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Current Evidence In Therapeutic Hypothermia For Postcardiac Arrest Care The ring of the red notification phone breaks the relative calm of an otherwise typical Monday morning and heralds the arrival of a critically ill patient. The dispatcher announces that EMS is on the way with a 57-year-old man in cardiac arrest, with an ETA of 3 minutes. Shortly after preparations for their arrival are complete, EMS personnel enter with CPR in progress and the patient already intubated. As monitor/defibrillator attachment, ETT placement confirmation, additional IV access, and complete exposure of the patient occur, you hear more about the clinical scenario from EMS. Mr. I.C. is a 57-year-old male who was moving furniture when, as described by witnesses, he complained of difficulty catching his breath and a slight tightness in his chest. He began coughing violently, vomited once, gasped, and collapsed. Emergency medical services personnel state that they arrived approximately 20 minutes after the patient had collapsed, with CPR in progress. The patient was intubated in the field, and EMS reports that the initial rhythm was PEA. Upon the patient’s arrival in the ED, the rhythm is noted to be ventricular fibrillation. Defibrillation is attempted twice over the next 4 minutes, with concomitant administration of medications. During the next rhythm check, QRS complexes are noted on the monitor and a pulse is palpated. The patient has had a return of spontaneous circulation, apparently 50 minutes from onset of the arrest. As you initiate postresuscitation care, you consider the patient’s prognosis and wonder if he qualifies for therapeutic hypothermia; ie, will therapeutic hypothermia make a difference in his outcome? Editor-in-Chief Professor, UT College of Medicine, Chattanooga, TN Andy Jagoda, MD, FACEP Professor and Chair, Department of Nicholas Genes, MD, PhD Emergency Medicine, Mount Sinai Assistant Professor, Department of School of Medicine; Medical Director, Emergency Medicine, Mount Sinai Mount Sinai Hospital, New York, NY School of Medicine, New York, NY Editorial Board William J. Brady, MD Professor of Emergency Medicine and Medicine Chair, Resuscitation Committee & Medical Director, Emergency Preparedness and Response, University of Virginia Health System Operational Medical Director, Charlottesville-Albemarle Rescue Squad & Albemarle County Fire Rescue, Charlottesville, VA Peter DeBlieux, MD Louisiana State University Health Science Center Professor of Clinical Medicine, LSUHSC Interim Public Hospital Director of Emergency Medicine Services, LSUHSC Emergency Medicine Director of Faculty and Resident Development Wyatt W. Decker, MD Professor of Emergency Medicine, Mayo Clinic College of Medicine, Rochester, MN Francis M. Fesmire, MD, FACEP Director, Heart-Stroke Center, Erlanger Medical Center; Assistant April 2011 Volume 13, Number 4 Author Matthew Constantine, MD Clinical Assistant Professor, Department of Emergency Medicine, State University of New York, Downstate/Kings County Hospital, Brooklyn, NY Peer Reviewers Marie-Carmelle Elie-Turenne, MD, FACEP Assistant Professor, Department of Emergency Medicine, Critical Care, Hospice and Palliative Care Medicine; University of Florida School of Medicine, Gainesville, FL Marc M. Grossman, MD, FACEP, CPHM Associate Medical Director, City of Miami Fire-Rescue, Voluntary Assistant Professor of Medicine and Neurology, University of Miami Miller School of Medicine, Jackson Memorial Hospital Emergency Services, Miami, FL CME Objectives Upon completion of this article, you should be able to: 1. 2. 3. 4. List the major indications and contraindications for instituting therapeutic hypothermia. Describe the focus of the initial patient evaluation to help determine possible benefits of therapeutic hypothermia. Recognize the physiologic response to therapeutic hypothermia as well as the clinical responses. Be familiar with the practical aspects of applying therapeutic hypothermia. Date of original release: April 1, 2011 Date of most recent review: March 10, 2011 Termination date: April 1, 2014 Medium: Print and online Method of participation: Print or online answer form and evaluation Prior to beginning this activity, see “Physician CME Information” on the back page. Shkelzen Hoxhaj, MD, MPH, MBA Scott Silvers, MD, FACEP Chief of Emergency Medicine, Baylor Chair, Department of Emergency College of Medicine, Houston, TX Medicine, Mayo Clinic, Jacksonville, FL Keith A. Marill, MD Assistant Professor, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA International Editors Peter Cameron, MD Academic Director, The Alfred Emergency and Trauma Centre, Monash University, Melbourne, Australia Corey M. Slovis, MD, FACP, FACEP Professor and Chair, Department of Emergency Medicine, Vanderbilt University Medical Center; Medical Giorgio Carbone, MD Michael A. Gibbs, MD, FACEP Director, Nashville Fire Department and Chief, Department of Emergency Professor and Chief, Department of International Airport, Nashville, TN Charles V. Pollack, Jr., MA, MD, Medicine Ospedale Gradenigo, Emergency Medicine, Maine Medical FACEP Jenny Walker, MD, MPH, MSW Torino, Italy Center, Portland, ME; Tufts University Chairman, Department of Emergency Assistant Professor; Division Chief, School of Medicine, Boston, MA Amin Antoine Kazzi, MD, FAAEM Medicine, Pennsylvania Hospital, Family Medicine, Department of Associate Professor and Vice Chair, Steven A. Godwin, MD, FACEP University of Pennsylvania Health Community and Preventive Medicine, Department of Emergency Medicine, Associate Professor, Associate Chair System, Philadelphia, PA Mount Sinai Medical Center, New University of California, Irvine; and Chief of Service, Department