the exception of those patients with low pretest clinical suspicion to . Pretest probability of PE was ascertained for all subjects. Other potential causes of hypoxemia in massive PE include low mixed venous oxygen due to low cardiac output. a negative spiral CT result makes pulmonary emboli very unlikely when using the most recent CT imaging with digital reconstruction and a welltrained reader. production of atelectasis surfactant depletion over hours. In patients other than those with pretest high clinical suspicion to . Positive and negative predictive values of CTA referenced to pretest clinical probability are shown Table . kPa. Venous Thromboembolic Disease Dellinger . except in those patients who present with a high pretest clinical probability of embolism. In the presence of very high rightheart pressures. therefore. since the natural history of pulmonary emboli limited to subsegmental arteries is usually a benign course. normal arterial blood gases. The PIOPED II trial was designed to study the ability of the CTA to predict presence or absence of PE. CTA looses diagnostic yield in circumstances of extreme discordance high clinical probability/negative CTA and low clinical probability/positive CTA. Nonmassive PE produces hypoxemia by release of bronchoconstrictors. do not allow discontinuation of the pursuit of PE. It typically allows diagnosis and treatment. This may be of less clinical relevance. All other subjects received digital subtraction angiography for de nitive diagnosis of presence or absence of PE. In addition to the same causes of hypoxemia as related above for nonmassive PE. and fullled all of the following criteria Pao mm Hg . like perfusion scanning. Therefore. Diagnosis The treatment of PE or DVT is essentially the same as in patients with suspected PE. It is apparent that. in general. The same is true for a positive result. PE was considered absent in the presence of a normal perfusion scan. Sixteen patients had angiographically documented PE. The specicity of CT for the diagnosis of PE has traditionally been better than sensitivity. although the latter has improved with newer generation scanners multidetector/digital reconstruction. In patients who had prior cardiopulmonary disease and who met all three criteria mentioned above. and normal alveolararterial gradient. Paco mm Hg . A probepatent foramen ovale is present in a small but signicant percentage of the general population. kPa. Withholding anticoagulant therapy in patients with a Venous Thromboembolic Disease Dellinger negative CT scan coupled with a negative ultrasonographic study of the legs is a safe strategy. spiral helical or electron beam is of signi cant value in detecting pulmonary emboli. no prior cardiopulmonary disease. CT CT angiography CTA. PE was considered present in the presence of a high. and a CTA that was not used to make or exclude the diagnosis of PE and was read blinded to the following other test results. All patients being evaluated for possible PE underwent a ventilation/perfusion scan. however. and pretest assessment of likelihood of PE. Sensitivity and speci city were ascertained. causing low ventilation/perfusion ratio due to overperfusion with resultant hypoxemia. and perhaps reperfusion injury to the endothelialepithelial barrier. either diagnosis is sufcient for decision making. in particular. Massive PE is almost always associated with hypoxemia and frequently with CO retention. the amputation of pulmonary vascular bed in massive PE produces both a large increase in dead space as a cause of increased Paco and a large amount of blood ow diverted to noninvolved areas of the lung.probability ventilation/perfusion scan or a positive leg ultrasound. One sensitivity issue with the CTA diagnosis of PE is the decreased ability to detect vessels beyond the segmental arteries. and c no history of pulmonary emboli. The PIOPED I study supported the following ndings normal lung scans make PE very unlikely. Impressive sensitivity and specicity for proximal vein thrombosis are usually obtained with this technique in patients with leg symptoms. have slower ow. low. and normal. b no underlying cardiopulmonary disease. physical examination. unlikely that these areas will be involved unless thrombus is also present in the more readily imageable popliteal and deep femoral system. intermediate probability. lymphadenopathy. intermediateprobability scans cannot be used for denitive decision making. a minority of patients have highprobability perfusion scans. a baseline perfusion scan should be considered even when the clinical diagnosis of PE is made by other methods. and clinical information. The PIOPED study is the most frequently utilized reference for assessing utility of perfusion scanning in the diagnosis of PE. or intermediate probability scans. CUS may also diagnose other etiologies of clinical ndings such as Baker cyst. a lowprobability scan does not exclude PE. and perfusion defects that are signicantly larger than ventilation defects or present in the absence of ventilation defects. PIOPED II Results Clinical Suspicion of PE Variables Truepositive CT positive predictive value. and have more anatomic variability. matching of vascular tree distribution. High Moderate Low CT sensitivity. CUS may also be limited by pain and edema. CUS cannot be performed if the leg is cast. the great majority of patients with suspected PE cannot have PE excluded with perfusion scanning. perfusion scans are classied as normal. with the classication system then becoming high probability. Although ventilation scanning is usually performed in combination with perfusion scanning to quantify ventilation defects. This technique does not detect isolated thrombosis in the iliac veins or the supercial femoral veins within the adductor canal. nondiagnostic. Probability of PE increases with size of perfusion defect. It is. however. Diagnosis of calf vein thrombosis is more challenging because these veins are smaller. In anticipation of a later question of failure of heparin therapy. it is best to call low. Nondiagnostic scans require additional testing because they do not allow a decision as to the presence or absence of PE. Truenegative CT negative predictive value. and normal. hematoma. . number of moderatetolarge size defects.and intermediateprobability scans nondiagnostic.Table . lowerlobe distribution. chest radiographs can be used in place of ventilation scanning in patients without chronic pulmonary disease or acute bronchospasm. The chance of a perfusion defect being due to PE increases with increasing number and size of defects. a clinical impression of low ACCP Critical Care Medicine Board Review th Edition likelihood of PE when combined with a lowprobability scan increases the predictive value of the lowprobability scan. This will allow repeat scanning for the presence or absence of additional perfusion defects if new symptoms develop or symptoms continue. and abscess. LowerExtremity Ultrasound Compression ultrasound CUS combines Doppler venous ow detection with venous imaging and has become the imaging procedure of choice for DVT in most medical centers in the United States. Diagnosis of DVT by CUS allows treatment because treatments for PE and DVT are essentially . low probability. specicity. . The diagnostic utility of CUS is related to imaging of a venous lling defect that persists with compression of the lesion. reliability of a highprobability scan increases with a the degree of clinical suspicion using history. Using these characteristics. and defect larger than any ventilation defects that may accompany the perfusion defect by chest radiograph or ventilation scanning socalled mismatched defect. Perfusion Lung Scanning Perfusion lung scanning usually done in combination with ventilation scanning is typically classied into high probability. targeting an aPTT of . Despite early studies that suggested a higher incidence of mortality due to pulmonary angiography in patients with high pulmonary artery pressures. Absence of DVT by CUS. The risk of pulmonary angiography to the patient is usually greater from anticoagulation in the absence of PE or failure to treat PE that is present. Warfarin is an absolute contraindication in the rst trimester and a relative contraindication in the second and third trimesters. Adequate heparinization prevents additional clot formation. to times control with heparin therapy. at least h of warfarin therapy. and in the majority for days. a supratherapeutic aPTT does not appear to correlate with important bleeding complications. Ventilation/perfusion scanning is low risk. in combination with lowprobability perfusion scan or failure to detect PE on helical CT and the absence of high clinical suspicion. Risk is increased if angiography is followed by thrombolytic therapy. having received therapy for a considerable period of time. The death rate from pulmonary angiogram in the PIOPED I study was . bleeding complications correlate with concurrent illness such as renal disease. but the bodys own brinolytic system must clear the clot that is already present so that patients who are hemodynamically unstable or who have poor cardiopulmonary reserve may remain at risk during early anticoagulation therapy. The activated partial thromboplastin time aPTT should be maintained at . renal failure or hematoma necessitating transfusion. Clinically evident pulmonary emboli are even more unlikely in the presence of serial negative noninvasive leg studies typically repeated one to three times over a period of to days and if negative further enhance clinical acumen. A negative leg ultrasound in a patient with an intermediateprobability scan usually implies the need for a spiral CT or pulmonary angiography. Although subtherapeutic aPTT is strongly correlated with thromboembolic recurrence. of major nonfatal complications respiratory failure. this target is typically higher . Longterm heparin administration in the pregnant woman is a signicant risk for osteoporosis. PE. One concern with regard to this approach.. This is an important consideration since patients may be referred to a tertiarycare center with uncertain diagnosis of Treatment Anticoagulation Heparin therapy is discontinued after a minimum of to days of therapy. is that the sensitivity of CUS is signicantly diminished in highrisk patients without leg symptoms or signs. with a low incidence . Pulmonary angiography done within week of acute symptoms should reliably detect pulmonary emboli even in the presence of anticoagulation. heavy ethanol consumption. identifying the location of perfusion defects on an indeterminant diagnosis perfusion scan and following with selective pulmonary angiography targeting those defects is likely the best approach because it potentially minimizes dye load if PE is present. Instead.. In patients with angiographically proven PE. times normal rather than .. Diagnosis of PE With Pulmonary Angiography Pulmonary angiography remains the gold standard for diagnosis of PE. times normal may be ideal. In patients without Venous Thromboembolic Disease Dellinger . Major nonfatal complications were four times more likely to occur in ICU patients. however. For patients with antiphospholipid syndrome. and a warfarininduced prolongation of international normalized ratio for prothrombin time . and peptic ulcer disease.the same. and morbidity and mortality rates are low and usually acceptable. Diagnosis of PE in Pregnancy The pursuit of diagnosis of PE in pregnant women is challenging. this was not found to be true in the PIOPED I study. Angiography is considered positive when a persistent lling defect or cutoff sign is noted. aspirin use. perfusion defects persist for at least days without resolution. In pregnant patients with negative leg ultrasound ndings. usually allows withholding treatment. Based on this information. heparin therapy should be stopped. switching to LMWH is not a good option. A more dramatic and clinically signicant decrease in platelet count HIT may rarely occur in heparin therapy days to or earlier with previous heparin exposure. Thrombolytic therapy followed by heparin has. When the platelet count falls precipitously or in a sustained fashion and HIT is suspected. . subsequent platelet counts should be done. such as mortality rates in randomized clinical trials. LMWH dose adjustment is required in patients with renal insufciency creatinine clearance of mL/min in very large persons kg or very small persons kg. The addition of a direct thrombin inhibitor at this time to prevent or treat heparininduced thrombosis is indicated. Antifactor Xa levels reect LMWH activity but are not routinely necessary in most treated patients. A loading dose of . although rTPA is almost exclusively used in the United States. It is at least as effective as standard heparin therapy in inpatient nonmassive PE and may be cost efcacious. heparin dosage requirements are increased in pregnancy. to . is that the longer halflife may be problematic. Therefore. Additionally. once thrombocytopenia occurs on unfractionated heparin. its utility in the face of hemodynamic instability is assumed. for whom invasive procedures may be required. Thrombocytopenia is uncommon enough that no more than one platelet count is recommended during a treatment period of to days. however. Since to days may be required to achieve anticoagulation with warfarin in that circumstance. less heparin is typically required to maintain adequate anticoagulation after the rst lowmolecularweight heparin LMWH is an effective subcutaneous therapy for DVT and PE. Traditional absolute contraindications for thrombolytic therapy are active internal bleeding. been shown to provide more rapid improvement in RV function than heparin alone. A disadvantage in the critically ill patient. a direct thrombin inhibitor or a heparinoid is recommended to protect in the interim. persistent hypoxemia despite maximum oxygen supplementation is also an accepted indication. protamine is recommended for reversal. LMWH does not prolong the aPTT./ L. and does not usually require discontinuation of ACCP Critical Care Medicine Board Review th Edition heparin. If therapy is prolonged days.a contraindication for anticoagulation. There is a chance for crossreactivity with LMWH. When bleeding occurs after recent administration of LMWH. warfarin should not be instituted for days because of the possibility of increased clot formation. Decreased administration costs and no need for monitoring coagulation in most patients may make LMWH cost efcacious in the appropriate patient group. recent acute cerebrovascular event months. therefore. heparin therapy should be stopped. occurs early in treatment. Decreases in platelet count heparininduced thrombocytopenia HIT may occur with heparin therapy. is immunologically mediated. U of heparin is indicated for PE. When the platelet count falls to . and does require immediate discontinuation of heparin therapy. heparin therapy should be instituted as soon as thromboembolic disease is considered. A nonimmunologically mediated decrease in heparin HIT may occur. and that is not advisable as a therapeutic option. although LMWH might be chosen as a better option than unfractionated heparin in patients with thrombocytopenia at baseline. An advantage of LMWH over unfractionated heparin is a decreased incidence of heparininduced thrombocytopenia. Streptokinase and recombinant plasminogen activator rTPA are both thrombolytic agents for consideration of treatment of PE. Failure to achieve adequate heparinization in the rst h of treatment has been demonstrated to increase the risk of recurrent emboli. In addition. Thrombolytic Therapy Indications for thrombolytic therapy are controversial because thrombolytic therapy has not been proven to alter clinical end points. and is usually mild without dramatic drops in platelet count. Arterial thrombosis white clot and worsening vs thrombosis may be a part of this more severe syndrome. Antifactor Xa levels may be needed to optimize dosing if LMWH is used in these groups. Although rarely encountered. but the degree of effectiveness in this circumstance is difcult to judge. It is important to remember that warfarin therapy is contraindicated in pregnancy and anticoagulation should be maintained with heparin. With HIT. recent serious internal trauma. recent organ biopsy or puncture of a noncompressible vessel. Those who argue against thrombolytic use in this circumstance point to the low mortality rate once PE is diagnosed in the presence of RV dysfunction. Intracranial bleeding. if not contraindicated. intubation/mechanical ventilation. its use is advocated by some in the presence of large clot burden or especially with echocardiographic evidence of acute RV dilation. lumbar puncture. paradoxical interventricular septal motion . Another study showed that although thrombolytic therapy of acute RV dysfunction in the absence of hemodynamic instability did not decrease mortality. offers support for diagnosis in this circumstance. thoracentesis. it did decrease escalation of therapy institution of vasopressor therapy. there were no differences in recurrences or death rate from PE except increased death rate from bleeding. the successful use of urokinase thrombolytic therapy of PE in nine neurosurgical patients mean. In general. Echocardiography usually demonstrates evidence of RV overload . and pulmonary hypertension .or recent cerebrovascular procedure months. One report noted. CTA. There are some data in the radiology literature that suggest this approach is useful for DVT. Infusion of a thrombolytic agent directly onto a pulmonary thrombus via the pulmonary artery has never been shown to be superior to infusion of the agent through a peripheral vein. This latter argument is based on the fact that RV dysfunction strongly correlates with mortality in patients with PE. however. or angiography who had echocardiography to document the presence or absence of acute RV dysfunction. If bleeding should persist. paracentesis. Retroperitoneal hemorrhage can also be life threatening. mortality rate is high . angiographic or CTA documentation of PE should be obtained before thrombolytic therapy. Of the normotensive patients with acute RV dysfunction of patients. Blood samples should be limited during the thrombolytic agent infusion period. Using a retrospective cohort analysis of two matched groups of patients. surgery within the last days. echocardiography supporting PE should be adequate for initiating therapy. and the clinical scenario is strongly suggestive. the patient is at risk for death. and any other conditions that place the patient at risk for bleeding. the study concluded that although thrombolytic therapy improved lung scan more rapidly. and the low but potentially catastrophic incidence of intracranial hemorrhage with thrombolytic therapy. The management of freeoating RV thrombi remains controversial. occurs in to of patients with PE who are treated with thrombolytic therapy. a day postpartum period. One study evaluated consecutive patients with documented PE diagnosis made by highprobability perfusion scan spiral CT. and thrombolytic therapy. if immediately available. cryoprecipitate infusion or freshfrozen plasma should be considered. Occasionally. If bleeding should occur during thrombolytic therapy. Although no study has demonstrated thrombolytic therapyinduced improvement in survival or decrease in recurrent thromboembolic events. The clots are usually wormlike. or perfusion scanning are possible. uncontrolled coagulation defects. days after surgery with no intracranial hemorrhage one subgaleal hematoma. and most frequently occurs as a sequela of previous femoral vein access for pulmonary angiography or other associated femoral lines. Bedside echocardiography. The use of thrombolytic agents in PE remains controversial. Venous Thromboembolic Disease Dellinger . the absence of studies demonstrating clinical outcome benet in this group. A contrasting study comes to an opposite opinion. The American College of Chest Physicians ACCP consensus statement on thromboembolism states that the use of thrombolytic agents continues to be highly individualized. but heparin therapy should be resumed without a bolus when the aPTT is . to times control. thrombolytic therapy may be considered in hemodynamically unstable patients with a highprobability perfusion scan who cannot be moved to receive additional testing. is recommended as the treatment of choice by some investigators. When neither angiography. a primary concern. Relative contraindications to thrombolytic therapy include any history of cerebrovascular event. and secondary thrombolysis. PErelated shock developed in patients after admission and died. pregnancy. cardiopulmonary resuscitation with rib fracture. No coagulation tests are typically necessary during thrombolysis. Heparin should not be administered during thrombolysis. drug should be discontinued halflife is short. with both diagnoses amenable to treatment with thrombolytic therapy. if available. are less invasive and more appropriate alternatives in this situation. the most frequently used thrombolytic agent for the treatment of PE is rTPA. Patency can be maintained. Complications of lter placement include vessel injury at the time of insertion. the right ventricle dilates as ejection fraction decreases. suggesting that the normal right ventricle is incapable of generating pressures mm Hg in the setting of acute pulmonary vascular bed obstruction. This is usually accomplished at the time of lter placement using dye venogram. Direct thrombin inhibitors. A lter may also benet patients at high risk for chronic anticoagulation. One proposed alternative that seems reasonable in that circumstance is mg over minutes followed by mg over the remainder of the h period. it is estimated that up to of sudden unanticipated inhospital arrests are due to either PE or acute myocardial infarction. without concomitant heparin therapy. In the United States.and clinicians should have latitude in their use. If the decision is made to administer thrombolytic therapy in this circumstance. Studies of hemodynamic proles in patients with acute PE have demonstrated mean pulmonary artery pressures mm Hg only in patients with preexisting cardiopulmonary disease. and IVC obstruction. lter migration and embolization into the heart. Pulmonary artery catheterization may be useful to optimize therapy in the hypotensive patient. Dosing considerations for initial front loading vary from to of standard infusion dose as bolus. subsequent venous thrombosis at the insertion site. for anticoagulation prophylaxis of DVT. A right atrial pressure RAP of approximately to mm Hg is probably optimal. lter erosion through the IVC. Overdistention of the right ventricle more likely when mean RAP is mm Hg may be problematic for IVC Filter Traditional indications for IVC lter placement include contraindication to anticoagulation. the timing and dosing are less clear and best left to the bedside clinician. Documentation of DVT disease is usually required before placement of an IVC lter. Instead. Timing considerations vary from too early patient was going to be successfully resuscitated without thrombolytic therapy to too late missed opportunity for thrombolytic therapy to make a difference. PEInduced Tissue Hypoperfusion The right ventricle cannot increase stroke volume in response to sudden increases in afterload. but the use of anticoagulation may prevent further clot formation and increase the patency rate of the lter over time and. Retrievable lters are now available and offer utility in patients who have shortterm need for lter and who are expected to return to an active lifestyle. therefore. if severe. but the catheters may be difcult to pass due to high pulmonary artery resistance and lowow state. however. Filter placement may also be considered in patients with high risk for DVT and relative or absolute contraindications ACCP Critical Care Medicine Board Review th Edition . The lter should be removed within several months. more rapid administration may be appropriate. Empiric thrombolytic therapy might be considered in hospitalized patients with sudden unexpected arrest who are at risk for PE and in whom there is no obvious alternative diagnosis. syncope. onset of bleeding with anticoagulation. however. such as poorly compliant patients or patients at risk for falls. The decision to anticoagulate patients who have had an IVC lter placed is controversial. The empiric use of IVC lter in patients with a large clot burden or poor cardiopulmonary reserve is more controversial. recommended in general for hemodynamic instability and massive ileofemoral thrombosis. They are. Failure of the right ventricle to compensate for the increased afterload produces hypotension and. and failure of anticoagulation to abate thromboembolic events. Other indications for lter placement include hemodynamically unstable patients who will not be given thrombolytic therapy and patients with HIT as a bridge to warfarin therapy. Based on autopsy series. In the patient with massive PE in whom death appears imminent without thrombolytic intervention. Food and Drug Administrationapproved dosing is mg over h. facilitate venous drainage. There are good data to indicate that one tradeoff of IVC lter ability to decrease PE is subsequent development of femoral vein thrombosis at the site of insertion. First. Interventional radiology use of mechanical fragmentation may be an alternative to surgery in patients with severe hemodynamic instability and contraindication to thrombolytic therapy. Dobutamine may be preferred in the presence of hypoperfusion but absence of hypotension. With high rightsided pressures. Length of surgery. It also offers the advantage of one injection vs three in all patients. Vasoconstriction of systemic vascular bed with selective vasodilation of pulmonary vascular bed would be ideal. Vasopressors may also be benecial by increasing aortic diastolic pressure when it is critically low. Lowdose LMWH is the heparin of choice in knee surgery patients. additively or as a replacement. the frequency of fatal PE is approximately for emergency hip surgery. It should also be considered when hemodynamic instability persists despite thrombolytic therapy. independent of type. and maintaining adequate aortic diastolic pressure upstream lling pressure for the left and right ventricles. Benet could only occur through vasodilation of PEreleased humorally mediated vasoconstriction because clot burdeninduced increase in pulmonary vascular resistance is not reversible except through dissolution of clot. Surgical thrombectomy may be considered in situations of severe hemodynamic instability with a contraindication to thrombolytic therapy and close proximity to the operating room. Based on the above. and after elective surgery. volume therapy is typically ineffective and may be deleterious. Without prophylaxis. knee. U bid or tid of unfractionated heparin subcutaneously or LMWH once daily. respectively. prostate are important considerations for risk of emboli. The frequency of PE after myocardial infarction in the absence of prophylaxis may be . the right ventricle may be made ischemic due to decreased coronary perfusion related to the high RV pressure since perfusion pressure of the right ventricle is approximated by aortic diastolic pressure minus mean RV pressure. which is not long for most forms of treatment to be effective. the use of either LMWH. Recent reports of epidural hematoma after LMWH use in patients who have had epidural puncture should alert the physician to this potential complication with any anticoagulation in place. hip surgery patients. Therapy should be targeted toward reducing RV afterload RV work by reducing pulmonary clot burden. Hemorrhagic side effects of lowdose heparin are rare in patients without hemorrhagic diathesis. adjusteddose unfractionated heparin targeting heparin to prolong middosing prothrombin time measurement by to s. Autopsy ndings demonstrate that PE causes of deaths in patients receiving mechanical ventilation. Prevention of PE The most powerful statement that can be made for prophylaxis is that. and the clinical scenario should indicate a certain or almost certain clinical diagnosis of massive PE. The great majority of patients in the ICU should receive heparin prophylaxis for thromboembolic disease. IPVC can be added to heparin prophylaxis in patients with additive risk factors. In highrisk patients such as those undergoing elective hip surgery. after elective hip surgery. Combination inotrope/vasoconstrictor therapy such as dopamine or norepinephrine is recommended in the hypotensive patient. Inhaled nitric oxide has anecdotally been demonstrated to improve hemodynamics in PE by this mechanism. The dose for general surgical patients or in medical patients is typically . LV compliance may also be decreased as the interventricular septum shifts into the left ventricle. RV contractility may be improved by the use of inotropic drugs. age. Bypass capability is necessary. with resultant overdistension of the right ventricle. Venous Thromboembolic Disease Dellinger . Highrisk patients or those who have contraindications for heparin should receive intermittent pneumatic venous compression IPVC. Dopamine at doses beginning at g/kg/min is the recommended inotrope in the presence of hypotension. and type of surgery hip. pelvis. of the patients who die of pulmonary emboli. IPVC is contraindicated in the face of arterial compromise of extremity.several reasons. avoiding volumeinduced RV overdistension RAP mm Hg. and CNS trauma patients. RV ischemia may be a primary cause or a major contributing factor to hypotension. most patients survive min after the event. IPVC is a nonpharmacologic prophylaxis alternative for knee surgery. but rigorous data are lacking. prolonged immobilization. Cardiomegaly was most common abnormal nding. shock. Thromb Haemost . Thrombolytic therapy for pulmonary embolism. General review on diagnosis with algorithms. JAMA . Review of chest radiographs in . Cochrane Database Syst Rev . Chest . Getting a grasp on incidence and timing of postoperative pulmonary embolism. Buller HR. were normal. Baile EM. better prophylactic alternatives are needed. Monreal M. Chest radiographs in acute pulmonary embolism. still offers signicant clinical information. Lowdose