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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
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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,
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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
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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
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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
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Sobel JD. Pappas PG. Pseudomonas bacteremia. both for to days. MO MosbyYear Book.
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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.
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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
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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
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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. . .
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myocardial infarction randomised between alteplase and streptokinase with or without
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tissue plasminogen activator. Am Heart J . GUSTO IIb Investigators. . Circulation . . ASSENT
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TT. Vorac D. Lambrew CT. . . Gibson CM. ACC/ AHA guidelines for the management of
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myocardial infarction. Eur Heart J . Primary coronary angioplasty compared with intravenous
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individual patient data from randomized trials. Libby P. Rescue angioplasty after failed
thrombolytic therapy ACCP Critical Care Medicine Board Review th Edition . and survival
after acute myocardial infarction. Effects of tissue plasminogen activator and a comparison of
early invasive and conservative strategies in unstable angina and nonQwave myocardial
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Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction a
quantitative review of randomised trials. Gershlick AH. et al. Long distance transport for
primary angioplasty vs immediate thrombolysis in acute myocardial infarction nal results of
the randomized national multicentre trial. Zijlstra F. Grines CL. Croft CH. a report of the
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Thrombolysis in Myocardial Infarction TIMI phase II trial. McCabe CH. Pan HC. patients with
acute myocardial infarction randomised placebocontrolled trial. Circulation . Chen YP.
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Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and
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DP. Cairns JA. MacMahon S. Lancet . Antman EM. A comparison of aspirin plus tiroban with
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with acute nonQwave myocardial infarction randomly assigned to an invasive as compared
with a conservative management strategy. Mehta SR. et al. Yusuf S. . Crawford MH. et al.
Chrolavicius S. Protective effects of aspirin against acute myocardial infarction and death in
men with unstable angina results of a Veterans Administration cooperative study. N Engl J
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in patients with acute coronary syndromes without STsegment elevation. FRagmin and Fast
Revascularisation during InStability in Coronary artery disease Investigators. Gent M. .
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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.
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aspirin reduces the incidence of myocardial infarction and death in patients with unstable
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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. Circulation . N Engl J Med . JAMA . Peto R. . Antman EM. et al. ACC/
AHA guidelines for the management of patients with unstable angina and nonSTsegment
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randomised multicentre study. J Am Coll Cardiol . et al. Antman EM. Boden WE. Circulation .
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infarction TIMI BESSENCE metaanalysis. Effects of prophylactic lidocaine in suspected
acute myocardial infarction an overview of results from the randomized. Invasive compared
with noninvasive treatment in unstable coronary. Braunwald E.
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shock. Bolooki H. Killen DA. N Engl J Med . Kauder E. II . Armonk. Grines C. Valvular
emergencies. Early repair of postinfarction ventricular septal rupture. N Engl J Med . Ann
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ventricular infarction as an independent predictor of prognosis after acute inferior myocardial
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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
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revascularization in acute myocardial infarction complicated by cardiogenic shock SHOCK
Investigators should we emergently revascularize occluded coronaries for cardiogenic shock.
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. DellItalia LJ, Starling MR, Blumhardt R, et al. Comparative effects of volume loading,
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SL, et al. Profound but reversible myocardial depression in patients with septic shock. Ann
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. Bone RC. Why sepsis trials fail. JAMA . Kidokoro A, Iba T, Fukunaga M, et al. Alterations in
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induced by levosimendan does not impair relaxation. J Cardiovasc Pharmacol . Ukkonen H,
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heart failure. Clin Pharmacol Ther . Yokoshiki H, Katsube Y, Sunagawa M, et al.
Levosimendan, a novel calcium sensitizer, activates the glibenclamidesensitive K channel in
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. Marik PE, Mohedin M. The contrasting effects of dopamine and norepinephrine on systemic
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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
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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.
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Collaborative Group. and outcome of a twohour Tpiece trial in patients weaning from
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this setting are associated with shorter weaning duration than that of traditional approaches.
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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.
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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