York, NY Michael S. Radeos, MD, MPH American University, Beirut, Lebanon of Emergency Medicine, Assistant Assistant Professor of Emergency Ron M. Walls, MD Dean, Simulation Education, Hugo Peralta, MD Medicine, Weill Medical College Professor and Chair, Department of University of Florida COMChair of Emergency Services, of Cornell University, New York; Emergency Medicine, Brigham and Jacksonville, Jacksonville, FL Hospital Italiano, Buenos Aires, Research Director, Department of Women’s Hospital, Harvard Medical Argentina Gregory L. Henry, MD, FACEP Emergency Medicine, New York School, Boston, MA CEO, Medical Practice Risk Hospital Queens, Flushing, New York Dhanadol Rojanasarntikul, MD Scott Weingart, MD, FACEP Assessment, Inc.; Clinical Professor Attending Physician, Emergency Assistant Professor of Emergency of Emergency Medicine, University of Robert L. Rogers, MD, FACEP, Medicine, King Chulalongkorn FAAEM, FACP Medicine, Mount Sinai School of Michigan, Ann Arbor, MI Memorial Hospital, Thai Red Cross, Assistant Professor of Emergency Medicine; Director of Emergency Thailand; Faculty of Medicine, John M. Howell, MD, FACEP Medicine, The University of Critical Care, Elmhurst Hospital Chulalongkorn University, Thailand Clinical Professor of Emergency Maryland School of Medicine, Center, New York, NY Medicine, George Washington Baltimore, MD Maarten Simons, MD, PhD Senior Research Editor University, Washington, DC; Director Emergency Medicine Residency of Academic Affairs, Best Practices, Alfred Sacchetti, MD, FACEP Joseph D. Toscano, MD Director, OLVG Hospital, Amsterdam, Assistant Clinical Professor, Inc, Inova Fairfax Hospital, Falls Emergency Physician, Department The Netherlands Department of Emergency Medicine, Church, VA of Emergency Medicine, San Ramon Thomas Jefferson University, Regional Medical Center, San Philadelphia, PA Ramon, CA Accreditation: EB Medicine is accredited by the ACCME to provide continuing medical education for physicians. Faculty Disclosure: Dr. Constantine, Dr. Elie-Turenne, Dr. Grossman, Dr. Jagoda, and their related parties report no significant financial interest or other relationship with the manufacturer(s) of any commercial product(s) discussed in this educational presentation. Commercial Support: This issue of Emergency Medicine Practice did not receive any commercial support. C ardiac arrest is one of the most intense clinical scenarios faced by the emergency clinician. The challenges are twofold: restarting spontaneous circulation and simultaneously attempting to find―and then reverse―the cause of the cardiac arrest. Chaos, confusion, fear, misinformation, and missing information are all common obstacles to managing the patient in cardiac arrest. To assist emergency clinicians in this situation, protocols such as Basic Life Support and Advanced Cardiovascular Life Support (ACLS) have been codified and refined in the past decade.1-3 These protocols have helped clinicians to think in a clear and goal-oriented manner and lead to one of two clinical outcomes: If their efforts are unsuccessful, the patient will be pronounced dead. If their efforts are successful, however, they will oftentimes find themselves facing the question (though perhaps not openly admitting it) of, “Now what?” With the return of spontaneous circulation (ROSC), one of the emergency clinician’s initial challenges has been met. The heart is spontaneously circulating blood. The second challenge of attempting to find and reverse the cause of the cardiac arrest remains, however; efforts now shift to these investigative ends while the emergency clinician simultaneously attempts to keep the newly resuscitated patient stable. Within the last several years, a more specific continuing treatment plan―beyond that of simple stability―has emerged. This plan is aimed at addressing the patient’s postarrest pathology, which includes the initial disease process that led to the cardiac arrest and the aftermath of the event.4 No organ system is exempt from the insult of cardiac arrest. Cardiac, neurologic, renal, and hepatic functions all suffer, not only from the momentary decrease in perfusion, but also from the massive inflammatory responses/cascades present during reperfusion.5 Historically, hypothermia has appeared to confer some degree of protection from these insults.6 Case reports of victims of cold water drowning who make full neurologic recoveries after having been in arrest for extended periods are well-known.7-10 Brain death—or severe neurologic compromise—is an unfortunate and devastating result of cardiac arrest. This event undermines all prior efforts to save the patient. Although other organ systems can be compensated for, artificially circumscribed, or even replaced (as is the case with renal and liver failure after cardiac arrest), neurologic function must stand on its own. It can determine the extent to which the patient is functional, even despite a perfusing rhythm. Simple speculation about the practice of inducing hypothermia after cardiac arrest, followed by intense and promising research, has led to its use for the specific purpose of improving neurologic outcomes.11 A growing body of evidence12 suggests that control of body temperature (ie, preventing hyperthermia and, more specifically, inducing hypothermia) should become the standard of care. Many emergency medical services (EMS) providers are also investigating the use of specific guidelines and procedural protocols for inducing hypothermia in postcardiac arrest patients.13 A wide variation still exists in the technical application of hypothermia therapy, however. Table Of Contents Critical Appraisal Of The Literature........................3 Etiology And Pathophysiology: Postcardiac Arrest Syndrome.............................3 