heparin or IPVC may not be effective in the highestrisk patient. et al. CD This is a Cochrane metaanalysis of thrombolytic therapy for PE that. In trauma patients at high risk for bleeding and those at high risk for pulmonary emboli. Use of emboliblocking lters increases. Lowdose warfarin can be instituted at mg/d beginning days before elective surgery and continuing through the postoperative hospitalization. Occasionally. Serial Point ultrasonography plus Ddimer vs wholelegcolorcoded Doppler ultrasonography for diagnosing suspected symptomatic deep vein thrombosis. CT scanning has become the primary diagnostic test. For hip fracture surgery. to . direct venous trauma. negative leg ultrasound. King GG. Caprini JA. A randomized controlled trial. Jirong Y. Curr Opin Crit Care . Similar rationale has been offered when PE is diagnosed in advanced malignancy.or lowdose warfarin is recommended. One study demonstrated that only of hospitalized patients who had documented PE had received prophylactic therapy. This is a nice concise review of where we stand with retrievable lters. Visani L. Wag Q. patients with diagnosis of PE. The evaluation of suspected pulmonary embolism. Resolution rate of acute pulmonary embolism in man. Pig model using colored methacrylate beads and postmortem methacrylate casting showing no difference in diagnosis of subsegmental clot between angiography and spiral CT. Clinically signicant DVT develops in many trauma cases. Bernardi E. Thrombolytic therapy during cardiopulmonary resuscitation and the role of coagulation activation after cardiac arrest. et al. as well as the most common nding. Retrievable IVC lters are experiencing increased utility despite limited trials that would allow higher level of evidence for their utility. Summary PE is a treatable condition with a nonspecic clinical presentation that makes diagnosis difcult. et al. and lowprobability perfusion scan. Where is the value Bttiger B. Brooks HL. Neither of these uses has been validated. et al. pulmonary angiography is necessary. pelvic and lowerextremity fractures. Predictive capability of negative CT ndings in higherrisk patients is enhanced by additional studies nonelevated ddimer. ACCP Critical Care Medicine Board Review th Edition . Brender E. although heavy with methods. JAMA . Elliott CG. Questionandanswer format for controversial areas of VTE management. No resolution of PE by angiogram before day . Dalen JE. Am J Respir Crit Care Med . Camporese G. Risk factors include advanced age. paralysis. Thrombolytic therapy is indicated in patients with hemodynamic instability and no contraindications. Chest . severe head trauma. Clinical presentation and timecourse of postoperative venous thromboembolism Results from the RIETE Registry. LMWH or fulldose warfarin international normalized ratio. N Engl J Med . Goldhaber SZ. Annotated Bibliography ACCP Consensus Committee on Pulmonary Embolism. is recommended. Arcelus JI. et al. Tapson VF. Banas JS. N Engl J Med . et al. Opinions regarding the diagnosis and management of venous thromboembolic disease. especially if leg injury prevents application of pneumatic compression devices. Mller NL. Fedullo PF. Dong B. Mixing and matching ultrasound and Ddimer. . Obviously. prophylactic IVC lter placement has been recommended by some investigators. Eike M. and multiple transfusions. Spiral computed tomography is comparable to angiography for the diagnosis of pulmonary embolism. J Vasc Interv Radiol . Streptokinase and heparin versus heparin alone in massive pulmonary embolism a randomized control trial. Subsequent pulmonary embolism risk after a negative helical CT pulmonary angiogram prospective comparison with scintigraphy. Giordano A. Points to improving ability to use CT results in decision making. and echocardiographic right ventricular dysfunction. supplSS Konstantinides S. et al. Thromb Res . Krkciyan I. normal blood pressure. J Thromb Thrombolysis .Gibson NS. Chest . et al. Faucher LD. RamirezRivera A. Major bleeding complications in cardiopulmonary resuscitation the place of thrombolytic therapy in cardiac arrest due to massive pulmonary embolism. Antithrombotic therapy for venous thromboembolic disease. Grifoni S. et al. General review of diagnostic modalities available for diagnoses and their severity and specicity. there were no differences in recurrent PE with increased bleeding deaths in the thrombolytic group. Konstantinides S. Goldhaber SZ. Goodacre S. Garcia M. Acute pulmonary embolism. N Engl J Med . Kuzo RS et al. Geibel A. all four patients in the thrombolytic therapy group had PE diagnosed in the emergency department of the hospital performing the study. while all four patients in the heparinonly group were transferred to that institution from other hospitals with recurrent PE receiving heparin. Angiolillo DJ. Thrombolytic therapy Venous Thromboembolic Disease Dellinger . et al. Medical intelligence review article of PE management. et al. Janata K. A view on utility of perfusion lung scanning from the nuclear medicine side. Holzer M. JergesSanchez C. Retrievable inferior vena cava lters in highrisk trauma and surgical patients factors inuencing successful removal. Current role of lung scintigraphy in pulmonary embolism. VV Highlights areas of ongoing uncertainty. Q J Nucl Med . Heparin plus alteplace compared with heparin alone in patients with submassive pulmonary embolism N Engl J Med . Venous thromboembolic disease CT evaluation. Olivotto I. Goodman LR. World J Surg . it supports use of pooled estimates. A very good case based study highlighting key concepts of management. Vincentelli D. Two retrospective cohort massive PE groups were matched with the exception of thrombolytic therapy. Sohne M. Pretest clinical probability important for Ddimer interpretation as well. Goldhaber SZ. Sutton AJ. This article evaluates the potential utility of individual single clinical variables vs pooled estimates of risk for DVT. Q J Nucl Med . et al. PE is one of the primary diagnoses in the differential diagnosis of unexpected cardiac arrest in the hospital. Furthermore. however. and initial hemodynamic stability. acute RV dysfunction. Although lung scan improved more rapidly in the thrombolytic group. Chest . Meron G. Lipchik RJ. Demonstrated signicant morbidity and mortality developing in patients with PE. Primary thrombolytic therapy decreased subsequent death and use of vasopressors/mechanical ventilation/secondary thrombolysis as a combined end point but no difference in mortality. Kahn SR. Useful information on safety data as well as thought on timing of removal. Johnson MS. Krkciyan I. Chest . Shortterm clinical outcome of patients with acute pulmonary embolism. et al. Kearon C. Metaanalysis the value of clinical assessment in the diagnosis of deep venous thrombosis. Cecchini P. Hamel E. Pacouret G. Gerdes VEA. Ibele AR. there were only four patients in each group. Current strategies for the diagnosis of pulmonary embolus. Agnelli G. Arch Intern Med . JAMA . et al. Ann Intern Med . Paper occasionally used to justify utility of thrombolytic therapy in massive PE and value of streptokinase in particular. Pulmonary embolism. Resuscitation . These three articles address the issue of the use of thrombolytic therapy in the situation of cardiac arrest. Radiology . The importance of clinical probability assessment in interpreting a normal dDimer in patients with suspected pulmonary embolism. Sterz F. Hermsen JL. et al. Sampson FC. N Engl J Med . Goodman LR. Pulmonary embolism as cause of cardiac arrest. Heuset G. such as the Wells score and limited value of individual variables. Unsolved issues in the treatment of pulmonary embolism. Thrombolysis or heparin therapy in massive pulmonary embolism with right ventricular dilation results from a patient monocenter registry. Noninvasive diagnosis of deep vein thrombosis. the review concluded that there are not currently enough data to support withholding of heparin after negative spiral CT ndings without additional testing. A protocol was used for evaluation and decision as to presence or absence of PE using CT. days used modied urokinase regimen to demonstrate complete lysis of PE with no bleeding complications. this could be of great utility in patients referred from another institution. Rathbun SW. and ddimer. Maseri C. Lowmolecularweight heparin compared with intravenous unfractionated heparin for treatment of pulmonary embolism. This article presents the challenges of reacting to the presence of rightheart clot on ultrasound as it is pertinent to decision making in patients with PE. Regional right ventricular dysfunction detected by echocardiography in acute pulmonary embolism. et al. Am J Surg . Solomon SD. et al. Blonde MC. et al. of untreated patients had PE over next months. and with the diagnosis of PE in doubt. Mickleborough LL. Pandey AS. Sensitivity and specicity of helical computed tomography in the diagnosis of pulmonary embolism a systematic review. et al. et al. Am J Respir Crit Care Med . another look at thromboemboli resolution. McConnell MV. Parent F. Fayan ME. Ddimers in the diagnosis of pulmonary embolism Am J Respir Crit Care Med . Am J Respir Crit Care Med . ACCP Critical Care Medicine Board Review th Edition . salvage rate when rTPA is administered to patients with either conrmed PE or those highly likely to have PE. McQuillan A. The addition of pretest clinical probability further heightened predictive capability. This nding is particularly problematic in the unstable patient and the patient with contraindication to thrombolytic therapy. This article offers a perspective on surgical embolectomy following failed thrombolysis. Hunter DW. JAMA . and only study included a broad spectrum of patients. A review of the prospective Englishlanguage studies of use of helical spiral CT in the diagnosis of PE found that only two studies had consecutive patients. Concise update on value and limitations of ultrasound diagnosis of DVT. Ultrasound was used in middleground situation as a nal decision maker. Large prospective trials are needed. Miniati M. Can J Cardiol . already having received therapy. and PE if they did not. Meneveau N. Davidson BL. Studied the use of perfusion scanning/chest radiograph analysis without ventilation scanning in consecutive patients with suspected PE.not only might offer potential utility if the arrest was due to PE but also with acute myocardial infarction. et al. The nding of abnormal wall motion in RV midfree wall and normal motion in apex was very predictive of PE among patients with acute symptoms and evidence of pulmonary artery hypertension. Value of perfusion lung scan in the diagnosis of pulmonary embolism results of the Prospective Investigative Study of Adult Pulmonary Embolism Diagnosis PISAPED. Quinlan DJ. Right heart pulmonary embolism in transit a review of therapeutic considerations. Fogel RB. Lorut C. These three articles assess the empiric use of thrombolytic therapy in patients who do not quickly respond to resuscitation. Thirteen patients within weeks of surgery mean. For the rst time in years. et al. Molina JE. Hovens MM. et al. Sensitivity was most patients with angiographically proven PE had PEpositive scans and specicity was most patients without angiographically proven PE had PEnegative scans. Sronde MF. Nonelevated ddimers make PE very unlikely. Howarth N. Meyer G. Chest . Landefeld CS. Didier D. A noninvasive diagnostic strategy including spiral computed tomography in patients with suspected pulmonary embolism. Raskob GE. et al. Ann Intern Med . Rakowski H. Abnormal scan ndings were considered PE positive if scans demonstrated one or more wedgeshaped perfusion defects. Ghossains M. Ann Intern Med . studies had independently interpreted angiogram and CT. Resolution of thromboemboli in patients with acute pulmonary embolism. Perrier A. Q scan. Am J Cardiol . et al. Performance of helical computed tomography in unselected outpatients with suspected pulmonary embolism. Smith CD. Yedlicka JW. Quinn DA. Only . Chest . while elevated ddimers were not useful. Whitwett TL. Management of unsuccessful thrombolysis in acute massive pulmonary embolism. Ann Intern Med . Diagnostic strategy for patients with suspected pulmonary embolism a prospective multicentre outcome study Lancet . Pistolesi M. Musset D. Eikelboom JW. Nijeuter M. . Thrombolytic therapy for postoperative pulmonary embolism. Horellou MH. et al. Swensen SJ. Veseley SK. Wells PS. Afzal A. Urokinase thrombolytic therapy of pulmonary embolism in neurosurgical patients. Severi P. Ann Intern Med . van Strijen MJL. Complications and validity of pulmonary angiography in acute pulmonary embolism. et al. de Monye W. Does this patient have deep vein thrombosis JAMA . The diagnostic approach to acute venous thromboembolism clinical practice guidelines. Singledetector helical computed tomography as the primary diagnostic test in suspected pulmonary embolism a multicenter clinical management study of patients. This is the report of the PIOPED II study. Interobserver radiologist agreement on angiographic diagnosis of PE lobar. Miller GAH.Rathburn SW. Owen C. et al. Diagnosis of pulmonary embolism with use of computed tomographic angiography. days following surgery received urokinase. General review of role of CT scanning in PE. Incidence of acute pulmonary embolism in a general hospital. utility of LMWH. Intravenous and intrapulmonary recombinant tissuetype plasminogen activator in the treatment of acute massive pulmonary embolism. Segal JB. Schiereck J. but infrequently addressed questions with PE. et al. et al. F. Doucette S. Mechanical fragmentation of clot with local brinolysis and manual clot aspiration are interventions that may be of utility in some patients with lifethreatening PE. et al. Henry JW. Alavi A. Tajima H. have greater incidence of PE than men. Mayo Clin . extensive discussion of DVT diagnostic strategy. Hoffman LV. Clinical utility of ddimer in patients with suspected pulmonary embolism and nondiagnostic lung scans or negative CT ndings. et al. one subgaleal hemorrhage. catheterdirected thrombolysis. . This report points to the value of spiral CT with the exception of discordance between clinical suspicion and test results. Multidetector computed tomography for acute pulmonary embolism. local brinolytic therapy. Venous Thromboembolic Disease Dellinger . . Hybrid treatment of acute massive pulmonary thromboembolism mechanical fragmentation with a modied rotating pigtail catheter. Fowler SE. Ann Intern Med . Surg Neurol . et al. Athanasoulis C. Stein PD. subsegmental. Stein PD. Demonstrated no benecial effect of thrombolytic therapy infused into pulmonary artery versus peripheral administration. Circulation . positive leg ultrasound. or positive to negative digital subtraction angiography. Circulation . Comprehensive clinical practice guideline for the diagnosis and treatment of DVT and PE. The PIOPED Investigators. JAMA . Fever in pulmonary embolism. Chest . Bounameaus H. Whitsett TL. Ryu JH. This is a systematic review done as a practice guideline that addresses numerous important. Davidson BL. Afzal A. Kumazaki T. all survived. Stein PD. et al. and clot aspiration followed by systemic brinolytic therapy. but not women years old. . Strieff MB. and recurrence of PE after IVC lter placement. This article offers perspective on how this technology might be utilized. This study. Olson EJ. such as outpatient therapy. F other than PE in of patients with angiographically documented PE. et al. Women years old. et al. Goodman LR. Am J Respir Crit Care Med . Chest . done at an academic health center. segmental. Ddimer of limited value with high clinical suspicion. also very good review on utility and risk of pulmonary angiography. no intracranial hemorrhage. supports the limited use of plasma ddimer for decision making in patients with clinically suspected PE and nondiagnostic lung scans or negative helical CT studies. Nine neurosurgery patients mean. Verstraete M. Chest . Stein PD. as well as the role of the previous cardiopulmonary disease and previous PE in reliability of scanning. et al. Only of patients had temperatures . Huang H. et al. Demonstrated no source of fever temperature . The gold standard was diagnosis by highprobability or normal ventilation/perfusion scan. LoPinto G. N Engl J Med . Murata S. Value of the ventilation/ perfusion scan in acute pulmonary embolism results of the Prospective Investigation of Pulmonary Embolism Diagnosis PIOPED. Tapson VF. The article includes a discussion of the use of Bayes theorem. which looked at the positive and negative predictive power of spiral CT in predicting presence or absence of PE. AJR Am J Roentgenol . Carroll BA. Management of venous thromboembolism a systematic review for a practice guideline. Doggio R. Fever correlated with DVT but not with infarction. Giannitsis E. Kurowski V. Wood KE.Wiegand UKH. Chest . Effectiveness of endtidal carbon dioxide tension for monitoring of thrombolytic therapy in acute pulmonary embolism. et al. Major pulmonary embolism review of a pathophysiologic approach to the golden hour of hemodynamically signicant pulmonary embolism. Endtidal CO decreases as thrombolytic therapy improves hemodynamics as indicator of decreased dead space. ACCP Critical Care Medicine Board Review th Edition . Excellent general review devoted to massive PE. Crit Care Med . Notes Venous Thromboembolic Disease Dellinger . and respiratory muscle fatigue or structural injury. Prolonged weaning is dened by a failure of at least three SBTs or taking days after the rst SBT. An early step is readiness testing. the clinician should focus on rapidly removing the patient from the ventilator. When mechanical ventilation results from a rapidly reversible cause such as drug overdose or cardiogenic pulmonary edema. weaning Invasive mechanical ventilation reverses some causes of acute respiratory failure while providing crucial ventilatory support as the respiratory system recovers from the initial insult. recognizing that respiratory failure has partially or totally resolved. Readers are referred to the published results of two recent consensus conferences. the clinician must address whether the patient is ready for extubation Fig . In contrast.Weaning From Ventilatory Support Scott K. and gastrointestinal bleeding.. Approximately of patients fall into this category. liberation. mechanical ventilation. readiness testing can start within hours of intubation. sinusitis. The terms weaning. respiratory muscle function has improved. all without difculty. Approximately one in four patients fail to tolerate spontaneous breathing and require a more prolonged process. thromboembolism. MD. For these patients. A number of studies demonstrates that respiratory therapists and ICU nurses can effectively implement readiness testing. although not yet prospectively validated. reintubation. Difcult weaning refers to failure to tolerate the initial SBT with a need for up to three SBTs or taking up to days from rst SBT to successful weaning.. psychological discouragement. Increasing duration of mechanical ventilation is associated with increased mortality. airway injury. weaning consumes to of the total ventilator time. Successful weaning depends on identifying and correcting treatable causes for weaning failure. Those risks include precipitating cardiac dysfunction.. and discontinuation have been used to describe the process of freeing the patient from the ventilator. The weaning process can be further described as a continuum stretching from onset of acute respiratory failure through discharge from the hospital. Once signicant clinical improvement occurs. Epstein. A considerable evidence base is now available to assist the clinician in making weaning and extubation decisions. with other causes of acute respiratory ACCP Critical Care Medicine Board Review th Edition . FCCP Objectives Learn readiness testing using clinical factors and weaning predictors Discuss use of spontaneous breathing trials to test readiness Review causes of weaning failure Understand use of modes of progressive withdrawal and application of weaning protocols Describe weaning patients with prolonged mechanical ventilation Key words extubation. A new classication of the weaning process had been suggested. Simple weaning refers to those who tolerate their rst spontaneous breathing trial SBT and are successfully extubated. Once the patient tolerates spontaneous breathing. There is a tradeoff because invasive mechanical ventilation is associated with substantial complications including ventilatorassociated pneumonia. and the patient is ready to breathe spontaneously. Readiness Testing Using Clinical Factors and Weaning Predictors Rapid weaning must be weighed against the risks of allowing a patient to breathe spontaneously before he or she is ready. respiratory failure. Approximately three of every four patients meeting readiness criteria tolerate spontaneous breathing without ventilator assistance or on low levels of support indicating that mechanical support is no longer required. Thirty percent experience difcult and prolonged weaning and these patients experience higher mortality than simple weaning. A threshold of Pao/Fio can be used for patients with chronic hypoxemia. an evidencebased systematic review identied few predictors associated with clinically signicant changes in the probability of weaning success or failure. Extubation is carried out if the patient has no evidence of upper airway obstruction. is without excessive airway secretions. measured during the initial few minutes of spontaneous unassisted breathing. and has an adequate cough see text for details. cm HO . Weaning parameters respiratory rate breaths/min. ICURN intensive care unit nurse. methodology of predictor measurement differs between studies and displays large coefcients of variations. or Sao on Fio and PEEP. objective criteria are used as surrogate markers of recovery Table . To be clinically useful weaning predictors should accelerate liberation from mechanical ventilation while avoiding the adverse consequences of Table .. failure the clinician should employ full ventilatory support and respiratory muscle rest for to h before readiness testing. Unfortunately. Overview of weaning.C . spontaneous tidal volume mL/kg. RCP respiratory care practitioner. Mental status awake and alert or easily arousable Sao arterial oxygen saturation.Assess Readiness RCPRN Driven Protocol Ready Not Progressive withdrawal Rest for h Read y min SBT If Tolerated F ai l Identify and then Treat Reversible Causes of Weaning Failure Extubate Return to Full Ventilatory Support Figure . f/Vt . These problems include. Only ve predictors measured during ventilatory support had possible value in predicting weaning outcome. Some patients require higher levels of PEEP to avoid atelectasis during mechanical ventilation. Numerous design problems. The frequency/tidal volume ratio. Objective criteria should serve as guidelines rather than inexible standards as many patients never satisfying objective readiness criteria are still successfully weaned. insufcient blinding of physicians determining weaning tolerance. was more accurate but. Similarly. Criteria Used to Determine Readiness for Trials of Spontaneous Breathing Required Criteria ... breaths/L/min . Weaning From Ventilatory Support Epstein . Hemoglobin. failed weaning trials. . studies have noted that neither depressed neurologic status nor anemia necessarily preclude successful liberation from the ventilator. for example. Pao/Fio ratio. Because subjective assessment is notoriously inaccurate in determining readiness. negative inspiratory force to cm HO. but predictive capacity was either relatively weak or inadequately studied. SBT spontaneous breathing trial. Hemodynamic stability no or lowdose vasopressor medications Additional Criteria optional criteria . Core temperature. Many objective physiologic tests weaning parameters have been studied as predictors of readiness for spontaneous breathing Table . f/ Vt.. mg/dL . have been identied. and absence of objective criteria to determine weaning tolerance. weaning predictors were used a priori to determine which patients undergo weaning. inating the accuracy of weaning predictors. Laghi et al used phrenic nerve stimulation and found that lowfrequency fatigue did not occur in patients failing a Tpiece trial. including. Predictors found to be most accurate in a systematic review. and were then considered for extubation if the SBT was tolerated. mental status. and possibly structural respiratory muscle injury. PEEP cm HO nding that tolerated the resulting SBT. associated with only a moderate change in the probability of success or failure. Criteria Indicating That a Patient Is Not Tolerating a Trial of Spontaneous Breathing Objective criteria Sao . The group randomized to use of the f/ Vt experiences took longer to wean from the ventilator. Yet the more important question is whether the f/ Vt./MIP Esophageal pressure measurements Oxygen cost of breathing. work of breathing Gastric intramucosal pH Pao partial pressure of arterial oxygen. and the f/ Vt. facilitates weaning decision making and improves outcome. or Pao mm Hg on Fio . All patients underwent a vecomponent daily screen. One study randomized patients who required mechanical ventilation for at least h. Pao/fraction of inspired oxygen Fio.. MIP maximal inspiratory pressure. while in the other only patients with ACCP Critical Care Medicine Board Review th Edition f/ Vt breaths/L/min underwent an SBT. pressure Complex measurements usually require special equipment Airway occlusion pressure P. or any weaning predictor. the f/ Vt measured during pressure support or continuous positive airway pressure will be lower than that determined on Tpiece. Indeed. respiratory rate. Respiratory rate breaths/min Heart rate beats/min or an increase of baseline Systolic BP mm Hg or mm Hg or change of from baseline Subjective criteria Presence of signs of increased work of breathing. Support for the principle outlined here comes from the recently published Awakening and Breathing Controlled ABC trial. Weaning Predictors Measurements of oxygenation and dead space Pao/Fio Pao/Pao Dead space Vd/Vt Simple tests of respiratory load and muscular capacity Negative inspiratory force maximal inspiratory pressure Respiratory system compliance and resistance Minute ventilation Maximal voluntary ventilation Vital capacity Respiratory frequency Tidal volume Tests that integrate more than one measurement f/Vt CROP index compliance. and concluded that the wide range of pretest probability of success explained much of the heterogeneity in performance of this test. they used very liberal oxygenation criteria oxygen saturation measured by pulse oximetry. The key is that patients were returned to ventilatory support as soon as signs of weaning intolerance occurred Table . Table . as of such patients . positive endexpiratory pressure PEEP. Performance of a weaning predictor also depends on how the test is performed. As an example. would ensue if the failed weaning trial was unduly extended. on Fio .Table . in one group the f/ Vt was not used for weaning decision making. Based on randomization. or Pao/Fio Increase in Paco mm Hg or decrease in pH . An analysis of studies of the f/ Vt found a sensitivity of . These ndings strongly indicate that patients are ready to breathe on their own earlier than detected by conventional criteria. unfortunately. oxygenation. The authors successfully used SBT screening criteria that did not include weaning predictors. adequate cough. Those passing the screen automatically underwent a h SBT. hemodynamic stability. Readiness Testing The Spontaneous Breathing Trial Direct extubation after satisfying readiness criteria alone is unwise. Along those lines. This result may derive either from the limited predicted value of weaning predictors or from the inherent safety of a closely monitored SBT. It is likely that fatigue.. including thoracoabdominal paradox or excessive use of accessory respiratory muscles Presence of other signs of distress such as diaphoresis or agitation Sao arterial oxygen saturation. but could be extubated. tolerance for a min SBT indicates that a patient no longer requires ventilatory support. One study found no difference comparing ATC. neurologic process can delay weaning initiation or lead to weaning intolerance. Not surprisingly. Another investigation of patients with acute respiratory failure used each patient as his or her own control and observed markedly elevated inspiratory loads and reduced respiratory muscle capacity Weaning From Ventilatory Support Epstein . as a consequence of capacityload imbalance. patients with weaning failure usually manifest elevated respiratory drive. and there is rapid reinstitution of ventilatory support. In contrast. Automatic tube compensation ATC has been advocated as it adjusts PSV level based on tube characteristics. One study. Advocates of Tpiece maintain that it best estimates work of breathing after extubation. detected by an elevated airway occlusion pressure P. Randomized controlled trials RCTs. resulting in more dynamic hyperination. a given PSV level may either over. Pao/Fio ratio is a prerequisite for initiating SBTs. Therefore a trial of spontaneous breathing SBT is strongly recommended. An observational study examined patients who failed a min Ttube trial and were immediately placed on a min trial of PSV at cm HO. found a median time to trial failure of min. although it did not reach statistical signicance. another underlying mechanism for failure should be sought. comparing pressure support to Tpiece and CPAP to Tpiece have shown the techniques to be essentially equivalent in terms of successful weaning and extubation. a study of patients with COPD. while another found a trend for better SBT success for ATC vs with CPAP. ventilator alarm and monitoring systems promptly identify weaning intolerance.require reintubation. The criteria may be insufciently sensitive in detecting incipient respiratory failure some patients satisfying criteria for weaning tolerance may demonstrate more sophisticated indicators of respiratory dysfunction followed by postextubation respiratory failure. Careful assessment during an SBT is based on both objective and subjective criteria. heat and moisture exchange devices. and these progressively increased until the trial was terminated. Excessive load may be imposed by the endotracheal tube. Pathophysiology of Weaning Failure Fifteen to of patients fail their initial SBT and should undergo a thorough investigation trying to identify. The ideal duration for the SBT may depend on the duration of ventilation or the underlying cause for respiratory failure. Ten of these patients failed the PSV trial. Rapid shallow breathing was noted. twice as many patients were extubated after min of PSV required reintubation. In general. As an example. mm Hg. found no difference in success rate comparing patients randomized to either or min of Tpiece breathing. As an example. and treat. The SBT can be performed on lowlevel pressure support PSV. if needed.. a study of patients with COPD found that the patients failing the SBT had higher loads increased resistance. When hypoxemia ensues during weaning. intrinsic PEEP.or undercompensate for imposed work. Depressed central respiratory drive oversedation. or unassisted through a Tpiece.. it has been argued that PSV more effectively counterbalances endotracheal tuberelated resistive workload. continuous positive airway pressure CPAP. anxiety. although the level required varies from to cm HO and is challenging to determine noninvasively. Practical advantages to conducting an SBT through the ventilator include there is no additional equipment is required. and increased inspiratory work. There was no difference in the percentage of patients passing the SBT. PSV.. Indeed. reversible factors Fig . tachycardia and may reect processes other than physiologic weaning intolerance eg. Adequate oxygenation eg. hypoxemia is an unusual cause for weaning failure. elastance. A smaller study compared or min SBT of PSV at cm HO after a weaning strategy of progressive decrease in pressure support. ventilated for at least days. and Tpiece. CPAP can improve ventilator triggering in the setting of signicant intrinsic PEEP. of them successfully. although these have not been rigorously validated Table . thus. or the ventilator tubing and valves. examining only the initial SBT attempt. Some criteria are nonspecic tachypnea. and intrinsic PEEP at SBT onset. Intrinsic factors are more commonly responsible. Patients intolerant of SBTs often fail to appropriately increase cardiac output and stroke volume during the trial. and glucose. noted that patients with weaning intolerance demonstrated a tensiontime index above the . ACCP Critical Care Medicine Board Review th Edition . positive uid balance has been associated with weaning failure. Ca calcium. phrenic nerve injury after cardiac surgery. critical illness neuromyopathy. This hypothesis is supported by the observation that healthy subjects breathing against an inspiratory load develop thoracoabdominal paradox in the absence of fatigue. cortisol. threshold at which respiratory muscle fatigue occurs in healthy subjects. Patients at risk for the latter may demonstrate an elevated brain natriuretic peptide BNP or Nterminal proBNP prior to the weaning trial or an elevated Nterminal proBNP at the end of the trial.PO Steroids Malnutrition Sepsis. during weaning failure compared with observations made at the time of weaning success. Potential causes of weaning failure. pleural effusions Abdomen distension Ventilatory drive Oversedation Metabolic alkalosis CNS process OHS Resistive load Secretions Bronchoconstriction Endotracheal tube problems Capacity Load Neuromuscular capacity Mg.. PTX pneumothorax. CNS central nervous system.Elastic load PEEPi. an effect that can be partially offset by the use of pressure support. PEEPi intrinsic positive endexpiratory pressure. In one study. Older studies have suggested that respiratory muscle fatigue was an important manifestation of weaning failure. the effects of endocrinopathy eg.Ca. VCO Metabolic acidosis Anxiety. hypothyroidism. can cause myocardial ischemia detected by nuclear technique or continuous ECG monitoring. K potassium. The transition from positivepressure ventilation to spontaneous negative pressure breathing can increase left ventricular preload and afterload. other studies. Pain Cardiac Disease Psychological Disease Figure . Pneumonia Pulmonary edema Atelectasis PTX. elevating transmural pulmonary artery occlusion pressure and causing pulmonary edema. Laghi et al found that patients intolerant of a wellmonitored SBT failed to develop evidence for lowfrequency respiratory muscle fatigue. Cardiac disease can cause weaning intolerance via a number of mechanisms. Reduced respiratory muscle strength is frequently seen in patients with weaning intolerance. myopathy Ventilatory demand Dead space. a preSBT BNP of pg/dL correlated with a longer duration of weaning. CIP critical illness polyneuropathy. OHS obesity hypoventilation syndrome.. This may occur from decreased diaphragmatic pressure generation secondary to dynamic hyperination. suggesting a response to increased loading rather than fatigue. A decrease in left ventricular ejection fraction has been observed in COPD patients undergoing Tpiece trials. Mg magnesium.K.phosphorus.. PO. Vco carbon dioxide production. injury CIP. But rapid shallow breathing and thoracoabdominal paradox have been observed to appear immediately after ventilator disconnection and do not progress during failed weaning. or malnutrition. respiratory muscle remodeling secondary to inactivity or muscle atrophy especially with neuromuscular blocking agents. In contrast. adrenal insufciency.. Using the twitch occlusion and magnetic stimulation. The stress of weaning is considerable as it results in increased levels of plasma insulin. Increased work of breathing. Medications Hypothyroidism Phrenic n. Psychological factors can limit weaning but few data exist to dene how often this occurs. or the associated release in catecholamines. Lastly. hypnosis. The latter approach theoretically slowly shifts work from ventilator to patient. small uncontrolled reports found that biofeedback. Examples of Reversible Causes of Weaning Failure and Their Associated Treatments Cause Ventilatory demand Examples of Treatment CO production by suppressing fever and avoiding overfeeding. One study found Tpiece to be superior and the other found PSV the most efcient. dead space by treating hypovolemia. when clinical evidence of respiratory muscle fatigue is absent. place larger endotracheal tube Diuretics for increased lung water. if evidence for fatigue is evident. Modes of Progressive Withdrawal Once the reversible factors causing weaning intolerance have been addressed. drainage of pleural uid and air. The clinician must next decide whether to perform another SBT or whether to more gradually reduce ventilatory support progressive withdrawal. paracentesis. treat sepsis and hypothyroidism Sedation algorithm to avoid oversedation. As an example. cm HO. In the most common clinical scenario. An imbalance between respiratory load and neuromuscular capacity is also suggested by an elevated f/Vt ratio breaths/L/min or increased airway occlusion pressure P. or therapy for depression contributed to successful weaning. minimize use of NMB agents. tachycardia.Delirium is present in the majority of ventilated patient and its presence is correlated with prolonged duration of intubation. PEEP inspiratory PEEP. decompression of abdomen with NG tube. comparison of data from two international surveys indicates that fewer ICUs are employing multiple daily SBTs than in the past. respiratory frequency breaths/min Elastic load Neuromuscular capacity Ventilatory drive NG nasogastric. Differences in patient populations and study design may explain the contrasting results. treat sepsis. agitation. further efforts to discontinue mechanical ventilation are indicated Table . These studies demonstrate that synchronized intermittent mandatory ventilation SIMV alone slows the process. multiple daily attempts may be appropriate. a nding that is concordant with physiologic investigations Table . It remains unproven whether this process reconditions or trains the respiratory muscles or simply allows time needed for recovery eg. then h of rest on full support should precede the next weaning effort. diaphoresis. bronchodilators to reduce PEEPi. A confounding factor is that criteria used to indicate weaning intolerance eg. NMB neuromuscular blocking. and respiratory system compliance mL/cm HO Presence suggested by poor maximal inspiratory pressure MIP to cm HO Presence suggested by unexplained hypercapnia. give NaHCO for severe metabolic acidosis Administer bronchodilators or steroids.. . relaxation techniques. a large RCT found no difference in outcome for patients given multiple daily SBTs and those given a single daily trial. correct metabolic alkalosis with acetazolamide Comment Presence suggested by Ve L/min Resistive load Presence suggested by measured airway resistance of cm HO/L/s Presence suggest by clinical examination. Interestingly. In contrast. Nevertheless. Weaning From Ventilatory Support Epstein . provide adequate nutrition. antibiotics for respiratory tract infection. reduction in respiratory load or increased respiratory muscle strength and endurance. chest radiograph. and tachypnea are also manifestations of anxiety or psychological distress. airway suctioning for secretions. Two large multicenter RCTs directly compared progressive withdrawal techniques in patients who satised readiness criteria but failed to tolerate a h SBT. One issue is how long to rest a patient after a failed weaning effort. treat pneumonia Correct electrolyte abnormalities. ventilatorassociated pneumonia.demonstrating that the degree of respiratory muscle rest on SIMV is not proportional to the level of ventilatory support. volumeassured pressure support. Finally. If the SBT is successful. one presented in preliminary form and the other a quasirandomized study in the Chinese literature. one RCT examined the use of a closedloop. duration of mechanical ventilation. A trial of spontaneous breathing is automatically conducted at the point a minimal level of PSV is achieved. Six RCTs have explored the use of NIV in patients having trouble weaning from mechanical ventilation. indicate that NIV is equal or superior to invasive weaning. the physician is prompted about extubation. minimal tidal volume. although the latter was associated with fewer complications. Using this design. Two additional studies. This effect can be overcome by adding PSV to the unsupported breaths during SIMV. and a lower incidence of nosocomial pneumonia and septic shock. Finally. duration of invasive ventilation. and maximal endtidal carbon dioxide to keep the patient in a zone of comfort. length of ICU stay. Nava et al studied COPD patients with acuteonchronic hypercapnic respiratory failure mean Paco. computerdriven ventilation decreased duration of weaning. The computerdriven ventilator continuously adjusts the level of pressure support based on respiratory rate. and manageable volume of respiratory secretions. although other outcomes were unchanged. approximately mm Hg ACCP Critical Care Medicine Board Review th Edition who failed an initial Tpiece trial. the weaning protocol not explicitly stated. one small RCT of patients with COPD noted a trend toward shorter weaning duration with SIMV/PSV compared with SIMV alone. The NIV group had statistically signicant reductions in duration of mechanical ventilation. these studies indicate that NIV is a reasonable approach in patients with COPD for whom the treatment has not allowed weaning. fewer tracheostomies. adequate mental status. and median ICU stay without adverse event or increased reintubation. and ICU length of stay. higher ICU survival. This study was stopped at an interim analysis nding that NIV was associated with shorter duration of mechanical ventilation. extubation criteria must be satised eg. Taken together. and day survival. and adaptive support ventilation facilitate the process of weaning compared with the techniques previously discussed. . Noninvasive ventilation NIV effectively treats acute respiratory failure complicating COPD and also benets select patients with acute hypoxemic failure. total duration of ventilation. effective cough. duration of intubation. and the patient must be a good candidate for NIV able to breath spontaneously for at least to min and not deemed to have difculty in reintubation. there is no RCT that indicates that modes such as volume support. Ferrer et al randomized patients who had failed three SBTs. A subsequent RCT only onethird of patients with COPD found no difference in survival. One study randomized patients to h SBTs with Tpiece or PSV and found the latter associated with decreased weaning time. Patients were randomized to standard PSV weaning or immediate extubation to NIV PSV mode delivered via a fullface mask and standard ICU ventilator. did not nd the closedloop system to be superior. particularly when psychological factors or the imposed work of breathing is contributing to weaning failure. and length of stay in ICU and in hospital. and better recognition of readiness for extubation. lower sedation requirements. knowledgebased system compared with usual care in patients. and the randomization unequal. Important caveats include the following SBT readiness criteria must be satised. The neuromuscular apparatus poorly adapts to changing loads because respiratory muscle contraction during lower levels of SIMV is similar during both intervening unsupported and mandatory supported breaths. involving the same computerized system. These results must be interpreted cautiously as the study was unblended. A metaanalysis of these ve studies of patients with COPD found that NIV was associated with decreased mortality. The benets of NIV include a reduction in the acquisition of pneumonia. shorter hospital stay. shorter ICU stay. To date. Indeed. and length of stay when comparing invasive weaning with NIV. singlecenter study. Another investigation of acuteonchronic respiratory failure patients found NIV reduced duration of invasive mechanical ventilation. In contrast a subsequent. of whom had chronic lung disease. Therefore. the rst is more important than the second. complication rate. and more frequently need longterm acute care. either through sedation assessment scoring or by daily cessation of sedative infusions. decreased time in coma. On the other hand. or to direct a search for treatable causes for weaning failure. decrease duration of mechanical ventilation and duration of ICU stay. hospital costs. delirium Semirecumbent positioning Transport out of ICU for procedures Physician and nurse stafng in the ICU Weaning From Ventilatory Support Epstein . Table . found that respiratory care practitioner/ICU nursedirected protocols are also able to shorten the duration of mechanical ventilation. the third strategy has yet to be fully investigated. unnecessary delays in extubation prolong ICU stay. protocols must be tailored to the environment in which they will be employed. pediatric. the two groups progressed to the point of passing an SBT at the same rate. Studies performed in a neurosurgical ICU. Risk Factors for Extubation Failure Medical. The intervention group experienced signicant reductions in weaning time. prolonged ICU and hospital stays. Although a protocol may serve as the default approach to weaning. Nevertheless. the improved outcome of combining a daily awakening trial and SBT resulted from patients being awake and ready for extubation once they passed the SBT. and improved survival at year. Reintubated patients suffer increased hospital mortality. Extubation When a patient has tolerated an SBT the clinician must next determine whether the endotracheal tube is still required. heighten the risk for pneumonia. no differences were noted in ICU or hospital length of stay. Strategies designed to avoid oversedation by limiting the use of continuous infusions. duration of mechanical ventilation. Protocols can be used to perform a daily screen to determine readiness for an SBT. Subsequent RCTs in medical and surgical ICUs. Intervention patients passing the daily screen underwent a min SBT and if the trial was passed.Application of Weaning Protocols Uncontrolled investigations and RCTs demonstrate improved outcome with weaning driven by a protocol and implemented by physicians or by respiratory care practitioners and ICU nurses. Additional factors are important as studies show reduced duration of mechanical ventilation when nurse/patient ratios improve and when a bedside weaning board and ow sheet are used to enhance communication between critical care practitioners. Girard et al recently published the results of a trial that employed a wake up and breathe strategy the ABC trial.. and increase hospital mortality. at least one study found that a sedation protocol did not hasten weaning from mechanical ventilation. Of these three applications. Approximately to of patients fail extubation require reintubation within to h of extubation. One study randomized mechanically ventilated medical patients to an intervention strategy combined daily readiness testing with SBTs compared to standard care. In contrast. Patients randomized to a daily awakening trial followed by an SBT vs SBT alone experienced increased time off of mechanical ventilation. and ICU costs. or multidisciplinary ICU patient Older age Pneumonia as cause for mechanical ventilation Higher severity of illness at the time of extubation Use of continuous IV sedation Abnormal mental status. or mortality. exibility and clinical judgment are highly recommended as too rigid an approach needlessly prolongs weaning and extubation... the managing clinicians received a prompt for extubation. a pediatric ICU. Interestingly. and in a medical ICU at a leading academic medical center found no superiority to a protocolized approach. to determine the pace of weaning using methods of progressive withdrawal. Control patients were screened daily but the information was not used to make weaning decisions. decreased ICU and hospital length of stay. Most randomized trials demonstrate that protocols directed at minimizing the use of sedative infusions decrease the duration of mechanical ventilation. This entails modifying the protocol for application to a distinct patient population. A number of risk factors for extubation failure have been identied Table . The ability to protect the airway also depends on cough strength and volume of respiratory secretions eg. More recently. of tidal volume to placebo or methylprednisolone injection multiple or single dose during the h prior to extubation. suction requirement more than every h. standard weaning predictors perform poorly in foretelling outcome for patients supported by prolonged mechanical ventilation.. Falsepositive test ndings result from secretions adhering to the external surface of the endotracheal tube or when an undetected increase in inspired volume machine tidal volume plus spontaneous gas inspired around the tube contributes to an elevated exhaled tidal volume. Because these confounders are difcult to detect prior to extubation. and reverse. Treatment with methylprednisolone signicantly reduced the risk for postextubation stridor and need for reintubation. indicate that immediate postextubation application of NIV in patients at highest risk for extubation failure is effective in preventing reintubation and may reduce mortality. the integration of parameters has been found most useful. . As in the acute ICU setting. Two recently published RCTs.As both extubation delay and extubation failure are linked to adverse outcomes. Mental status is also important. In contrast. Weaning efforts should start as soon as possible after transfer as nearly of patients supported by prolonged mechanical ventilation will tolerate their initial SBT and be liberated. Air leak can be quantied as the difference between the inspired and expired tidal volume during assistcontrol ventilation. although studies looking exclusively at this parameter have come to conicting conclusions. an imbalance between respiratory load and neuromuscular capacity often forms the basis of ventilator dependence. especially in highrisk patients. mL/h. Cheng et al randomized highrisk patients cuffleak volume. Despite these advances. For the remaining patients. one casecontrol study found that NIV effectively reduced reintubation in COPD patients with early evidence of postextubation hypercapnic respiratory failure. A recent multicenter observational study. continued efforts to identify. accurate prediction of extubation outcome remains challenging. importance has shifted to developing strategies to more accurately predict and prevent postextubation respiratory failure. In general. Recently. Failing all three criteria led to certain extubation failure. For example. RCTs indicate that routine use of nasal intermittent positive pressure ventilation after extubation or application in heterogeneous populations with overt or those with early signs of extubation failure does not decrease need for reintubation or improve survival. secretions cutoff. The success of NIV for acute respiratory failure and its recent successful application in facilitating weaning has led to renewed interest in application to prevent extubation failure. an expert in airway management should be available immediately when extubating the patient with a positive cuffleak test. these patients are often transferred to a chronic ventilator or longterm acute care unit. Therefore. Weaning Patients Supported by Prolonged Mechanical Ventilation Approximately to of patients with acute respiratory failure require prolonged ventilatory support days. Once stable. patients transferred to longterm care hospitals found that could be successfully weaned from mechanical ventilation. factors that either increase work of breathing or contribute to respiratory muscle weakness should be undertaken. For example. parameters that can be qualitatively and quantitatively measured. and ACCP Critical Care Medicine Board Review th Edition abnormal mental status inability to complete four simple commands was highly predictive of extubation outcome. Salam et al found that measuring peak cough ow rates cutoff. Measuring blood gases at the end of the SBT has not been shown to accurately predict extubation outcome. several RCTs have demonstrated that systemic corticosteroids can reduce postextubation stridor. . weaning predictors perform poorly in predicting extubation outcome. L/min. Examining the f/ Vt at SBT conclusion or the time needed to return to baseline minute ventilation after resumption of full ventilatory support shows promise. and the absence of all three was associated with only a risk for reintubation. of . The upper airway can be assessed by identifying an audible air leak when the endotracheal tube balloon is deated cuffleak test. This is not unexpected as extubation failure often results from inability to protect the airway and manage respiratory secretions. Intensive Care Med . . Boles JM. Tobin MJ. Am Rev Respir Dis . The Spanish Lung Failure Collaborative Group. and outcome of a twohour Tpiece trial in patients weaning from mechanical ventilation. Jubran A. . Nevins ML. et al. Alia I. Connors A. weaning protocols in this setting are associated with shorter weaning duration than that of traditional approaches. A comparison of two methods to perform a breathing trial before extubation in pediatric intensive care patients. NY McGraw Hill. Am J Respir Crit Care Med . Laghi F. Wood LD. . A national survey of Spanish hospitals. A randomized. . . . Chest . JAMA . and the American College of Critical Care Medicine. et al. . . Kress JP. Ely EW Jr. Crit Care Med . Hendra KP. Abouqal R. Ibanez J. Principles and practice of mechanical ventilation. Compared with historic controls. Epstein SK. . Cook D. In Tobin M. Intensive Care Med . Madani N. Gordo F. et al. Liberation of the patient from mechanical ventilation. Chest . Hall JB. Weaning parameters. Anzueto A. ventilatory support a collective task force facilitated by the American College of Chest Physicians. Lorino H. et al. Eur Respir J . Respir Care Clin North Am . Intensive Care Med . Liberation from mechanical ventilation a decade of progress. Tobin MJ. ed. Evidencebased guidelines for weaning and discontinuing . Meade M. Extubation outcome after spontaneous breathing trials with Ttube or pressure support ventilation. et al. Inspiratory pressure support prevents diaphragmatic fatigue during weaning from mechanical ventilation. Positive endexpiratory pressure vs Tpiece. Esteban A. Esteban A. Am J Respir Crit Care Med . Is weaning failure caused by lowfrequency fatigue of the diaphragm Am J Respir Crit Care Med . Byrne P. the American Association for Respiratory Care. et al. Retta A. Alia I. Chest . Intensive Care Med . et al. et al. Nevins ML. MacIntyre NR. . Farias JA. Clinical characteristics. Pt . Tanios MA. Fuchs BD. Esteban A. The Spanish Lung Failure Collaborative Group. Variable performance of weaningpredictor tests role of Bayes theorem and spectrum and testreferral bias. Alia I. . . Jamaleddine GW. Esteban A. Chest . Weaning from mechanical ventilation. Effect of spontaneous breathing trial duration on outcome of attempts to discontinue mechanical ventilation. Characteristics and outcomes in adult patients receiving mechanical ventilation a day international study. Girard TD. controlled trial of the role of weaning predictors in clinical decision making. Zeggwagh AA. References . . Jones DP. . . . Morgan C. Spanish Lung Failure Collaborative Group. . Chest . Guyatt G.An RCT in prolonged mechanical ventilation found no difference between PSV weaning and tracheotomy collar trials of increasing duration in COPD patients. Chest . Evans GW. . et al. Zeineldine SM. Intensive Care Med . Predictors of outcome for patients with COPD requiring invasive mechanical ventilation. et al. et al. SupplSS ElKhatib MF. et al. Weaning From Ventilatory Support Epstein . Harf A. Complications in ventilator supported patients. Jubran A. Vallverdu I. SupplSS Ely EW. Schmidt GA. . respiratory functional parameters. Alia I. Efcacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care Awakening and Breathing Controlled trial a randomised controlled trial. Frutos F. New York. et al. Predicting success in weaning from mechanical ventilation. JAMA . Brochard L. The prognostic signicance of passing a daily screen of weaning parameters. Lancet . Hall JB. Am J Respir Crit Care Med . Cook DJ. et al. Calaf N. Weaning from mechanical ventilation a model for extubation. Epstein SK. Extubation after mechanical ventilation. . . Effect of pressure support ventilation and positive end expiratory pressure on the rapid shallow breathing index in intensive care unit patients. et al. Cattapan SE. Modes of mechanical ventilation and weaning. Manthous CA. Subirana M. Baker AM. et al. Bion J. Epstein S. GarnachoMontero J. et al. Mechanical effects of airway humidication devices in difcult to wean patients. . Anesthesiology . Del Rosario N. et al. Prevalence of myocardial ischemia during mechanical ventilation and weaning and its effects on weaning success. Am J Respir Crit Care Med . Ttube. Mauri S. Lemaire F. Richard JC. . Reduced breathing variability as a predictor of unsuccessful patient separation from mechanical ventilation. Guenther SM. Vitacca M. Eur Respir J . et al. . DeHaven CB. Datta D. Intensive Care Med . or pressure support ventilation. Crit Care Med . Extubation outcome following a spontaneous breathing trial with automatic tube compensation versus continuous positive airway pressure. . et al. Effects of mechanical ventilation on diaphragmatic contractile properties in rats. Guyomarch S. Protocoldirected weaning from mechanical ventilation clinical outcome in patients randomized for a min or min trial with pressure support ventilation. Lynch KE. Association between adrenal insufciency and ventilator weaning. et al. Breathing pattern during acute respiratory failure and recovery. Anesthesiology . Grozovski E. Does ICUacquired paresis lengthen weaning from . et al. Huang CJ. Lin HC. Cohen JD. Strauss HW. Hemodynamic changes during discontinuation of mechanical ventilation in medical intensive care unit patients. Crit Care Med . Am J Respir Crit Care Med . . GarciaGarmendia JL. KonnoMead analysis of ribcageabdominal motion during successful and unsuccessful trials of weaning from mechanical ventilation. Crit Care Med . . Cardiac ischemia during weaning from mechanical ventilation. Chest . Pathophysiologic basis of acute respiratory distress in patients who fail a trial of weaning from mechanical ventilation. AmayaVillar R. Zakynthinos S. Teboul JL. Acta Anaesthesiol Scand . Stone KS. Am J Respir Crit Care Med .. Tobin MJ. Weaning from mechanical ventilation with pressure support in patients failing a Ttube trial of spontaneous breathing. Elsasser S. et al. Sassoon CS. et al. . . Mols G. et al. Myocardial perfusion as assessed by thallium scintigraphy during the discontinuation of mechanical ventilation in ventilatordependent patients. . Frazier SK. . Le Bourdelles G. et al. Tobin MJ. Breathing measurement reduces falsenegative classication of tachypneic preextubation trial failures. Diconne E. Chetty KG. Sharshar T. . Colombo D. Frazier SK. Cinotti L. Anzueto A. Roussos C. Cracco C. Am J Respir Crit Care Med . quiz ACCP Critical Care Medicine Board Review th Edition . Hypothyroidism and failure to wean in patients receiving prolonged mechanical ventilation at a regional weaning center. Wysocki M. Am J Respir Crit Care Med . Kirton OC. Crit Care Med . et al. Morgan JP. . Tobin MJ. . Chatila W. et al. Peters JI. Guenther SM. Crit Care Med . Acute left ventricular dysfunction during unsuccessful weaning from mechanical ventilation. et al. . et al. Heart Lung . Comparison of two methods for weaning patients with chronic obstructive pulmonary disease requiring mechanical ventilation for more than days. Ani S. . Brom H. et al. . Vianello A. . Effect of critical illness polyneuropathy on the withdrawal from mechanical ventilation and the length of stay in septic patients. . et al. . Scalise P. Domenighetti G. Moser D. De Jonghe B. Crit Care Med . Am Rev Respir Dis . Girault C. et al. Perez W. et al. Shapiro M. Intensive Care Med . Perez W. Boczkowski J. . Haberthur C. Jubran A. . The tensiontime index and the frequency/tidal volume ratio are the major pathophysiologic determinants of weaning failure and success. BastujiGarin S. . et al. Viires N. et al. Widener J. Effects of prolonged controlled mechanical ventilation on diaphragmatic function in healthy adult baboons. Am J Crit Care . Breton L. Teixeira A. Ezingeard E. Guaglianone D. Does rib cageabdominal paradox signify respiratory muscle fatigue J Appl Physiol . Chest . Tobin MJ. Vassilakopoulos T. Extubation after breathing trials with automatic tube compensation. Hurford WE. . Perren A. mechanical ventilation Intensive Care Med . The impact of delirium in the intensive care unit on hospital length of stay. Upadya A. . . Lin D. et al. Esquinas A. Left ventricular function during weaning of patients with chronic obstructive pulmonary disease. et al. Karlinsky J. Girault C. In Crapo J. . Jubran A. et al. Tobin MJ. N Engl J Med . Intensive Care Med . Arancibia F. Ferguson ND. Comparison of pressure support and Ttube weaning from mechanical ventilation randomized prospective study. Rose L. Can J Anaesth . . Imsand C. Am J Respir Crit Care Med . DAlfonso N. synchronized intermittent mechanical ventilation. Rauss A. PA Lippincott. Koksal GM. Am J Respir Crit Care Med . Regulation of inspiratory neuromuscular output during . Textbook of pulmonary diseases. and dyspnea. Richard C. Jounieaux V. Leung P. Benito S. Duran A. Feihl F. A comparison of four methods of weaning patients from mechanical ventilation. Crit Care Med . patient effort. Archambaud F. Intensive Care Med . et al. et al. Sayilgan C. randomized controlled study. Philadelphia. Mancebo J. Am J Respir Crit Care Med . Tobin MJ. Levy M. . Nava S. et al. Am J Respir Crit Care Med . . . Mathru M. . Noninvasive mechanical ventilation in the weaning of patients with respiratory failure due to chronic obstructive pulmonary disease. Clini E. Spanish Lung Failure Collaborative Group. et al. R . Chest . Margolin R. Noninvasive ventilation during persistent weaning failure a randomized controlled trial. Girou E. Intensive Care Med . Jolliet P. Fluid balance and weaning outcomes. et al. . Synchronized intermittent mandatory ventilation with and without pressure support ventilation in weaning patients with COPD from mechanical ventilation. Noninvasive positive pressure ventilation NPPV to facilitate extubation after acute respiratory failure a feasibility study abstract. Intensive Care Med . Ely EW. Zhonghua Jie He He Hu Xi Za Zhi . A randomised. Leone A. Comparison of three methods of gradual withdrawal from ventilatory support during weaning from mechanical ventilation. Presneill JJ. Tilluckdharry L. Crit Care . Am J Respir Crit Care Med . et al. A Chen J. Jubran A. . . Am J Respir Crit Care Med . Time for extubation and sequential noninvasive mechanical ventilation in COPD patients with exacerbated respiratory failure who received invasive ventilation in Chinese. . MajericKogler V. Epstein S. Brochard L. et al. MekontsoDessap A. Comparison of assisted ventilator modes on triggering. Williams amp Wilkins. A randomized. . Ambrosino N. Evolution of mechanical ventilation in response to clinical research. . eds. The effects of different weaning modes on the endocrine stress response. Continuous recordings of mixed venous oxygen saturation during weaning from mechanical ventilation and the ramications thereof. Meade MO. Btype natriuretic peptide and weaning from mechanical ventilation. Qiu D. Croat Med J . controlled trial. Intensive Care Med . Pattern of recovery from diaphragmatic fatigue over hours. et al. J Appl Physiol . controlled trial of conventional versus automated weaning from mechanical ventilation using SmartCare/PS. . Johnston L.. . Daudenthun I. . Matic I. . . Hill N. Ferrer M. et al. Ann Intern Med . Am J Respir Crit Care Med . Noninvasive ventilation as a systematic extubation and weaning technique in acuteonchronic respiratory failure a prospective. Teboul JL. A metaanalysis of noninvasive weaning to facilitate liberation from mechanical ventilation. . Gautam S. Anesthesiology . . Weaning from ventilatory support. Grasso S. et al. Laghi F. Burns KE. Meade MO. Use of Nterminal probrain natriuretic peptide to detect acute cardiac dysfunction during weaning failure in difculttowean patients with chronic obstructive pulmonary disease. et al. Weaning From Ventilatory Support Epstein . Tobin MJ. LeviValensi P. Perret C. de Prost N. Glassroth J. et al. Esteban A. Tao D. Esteban A. De Michele M. Muralidharan V. Am J Resp Crit Care Med . . Lellouche F. et al. et al. Sen O. Adhikari NK. Chevron V. Dries D. et al. Frutos F. A multicenter randomized trial of computerdriven protocolized weaning from mechanical ventilation. . . Pierson DJ. Pawson SR. et al. . Baker AM. et al. Ganz T. Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. Ferguson ND. et al. A prospective. Decision to extubate. Am J Respir Crit Care Med . et al. A randomized trial of protocoldirected sedation management for mechanical ventilation in an Australian intensive care unit. Crit Care Apr Epub ahead of print . R ACCP Critical Care Medicine Board Review th Edition . Intravenous injection of methylprednisolone reduces the incidence of postextubation stridor in intensive care unit patients. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. Crit Care Med . Wypij D. Salam A. N Engl J Med . Effect of a collaborative weaning plan on patient outcome . Pohlman AS. Venkataraman ST. et al. Silver P. Wong JB. Bellissant E. et al. Presneill JJ. Manias E. Effect of mechanical ventilator weaning protocols on respiratory outcomes in infants and children a randomized controlled trial. et al. Thorens JB. Am J Respir Crit Care Med . h pretreatment with methylprednisolone versus placebo for prevention of postextubation laryngeal oedema a randomised doubleblind trial. DePriest JL. Coplin WM. Dexamethasone to prevent postextubation airway obstruction in adults a prospective. Epstein SK. Smina M. . Cheng KC. OConnor MF. Lancet . Namen AM. Intensive Care Med . Inuence of the quality of nursing on the duration of weaning from mechanical ventilation in patients with chronic obstructive pulmonary disease. Kuo PH. Brook AD. . Esteban A. Chest . et al. doubleblind. . Randolph AG. Tatter SB. . Robeson C. . Ahrens TS. Am J Respir Crit Care Med . Minute ventilation recovery time a predictor of extubation outcome. . The effect of arterial blood gas values on extubation decisions. Ely EW. Predictors of successful extubation in neurosurgical patients. Seymour C. et al. et al. Are blood gases necessary in mechanically ventilated patients who have successfully completed a spontaneous breathing trial Respir Care . et al. controlled trial of a protocolbased strategy to discontinue mechanical ventilation. Kaelin RM. Ciubotaru RL. N Engl J Med . Battistella F. . randomized. Epstein SK. Lee CH. . . Bucknall TK. Murin S. Hou CC. Predictive value of rapid shallow breathing index measured at initiation and termination of a hour spontaneous breathing trial for weaning outcome in ICU patients. et al. et al. Crit Care Med . Noninvasive mechanical ventilation may be useful in treating patients who fail weaning from invasive mechanical ventilation a randomized clinical trial. et al. Kollef MH. Peng MJ. Chest . . JAMA . Epstein SK. Crit Care Med . . Cooley KD. . Wu HD. in the critical care setting. Am J Respir Crit Care Med . . Gada P. Martinez A. A randomized. Jolliet P. Crit Care Med . Crit Care . et al. J Formos Med Assoc . Shapiro SD. Krishnan JA. Schaiff R. FrutosVivar F. Protocol weaning of mechanical ventilation in medical and surgical patients by respiratory care practitioners and nurses effect on weaning time and incidence of ventilatorassociated pneumonia. Pt . . Wu CL. . Chest . Dunagan DP. Implications of extubation delay in braininjured patients meeting standard weaning criteria. Henneman E. . Dracup K. Epstein SK. Risk factors for extubation failure in patients following a successful spontaneous breathing trial. et al. Etiology of extubation failure and the predictive value of the rapid shallow breathing index. . Huang HC. Respir Care . Ciubotaru RL. Independent effects of etiology of failure and time to reintubation on outcome for patients failing extubation. Vieira SR.. Gissot V. Francois B. Am J Respir Crit Care Med . Crit Care Med . Marelich GP. Crit Care Med . Chest . Kress JP. Trevisan CE. Lu BY. Moore D. Effect of a nursingimplemented sedation protocol on the duration of mechanical ventilation. controlled trial of protocoldirected versus physiciandirected weaning from mechanical ventilation. . Nam M. placebocontrolled study. Effect of failed extubation on the outcome of mechanical ventilation. . Ely EW. Purro A. et al. Hilbert G. Chest . Outcomes in postICU mechanical ventilation a therapistimplemented weaning protocol. et al. Ferrer M. Tilluckdharry L. Early noninvasive ventilation averts extubation failure in patients at risk a randomized trial. Am J Respir Crit Care Med . et al. Wang SN. Esteban A. Epstein SK. Appendini L. Noninvasive ventilation to prevent respiratory failure after extubation in highrisk patients. et al. et al. Ferguson ND. . Keenan SP. Physiologic determinants of ventilator dependence in longterm mechanically ventilated patients. Nevins ML. Chest . et al. Salam A. Chest . Fanfulla F. secretions and extubation outcomes. . Chao DC. De Gaetano A. Clin Chest Med . Kao SJ. Gruson D. Ventilatordependent survivors of catastrophic illness transferred to longterm care hospitals for weaning from prolonged mechanical ventilation. . Hassenpug MS. et al. Effect of early application of biphasic positive airway pressure on the outcome of extubation in ventilator weaning. Hassenpug MS. StearnHassenpug M. Valencia M. N Engl J Med . et al. McCormack DG. . Scheinhorn DJ. Intensive Care Med Mar Epub ahead of print . Powers C. Noninvasive positivepressure ventilation for postextubation respiratory distress a randomized controlled trial. FrutosVivar F. Pt . Scheinhorn DJ. . PostICU mechanical ventilation at longterm care hospitals a multicenter outcomes study. Gregoretti C. Nicolas JM. . Nava S. . . . et al. Crit Care Med . JAMA . Weaning From Ventilatory Support Epstein . Eur Respir J . Weaning from prolonged mechanical ventilation. cough. Neurologic status. Votto JJ. Respirology . Scheinhorn DJ. Votto JJ. Portel L. Am J Respir Crit Care Med . Jiang JS. Noninvasive positivepressure ventilation for respiratory failure after extubation. Noninvasive pressure support ventilation in COPD patients with postextubation hypercapnic respiratory insufciency.. AmoatengAdjepong Y. et al. requires spontaneous respiration. awake. CT scans. or MRI scans may be obtained. inhalation injury. those who are unresponsive due to either primary injury or the effects of pain medication. pneumothorax. Thus. and without mental status changes and neck pain and who have no distracting injuries or neurologic decits may be considered to have a stable cervical spine and need no radiologic studies. a surgical airway may be required. The international process for injury identication and treatment is discussed in the Advanced Trauma Life Support Course published by the American College of Surgeons Committee on Trauma. FCCP Objectives Identify the multisystem manifestations of trauma Recognize common patterns of presentation for cardiopulmonary injury Recognize evolving management of secondary brain injury Identify patients at high risk for venous thromboembolism following injury Recognize burn injury of various degrees and associated treatment options Assess and manage inhalation injury Review the latest available data regarding the outcome of burn injury Key words blunt cardiac injury. care is taken to prevent movement of the cervical spine. Patients with unknown cervical spine status and need of emergency airway control may be intubated safely by temporary removal of the immobilizing cervical collar. and those who receive muscle relaxants. the collar is reapplied and the patient remains on logroll precautions until the complete spine status has been assessed. duplex ultrasonography. When other means of airway control have failed. both emergency department management and critical care support. Neurologic examination alone does not exclude a cervical spine injury. After securing the airway. Certain types of injury have implications for all members of the trauma care team. Nasotracheal intubation. hemothorax. In addition. is a critical component of the management team. All other patients should have at least a lateral view of the cervical spine. All team members should therefore be able to identify and act immediately on identication of injury and complications of initial treatment. secondary brain injury. All patients with blunt trauma are at risk for cervical spine injury. The integrity of the bony components of the cervical spine may be assessed in various ways. particularly in the setting of blunt injury with multiple system dysfunction and less need for acute operative intervention. MD. At the same time.Trauma and Thermal Injury David J. This chapter reviews recent developments and discusses common patterns of injury or complications of injury according to organ system. The choice of nasotracheal vs orotracheal intubation technique is based on provider preference and experience. the airway. however. venous thromboembolism Trauma Principal decision making in the management of multiple organ injury rests with the trauma surgeon. Dries. A variety of plain radiographs. while inline stabilization is maintained during intubation. however. including the base of the occiput to the upper border of the rst Airway and Spine The initial priority in the management of any injured patient is assessment and management of ACCP Critical Care Medicine Board Review th Edition . The following patients are excluded from examination those who cannot relate neurologic examination changes. recommendations were developed to determine the presence or absence of cervical spine instability. no tubes should be passed through the nose of a patient who has midfacial trauma with a risk of cribriform plate fracture. lowmolecularweight heparin. The following recommendations were made for patients at risk for cervical spine injury Patients who are alert. MSE. The intensivist. When the use of helical CT was compared to conventional radiographs of the thoracic and lumbar spine. Most recent work suggest that CT scans may facilitate evaluation of the cervical spine in any headinjured or intubated patient. but the patient may have minimal evidence of injury. hemopneumothorax. Tracheobronchial Injury Tracheal or laryngeal disruption or fracture most commonly occurs at the junction of the larynx and the trachea. A dedicated spine CT examination is no longer required. lateral. Signs and symptoms may include hoarseness. Longterm followup to identify all cases of cervical spine injury missed in the acute setting is frequently unavailable. if the studies are technically adequate and properly interpreted. thoracic vertebra. Hemoptysis. Cricothyroidotomy should be avoided. The threeview plain spine series anteroposterior. and an openmouth odontoid view indicating lateral masses of the rst cervical vertebra and the entire odontoid process. Airway management by an experienced physician may include an awake tracheostomy. Patients with subcutaneous air or dissecting air within the cervical fascia should be suspected for tracheal and/or esophageal injury. While plain radiographs in the . Injury to the larynx is the most common blunt injury. and anteroposterior view showing the spinous processes of the second cervical through the rst thoracic vertebra. this position may include sitting if spinal injury is unlikely during the patients initial assessment. Injury to the trachea may also occur from the shoulder restraint harness of a seat belt. Axial CT scans with sagittal reconstruction may be obtained for any questionable level of injury or any area that cannot be adequately visualized on plain radiographs. or airway obstruction. The patient should be allowed to assume the position of comfort. there is little supporting evidence that denes the criteria for determining who gets cervical spine radiographs and who does not. The lessons of cervical spine evaluation have also been applied to injuries to the thoracic and lumbar regions. improved sensitivity and specicity were obtained. This information can be obtained in patients receiving chest and abdominal CT scanning protocols for other visceral injuries. subcutaneous air. adjacent spine reconstructions are obtained in any patient receiving torso scans as a part of evaluation for injury. or crepitus at the neck. and openmouth odontoid view. The true incidence of cervical spine injury is thus not known. MRI may also facilitate clearance of ligamentous injury. bleeding. Injury to the proximal trachea may be caused by blunt or penetrating trauma. Blunt injury to the cervical trachea occurs in in all patients with blunt trauma to the trunk. In our center. Patients presenting with massive subcutaneous or mediastinal emphysema are suspected to have a distal tracheal or bronchus injury. Hemoptysis and airway obstruction indicate the need for urgent access to the airway. More and more centers are adding CT scans of the cervical spine when scans of the head are obtained after injury. In the literature of cervical spine injury. Flexion and extension views of the cervical spine may be appropriate in patients complaining of signicant neck pain with normal plain radiograph results. Patients with an altered level of consciousness secondary to traumatic brain injury or other causes may be considered to have a stable cervical spine if adequate threeview plain radiographs and thincut axial CT images through C and C are normal. A direct blow to the trachea may cause compression or fracture of the cartilaginous ring. provides a falsenegative rate . hematoma formation. Patients with neurologic decits that may refer to a cervical spine injury require subspecialty consultation and MRI evaluation. Proximal tracheal injuries may be caused by gunshot wounds or stab wounds to the neck. edema. or a collapsed lung on a plain chest radiograph conrm injury in the major intrathoracic airways. When chest tubes are Trauma and Thermal Injury Dries Cervical spine injury following blunt trauma reportedly occurs at a frequency of to . helical CT allows reconstruction of the thoracic and lumbar spine from various views. majority of patients are adequate to screen in individuals with highrisk mechanisms. supplemented by thincut axial CT imaging with sagittal reconstruction through suspicious areas or in adequately visualized areas. pain. If an airway can be established and maintained. while tracheal wounds and injuries to the mainstem bronchus were identied. such as intraabdominal hemorrhage. In all. Six injuries involved the larynx and trachea. Intrabronchial bleeding. Three of these patients had stump leaks with empyema. Recognizing the paucity of literature on tracheobronchial injuries. manifest as hemoptysis and air hunger. lobar or segmental bronchi are seldom injured. Pain control is essential for ensuring adequate spontaneous ventilation. thoracotomy should be performed with clamping of the involved bronchus at the hilum. Clearly.placed and there is constant air loss. Rapid loss of . in two cases. These patients may rapidly become hypoxic before other evidence of respiratory failure is apparent. other lifethreatening problems. Where severe bleeding continues. Massive hemothorax is suggested by physical examination and the chest radiograph. Mechanical ventilation should be provided to minimize the pressure within the airways. to . inward movement of the segments during inhalation. major airway disruption must be suspected. In general. Rib and Pulmonary Parenchymal Injury Rib fractures are frequently not detected on chest radiographs. is poorly tolerated and may lead rapidly to death due to alveolar ooding. Only one of six laryngotracheal wounds had a good result. The uninvolved lung must be free of blood. The clinical manifestation of ail chest is paradoxical movement of the involved portion of the chest wall ie. In this situation. One patient required tracheal resection. Of tracheal injuries. a doublelumen endotracheal tube may be inserted to conne the bleeding and protect the uninvolved lung. Airway control and ventilation may be difcult in these patients. Bleeding is typically caused by injury to bronchial arteries or stulas between pulmonary veins. Where endtoend tracheal repairs can be created and direct repair of mainstem bronchus injuries provided. and hypoxemia. Where multiple adjacent rib segments are fractured. patients were treated from to for blunt and penetrating injuries. Surgical repair must be prioritized. these patients frequently have suboptimal outcome. and secretion management may be difcult. A doublelumen endotracheal tube may be required. and three of these individuals had cor pulmonale on followup. Use of pressure control modes of ventilation may be optimal. Injury to the distal trachea is associated with severe compression trauma to the chest. and the bronchus. Richardson reviewed a single institution experienced with a single lead surgeon in the management of tracheobronchial injuries. bronchial stenosis required pneumonectomy. He classied injuries into those involving ACCP Critical Care Medicine Board Review th Edition the larynx and trachea and those involving the mainstem bronchus. Postoperative management of these patients has several components. improved outcome can be anticipated. Of patients with injuries to the mainstem bronchus. One patient treated by a primary tracheal repair had stenosis requiring resection. mL of blood or ongoing blood loss mL/h through . Another complication of rib injury is hemothorax. Placement of these tubes requires skill. Open pneumothorax is generally associated with softtissue decit requiring dressings or closure and chest tube placement to reexpand the involved lung. if possible. pneumonectomies were performed with eight survivors. Ten patients had repair of blunt mainstem bronchial injuries. bronchoscopy should be done as soon as possible to exclude a tracheal or large bronchial tear or proximal bronchial obstruction by a foreign body or secretions. ail chest is associated with contusion of the underlying lung. Repair of distal tracheal or bronchial injuries typically requires a thoracotomy. More than of traumatic tracheobronchial tears occur within . these patients should be positioned to facilitate drainage of blood out of the trachea. For severe bleeding. patients surviving tracheal resection and endtoend anastomosis had good outcomes. and another required permanent tracheostomy. particularly when the glottis is closed. pulmonary arterial branches. cm of the carina. Nasotracheal suctioning or bronchoscopy may be necessary to keep the bronchial tree clear and the contralateral lung expanded. Frequently. Less common is pneumothorax associated with an open thoracic wound. a ail chest may occur. Repeat bronchoscopy may be required for secretion control. the fracture may be documented by tenderness on physical examination. may be addressed. Two granuloma complications were caused by the use of a permanent suture. requiring tube thoracostomy. the mortality rate approaches . More frequently than previously noted. All patients with ail chest were weaned successfully from mechanical ventilation. and thoracoscopic assistance was employed in three cases. Treatment is directed primarily at maintaining ventilation and preventing pneumonia. One third of pulmonary contusions do not manifest on plain radiographs until to h after injury. Indications included ail chest with failure to wean ve patients. Mechanical ventilation may be required in the hypoxic patient. This technique may be enhanced with further renements in minimally invasive surgical methods. coughing. Pain relief is essential for chest wall injuries. Patients with pain and instability reported subjective improvement or resolution of symptoms. not dehydrated. Hypoxia may be the rst evidence of severe pulmonary contusion. Perhaps the most feared complication of rib fracture is tension pneumothorax. respiratory distress. and a signicant chest wall defect. In general. This therapy may also be necessary in the patient with shock. epidural analgesia is superior to intrapleural medication administration or rib blocks. The patient should be euvolemic. CT scans have also demonstrated traumatic pneumatocele and parenchymal lacerations to the lung. Air is under pressure in the pleural space. or signicant preexisting lung disease. The trachea may deviate away from the side. ICU Resuscitation Patients sustaining major trauma without brain injury who survive the rst h after injury are at risk for multiple organ failure. A statistical model suggests that age. pneumothorax is associated with rib fractures and requires chest tube placement. and cardiovascular compromise. and one patient had a wound infection. To this end.a chest tube is an indication for thoracotomy. a signicant decrease in lung compliance may also occur with associated increase in shunt fraction. The patient sustaining pulmonary contusion from blunt trauma may have a more globular or diffuse pattern of injury. The extent of pulmonary contusion is usually underestimated on plain lm radiographs. Musclesparing incisions were used. injury severity score. Suction is applied routinely at approximately cm HO. Patients with penetrating trauma may have areas of hemorrhage surrounding a missile tract. An intriguing clinical series from the University of Oregon Health and Science University describes use of absorbable prostheses for rib fracture xation in patients. CT may also be useful in conrming the diagnosis of pulmonary contusion. A common result of rib and chest wall injury is pulmonary contusion. coma. These individuals underwent rib fracture xation with absorbable plates and screws. The overall mortality rate of patients with pulmonary contusion is to . and mobilization is critical. resulting in hemodynamic embarrassment and pulmonary dysfunction. jugular venous distention. If the contusion is large enough or is bilateral. Given the frequency of rib fractures and the morbidity associated with this problem. and severity of shock are independent risk factors for this complication. Two patients with screw xation only had loss of rib fracture reduction. A scan demonstrating a large contusion increases the likelihood of prolonged ventilatory support for acute respiratory failure. particularly ail chest. When chest wall injury is associated with this problem. Progressive respiratory therapy to promote deep breathing. absorbable plates are an option that warrants further evaluation for rib fracture repair in selected patients. acute pain with rib instability four patients. Pulmonary contusion is usually diagnosed on the basis of the history of blunt chest trauma and ndings of localized opacication on chest radiographs. Any patient with a pneumothorax who requires a general anesthetic should have a chest tube in place. The University of TexasHouston Medical School has developed a shock resuscitation protocol applied to major torso trauma patients at known risk for multiple organ Trauma and Thermal Injury Dries . Needle catheter placement into the pleural space at the second intercostal level in the midclavicular line may be necessary for urgent decompression of the involved hemithorax. CT scans evaluate and quantify pulmonary contusions. This clinical diagnosis is based on absent breath sounds. The patient with a chest wall defect returned to full athletic activity within months. increased work of breathing. This emergency should not be diagnosed using a chest radiograph. g/kg/min Dobutamine . ail chest. These publications prompted controversy that has persisted for years and has led to a host of trials offering conicting results. g/kg/min yes Fluid Boluses NS for CI lt. Shock resuscitation protocol applied to major torso trauma patients at known risk for multiple organ failure. . Trauma victims years old are also at increased risk if they have any two of the previous criteria. two or more long bone fractures. . The resuscitation strategy employed is a goaldirected. creation of Starling curves for oxygen transport determination. A more recent metaanalysis of goaldirected resuscitation suggests that the concept of achieving supranormal values for oxygen delivery does not work in patients in whom organ failure has . a complex pelvic fracture. A hierarchy of ve therapies including RBC ACCP Critical Care Medicine Board Review th Edition transfusion. lactated Ringers infusion. patients with severe brain injury Glasgow coma scale GCS score or abnormal brain CT scan results were not resuscitated by this protocol. and vasopressor administration with data managed in a database. PCWP lt with consecutive boluses STOP yes DO I gt ml/m/m n Norepinephrine . g/kg/min for MAP lt mmHg STOP J Trauma . This standardized process employs much of the contemporary thinking regarding protocoldriven resuscitation and comes from a group with an extensive database in this area. Figure . and/ or major vascular injury. and it was thought that oxygen delivery should be pushed until oxygen consumption plateaued. unrecognized owdependent oxygen consumption was a suspected cause of late organ failure. Notably. In a series of publications. shock resuscitation is employed. these workers provided data to support the concept that early management to supranormal oxygen delivery improved outcome. Patients likely to require this resuscitation were those with injuries including two or more abdominal organs. inotrope. Blood loss is a marker of need for aggressive resuscitation. rulebased process emphasizing hemoglobin and volume loading to attain and maintain oxygen delivery for the rst h of hospital stay. proposed that supranormal oxygen delivery be used as a resuscitation goal. Where patients are anticipated to need U of packed RBCs during the rst h after hospital admission and demonstrate an arterial base decit mEq/L during the rst h after hospital admission. Use of invasive hemodynamic monitoring and related end points of resuscitation remains controversial.ICU Resuscitation Protocol Transfuse PRBC for Hgb lt g/dl lt g/dl over STOP yes DO I gt ml/m/m DO I gt ml/m/m n yes STOP Infuse fluid to PCWP gtmmHg PCWP gt mmHg over DO I gt ml/m/m n Milrinone . In the late s. Shoemaker and coworkers. noting that survivors of severe injury increased oxygen delivery to supranormal levels compared with nonsurvivors. failure Fig . these workers suggest that outcome with the more modest resuscitation goal was comparable in patients with critical injury and that patients could be resuscitated with a smaller resuscitation uid volume for a lower target oxygen delivery index. the attempt to achieve high oxygen delivery is not benecial and may be harmful. Contraindications to use of recombinant activated factor VII include pH . As evidence of major inammation with organ failure progresses. Shortly after this metaanalysis. this is some of the best recent data incorporating an ICU resuscitation strategy after injury. Stimulated by recent work suggesting the efcacy of recombinant activated factor VII in hemophilia. factor deciency states. Factor IX is activated. and cryoprecipitate for brinogen mg/dL. with arrival base decit worse than and injury severity score of to . While acceptance of the invasive hemodynamic monitoring strategy and uid resuscitation end points of Moore and coworkers is not uniform among the trauma community. GCS score . An interesting concern with such aggressive protocols is an increased recognition of abdominal compartment syndrome. and possibly prior venous thromboembolic disorders. platelets. On presentation of a patient deemed likely to need massive transfusion. In an effort to optimize blood product administration in critically injured patients. or angiography suite. cardiac arrest. and tissue factordependent and independent activation of factor X is seen. Recombinant activated factor VII binds to platelets. Trauma and Thermal Injury Dries . this material is employed in doses approximating g/kg after administration of to U of packed RBCs in h. but acceptable. Clearly. Thrombin generation is enhanced. While available multicenter data does not support widespread use of recombinant activated factor VII in the setting of injury. myocardial infarction MI. Early use of invasive monitoring and aggressive resuscitation is supported by a recent retrospective assessment of the National Trauma Data Bank for outcome associated with management of the pulmonary artery catheter. a departure from previous strategies. and trauma during the later years of life is not inevitably associated with resuscitation futility. In general. operating room. Optimal results in highrisk patients. both as a primary consequence of injury and as a secondary effect of resuscitation strategy. which included later administration of plasma and platelet products. Other observations from this group suggest that female patients have a comparable if not better response to resuscitation after trauma. to U of FFP are provided as well as platelets for each U of packed RBCs used. a rebirth of early goaldirected resuscitation driven by the emergency department work of Rivers and others appeared. we still need to strike a balance. Comparing a wide range of hemodynamic variables. Individuals presenting in extremis typically receive noncrossmatched blood in the resuscitation room while specic component replacement begins in the ICU. Use of recombinant activated factor VII assumes prior administration of appropriate amounts of FFP. The role of supranormal targets for oxygen transport remains unclear. Consistent with recent data supporting increased administration of fresh frozen plasma FFP. trauma centers are incorporating administration of recombinant activated factor VII with massive transfusion protocols. come when hemodynamic optimization takes place before signicant organ dysfunction occurs. pregnancy. it appears. and offlabel administration in surgery and trauma. After stratication for injury severity. and platelet activation and aggregation are focused at sites of injury. a blood sample is sent to the laboratory for a type and crossmatch of products. a massive transfusion policy is being introduced in trauma centers in the United States to allow expedient and appropriate blood component replacement during acute patient management. or cerebral vascular accident CVA if recent. resuscitation end point of mL/min/m. The control patients were resuscitated to an oxygen delivery index of mL/min/m as compared to a more modest. pulmonary artery catheter use was associated with survival benet in patients aged to years. contemporary practice patterns support administration of this material in a controlled fashion within institutional massive transfusion protocols Table .developed. and effects are concentrated at the site of injury where bleeding and hemostatic alterations occur. An administration cycle providing to U of packed RBCs at a time with appropriate amounts of FFP and platelets continues with activation of this protocol until discontinued by the trauma team. Moore and coworkers in Houston address this issue by comparing two cohorts of patients. Treatment Recombinant factor VIIa. CVA. . mg. U if platelet count U of cryoprecipitate if brinogen Massive transfusion pack will have U packed RBCs U FFP Following administration of pack . urologic. orthopedic. repeat FFP dosing Monitoring International normalized ratio before and at . mo relative CI Dose of recombinant factor VIIa g/kg rounded to the nearest vial size Can repeat once if bleeding not controlled in h CI contraindications. Damage Control In use for over a decade. the technique continues to evolve. Transfusion Committee. or CVA.Table . Damage control is no longer conned to the abdomen. venous thromboembolic disorders. Regions Hospital. proven surgical ACCP Critical Care Medicine Board Review th Edition method with wide applicability and success. The group at the University of Pennsylvania Trauma Center rst published on the contemporary experience with damage control in . Indications for Damage Control Inability to achieve hemostasis due to coagulopathy Inaccessible major venous injury Timeconsuming procedure in a patient with suboptimal response to resuscitation Management of extraabdominal lifethreatening injury Reassessment of intraabdominal contents Another important. followed by physiologic optimization in the ICU and eventual restoration of GI. or MI within days before onset of symptoms for ICH. Table . or MI within days prior to the event Relative contraindications Pregnancy Transfusion Committee. Use of Recombinant Factor VIIa in Surgery and Trauma Indications for use of recombinant factor VIIa Active bleeding following the use of two massive transfusion packs U packed RBCs in h. recombinant activated factor VII may be administered in a low dose along with FFP. With growing experience and application. and its principles cross surgical disciplines. prothrombin time Complete blood examination and platelet count Fibrinogen Massive transfusion pack will have U packed RBCs U FFP U apheresis platelets Contraindications for use of recombinant factor VIIa pH Preceding cardiac arrest Patient not salvageable Pregnancy Recent VTE. . CVA. pulmonary embolism. . orthopedic. single dose Vitamin K. . mg slow IV FFP. The patient receiving damage control treatment is in extremis and undergoes a truncated laparotomy. There is a signicant need for further data in this area Table . at h after recombinant factor VIIa and FFP have been administered. mL/kg If international normalized ratio is . Table . and Appropriate use of clotting factor replacement U FFP U pheresis platelets if platelet count . Contraindications to administration of recombinant activated factor VII include pregnancy. This group has noted an improvement in survivability when abbreviated laparotomy and abdominal packing are combined with physiologic resuscitation and more extensive visceral repair at later operations. . and h Contraindications to recombinant factor VIIa Deep vein thrombosis. . . The concept is most often used in the massively injured exsanguinating patient with multiple competing surgical priorities Tables . the concept of damage control has become an accepted. MI. but investigational. Regions Hospital. This experience included abdominal injury patients. In this patient group with an elevated international normalized ratio. including thoracic. and other products as appropriate. and vascular surgery. . the following laboratory investigations are needed Partial thromboplastin time. and International normalized ratio . vitamin K. This aggressive approach is warranted due to high morbidity in patients sustaining head injury while receiving various anticoagulant therapies. . application of recombinant activated factor VII comes in the patient sustaining intracranial hemorrhage ICH while receiving warfarin therapy. Use of Recombinant Factor VIIa in ICH Patients Receiving Warfarin Indications for use of recombinant factor VIIa Active lifethreatening bleeding in a patient receiving warfarin. Stages of Damage Control Abbreviated resuscitative surgery Hemorrhage control Control of fecal spillage Packing Temporary abdominal closure Splinting. ureteral stents internal/ external Pelvic compression military antishock trousers. and acidosis. Classic triggers for damage control are well described and may include pH . With the escalation of gun violence in the late s and early s. transfusion of U of packed RBCs estimated blood loss L. sheet. These investigators gathered data prospectively on consecutive patients admitted from May to January . In general. Many of the damage control techniques used today were developed during this period. not splenorrhaphy Treat associated vascular injury drain succus Treat associated vascular injury drain pancreatic bed Rapid nephrectomy if hematoma expanding. the decision to proceed with a damage control approach comes from the operating surgeon prompted by the patients presenting pathophysiology and response to resuscitation. trauma centers accumulated signicant experience in treating severely injured patients.. Damage control is a term used by the US Navy to describe the capacity of a ship to absorb damage and maintain mission integrity. threephase surgical approach to the catastrophically injured patient. Damage control is neither a bailout procedure nor an abandonment of proper surgical technique. They found that efforts to proceed with denitive repair at initial operation often led to patient demise despite control of anatomic bleeding. simultaneous resuscitation. Success with damage control requires its application prior to onset of profound acidosis when rapid control of hemorrhage. temporary softtissue coverage Pelvic fracture Extremity fracture Table . and magnitude of blood loss. It has become the preferred descriptor of this modern. The best prospective data on the impact of damage control surgery came from the Shock Trauma Center at the University of Maryland. other injuries Table . planned reoperation. hypothermia. embolization Splenectomy. It is a deliberate and calculated surgical approach requiring mature surgical judgment. and temperature C. subsequent response to uid therapy. After stratifying patients Trauma and Thermal Injury Dries . transurethral or suprapubic bladder catheter. embolization External xator. The decision to use damage control is now often made on presentation on the basis of patient pathophysiology coagulopathy. Damage Control Approach to Specic Organ Injury Organ Liver Spleen Duodenum Pancreas Urology Treatment Packing.Table . external xation Critical care unit resuscitation Rewarming Control acidosis Treat coagulopathy Endorgan support Denitive reconstructive surgery GI continuity Removal of packs Abdominal closure Denitive stabilization of fractures. Complications of Damage Control Type Wound infection Abdominal abscess Dehiscence Bile leak Enterocutaneous stula Abdominal compartment syndrome Multisystem organ failure Mortality Rate. external xator. It has become increasingly apparent that damage control does not simply describe the initial truncated operation but the entire process from the rst moment of patient contact in the eld until denitive repair has been successfully completed. and reversal of hypothermia can best limit coagulopathy. Damage control philosophy has undergone maturation with involved personnel understanding the pathophysiology and supporting the steps necessary to reverse the cascade of events leading to resuscitation failure. and staged laparotomy. or thoracic integrity at a subsequent operation. abbreviated laparotomy. pack stable hematoma. Various descriptors have been used to describe the procedure temporary abdominal closure bailout surgery. Anuria is seen with higher IAPs. Increased intraabdominal pressure IAP signicantly decreases cardiac output and left and right ventricular stroke work and increases central venous pressure. Control of IAP leads to reversal of renal impairment. and the sterile barrier created in the operating room is maintained. which are laid within the layers of the dressing. In experimental preparations. which increase the abdominal domain. In our center. Ventilation and perfusion abnormalities result and blood gas measurements demonstrate hypoxemia. Two reports in and document survival of and . the nonadherent aspect of a small bowel bag is placed on the intestine with interposition of omentum between the dressing and intestine if possible. impairment of renal function persists in the setting of IAH. elevated bladder pressures are suggestive of its presence. A variety of temporary dressings including the vacuum pack technique are used for temporary abdominal closure in damage control patients. Abdominal decompression reverses these changes. The initial patient group managed with damage control intervention had a survival in . intraabdominal hypertension IAH was a common complication in patients receiving standard closure of the abdomen after massive uid resuscitation. Initial management entailed four abdominal surgical procedures per patient. decreased thoracic volume and compliance are seen. IAP as low as to mm Hg may produce oliguria. complications. Hospital length of stay was days. but these techniques allow sufcient expansion of the abdominal domain that makes this problem infrequent. respectively. followed by bowel. pulmonary artery wedge pressure. but even when cardiac output is maintained at normal or supranormal values by blood volume expansion. As the diaphragm protrudes into the pleural cavity. readmissions. Infection. abdominal compartment pressures were ACCP Critical Care Medicine Board Review th Edition . During this earlier time period. No patient who survived index hospitalization died during the followup interval. greatvessel. hypercarbia. Pulmonary infections may also result. and systemic and pulmonary vascular resistance. ventral hernia repair. not routinely measured and abdominal compartment syndrome less well recognized as a cause of refractory shock. Clearly. Contemporary approaches allow rapid detection of IAH and abdominal compartment syndrome when clinical signs distended abdomen. Decreased volume within the pleural cavities predisposes to atelectasis and deceases alveolar clearance. deterioration in cardiac output plays a role in diminished renal perfusion. and pancreatic injuries. elevated peak ination pressures. Elevation of IAP also causes renal dysfunction. Most operators now do not close skin or fascia after the initial operation. Seventysix percent of damage control patients were readmitted at least one time. Liver injuries were the most common solidorgan injury. Our temporary abdominal dressing allows rapid and effective temporary abdominal coverage and increase in abdominal capacity. animals die from congestive heart failure when abdominal pressure passes a critical threshold. Ventilated patients with abdominal hypertension require increased airway pressure to deliver a xed tidal volume.based on physiologic parameters. As both hemidiaphragms are displaced upward with increased IAP. Seventyfour readmissions and subsequent surgical procedures took place in the patients during the followup interval of this study. The mortality rate during the initial admission to the trauma center was . Renal dysfunction is also caused by Abdominal Closure A variety of methods to accomplish temporary abdominal closure have evolved with damage control techniques. decreased urine output. Abdominal Compartment Syndrome IAH has a variety of physiologic effects. Prior to use of temporary abdominal closure techniques. Controlled egress of uid from the abdomen is permitted by drains. The use of temporary abdominal closure does not eliminate the possibility of abdominal compartment syndrome. intrathoracic pressure increases with reduction of cardiac output and increased pulmonary vascular resistance. spleen. and acidosis. and stula management were the most common reasons for readmission. and longterm outcome were recorded. Blunt and penetrating injuries were seen in equal proportions. the aspiration port may be connected to a pressure transducer. In Irwin RS. or other critical illness. capillary leak. Abdominal perfusion pressure APP assesses not only severity of IAH but also the adequacy of the systemic perfusion. major burns. Secondary ACS develops due to conditions outside the abdomen. Recurrent ACS develops following initial successful surgical or medical treatment of either primary or secondary ACS or following closure of a previous decompressive laparotomy. Rippe JM. PA Lippincott. and lymphatics may create changes in mucosal pH. Intensive care medicine. Finally. IAP from to mm Hg. mL of sterile room temperature saline solution is instilled in the bladder. IAH may be divided into two types. where hepatic blood ow has been demonstrated to decrease with abdominal hypertension. ACS may be further divided into three types. chronic ascites. . Compartment syndrome of the abdominal cavity. and grade IV. Intracranial hypertension has been demonstrated to decrease when IAP is reduced in morbidly obese patients. eds. Other organs affected by increased IAP include the liver. Using a bladder catheter. and other factors of host defense may be impaired by reduced hepatic ow. and production of GI hormones. intraabdominal hemorrhage. APP mean arterial pressure minus IAP. or over days as a result of sepsis. IAP from to mm Hg. IAP should be expressed in millimeters of mercury and measured at endexpiration in the complete supine position after ensuring that abdominal muscle contractions are absent with a transducer zeroed at the level of the midaxillary line. compression of the renal vein. th ed. or other conditions requiring massive uid resuscitation. IAP mm Hg. Other GI functions may be compromised by increased IAP. and a stabilization period of to s is allowed. Causes of Abdominal Hypertension Peritoneal tissue edema Diffuse peritonitis Severe abdominal trauma Fluid overload secondary to hemorrhagic or septic shock Retroperitoneal hematoma Reperfusion injury after bowel ischemia Inammatory edema secondary to acute pancreatitis Ileus and bowel obstruction Intraabdominal masses Abdominal packing for hemorrhage Closure of the abdomen under tension Intraabdominal uid accumulations Modied from Wittman DH. Abdominal hypertension signicantly increases intracranial pressures at IAPs routinely used during laparoscopy. The current reference standard for IAP measurement is the pressure measured via an indwelling urinary drainage catheter within the bladder. A recent international conference has attempted to standardize denitions of intraabdominal hypertension and abdominal compartment syndrome. Grades of IAH have been proposed grade I. Splanchnic hypoperfusion may begin with IAP as low as mm Hg. IAH is dened by sustained or repeated IAP mm Hg or an APP mm Hg. and is characterized by progressive abdominal wall adaptation to increase in IAP. Compression of the abdominal aorta and renal arteries may contribute to increased renal vascular resistance. which creates partial renal blood outow obstruction.Table . capillary leak. IAP from to mm Hg. Williams amp Wilkins. intracranial hypertension is seen with chronic increase in IAP. Reduced perfusion of intraabdominal arteries. Igs. Acute IAH develops within hours as a result of trauma. Chronic IAH develops over months to years as a result of morbid obesity. It may be assumed that hepatic synthesis of acute phase proteins. intraabdominal tumor growth. veins. grade II. such as sepsis. Operative decompression is the method of choice in the patient with severe abdominal hypertension and evidence of intraabdominal organ Trauma and Thermal Injury Dries . or pregnancy. ACS is not graded but rather considered as an allornone phenomenon. bowel motility. Primary ACS develops due to conditions associated with injury or disease in the abdominal/pelvic region requiring emergent surgical or angioradiographic intervention. Direct pressure on the kidneys may also elevate cortical pressures Table . . translocation. ACS is dened by sustained or repeated IAP mm Hg and/or APP mm Hg in association with newonset single or multiple organ failure. An alternative and less expensive technique is to read the height of the urine column in urinary catheter drainage tubing for either pressure measurement. Abdominal compartment syndrome ACS is present when organ dysfunction occurs as a result of IAH. IAH is the pathologic evaluation of IAP. Philadelphia. and IAP read from the bedside monitor. grade III. death secondary to blunt liver injury dropped from to . Nonoperative management should be entertained only in hemodynamically stable patients. The practitioner must be aware. including hemodynamic monitoring with adequate venous access and controlled ventilation. Interestingly. To prevent hemodynamic decompensation during decompression. transfusions. missed blunt bowel injury has received increased attention. and quantity of hemoperitoneum. and renal function have been demonstrated in a variety of clinical settings. The sensitivity of CT scanning in dening bowel injury has been assessed by a variety of investigators. and a greater proportion of spleen injuries are associated with arterial or arteriolar injury. contrastenhanced CT scans. however. It has been speculated that ACCP Critical Care Medicine Board Review th Edition liver injuries are more commonly associated with lowpressure venous injuries.dysfunction. and hypothermia and coagulation defects corrected. In patients who are hemodynamically stable. intravascular volume should be restored. In another major report from the University of Louisville. and length of hospital stay. this improvement was attributed to improved methods of managing hepatic venous injuries. Failure was associated with increasing age. After decompression. Identifying hemodynamically stable patients may be challenging in the setting of multiple injuries. improvements in hemodynamics. A high percentage of liver injuries appear to be manageable nonoperatively. and a somewhat lower proportion of liver injuries fail nonoperative management in comparison with blunt injury to the spleen. with a resulting failure rate of . Proposed improvements in the management of hepatic venous injury include nonoperative management in stable patients and willingness to employ gauze packing in unstable individuals. Abdominal Organ Injury The focus on management for intraabdominal organ injury remains nonoperative. the contrast blush is a useful tool in identication of slow bleeding sites associated with lacerations to solid organs. Advances in nonoperative management have indicated differences between the spleen and liver. a failure rate of only was found. and angiography support are changing the face of management for injury to the solid abdominal and retroperitoneal organs. A recent multicenter study of blunt splenic injury from the Eastern Association for the Surgery of Trauma EAST included . Planned nonoperative management of the liver may be attempted in as many as of patients with liver injuries. other studies of nonoperative management of splenic injury suggest that many patients in highrisk categories can be managed nonoperatively. Patients requiring operation due to hemodynamic instability may be successfully treated with packing. In addition. of patients at greater risk for failure of that approach. injury severity score. As nonoperative management of abdominal solidorgan injury continues to advance. and that there is no increased mortality with failure of this approach. Lategeneration CT scanners. undergo nontherapetic laparotomies for bowel hematomas or contusions. As abdominal CT scans replace laparotomy as the denitive diagnostic procedure in injury. oxygen delivery maximized. however. A number of patients explored after CT scanning. After decompression. the abdomen and the fascial gap is left open using one of a variety of temporary abdominal closure methods. Nonoperative management was attempted in of these patients. Aggressive application of CT scanning and angiographic intervention has increased the rate of salvage and decreased length of stay and resource . Evolution to nonoperative management in stable patients with highgrade injury results in lower mortality. Adjunctive measures to combat expected reperfusion wash out from byproducts of anaerobic metabolism include prophylactic volume loading and use of vasoconstrictor agents to prevent sudden changes in BP. these sites may then be embolized with a high degree of success in both the liver and the spleen. GCS. Recent reports suggest that sensitivity with latestgeneration CT scans is as high as for bowel injury particularly if unexplained free uid is considered a critical nding. patients age years from centers. signicant improvement in outcome with nonoperative management was identied compared to operative management with respect to abdominal infection rates. The abdomen should be opened under optimal conditions in the operating room.. pulmonary function. grade of splenic injury. tissue perfusion. Two hundred thousand victims with such injuries require hospitalization each year and often are permanently disabled. Patients with GCS scores of to are considered to have mild head injuries. A recent multicenter study in Pennsylvania suggested that patients treated at level II trauma centers had a higher rate of operative treatment and lower rate of failure for nonoperative management than level I trauma centers. intracranial pressure ICP mm Hg. the brain continues to be injured by various mechanisms including the mechanical injury from cerebral edema or intracranial hematomas. It is the single most important factor in determining the outcome of various forms of trauma. the most important concept in the recent treatment of braininjured patients is the distinction between primary and secondary brain injury. Mortality for patients managed nonoperatively was lower at level I trauma centers. Indications for consideration of primary repair of injury perforating the GI tract include good response to resuscitation. is designed to identify rapidly the severity of patient injury. and secondary damage from a wide array of inammation mediators. The most important feature of the initial neurologic examination. whether due to blunt or penetrating injury. ischemia from hypotension. loss of potential income. cost of acute care. lack of acidosis. Finally. which is designed to examine the abdomen for the uid stripe indicative of free intraperitoneal blood. Clinical factors associated with poorer outcome with head injury include the following midline shift on CT scan. the management of traumatic brain injury now includes increasing emphasis on the prevention of secondary insults. These patients do not have normal neurologic examinations. These individuals have an excellent prognosis and may not require hospitalization. Level I trauma centers were also more likely to repair rather than remove the spleen. the GCS. secondary injury can be prevented or at least blunted. Given these realities. up to of patients with signicant trauma may not be appreciated with abdominal ultrasound. Thus. Trauma and Thermal Injury Dries . systolic BP mm Hg. This group of patients has a chance of declining into coma GCS score . and GCS score . It is important to note that patients with signicant solidorgan injury may present without signicant free intraperitoneal blood. Perforation of the GI tract. Individuals with GCS scores of to have moderate head injury. age years. Primary injury is injury that occurs at the time of the traumatic incident and includes brain lacerations or other mechanical injuries to the brain at the moment of impact. and serial neurologic examinations make this deterioration easy to detect. head injury outcomes are determined by the number of secondary insults. limited blood loss. They have a chance of deteriorating into coma.consumption for patients with these solidorgan injuries. hypoxia from inadequate ventilation. Traumatic Brain Injury Traumatic brain injury accounts for of all deaths from acute injuries. These realities mandate aggressive attention to the management of brain injury. After impact. is being managed with direct repair rather than diverting ileostomy or colostomy in an increasing number of patients. Many more persons suffer mild traumatic brain injury resulting in a physician visit or temporary disability. not the injuries to other organ systems or body regions. but the severity of their injuries usually is not appreciated until the full GCS score is obtained. and continued expenses of rehabilitation and medical care are enormous. While prevention is the only strategy to avert primary brain injury. Patients with severe head injury have the worst prognosis and require the most immediate care. Individuals at greatest risk for traumatic brain injury are typically young and at the beginning of potentially productive life. Therefore. immediate control of spillage from the gut is appropriate with diversion of the fecal stream at the primary operation or during staged repair in the patient receiving damage control management. Many investigators now recommend that abdominal ultrasound not be used as the sole diagnostic modality in stable patients at risk for blunt solidorgan injury. Where additional lifethreatening injuries that complicate evaluation or limit available time for primary bowel repair are present. it appears that the approach to blunt organ injury may vary with the type of hospital treating the patient. limited fecal spillage. cerebral edema or cerebral vascular dysregulation. and a small number of associated injuries. Notably. Thus. Most current data place mm Hg as the highest acceptable level for ICP at which treatment must begin. In normal gray matter. While the study of ICP initially focused on prevention of herniation by preventing swelling. high ICP is associated with poor outcome. the treatment priority has been control of cerebral edema and prevention of cerebral herniation. The goal of removing spaceoccupying lesions is to prevent cerebral herniation. Data are now emerging. Typical blood ow to gray matter within the rst h after head injury is mL/ g/min of tissue. It is. Ventriculostomy carries an increased risk of infection and a slightly increased risk of bleeding. As a group. emphasis is given to monitoring and control of ICP. As ICP rises. Recent head injury management therefore places maintenance of adequate CPP as a goal equivalent to prevention of high ICP. Autopsy ndings have indicated that of headinjured patients had ischemia. After evacuation of mass lesions. Experimental work beginning in the mids demonstrated that ischemia is a signicant threat to the headinjured patient. hematomas must be evaluated within hours to avoid a signicant risk of mortality. Ischemia had long been recognized as a factor in the outcome of head injury. Ischemia is common following head injury. Improved recent understanding of cerebral blood ow coincides with multiple studies demonstrating disastrous consequences of hypotension in the setting of head injury. however. cerebral blood ow is mL/ g/min of tissue. however. in individuals with more severe injuries. that even in patients with adequate cerebral perfusion pressure CPP. there is a chance of an increased ICP. Any technique reducing ICP was thought to be good for the headinjured patient. undetected hematomas were the principal cause of death. This . cerebral blood ow is mL/ g/min of tissue. In the past. Modern methods of ICP monitoring include the ventriculostomy and intraparenchymal beroptic or straingauge devices. Cerebral herniation. the current approach to the headinjured patient has evolved. the gold standard for ICP measurement. in which the two most important factors related to outcome from head injuries were time spent with an ICP mm Hg and time spent with a systolic pressure mm Hg. their depressed clinical examinations often preclude detection of changing neurologic status until their condition reaches catastrophic deterioration. These are examples of patients who survive primary brain injury with the ability to talk and interact at some level but who later succumb to preventable secondary brain injury. The autoregulatory mechanisms in the brain are designed to maintain cerebral blood ow constant over a range of CPP ranging from to mm Hg. By giving equal attention to ischemia. compared with mortality rates of to in patients who present with herniation before coma. Evacuation of mass lesions has been the traditional focus of brain injury management throughout this century. Once herniation regardless of the type has occurred. representing the compression of critical neurologic centers against the retaining structures of the skull. it was soon apparent that keeping ICP from rising was a desirable end. is the common nal pathway in these patients. Once herniation occurs and the patient progresses to coma. cerebral blood ow as low as mL/ g/min of tissue has been noted. cerebral perfusion decreases and the threat of brain ischemia increases. These data suggest that patients with only a single episode of systolic BP mm Hg have a signicantly worse outcome than those individuals who never experience this degree of hypotension. but recent work has changed the paradigm through which head injury was viewed. In previous studies among patients who talk and die. ICP monitoring was introduced years ago as a means to quantify the study of brain swelling and cerebral edema. except for select subpopulations. all of them require ICP monitoring. Up to this time. a variety of guidelines have been proposed for the optimal ICP level for treatment. Subarachnoid ACCP Critical Care Medicine Board Review th Edition bolts and epidural monitoring are used rarely or in select patient populations.All of these individuals require head CT scanning. An increased death rate in headinjured patients with hypotension was documented in the National Traumatic Coma Data Bank. Cerebral blood ow on the rst day after injury is less than half that of healthy individuals and may approach the ischemic threshold. Studies over the last years have demonstrated that once herniation occurs and the patient slips into coma. patient outcome is dramatically affected. the mortality rate reaches to . in white matter. Hypoxia is one of the ve top predictors of poor outcome in the National Traumatic Coma Data Bank. available data suggest that a level of mm Hg . a CPP of mm Hg has been suggested as a desirable level. Hyperventilation reduces ICP by reducing cerebral blood volume with increased cerebral vascular tone and induction of hypocapnia. At present. and administration of mannitol before resorting to hyperventilation. Hyperventilation may. as opposed to subarachnoid monitors. therefore. One prospective. In this practice. Traditional management strategies of the patient with severe head injury have changed with the knowledge of adverse effects of secondary brain insults. Increasing evidence indicates that hyperventilation is an ICP treatment with high cost. Hyperventilation can cause vasoconstriction independent of the metabolic demands of the brain. In the extreme case. it is unclear what an adequate CPP is. rather than the use of hyperventilation. The second important consideration after avoidance of hypotension during resuscitation of the headinjured patient is the prevention of hypoxia. with cerebral autoregulation disabled. Most head injury research protocols maintain this level. For example. reduce blood ow to the brain even if that reduction results in an ischemic injury. Current management therefore includes use of less toxic means of reducing ICP. Drainage of CSF may be the rst choice for the treatment Trauma and Thermal Injury Dries . cerebral ischemia results as patients are maintained in a hypovolemic state with low mean arterial pressure to reduce cerebral blood volume and thereby ICP. if available. brain ischemia and. ultimately. randomized trial evaluated severely headinjured patients managed with hypocapnia vs normocapnia. This practice avoids hypotension and the ischemic damage that almost certainly attended the old practice of keeping patients with severe head injury dry and their arterial pressure low. demonstrated a lower mortality in a cohort of patients thought to be similar to those enrolled in the Traumatic Coma Data Bank. cerebral blood ow passively follows CPP. hyperventilation has been a primary means of reducing ICP. Our views on the use of these modalities and the management of head injury continue to evolve. Seemingly paradoxically. the threat of ischemia. Recent studies using jugular venous oximetry have indicated that hyperventilation may produce cerebral ischemia. Later studies by other workers. leading to increased intracranial pressure. For many years. kPa is associated with poor outcome. Based on available data. Reduction in cerebral blood volume leads to intracranial blood volume loss and lower ICP. emphasis in the management of brain injury must be placed on avoidance of secondary insults to prevent extension of injury resulting from ischemia. When the combined effect of hypoxia and hypotension during resuscitation was analyzed. CPP was maintained below the autoregulatory threshold. in the patient with multiple injuries without head injury. a poor outcome. Much like the treatment of MI for which the original zone of injury cannot be restored to normal. drainage of cerebrospinal uid CSF through ventricular drains should be started early with aggressive use of sedation. which do not allow for CSF removal. While the optimal Pao level in the headinjured patient has not been determined. despite changes in position and activity. Drainage of CSF and use of mannitol may be employed to control ICP and to optimize CPP. ICP is controlled with a variety of modalities. Other studies demonstrated that desaturation found in jugular venous blood is more common with hyperventilation than with other means employed for reduction in ICP. including stepwise regression analysis. The normocapnic group had better outcome at month and month followups. Cerebral edema was thought to be aggravated by overzealous uid administration. aggressive volume resuscitation is a widely accepted method to maintain endorgan perfusion and adequate oxygen delivery. muscle relaxants.highly adaptive capacity allows the brain to see constant blood supply. Some medical centers are facilitating drainage of CSF by placing ventriculotomy catheters when possible. the best way to reduce ICP is to increase CPP into the autoregulatory range. An analysis of the Traumatic Coma Data Bank demonstrated that hypoxia and hypotension in the immediate period after head injury resulted in mortality rates of and . with to of severely headinjured patients presenting with hypoxia. the mortality rate increased to . respectively. In the severely injured brain. using an algorithm guided by optimization of CPP. However. using endovascular stented grafts. Various reports have suggested that operative management of injury to the descending aorta may be delayed in stable patients for a period that can range from hours to months. Without recognition and treatment of this injury. Mannitol drips therefore are not recommended. is also being reported. An estimated of the persons who sustain deceleration injury to the thoracic aorta live to reach the hospital due to containment of aortic rupture by connective tissue covering the aorta. At this time. Most often. disruption occurs at the aortic isthmus. Of the operative procedures for repairing injuries to the descending aorta. Unfortunately. expeditious repair of injury to the descending aorta remains the most costeffective approach with no additional risk of complications in adequately resuscitated patients. of these individuals will die within h and within week. no one causative or preventative factor has been identied. Mannitol may also act by improving cerebral blood ow through reduction in hematocrit and viscosity. of the time the angiogram does not show injury to the thoracic aorta as the cause of mediastinal widening. intimal aps are being reported in up to of studies. cannot be administered to hypotensive patients because it will magnify shock states. mannitol may also open the bloodbrain barrier and result in rebound cerebral edema. the most dreaded complication is paraplegia. Most of these lesions resolve spontaneously and may be managed nonoperatively. While mediastinal widening warrants aortography. Patients who are unstable at the scene of a crash or during the rst h of hospitalization have a mortality rate . To control ICP.of increased ICP. Thus. Unfortunately. Many victims of this injury are dead at the scene. The mechanism of injury is a combination of differential deceleration of the mediastinal contents and force provided by the steering wheel or dashboard impacting the chest. Mannitol. These individuals should receive an afterloadreducing agent or a drug to alter dP/dT change in pressure over time. With a suspicious mechanism of injury. Delayed reconstruction of chronic posttraumatic aneurysm of the descending aorta. latestgeneration CT imaging is becoming an acceptable method for evaluation of the widened mediastinum with aortography in cases requiring further denition. and hypotension with secondary ischemia are recognized as occurring with increasing frequency. Serum osmolarity must be monitored in individuals who receive mannitol for control of ICP and optimization of CPP. mannitol may lead to acute renal failure. Mannitol is an osmotic diuretic administered as a bolus that develops an osmotic gradient between the blood and the brain. In large doses. In studies of longterm outcome. however. Optimal modalities to control secondary brain injury focus on maintenance of optimal CPP with the lowest possible ICP consistent with avoidance of cerebral ischemia. Recent developments in the care of the headinjured patient focus on the importance of secondary brain injury as a determinant of prognosis. If administered as a constant infusion. Falls may also produce this injury. Injury to Thoracic Aorta Injury to the thoracic aorta is common among victims of highspeed motor vehicle crashes with an acute deceleration mechanism. a clear chest radiograph is inadequate to rule out aortic injury. Arteriography is the gold standard diagnostic study because of its ability to demonstrate the specic injury and reveal unsuspected vascular anomalies. hypoxia. the key elements of secondary brain injury. The initial anteroposterior chest radiograph is the single most important screening tool for injury ACCP Critical Care Medicine Board Review th Edition to the thoracic aorta. Hemodynamically stable patients whose systolic BP does not exceed mm Hg during the rst to to h after injury have a survival rate . Esophageal Perforation Esophageal perforation is a true emergency and therapeutic challenge because delay affects . just distal to the origin of the left subclavian artery at the ligamentum arteriosum. In the emergency setting. newer spiral CT scans have become useful at rapidly diagnosing thoracic aortic injuries particularly to the descending aorta because of their greater speed and resolution. and have a stable mediastinal hematoma. hyperventilation is now employed as an emergency tool rather than as a primary therapy. have their BP maintained at or / mm Hg. survival. Three factors affect management of esophageal perforation origin. Patients with perforations of the cervical esophagus have an survival. spontaneous pneumothorax. Before repair. Dysphasia appears late and is generally related to thoracic perforation. spontaneous perforation . Tachycardia and tachypnea are documented in to of patients. Hypotension and shock are present when sepsis or signicant inammatory third spacing occurs. mediastinal emphysema. Symptoms and signs vary with the cause and location of perforation as well as the time delay between perforation and diagnosis. Selfinduced esophageal injury by acid or alkali may cause extensive necrosis and esophageal destruction. dull epigastric pain radiating to the back may occur if the disruption is posterior and communicates with the lesser sac. all nonviable and grossly contaminated tissue in the mediastinum and around the esophagus is debrided. In the abdomen. Acute pain in the epigastrium often suggests perforated peptic ulcer disease or acute pancreatitis. Plain chest radiography suggests the diagnosis in of patients with esophageal perforation. Severe chest pain suggests thoracic perforation. or a mediastinal air uid level must prompt investigation to rule out esophageal perforation. Broadspectrum antibiotics. or MI is common. subcutaneous emphysema. mediastinal widening. postemetic perforation with massive contamination is the most morbid. pneumoperitoneum. and external trauma are responsible for the majority of esophageal ruptures. and delay between rupture and treatment. Neck ache and stiffness suggest perforation after endoscopy. Esophageal perforation from penetrating or blunt trauma is frequently obscured by associated injuries and has a poor prognosis if diagnosis is delayed. and respiratory failure are absolute indications for rapid surgical intervention. improved nutrition. Contrast esophagogram with watersoluble material followed by dilute barium reveals primary sites or areas of leakage and determines whether perforation is conned to the mediastinum or communicates freely with the pleural or peritoneal cavities. Pain is the most consistent symptom. broadspectrum antibiotics. the rate of falsenegative esophagogram results may be as high as . whereas pharyngeal perforation rarely ends in fatality because of relative ease of diagnosis. Late perforations usually can be repaired primarily with Trauma and Thermal Injury Dries . Misdiagnosis of dissecting thoracic aneurysm. chest radiographic ndings may be normal. Iatrogenic esophageal disruption . pneumothorax. Subcutaneous emphysema is seen frequently when perforation is cervical and less often with thoracic or abdominal injury. Morbidity and mortality increase as perforation extends into the thorax. drainage. Early surgical reinforced repair with drainage of contaminated spaces provides the best chance of survival after esophageal perforation. Sepsis. Surgery remains the mainstay of treatment. Conservative management is associated with a to mortality. and repair. and repairs may be buttressed by gastric fundoplication. Cervical perforation is best treated by direct suture closure and drainage of the neck. Perforation of the distal third of the esophagus leads to hydropneumothorax on the left. However. Decortication of trapped lung tissue may be necessary. when signs or symptoms are vague or misleading. CT of the chest can often show the site of perforation and is used when presentation is atypical. Thoracic esophageal perforation requires right thoracotomy for exposure of the upper two thirds and left thoracotomy for control of the lower third. immediately after disruption. The difculty with nonoperative management is determination that perforation will remain contained and not cause continued contamination with subsequent uncontrolled infection. Lesions at the esophagogastric junction are approached by left thoracotomy or upper midline laparotomy. present in to of patients. Pneumomediastinum. Esophagoscopy can easily miss a perforation or enlarge a hole. Mediastinal uid and air on CT of the chest are strongly suggestive of esophageal perforation. and IV uid resuscitation. Unfortunately. Abdominal esophageal perforation is associated with survival. and improved critical care have led to better results. whereas thoracic disruption is associated with survival rates of to . location. or when perforation involves the lesser sac. and it is usually related to the site of disruption. For example. This test is usually not performed to identify perforation. Preoperative preparation includes nasogastric intubation for gastric decompression. shock. prospective data. they recommend that an admission ECG should be performed in all patients in whom blunt cardiac injury is suspected. Perforations encountered late may initially be treated by wide drainage of the mediastinum by opening the pleura along the length of the esophagus. or parenteral hyperalimentation because gastrostomy should be avoided for later reconstruction. Additional recommendations included continuous ECG monitoring for to h in patients in whom the initial ECG was abnormal. valves. Pelvic Fracture Substantial blunt force is required to disrupt the pelvic ring. Conversely. control of sepsis.muscle or pleural reinforcement. crushing injuries from motor vehicle crashes and falling objects. cervical esophagostomy. Moderately severe lesions may include injury to the pericardium. Minor injury is a nonspecic condition frequently termed cardiac contusion. The presence of sternal fracture does not predict the presence of blunt cardiac injury. papillary muscles. The occurrence rate ranges from to in patients sustaining blunt chest trauma. These individuals may require placement of a pulmonary artery catheter. If repair is not possible. but cervical diversion with esophageal exclusion and longterm tube feeding may be necessary. Based on randomized. enzyme analysis is inadequate for identifying patients with blunt cardiac injury. resection of the esophagus with delayed reconstruction is preferable. evaluation should proceed with transthoracic echocardiography followed by transesophageal echocardiography if an optimal study cannot be obtained. or myocardial contusion. Similarly. operative drainage of the mediastinum and pleural cavity. To date. Key issues involve identication of a patient population at risk for adverse events from blunt cardiac injury and then appropriately monitoring and treating these individuals. enteral nutrition. patients who are not at risk for complications could be discharged from the hospital with appropriate followup. and enteral feeding tube placement with later reconstruction. Blunt ACCP Critical Care Medicine Board Review th Edition trauma to the heart ranges from minor injuries to frank cardiac rupture. Ttube drainage of the perforation creates a controlled esophagocutaneous stula. Exclusion of the perforated esophagus by division of the esophagus adjacent to the stomach and at the neck allows partial or total exclusion of the perforation. patients with coexisting cardiac disease and those with an abnormal admission ECG nding may undergo surgery if they are appropriately monitored. Finally. and esophageal resection have been proposed for patients with late esophageal disruption. One of the major disadvantages of this approach is the obligation to perform a second major reconstructive procedure. In summary. thereby making the available literature difcult to interpret. and reinforcement of the suture line with vascularized tissue particularly muscle. Ttube drainage. The extent of injury is related to . Alternative procedures esophageal exclusion. The true occurrence rate remains unknown because there is no diagnostic gold standard. blast injuries. Patients with complex perforations should preferably be administered a jejunostomy. most operators favor esophageal resection. treatment of esophageal perforation is directed toward uid resuscitation. The most severe of blunt cardiac injuries is the dramatic and often fatal condition of cardiac rupture. Postoperative care emphasizes control of infection and nutrition support until healing of an esophageal injury is demonstrated. and direct violent trauma from assault are less common causes of blunt cardiac injury. Primary repair may be possible. Falls from heights. The lack of such a standard leads to confusion with respect to making the diagnosis. If extensive mediastinitis and sepsis are present with continued contamination. if patients are hemodynamically unstable. EAST has recently reviewed studies that focused on the identication of blunt cardiac injury. suture repair of the esophagus if possible. Blunt Cardiac Injury Cardiac injuries from blunt chest trauma are usually the result of highspeed motor vehicle crashes. Delay in diagnosis makes repair more difcult because of friability and necrotic tissue at the site of the tear. The reported incidence of blunt cardiac injury depends on the modality and criteria used for diagnosis. but continued leakage may progress to mediastinal and pulmonary sepsis. and coronary vessels. Clinical evidence has suggested that provisional fracture stabilization using a simple anterior external xator or even wrapping in a bed sheet can control lowpressure bleeding. Therapeutic angiography may also be required after abdominal exploration if a rapidly expanding or pulsatile retroperitoneal hematoma is encountered. Sample sizes in these studies were small. denitive operative stabilization of pelvic fractures is delayed to days to allow the patient to recover from acute injury. Signicant retroperitoneal arterial bleeding occurs in only approximately of patients. Hemodynamic instability and biomechanical pelvic instability are separate though related issues. It is essential to examine for other sources of hemorrhage intrathoracic. and spinal cord injury. and those who are hemodynamically unstable. than in control subjects . Two recent prospective trials demonstrated that lowdose heparin was not better in preventing deep venous thrombosis than no prophylaxis in patients with an injury severity score of . Greeneld and associates have developed a risk factor assessment tool for VTE. with complete disruption of the pelvic ring and the posterior sacroiliac complex. are extremely important in the acute phase of patient management. using external skeletal xation. The results of lowdose heparin administration after injury with regard to pulmonary embolism were even more vague. in patients with no prophylaxis to . the occurrence rate of major hemorrhage was higher in patients treated with anticoagulation than in control subjects. intraperitoneal. thoracic. U subcutaneously bid or tid represents one pharmacologic treatment modality used for prophylaxis against deep venous thrombosis and pulmonary embolism. Deep Venous Thrombosis and Thromboembolism That deep venous thrombosis and thromboembolism occur after trauma is incontrovertible. Treatment of the patient is also directed by response to initial uid resuscitation. pulmonary embolism was halved by lowdose heparin treatment . The other type of displacement seen with pelvic fractures is vertical. such as wound hematomas. and head injuries are common.the direction and magnitude of the force. Early fracture diagnosis and stabilization. Angiography with embolization of the involved vessel is then indicated. external in patients with evidence of ongoing bleeding. The optimal mode of prophylaxis has yet to be determined. surgical patients demonstrated that lowdose heparin signicantly decreased the frequency of deep venous thrombosis from . The source of bleeding may be multifactorial and not directly related to the pelvic fracture itself. Dening the trauma patient at risk for VTE is subjective and variable in the literature. Forces applied to the pelvis can cause rotational displacement with opening or compression of the pelvic ring. in treated individuals. Patients with pelvic ring injuries are easily subclassied into two groups on the basis of clinical presentation those who are hemodynamically stable. Lowdose heparin .. with treatment compared with . the cancellous bone at the fracture site or adjacent venous injury. A metaanalysis of trials and . scores of represent low risk. and statistical error could not be excluded. Continued unexplained bleeding after provisional fracture stabilization suggests an arterial source. Associated abdominal. but the difference in incidence was not signicant. However. Retroperitoneal bleeding in a pelvic fracture patient usually arises from a lowpressure source. risk factors are weighted. Similarly. which tend to confuse the clinical picture. The following injury patterns appear to differentiate highrisk patients for VTE closedhead injury GCS score . There is a dramatic difference in the mortality rates between pelvic fracture patients who are hypotensive and those who are hemodynamically stable . preliminary evidence supported this risk factor assessment tool as a valid indicator of the development of VTE. In general. in control subjects. scores of to represent Trauma and Thermal Injury Dries . pelvic fracture blood loss that contributes to hemodynamic instability is a signicant risk factor. pelvis plus longbone fractures multiple longbone fractures. Minor bleeding complications. Unfractionated lowdose heparin has not been shown to be particularly effective in preventing venous thromboembolism VTE in trauma patients. In this scale. In doubleblind trials. were more frequent in lowdose heparin treatment patients . We now have data suggesting that lowmolecularweight heparin is superior to unfractionated heparin for prophylaxis in moderate. moderate risk.Table . ACCP Critical Care Medicine Board Review th Edition For established deep venous thrombosis or pulmonary embolism. which support clear . impedance plethysmography has high sensitivity and specicity in the detection of proximal deep venous thrombosis in symptomatic patients. Patients in whom the risk of recurrent VTE extends months may have anticoagulation extended indenitely. Recent evidence also supported initial treatment of VTE with lowmolecularweight heparin. The overall accuracy of screening ultrasonography in the asymptomatic patient is less clear. Similarly. There are a wide variety of randomized prospective data available. patients whose injuries preclude the use of anticoagulants because bleeding would exacerbate their injury should have consideration given to placement of a vena cava lter. Risk Factors Associated With VTE in Trauma Underlying condition Obesity Malignancy Abnormal coagulation factors on hospital admission History of VTE Iatrogenic factors Central femoral line h transfusions in rst h Surgical procedure h Repair or ligation of major vascular injury Injuryrelated factors Abbreviated injury scale for chest Abbreviated injury scale for abdomen Abbreviated injury scale for head Coma GCS score for h Complex lowerextremity fracture Pelvic fracture Spinal cord injury with paraplegia or quadriplegia Age sequential increased risk with age but yr but yr yr From J Trauma . This literature is derived primarily from total hip replacement and knee replacement patients. Studies in the nontrauma literature support the accuracy of both Doppler and duplex ultrasonography in the detection of deep venous thrombosis in the symptomatic patient. Logistical problems and complications associated with venography make the procedure less appealing than other noninvasive diagnostic measures. Venography still has a role in conrming deep venous thrombosis in trauma patients if diagnostic studies are equivocal. it appears that future investigational efforts are best directed at developing the role of duplex ultrasonography in screening for deep venous thrombosis in the setting of injury. Early identication of this complication would allow treatment to be initiated. Antibiotic Management Much of the data surrounding antibiotic use in patients following injury comes from studies of patients with penetrating abdominal trauma. Lowmolecularweight heparin should be the standard form of VTE prophylaxis in trauma patients with complex pelvic and lowerextremity injuries as well as in those patients with spinal cord injuries. thus decreasing the frequency and severity of complications. Finally. This agent is also safe for patients receiving craniotomy or nonoperative management of solid organ injury if started or h after injury respectively. There is a wealth of randomized. and scores of represent high risk Table . . Most data in many different types of patients conrm improved efcacy of lowmolecularweight heparin with the same or even less bleeding risk compared with prophylaxis with unfractionated heparin.to highrisk trauma patients. Current evidence suggests that a . prospective data supporting the use of lowmolecularweight heparin as VTE prophylaxis in orthopedic surgery. At present.to month period provides adequate treatment for the rst episode of deep venous thrombosis or pulmonary embolism in a patient without clotting abnormality. Its low sensitivity in detecting deep venous thrombosis in asymptomatic patients precludes use as a surveillance technique in trauma patients at high risk for deep venous thrombosis. In addition. the literature is beginning to support the use of inferior vena cava lters in highrisk trauma patients without a documented occurrence of deep venous thrombosis or pulmonary embolism and who cannot receive prophylactic therapy. Evaluation for deep venous thrombosis in the setting of injury receives continued study. anticoagulation is a wellestablished treatment. administered antibiotic doses may be increased twofold to threefold and repeated after every tenth unit of blood transfusion until there is no further blood loss. a rstgeneration cephalosporin with h of coverage is appropriate. evidence regarding antibiotic use in penetrating abdominal trauma was reviewed. the intensivist should be aware of available recommendations regarding appropriate agents. Antibiotic support may be continued until closure is accomplished. and of all reported injuries to the population years old. Controversy continues regarding appropriate antibiotic therapy for open fractures. Where lesser degrees of softtissue injury are present. scald injuries in patients years of age. The second issue addressed is the duration of therapy in the presence of injury to any hollow viscus. duration of therapy. while electrical and chemical injuries affect adults in the workplace. To alleviate this problem. probably due to altered pharmacokinetics of drug distribution. Trauma and Thermal Injury Dries . Finally. Mean age for all cases was years. While antibiotic therapy must be initiated prior to operation or in the emergency department. Many practitioners. age. antibiotics with activity against obligate and facultative anaerobic bacteria should be continued for periods dependent on the degree of identied wound contamination. The most difcult open fracture is the tibial fracture with signicant softtissue damage. In a clinical management update produced by the Practice Management Guidelines Workgroup of EAST. Fewer data are available regarding the use of antibiotics in patients following blunt injury. to . These wounds require Gramnegative as well as Grampositive coverage. Thermal injury results in . Factors shown to relate to mortality in thermal injury include the size of cutaneous involvement. to . and the presence or absence of inhalation injury. Infants accounted for of cases. aminoglycosides have been demonstrated to exhibit suboptimal activity in patients with serious injury. antibiotics are not warranted. accounting for almost of cases. If no hollow viscus injury is noted subsequently. million people who seek medical treatment in the United States each year. The two most common reported etiologies were ame burns and scalds.recommendations regarding the use of antibiotics in this patient group. a metaanalysis has examined studies assessing effectiveness of a single agent vs combination therapy containing aminoglycosides for penetrating wounds. Sixtytwo percent of reported total burn sizes were total body surface area TBSA. and the impact of shock and resuscitation. There are no randomized prospective data or multidisciplinary guidelines available to address this issue. and patients years old represented of individuals. There were . As the patient is resuscitated. Unfortunately. The likelihood of infection is generally associated with the degree of softtissue injury. believe Grampositive antibiotic coverage is appropriate in the patient with tube thoracostomy or with invasive monitors of ICP. Thermal Injury Thermal injury is a major public health problem for to . Based on available prospective randomized data. These writers suggest that there are sufcient randomized prospective data to recommend the use of only a single preoperative dose of prophylactic antibiotics with broadspectrum aerobic and anaerobic coverage as a standard of care for trauma patients sustaining penetrating abdominal wounds. no further antibiotic administration is warranted. Death rates are highest in the very young and the very old. however. there are insufcient data to provide meaningful guidelines for reducing infection risks in trauma patients with hemorrhagic shock. In the absence of monitoring device placement or the use of tube thoracostomy. fatalities. resulting in reduced tissue penetration. Nearly of burn patients in the recent iteration of the National Burn Repository were men. hospitalizations and . Notably. This report concludes that single lactam agents were as effective as combination therapy in the setting of penetrating abdominal trauma. Inhalation injury was present in of the total reported cases but played a signicant role in increasing hospital length of stay and risk of death. Vasoconstriction alters the normal distribution of antibiotics. Fortythree percent of burn injuries occurred in the home. there is sufcient evidence to recommend continuation of prophylactic antibiotics for only h even in the presence of injury to any hollow viscus. making up of all scald injuries. Scalds are the most common form of childhood thermal trauma. He noted a decrease in cell membrane potential involving burned and unburned tissues. Neutrophils are present in large numbers in the dermis within hours after a supercial burn. Sebum has noted antibacterial properties. the dermis is times thicker than the associated epidermis. At exposure to C. damage to the skin results from temperature of the thermal source and the duration of exposure. Skin has various sensory functions. These tissues are susceptible to secondary insults such as ACCP Critical Care Medicine Board Review th Edition dehydration. The rate of neutrophil sequestration in the deeper burn is slower but persists for a longer time. Lymphocytes begin to accumulate in the supercial burn at h as well as macrophages. probably due to a decrease in sodiumadenosine triphosphate activity. In thermal injury. Three cutaneous zones of injury have been described The zone of coagulation is the site of irreversible cell death with new eschar formation from local degradation of protein. The zone of stasis is the site of local circulatory impairment with initial cell viability. overresuscitation. and is associated with vitamin production. Most importantly. In general. pressure. This potential change is associated with increased intracellular sodium. and electrolyte homeostasis. Cellular Changes Baxter described the cellular changes that provide the foundation of our present resuscitation strategies. peaking at h then beginning to resolve by h. The zone of hyperemia is characterized by minimal cellular injury but prominent vasodilation and increased blood ow. supercial burns have more inammatory cells earlier but progressive damage usually does not occur. whereas measurable progression of dermal microvascular damage occurs in deeper burns but with fewer initial neutrophils. brin deposition. Inadequate resuscitation leads to further decline in cell membrane potential and cell death. Male subjects have thicker skin than female subjects. and topical antimicrobials. necrosis occurs in h with release of oxygen free radicals. Skin also helps to maintain antigen presentation to immune cells and protects uid. the skin is a principal barrier against infection. Therefore. Measures implemented to minimize further tissue loss include nondesiccating dressings. Resuscitation only partly restores normal intracellular sodium and membrane potentials. Later work on burn shock concluded that this phenomenon is due not only to intravascular hypovolemia but also extracellular sodium depletion. The skin serves a number of critical functions. . The dermis itself consists of a supercial papillary dermis and a thicker reticular dermis. skin progressively thins. Cell types in the epidermis are predominately keratinocytes and melanocytes. which produces collagen and elastin. endothelial cell swelling. Cell recovery generally occurs in this zone. The longer time to accumulation in the deeper burn is the result of occlusion of supercial vessels in the upper dermis and damage to deeper vessels. and infection. careful uid resuscitation. ground substance of glycosaminoglycans and proteoglycans. and loss of erythrocyte deformability. If ischemia follows in this zone. Impaired circulation is thought to be secondary to platelet and neutrophil aggregates. which occurs in the burn wound as suggested by increases in xanthine oxidase activity. Lymphocytes do not appear to accumulate in the deeper burn.Wound Characteristics of skin affect patterns of cutaneous injury. Neutrophils are part of the ischemia reperfusion injury. all of these functions may be lost with thermal injury. At to C. The latter cells provide pigment generation against ultraviolet radiation. protein. enzymatic failure occurs within the cell with rising intracellular sodium concentration and swelling due to failure of the membrane sodium pump. After this. Unfortunately. cell death will occur. Neutrophils are a major source of oxidants released in the burn wound and arrive during early inammation. affects heat preservation. Average skin thickness is to mm. The predominant cell type in the underlying dermis derived from the mesoderm is the broblast. Skin is very thin in infants and increases in thickness until to years of age. allowing less edema.Table . Pathophysiologic Changes in Burn Tissue Leading to Edema Marked immediate and sustained increase in the rate of uid and protein crossing from the capillary to the interstitial space Rate of edema formation is extremely rapid in the rst h Early disruption of the integrity of the interstitial space with disruption of collagen and hyaluronic acid scaffolding Progressive increase interstitial space compliance as edema forms Marked transient decrease in interstitial pressure caused by the release of osmotically active particles. Peak burn edema formation after a partialthickness burn occurs at approximately h. Clinical edema. protease Histamine. It is not unusual to see patients with a increase in body weight after a major burn. rate of edema production was matched by rate of uid clearance after h. whereas after a burn. Complications of edema formation are familiar to all who treat burn patients. Where uid ux has been studied. The edema process is responsible for losses of intravascular uid. leukotrienes Cytokines. distant nonburn tissues Local increase in a large number of vasoactive mediators that can damage the capillary and interstitium Prostaglandins. hematocrits of to are not uncommon in the early postburn period. Mediators Involved With Burn Edema Marked early and sustained increase in oxidant activity leading to oxidant damage to the following interstitial gel. It binds together structural and cellular elements into a tissue such as the skin dermal matrix. indicating continued loss of plasma volume into burn soft tissues. Virtually all components controlling uid and protein loss from the vascular space are altered after burns. particularly in the initial hours after injury when edema formation is most rapid. causing a vacuum effect sucking in uid from the plasma space Marked and sustained increase in capillary permeability in the burn wound Decrease in plasma proteins and oncotic pressure and increase in interstitial protein and oncotic pressure due to increased capillary permeability to protein Inability to maintain a plasma to interstitial oncotic gradient Likely a transient increase in capillary hydrostatic pressure in the burn capillaries Marked and sustained decrease in the surface area of the perfused capillaries and lymphatics. Edema itself results in tissue hypoxia and increased tissue pressure with circumferential injuries. Hypovolemia will occur after large burns if massive volume resuscitation is not provided. Edema Tissue edema after thermal injury is a wellrecognized entity. which occurs after a larger burn. an increase in capillary permeability to protein. severe edema formation occurs. Table . owing to the large uid loads employed in resuscitation. and hyaluronic acid. Hypoproteinemia occurs from the loss of protein in the edema uid. which can result in further downstream damage. Increased protein permeability persists for several days after burn injury. Marked increase in uid ux into the interstitium is seen due to a combination of decrease in interstitial pressure. leading to increased permeability. Edema formation is found in burned and unburned tissue. This is because intravascular volume depletion. . bradykinin Neuropeptides Complement components From J Burn Care Rehabil . as seen after burns. Even with massive uid infusion. The interstitium is the intervening space between the vascular and cellular compartments. especially in the deep burn Increase in the ease of uid accumulation in the interstitium increase in hydraulic conductivity From J Burn Care Rehabil . If volume resuscitation keeps up with losses in large burns. Total edema is usually less after a larger burn. is an expansion of the interstitial liquid volume. Additional edema is not visible because clearance appears to keep up with uid deposition Table . decreases blood volume and blood ow to burned tissue. and further imbalance in hydrostatic and oncotic forces favoring uid movement into the interstitium. . Increased interstitial pressure in burn soft tissue compartments often requires escharotomy or even fasciotomy. peak edema does not occur until after h. Increased vascular permeability causes marked increase in Trauma and Thermal Injury Dries . capillary membrane. fragmenting collagen. whereas other abnormalities such as increased permeability persist as noted above. The combination of abnormalities favoring edema further accelerates plasma protein losses. Thirddegree or fullthickness injuries involve all layers of epidermis and dermis. Partialthickness injuries should heal within weeks and leave the stratum germinosum intact. In all probability. cause. Anatomic criteria can also be employed to recognize the depth of injury and coincident likelihood of healing Table . These agents are numerous. protein content of edema uid. As edema forms. There is overwhelming evidence that biochemical mediators released into the burn also play a signicant role in the edema process. These mediators are released from injured cells as well ACCP Critical Care Medicine Board Review th Edition as from neutrophils. Wound Care The degree of injury is assessed by the wellknown rule of nines Fig .Figure . Some of these changes are transient. and effect Table . and it remains difcult to sort out the most important agents. Some authors . Rule of nines. the interstitium is altered such that more edema is easier to accumulate for the same intravascular and interstitial physical changes. this reects breakdown of the matrix molecules in the interstitium. which rapidly accumulate in injured dermis. such as negative interstitial pressure. Table . In general. which involve deep structures such as tendon. Classication of Burn Depth Degree of Burn First degree Second degree Depth of Tissue Partial thickness Supercial partial thickness Penetration Characteristics Injury to the supercial epidermis. speak also of fourthdegree injuries. Trauma and Thermal Injury Dries . Rate of epithelialization is also increased. systemically absorbed. and is anesthetic. rare sensitivity. Biological dressings gauge readiness of a wound for autografting via early take. will not blanch. transparent. broad spectrum Disadvantages May produce transient leukopenia. It heals without grafting but requires wk with suboptimal cosmesis. Deep partial thickness Third degree Full thickness Reproduced with permission from the Society of Critical Care Medicine. Tough. moist. These topical antimicrobials are applied in occlusive dressings that also help maintain uid balance. Biological dressings may facilitate removal of necrotic tissue from granulating wounds. Injury has destroyed both the epidermis and the dermis. minimal penetration of eschar. and uid and protein loss. nonelastic. promotes acidbase imbalance. one of the major advances in burn wound care. solution Advantages Painless application. discolors the wound and environment Painful application. This wound may appear red and wet or white and dry. discolors wounds Oto/nephrotoxic. must be kept moist Broad spectrum Painless application. which tend to cause relative inhibition of wound epithelialization. Topical Antimicrobial Agents Agents Silver sulfadiazine Mafenide acetate Bacitracin. systemic antibiotics are not employed in the initial days after injury. broad spectrum. Polysporin Silver nitrate . Local care begins with serial debridement of nonviable tissue and blisters. usually caused by overexposure to sunlight or brief heat ashes. Injury is to the epidermis and upper layers of the dermis. Will heal within wk from epidermal regeneration from remaining remnants found in the tracts of hair follicles. electrolyte imbalances. blanchable. frequent sensitivity No eschar penetration No eschar penetration. The burn wound affords a warm. some Gramnegative species resistant Painful application. Excision and splitthickness skin grafting are recommended. and extremely painful. requires frequent reapplication. Injury is through the epidermis and may affect isolated areas of the deep thermal strata from which cells arise. The wound appears white. penetrates eschar Painless application Nonirritating. and bone. muscle. wet. and tenacious coagulated protein eschar tissue may be present on the surface. This wound will not heal without surgical intervention.Table . broad spectrum. Wounds characteristically appear red. proteinladen growth medium to Grampositive and later Gramnegative bacteria. are applied once or twice daily after washes with antiseptic solutions Table . depending on the extent of deep dermal damage. Biological dressings cover granulating excised wounds awaiting autografts. bacterial colony counts. encourages development of resistant organisms Povidoneiodine Gentamicin Reproduced with permission from the Society of Critical Care Medicine. or blistered. Topical antimicrobials. easy application Broad spectrum. Biological dressings cadaver allograft. classically described as sunburn. more so than with topical antimicrobials. easy application. porcine xenograft are used for relatively clean wounds to reduce pain. may be used on nonburn wounds Painless application. Biological dressings may be placed on newly debrided partialthickness wounds in anticipation of healing without surgery. large thermal injuries. After healing. While blood loss is greater with this method. The principal site of volume loss was the functional extracellular intravascular uid. back. A recent option for permanent wound coverage is a commercially available crosslinked collagen and chondronitin sulfate dermal replacement covered by a temporary silicone epidermal substitute. Thus. Progressive tissue edema during resuscitation creates the need for escharotomy even if initial perfusion of circumferential torso burns is adequate. During the rst h. Cadaveric allograft can be used to cover excised areas where donor skin is unavailable. Within to weeks of application of this material. we do not excise TBSA at a time. TBSA. Grafts can be meshed onto the burn area in a ratio from to to increase coverage with the assumption that the wound will reepithelialize within the mesh network. Usually.. cosmetic outcome is improved and the maximum amount of viable tissue is preserved. Excellent mean rate of take for the dermal substitute was noted at . fullthickness injuries. Over the past decade.Where circumferential injury with seconddegree or thirddegree depth exists. This large study supports the role of dermal substitutes as a standard of care for reconstruction of deep. Abdominal wall escharotomy or laparotomy for abdominal compartment syndrome with respiratory embarrassment is sometimes required. Good harvest sites are the thighs. the synthetic dermissupported skin graft appears to have histologic structure and physical properties similar to those of normal skin. Wound Excision Excision of burned tissue that will clearly not heal determined by clinical assessment is generally performed within to days of injury. Hemodynamic Response Global hemodynamic changes include a decrease in extracellular uid of as much as to in unresuscitated animal models by h after burn. and scalp. open wounds lead to uid loss and an ACCP Critical Care Medicine Board Review th Edition increase in metabolic rate that may impact overall physiologic condition of the patient. A large postapproval study of this material was performed involving burn patients at burn care centers. Generally. Mean rate of healing for epidermal overlying autografts was . surgeons are often left with few choices for wound coverage that will eventually result in minimal contraction and scarring. a new dermis forms and ultrathin autografts may then be placed over the neodermis. the need for escharotomy is clear within h of injury. If possible.inch thickness with a power dermatome from unburned sites. Excision to fascia is limited to large. Subsequent studies with salt solutions conrmed a variety of approaches to minimize extracellular uid loss and maximize hemodynamic response in the rst h after burn. wounds are covered with sheet or meshed autograft. colloids should not be used in the rst h of burn resuscitation. These patients had large injuries average . the wound may need to be divided at the lateral aspects of extremities or on the torso to facilitate extremity perfusion or chest wall movement respectively. A low incidence of invasive infection or early application of the dermal substitute was noted . Because the body does not naturally regenerate dermal tissue. Sequential layered tangential excision of burned tissue is employed to reach viable tissue with visible punctate bleeding. Median take rate was . harvested / to /. In addition. with a median healing rate of . We generally do not use meshing due to increased incidence of contractures and graft shear. cardiac output decreased to of control at h after injury and increased to only of control at h after a TBSA injury. In one study. the work of Baxter showed that plasma volume changes were independent of the uid type employed. Division of wound eschar for this purpose is termed escharotomy. where the risks of blood loss and potential graft compromise from a suboptimal recipient bed may cause increased mortality. Management of deeper thermal injury has always been complicated by loss of dermal tissue. . burn treatment has evolved to include early excision of necrotic tissue and immediate coverage of excised open wounds. A clear role for hypertonic resuscitation has not yet been dened. Resuscitation Formulas Formula Parkland Calculation First Hours this process requires perfusion as indicated by a urine output of to mL/h in the adult. administer total volume during the rst h after burn and the remaining over the subsequent h . comorbid conditions. or function studies. limited cardiac reserve. Groups most likely to benet from supplemental colloid are the elderly. and replace extracellular salt lost into cells and burned tissue with crystalloids and lactated Ringers solution. patients with large burns TBSA. giving mL/kg/percentage of TBSA burn of uid lactated Ringers solution with half of the h volume required administered in the rst h. Burn wound edema is caused by dilation of precapillary arterioles and increased extravascular osmotic activity due to various products of thermal injury. mL/m TBSA burn . administer total volume during the rst h after burn and the remaining over the subsequent h . Probably the most popular resuscitation approach utilizes a modied Parkland formula. urine output. Inhalation injury increases the overall uid requirement of the burned patient from volume and total salt requirement standpoints. two principles are agreed on administer the least amount of uid necessary to maintain adequate organ perfusion as determined by vital signs. Overall. a pulmonary artery catheter may be needed. a combination of crystalloid and colloids may be optimally employed. All represent guidelines for the initiation of resuscitation. After h. to . Continuation of Table . Patients receiving crystalloid resuscitation will frequently require supplemental colloid during the second h after burn injury. infused colloids can increase plasma volume by anticipated amounts as capillary integrity is restored. mL/kg/h Brooke Shrine L/kg/ TBSA burn lactated Ringers solution. and/or patients who have inhalation injury. All elements in the vascular space except RBCs can escape from this site during the initial period of increased permeability. The resuscitation target is generally to mL/h of urine output with acceptable vital signs. Trauma and Thermal Injury Dries . intracellular and interstitial volume increase at the expense of plasma and blood volume. This uid may come from IV repletion or enteral Calculation Thereafter dextrose in water. Some groups add colloid to resuscitation uids as protein formulations or dextran after the rst h when much of the capillary leak has subsided. Edema formation is affected by resuscitation uid administration. Burn Resuscitation Strategies In burn injury. mL/m BSA. Peripheral vascular resistance was actually very high in the initial h after burn but decreased as cardiac output improved to supranormal levels coincident with the end of plasma and blood volume losses. administer total volume during rst h after burn and the remaining over the subsequent h mL/kg/ TBSA burn lactated Ringers solution. mL/m BSA lactated Ringers solution. mL/m TBSA burn . may replace IV uid with enteral feedings if GI function is normal Reproduced with permission from the Society of Critical Care Medicine. Where coexistent injury. plasma to maintain normal serum sodium and potassium levels and colloid oncotic pressure Maintain urine output . Thus. A variety of other formulas have been described Table . Hypertonic resuscitation solutions have the theoretical advantages of improved hemodynamic response and diminished overall uid needs as intracellular water is shifted into the extracellular space by the hyperosmolar solution. Maintenance uids must include allowance for evaporative losses. and inhalation injury complicate burn trauma. potassium. patients in good health with burns of TBSA can be resuscitated with crystalloids alone. In the patient with complicated trauma or thermal injury management. Hypoproteinemia and edema formation complicate the use of isotonic crystalloids for resuscitation. mL/ h of urine output to excrete the osmolar products of large burns. which is magnied by cutaneous burns if present. Carbon monoxide exposure is also associated with inhalation injury but does not dene this process because the true degree of exposure to carbon monoxide is frequently not detected. yields up to toxic compounds. for example. ACCP Critical Care Medicine Board Review th Edition Degradation of polyvinyl chloride. serotonin. Aldehydes. min at oxygen. Potassium. increased carboxyhemoglobin levels are not often found. Adults require . After to h. Chest radiography is frequently normal on hospital admission. This test picks up far more injuries than standard clinical criteria including history of closedspace burn injury. a urine output of to mL/h is an inadequate guide to perfusion due to relative osmotic diuresis with the metabolite loss of burns and deranged antidiuretic hormone metabolism. sometimes in association with high carbon monoxide exposure. facial burns with nasal hair singeing. which obstruct small airways. Optimal initial management of inhalation injury requires directed assessment and ensurance of airway patency. wheezing. to . Pulmonary edema with acute airway swelling usually resolves by the passage of the rst several days after injury. and soot in the sputum. Diagnosis of inhalation injury is most commonly made with bronchoscopy. intake and output records. and hypoxia on blood gases is not frequently seen. Neutrophils and other activated inammatory cells also release oxygen radicals and lytic enzymes. The halflife of carboxyhemoglobin in room air is h. while laryngeal reexes protect the lung from thermal injury in all cases except possibly highpressure steam exposure. Acute hypoxia with asphyxia typically occurs at the re scene. Upper airway injury is frequently due to direct heat exposure. Evaporative losses percentage of TBSA burn body surface area BSA in meters squared h. Therefore. Three stages of clinical inhalation injury have been identied. inhalation injury causes several physiologic derangements including Loss of airway patency secondary to mucosal edema Bronchospasm secondary to inhaled irritants Intrapulmonary shunting from small airway occlusion caused by mucosal edema and sloughed endobronchial debris Diminished compliance secondary to alveolar ooding and collapse with mismatching of ventilation and perfusion Pneumonia and tracheobronchitis secondary to loss of ciliary clearance endotracheal bronchial epithelium Respiratory failure secondary to a combination of the above factors Injuries evolve over time and parenchymal lung dysfunction is often minimal for to h. Chemical injury to the lung stimulates release of substances including histamine. soot accumulation. The upper airway is also an extremely efcient heat sink. Edema of airway mucosa and sloughing can combine with formation of plugs of brin and purulent material to create casts. weight change. To a degree that varies unpredictably among affected patients. Later complications are infections with the morbidity of pneumonia complicating that of inhalation exposure to heat and chemical irritants. which reveals airway edema. oxides of sulfur and hydrochloric acid. and kallikreins with recruitment of leukocytes to airways and lung parenchyma. combine with water in the lung to yield corrosive acids and oxygen radicals. Patients with cutaneous injury alone do not increase extravascular lung water. m. erythema. Lower airway injury is predominantly due to chemical products of combustion carried to the lung on particles of soot particle size. Prophylactic intubation is not indicated for a diagnosis of inhalation injury alone. However. Inhalation Injury Inhalation injury has emerged as a persisting cause of increased mortality in burn victims. Pulmonary edema is also seen due to increased capillary permeability. if there is concern over . which magnify tissue change. calcium.feeding. and physical examination also guide ongoing uid administration. and is followed by acute upper airway and pulmonary edema. and sometimes mucosal sloughing. magnesium. and phosphorus losses should be monitored and aggressively replaced. Serum sodium concentration. Cognitive sequelae memory. Carbon monoxide competitively inhibits intracellular cytochrome oxidase enzyme systems. or if impaired chest wall compliance suggests that inating pressures measured at the endotracheal tube did not reect transpulmonary pressures. Intubation is indicated if upper airway patency is threatened. Resuscitation uid administration should not be delayed or withheld in inhalation injury patients. and nonirritating gas. to ensure adequate oxygenation and ventilation. With afnity for hemoglobin times greater than for oxygen. and to avoid ventilatorinduced lung injury. particularly if they have lost consciousness or have high carboxyhemoglobin levels. Carbon monoxide levels may be in a closed space re signicant injury may occur in a short period of time with exposure to as little as carbon monoxide. gas exchange or compliance mandate mechanical ventilatory support. Carbon monoxide is an odorless. In patients requiring mechanical ventilatory support. most notably cytochrome P resulting in an inability of cellular systems to use oxygen. late endobronchial bleeding from granulation tissue. In thermal injury. Cognitive sequelae lasting month appear to occur in to of patients with loss of consciousness or carboxyhemoglobin levels . Survivors of inhalation injury may have permanent pulmonary dysfunction. Any mode of mechanical ventilation consistent with these limits is appropriate. Carbon monoxide poisoning may be difcult to detect. In any situation where carbon monoxide exposure is possible. Management goals during the rst h are to prevent suffocation by ensuring airway patency. Recommended treatment for acute carbon monoxide intoxication is normobaric oxygen. While there is no specic therapy for inhalation injury. It is a product of incomplete combustion. and upper airway stenosis. Cerebral oxygen consumption and metabolism are decreased. Inhaled hydrogen cyanide. Prophylactic use of steroids and antibiotics is not indicated in the initial management of inhalation injury. and affect may occur immediately after exposure and persist or can be delayed.progressive edema. In general. neurologic changes occur within days after carbon monoxide exposure. This is commonly delivered through a face mask or endotracheal tube. Heparin nebulization is now employed in some centers over the initial days after inhalation injury due to presumed mucolytic and antiinammatory effects. tasteless. pulse oximeters cannot distinguish between the two forms of hemoglobin. carbon monoxide effectively competes with oxygen for hemoglobin binding. attention span or concentration. it may be a signicant source of additional morbidity. intubation should be strongly considered. This process may stimulate expectoration of accumulated proteinaceous material. also inhibits the cytochrome oxidase system and may have a synergistic effect with carbon monoxide. proper initial management can have a favorable inuence on outcome. oxygen should be provided to eliminate carbon monoxide. As the absorbent spectrum of carboxyhemoglobin and oxyhemoglobin are very similar. require additional uid. The role of early hyperbaric oxygen is minimized in the burn care community but remains popular among pulmonologists. pH . prospective randomized clinical data are limited. These individuals may. visits to emergency departments annually in the United States. or Pao mm Hg. Humidication of inhaled gases may help to reduce desiccation injury. Oxygen delivery to tissues is severely compromised as the result of both reduced oxygen carrying capacity of blood and less efcient dissociation of oxygen from hemoglobin at the tissue level. Oximeter readings will be normal even if lethal amounts of carboxyhemoglobin are present. to forego the use of agents that may complicate subsequent care. The Pao measured from an Trauma and Thermal Injury Dries . Carbon monoxide poisoning is a major source of early morbidity in the burninjured patient with many fatalities occurring at the scene of injury. transpulmonary inating pressures cm HO should be avoided except in exceptional circumstances eg. Carbon Monoxide Poisoning Carbon monoxide poisoning is a serious health problem resulting in approximately . or mental status is inadequate for airway protection. This competition not only shifts the oxyhemoglobin dissociation curve to the left but it alters its shape. produced during combustion of household materials. Hyperbaric oxygen therapy is sometimes recommended for patients with acute carbon monoxide poisoning. in fact. intubation for administration of high oxygen concentrations is indicated. There are insufcient data regarding troponin levels to formulate a guideline. this is reduced to to min with inhalation of oxygen. Children and adults sustaining lowvoltage electrical injuries. Potential benets of hyperbaric oxygen treatment include prevention of lipid peroxidation in the CNS and preservation of adenosine triphosphate levels in tissue exposed to carbon monoxide. levels measured on arrival at a healthcare facility will not reect the extent of poisoning. Cardiac monitoring is also advised for patients with ECG evidence of ischemia.arterial blood gas reects the amount of oxygen dissolved in the plasma but does not quantitate hemoglobin saturation. no loss of consciousness. Carboxyhemoglobin levels may be measured directly. Hyperbaric oxygen has been proposed as a treatment for acute carbon monoxide exposure. the patient sustaining signicant thermal cutaneous injury is not represented in these studies. Final carboxyhemoglobin levels in the fetus may signicantly exceed levels in the mother. Creatine kinase levels are not reliable indicators of cardiac injury after electrical burns and should not be used in decisions regarding patient disposition. Notably. In the setting of pregnancy. If the patient is unconscious or cyanotic. the American Burn Association published a set of practice guidelines for various aspects of burn care. particularly when the patient has been breathing high concentrations of oxygen. Reported advantages include increased dissolved oxygen content in the blood and accelerated elimination of carbon monoxide. Because of the delay between exposure and testing. the duration of monitoring and role of other testing has not been established. telemetry monitoring and hospital admission are recommended. and the challenges of early administration of hyperbaric oxygen in the setting of multisystem trauma remain daunting. perform resuscitation. the hyperbaric chamber is a difcult environment in which to monitor the patient. but this test is rarely available at the scene of injury. Additional recommendations from the American Burn Association regarding management of electrical injury are in preparation. The optimal management of carbon monoxide exposure in the setting of signicant thermal cutaneous injury remains unclear. which is the most important determinant of oxygen carrying capacity of the blood. Exaggerated leftward shift of the fetal carboxyhemoglobin dissociation curve makes tissue hypoxia more severe by causing even less oxygen to be released to fetal tissues. and no other indications for admission can be discharged from the emergency department. Electrical Injury In . In the presence of loss of consciousness or documented dysrhythmia either before or after admission to the emergency department. Beyond recommendations pertaining to ECG. Data from animal studies suggest a lag time in carbon monoxide uptake between the mother and the fetus. The critical care practitioner should be aware that an ECG should be performed on all patients sustaining electrical injuries high and low voltage. Outcome Three contemporary articles detail outcome of burn patients. Although hyperbaric oxygen will further reduce the halflife of carboxyhemoglobin. Most burn experts reserve hyperbaric oxygen for the patient with minimal to no other injuries. Recent work with patients with signicant carbon monoxide exposure in the ACCP Critical Care Medicine Board Review th Edition absence of signicant thermal injury suggests that neurologic outcome measured at weeks and months after acute exposure will improve with acute hyperbaric oxygen administration. Signicant disadvantages of hyperbaric oxygen therapy include the risks associated with transport of patients and maintenance of critically ill individuals in the hyperbaric setting. having no ECG abnormalities. The halflife of carboxyhemoglobin is min for the victim breathing room air. and provide early burn care. Fetal studies state that carbon monoxide levels occur up to h after maternal steadystate levels are achieved. Guidelines for the management of electrical injury were not included. This shortcoming is now being addressed by the American Burn Association with additional guidelines for the management of electrical injuries. greater sensitivity of the fetus to harmful effects of carbon monoxide has been noted. The most recent comes from . Sixtytwo percent of patients had a total burn size TBSA. A second review of . J Trauma . respectively. of patients. Thirtytwo percent of admissions were years old. Sixty percent of patients were from to years old. St Louis. Mayberry JC. . and patients aged years comprised . Trauma and Thermal Injury Dries . to years. and the older patients saw a decline in mortality of approximately /yr. with of patients having a burn size between and . .the National Burn Repository. In patients sustaining inhalation injury. In all. The leading cause of death was multiple organ failure. patients admitted to Massachusetts General Hospital and the Schriners Burn Institute in Boston was published in early . TBSA burned . MO Mosby. years. In this important study. Survival in the study cohort has remained constant over recent years approximately . of TBSA. Feliciano DV. with the largest fraction of injuries occurring in the home . . th ed. From J Burn Care Rehabil . Absorbable plates for rib fracture repair preliminary experience. . et al. Logistic progression analysis was employed to develop probability estimates for mortality based on a small set of welldened variables. The following three risk factors for death were identied age years. Mean burn size and survival were similar to the larger report above. Mattox KL. Malhotra AK. Trauma. Lewis FR. yr Mid s . Flame and scald burns accounted for of total cases. wound infection. Thus. Workrelated injuries comprised of all cases. Intentional injuries accounted for of cases. Miller PR. . . The mortality formula developed from these data predicts . Trends in mortality according to age among adult burn patients have recently been examined over a year period. Deaths from burn injury increased with advanced age and burn size and in the presence of inhalation injury. Case Fatality Rates Case Fatality Ratios Patient Age. NY McGrawHill.. Examination of relative rates of mortality suggests a reduction in death among adult burn patients across the age spectrum over the year study. Richardson JD. of cases. Ellis TJ.. acute burn admissions to US burn centers were described. while the middleaged group saw an annual change in mortality of approximately /yr. and inhalation injury. J Trauma . New York. and mortality rates were examined over time Table . patients admitted to a regional burn center between and were classied into three Table . J Trauma . Trunkey DD. which published a year review in . age groups to years. Infants accounted for of cases. et al. Outcome of tracheobronchial injuries a longterm perspective. Terhes JT. . Inhalation injury was reported in . and cellulitis. Minimal aortic injury a lesion associated with advancing diagnostic techniques. ARDS after pulmonary contusion accurate measurement of contusion volume identies high risk patients. mortality was as opposed to for the patient group as a whole. Suggested Readings General Trauma Management Moore EE. Fabian TC. J Trauma . Bee TK. inhalation injury continues to have a disproportionate effect on mortality following burns. During the year period from to . and years. Seventy percents of hospital admissions were male mean age. Reduction in mortality is greatest for young patients at approximately /yr. Only of patients had a burn size TBSA. Current therapy of trauma. . Mid s . or mortality depending on whether . Pulmonary contusion review of the clinical entity. J Trauma . . Croce DS. eds. or risk factors are present. . average length of stay declined from days to days. th ed. Croce MA. eds. Leading complications were pneumonia. Chest Trauma Cohn SM. et al. Supranormal trauma resuscitation causes more cases of abdominal compartment syndrome. et al. et al. Begtrup K. The abdominal compartment syndrome the physiologic and clinical consequences of elevated intraabdominal pressure. McGonigal MD. Pulmonary artery catheter use is associated with reduced mortality in severely injured patients a National Trauma Data Bank analysis of . Abdominal Compartment Syndrome Cheatham ML. Recombinant activated factor VII for acute intracerebral hemorrhage. Kirkpatrick A. Damage control an approach for improved survival in exsanguination penetrating abdominal injury. Results from the International Conference of Experts on intraabdominal hypertension and abdominal compartment syndrome I. Early goaldirected therapy in the treatment of severe sepsis and septic shock. J Trauma . Wolberg AS. Meng ZH. Arch Surg . Cocanour CS. J Trauma . White MW. Reformatted visceral protocol helical CT scanning allows conventional radiographs of the thoracic and lumbar spine to be eliminated in the evaluation of blunt trauma patients. Bochicchio GV. J Am Coll Surg . et al. Schwab CW. J Trauma . randomized. Kozar RA. Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients two parallel Abdominal Organ Injury Bee TK. Bochicchio K. Marvin RG. et al. Cocanour CS. Croce MA. Standardized trauma resuscitation female hearts respond better. Gentilello LM. Blunt trauma resuscitation the old can respond. Schwab CW. Denitions. et al. Miller PR. doubleblind clinical trials. J Trauma . J Trauma . ICU Resuscitation Balogh Z. Rotondo MF. Sagraves SG. The effect of temperature and pH on the activity of factor VIIa implications for the efcacy of highdose factor VIIa in hypothermic and acidotic patients. Failures of splenic nonoperative management is the glass half empty or half full J Trauma . Schwab CW. et al. Crit Care Med . et al. Shoemaker WC. Cocanour CS. Aprahamian C. et al. Havstad S. Nguyen B. McKinley BA. Fingerhut A. placebocontrolled. Rhea J. McKinley BA. Arch Surg . patients. J Trauma . J Trauma . et al. J Trauma . Jenkins DH. Transfusion Dutton RP. Massive transfusion practices around the globe and a suggestion for a common massive transfusion protocol. Arch Surg . Indications for early RBC transfusion. N Engl J Med . Cheatham ML. Evolution in damage control for exsanguinating penetrating abdominal injury. ACCP Critical Care Medicine Board Review th Edition . Peralta R. Kern JW. J Trauma . SS Malone DL. J Trauma . McKinley BA. Crit Care Med . et al. Mayer SA. Metaanalysis of hemodynamic optimization in highrisk patients. Abdominal perfusion pressure a superior parameter in the assessment of intraabdominal hypertension. J Trauma . Malbrain ML. Hess JR. Sutton E. Sha S. et al. Normal vs supranormal oxygen delivery goals in shock resuscitation the response is the same. Kozar RA. N Engl J Med . et al. Damage Control Johnson JW. Riou B.Sheridan R. SS Factor VII Boffard KD. Carson JL. et al. Rivers E. Gracias VH. Schein M. et al. Brun NC. et al. Wittmann DH. et al. Friese RS. Damage control collective review. et al. Monroe DM. Intensive Care Med . Warren B. Shapiro MB. Longterm impact of damage control surgery a preliminary prospective study. McKinley BA. Cocanour CS. Haan J. Zenati MS. Heil B. Kramer M. Toutouzas K. Arch Surg . Harbrecht BG. Multicenter postapproval clinical trial of Integra dermal regeneration template for burn treatment. et al. Fabian TC. Lukan JK. Letarte P. J Am Coll Surg . CA Society of Critical Care Medicine. et al. Initial management of burns. Longterm trends in mortality according to age among adult burn patients. In Roberts PR. LAvery RF. NY Thieme. Angiographic embolization for liver injuries low mortality. Klein M. Sarrafzadeh AS. Barone A. Borzotta AP. J Trauma . Gibran NS. ed. Blunt splenic injury in adults multiinstitutional study. Management Guidelines for Common Problems in the Initial Care of Injury Luchette FA. EAST Ad Hoc Committee on Practice Management Guideline Development practice management guidelines for trauma from Eastern Association for the Surgery of Trauma. J Trauma . McGwin G. Velmahos GC. Neurologic and neurosurgical intensive care. Dunham M. Malhotra AK. Richardson JD. New York. Practice management guidelines for prophylactic antibiotic use in penetrating abdominal trauma the EAST practice management guidelines workgroup. Philadelphia. Warden GD. Radin R. Blunt bowel and mesenteric injuries the role of screening CT. Helical CT of bowel and mesenteric injuries. Achauer and Soods burn surgery reconstruction and rehabilitation. Peltonen EE. Pasqulae M. Monafo WW. Brain and spinal cord injury. High success with nonoperative management of blunt hepatic trauma. eds. et al. J Trauma . General Burn Management Arnoldo B. et al. Killeen KL. Multidisciplinary critical care board review course. Knudson MM. ed. Management and prognosis of severe traumatic brain injury. Secondary insults in severe head injurydo multiply injured patients do worse Crit Care Med . Ford JW. PA Lippincott Williams amp Wilkins. Practice guidelines for the management of electrical injuries. Fabian TC. Implications of the contrast blush nding on CT scan of the spleen in trauma. J Trauma . Anaheim. J Burn Care Rehabil . et al. Demling RH. Signicance of minimal or no intraperitoneal uid visible on CT scan associated with blunt liver and splenic injuries a multicenter analysis. et al. Salyer D. J Trauma . Mohr AM. J Burn Care Rehabil . high morbidity. ed. Head Injury Brain Trauma Foundation. J Trauma . Rosner MJ. J Trauma . Achauer BM. et al. Ann Surg . Cross JM. Management of adult blunt splenic injuries comparison between level I and level II trauma centers. et al. Franklin GA. Philadelphia. et al. Protocoldriven nonoperative management in patients with blunt splenic trauma and minimal associated injury decreases length of stay. Sood R. Daughton S. et al. Green DM. Shanmuganathan K. London. Ilahi ON. Traumatic brain injury. Rivera L. Gress DR. et al. Poletti PA. UK WB Saunders. nd ed. Total burn care. J Trauma . Herndon DN. Omert LA. J Trauma . Burn Outcome Heimbach DM. et al. Diringer MN. Trauma and Thermal Injury Dries . Evolution in the management of hepatic trauma a year perspective. et al. Ochsner MG. Kaisers U. J Burn Care Rehabil . N Engl J Med . PA Saunders Elsevier. Ochoa JB. J Burn Care Res . Katsis SB. Marion DW. Luterman A. J Trauma . Croce MA. The burn edema process current concepts. Peitzman AB. Pachter L. Cerebral perfusion pressure in the management of head injury. J Neurotrauma . . et al. et al. Weaver LK. J Burn Care Rehabil . Carbon monoxide poisoning. et al. McCall JE. Schoeneld DA. Hopkins RO. N Engl J Med . et al. Objective estimates of the probability of death from burn injuries. Berliner E. Wang C. Bessey PQ. Hyperbaric Oxygen/Carbon Monoxide Ernst A. Chan KJ. et al. Zibrak JD. Thorpe WP. Cahill TJ. National Burn Repository a tenyear review. N Engl J Med . N Engl J Med . ACCP Critical Care Medicine Board Review th Edition .Miller SF. Ryan CM. Hyperbaric oxygen therapy. J Burn Care Res . N Engl J Med . Schurr MJ. Hyperbaric oxygen for acute carbon monoxide poisoning. et al. Edelsberg JS. Tibbles PM. Hyperbaric oxygen for treating wounds a systematic review of the literature. Arch Surg . Respiratory care of the burn patient. Schwaitzberg S. Notes Trauma and Thermal Injury Dries . If the patient has been hypoventilated during and after the surgery. and postoperative hemorrhage Review the denition. establishing an understanding of drains. I will discuss several postoperative crises involving cardiac surgery patients. the more total tissue uptake occurs. enteral nutrition. and treatment of malignant hyperthermia Discuss the mechanisms. wound care differ from the nonsurgical patient. drain care. this may also lead to delayed emergence from anesthesia. timing and route of nutrition. plus. including volatile anesthetics. Narcotics and benzodiazepines have variable duration of action depending on the amount administered during surgery. and postoperative hypothermia Understand basic aspects of postoperative extubation Review and understand general postoperative and posttrauma management including deep vein thrombosis prophylaxis. MSc. he or she is unconscious because of a variety of medications. Following this. timing and route of nutrition. wound care. narcotics. the understanding of the disease and how it is treated is imperative to good outcomes. and neuromuscular blockers. delayed emergence. The speed of emergence is directly proportional to alveolar ventilation. Malignant hyperthermia MH will be discussed because patients with this condition require care in an ICU following the initial event. pathophysiology. ancillary personnel. This discussion is not all inclusive because many aspects are discussed in other chapters within this text. communication with nursing. which are covered throughout this text. FCCP Objectives Review basic postanesthesia care including awakening. and what potential complications may occur. Any critical care provider who cares for surgical. and postoperative wound care will be discussed. but inversely proportionate to solubility of the agent within the blood. and/or trauma patients should be acutely aware of their general management and be able to recognize and respond to postoperative emergencies. Volatile anesthetics tend to dissipate quickly but can maintain their effects for to min postoperatively. malignant hyperthermia. The longer the anesthesia time. Simmons. clinical signs. parenteral nutrition. Communication with the surgical team bringing the patient to the ICU should occur to ensure that the critical care provider understands what surgical procedure occurred. and treatment of several postoperative cardiac surgery crises Key words acute pulmonary hypertension. As with all aspects of patient care. cardiothoracic. which can affect the duration of time it takes to emerge from the anesthesia. sedation. right ventricular failure. deep vein thrombosis.Postoperative Critical Care Management and Selected Postoperative Crises Jonathan S. postoperative extubation. DO. surgical drains. postoperative atrial brillation. vacuum assistedclosure devices. postoperative bleeding. what events may be expected. Recovery is generally fastest with desurane and nitrous oxide and slowest with isourane. Finally. delayed emergence. postoperative agitation. such as sepsis. and other healthcare providers is essential to appropriate care. Care has been taken to avoid duplication of more common postoperative problems. and renal failure. awakening. postoperative hypothermia. ARDS. postsurgical deep vein thrombosis DVT prophylaxis. this discussion covers the rst several postoperative days from surgical intervention. Awakening From Anesthesia Overview The general postoperative management treatment guidelines and postoperative emergencies have been historically glossed over in critical care board review courses. Recovery from IV ACCP Critical Care Medicine Board Review th Edition . instead. cardiac tamponade. General aspects of the postoperative anesthesia care and postoperative extubation will be discussed because this may When the patient presents to the ICU following surgery. benzodiazepines. and/or hepatic disease can all affect duration of action of IV anesthetics. large open wounds and raw surfaces. An adequate amount of time should be given for these to wear off before becoming unduly concerned about mental status. the majority of postoperative patients should be returned to normothermia. increase risk of cardiac ischemia. renal impairment. although controversial. In some instances. This usually can be accomplished without causing further sedation. as well as the verbal report from the anesthesia team. patients should be able to protect their airway before extubation should occur. which will reduce the risk of further complications. As the total dose administered during an anesthetic application increases. then conditions such as sepsis. Forcedair rewarming devices should be used to normalize temperature C and reduce shivering. In these patients. anxiety. A trainoffour twitch monitor can assist with determining whether or not paralysis has been reversed. and increase shivering and overall discomfort. it is possible to have patients follow commands and participate in working toward extubation. neostigmine . the most common being residual anesthetic. and encephalopathy should be considered. to mg and glycopyrrolate can be used to reverse the action of the neuromuscular blockers. Emergence can also be delayed by electrolyte abnormalities such as hyperglycemia and hyponatremia. Neuromuscular blockade can have prolonged duration of action in some cases and should be considered when a patient is unable to move adequately or cannot hold up the head for s. increase susceptibility to infection. acidosis. a false sense that the blockade has worn off can be seen and. shock. which is imperative to obtain on patient arrival to the ICU. following extubation. such as in postcardiac arrest or traumatic/anoxic brain injury. hypoxemia. In most cases. hypotension.anesthetics is mainly dependent on redistribution rather than the elimination halflife of the drug. cool air temperature for operating personnel comfort. The anesthetic record is an excellent resource. cumulative effects become apparent and lead to prolonged emergence. Postoperative Hypothermia Patients returning from the operating room frequently have moderatetosevere hypothermia. selfextubation. or other complications.mg increments and/or umazenil in . the halflife will become more involved in the duration of emergence. A basic metabolic prole should be checked if emergence appears delayed. or other complications Postoperative Extubation In the immediate postoperative period. Agitation and CNS Depression Patients may become restless before they are fully responsive or they may experience disorientation. then naloxone in . and. should be considered and evaluated. bladder distention. increase transfusion requirements. nally. The goal should be rewarming during emergence and on presentation to the ICU. respectively. sedative. Generally. Much of the time. mgincrements can be given to rule out opioid or benzodiazepine effects. Postoperative hypothermia has been shown to worsen coagulopathy. the use of lowdose fentanyl or morphine for pain and/or . Although there may be times when hypothermia is useful. Advanced age. many patients can be extubated quickly following Postoperative Critical Care Management and Selected Postoperative Crises Simmons . Propofol and remifentanil lead to the shortest emergence time. Delayed emergence can occur because of several reasons. agitation or somnolence should improve within to min with appropriate management and monitoring. vasodilation from the use of volatile anesthetics. The causes are multifactorial and include IV uids and blood products that are not warmed prior to infusion. decisions regarding extubation can be difcult. evaporation. If paralysis is persistent. despite this restlessness. In general. If not. If the length of emergence becomes prolonged. and analgesic drug effects. the patient has difculty maintaining ventilation without assistance. Generally. Use of other sedating or interacting agents such as alcohol or recreational drugs prior to anesthesia may also contribute. this is selflimited. to mg of midazolam intermittently can control agitation. and pain. Small doses of narcotics and/or benzodiazepines may be necessary to help relax the patient enough to avoid selfharm. however. extubation may need to be delayed if there are plans to return to the operating room within the next h.a Finally. KingDenborough syndrome. These diseases include myotonia. tachycardia. if the condition is not recognized. and severe hyperpyrexia. The diaphragm has been shown to be the last muscle ACCP Critical Care Medicine Board Review th Edition that is paralyzed during an anesthetic application and tends to be the rst to recover. and comfort. and vital signs are relatively stable. and the overall incidence is relatively rare approximately in . Patients will then quickly become unstable if not aggressively treated. anesthetic agents should be adequately cleared and gas exchange abnormalities should be corrected to reduce risk of postextubation complications. In patients who undergo major surgery. Patients who fall into groups with musculoskeletal disorders have the highest prevalence. As the crisis develops. several factors may necessitate increased weaning time. the MH crisis must be aggressively treated. signicant metabolic acidosis resolved. The frequency is more prevalent in men than women and seems to be reduced after the age of years. . the mortality rate is . If trauma is involved. One main difference in the postoperative patient is the assessment of when the diaphragm is ready for respiration without mechanical assistance. especially if the chest wall has been damaged. repair of ptosis. including succinylcholine. and any vasoactive agents should be minimized. osteogenesis imperfecta. Fever. A familial relationship does seem to exist but is no