Differential Diagnosis: Disease Management Considerations.............................5 Prehospital Care..........................................................6 Emergency Department Evaluation.........................7 Diagnostic Studies.......................................................8 Treatment......................................................................9 Clinical Pathway For The Application Of Therapeutic Hypothermia...........................10 Critical Care Basics...................................................12 Cost-Effective Strategies...........................................13 Risk Management Pitfalls For Therapeutic Hypothermia................................14 Controversies.............................................................16 Disposition.................................................................16 Summary....................................................................16 Case Conclusions......................................................17 References...................................................................17 CME Questions..........................................................22 Definition: Moderate Hypothermia Early research suggested that at temperatures greater than 30°C (86°F), the benefits of hypothermia outweigh the risks of adverse effects, whereas temperatures less than 30°C (86°F) are associated with a greater incidence of more severe adverse effects.14 The goal temperature for hypothermia used most often in studies showing improvement of outcomes was 32°C (90°F) to 33.9°C (93°F).11,15 The literature has recently proposed that this range be referred to as moderate therapeutic hypothermia.16 The goal of this literature review is to assist the emergency clinician in adapting the known body of evidence and techniques into an easily applicable protocol to maximize outcomes after cardiac arrest. The online version of this issue includes the Mount Sinai Hospital Induced Hypothermia Protocol and PostROSC Care Package documents (available at www. ebmedicine.net/MSSMProtocol), which readers may find helpful in establishing institutional protocols. Available Online At No Charge To Subscribers EM Practice Guidelines Update: “Pediatric Advanced Life Support: The 2010 AHA Guidelines,” www.ebmedicine.net/PALS Emergency Medicine Practice © 2011 2 EBMedicine.net • April 2011 Critical Appraisal Of The Literature reperfusion does not instantly stop or reverse these cascades and in fact may exacerbate certain deleterious responses.25 This conglomeration of symptoms resulting from the interactions of arrest-injured and reperfusion-injured organ systems is referred to as “postcardiac arrest syndrome.”26 In 2008, the International Liaison Committee on Resuscitation published a consensus statement on the epidemiology, pathophysiology, treatment, and prognostication of postcardiac arrest syndrome.26 This document coherently defines and addresses several of the major issues experienced by patients with an arrest followed by ROSC and subdivides the syndrome into 4 categories to help guide treatment efforts: • Postcardiac arrest brain injury • Postcardiac arrest myocardial dysfunction • Systemic ischemia/reperfusion response • Persistent precipitating pathology The MEDLINE® database was searched for articles published from 1950 to October 2010 that used the term hypothermia. This generalized search yielded well over 3000 publications. The effort was narrowed to English publications using 1 or more of the following terms: induced, therapeutic, cardiac arrest, heart, brain, emergency, resuscitation, and central nervous system. This search produced approximately 500 publications, which formed the basis for this review. Within this set, most of the publications involved either animal studies or small, human studies. The greatest difficulty in searching the literature on hypothermia is the nature of the therapy. It is not a single intervention, but rather a combination of various interventions. Variations in inclusion/exclusion parameters, methodologies of cooling, goal temperatures, timing, and outcome measures are a major limitation to synthesizing the evidence.17-19 The results of 2 landmark prospective randomized clinical trials published in 2002 established the foundation for inducing hypothermia in postcardiac arrest patients.11,15 These 2 studies have been used as the basis for many of the recommendations and guidelines published in the last decade. (See Table 1.) Bernard et al conducted a randomized controlled trial of therapeutic hypothermia in patients from Australia who had suffered cardiac arrest from ventricular fibrillation with ROSC. The study included 77 patients divided into normothermic and hypothermic groups. The absolute risk reduction of death or severe disability from normothermic to hypothermic groups was 23%, making the number needed to treat 4.5.15 The Hypothermia After Cardiac Arrest (HACA) group conducted a multicenter randomized blinded assessment of 273 patients presenting with ROSC after ventricular fibrillation arrest. The absolute risk reduction for an unfavorable neurologic outcome was 24% (a 69% probability of an unfavorable neurologic outcome in the normothermic group minus a 45% probability in the hypothermic group). Thus, the number needed to treat to avoid 1 severe neurologic outcome (including death) was 4.11 Postcardiac Arrest Brain Injury The mechanisms of brain injury in response to both decreased perfusion and subsequent reperfusion involve a complex series of events that begins almost immediately after the initial insult. Any period of ischemia, regardless of length, initiates certain responses and cascades of chemical events leading to cell death. Whether through disruption of homeostasis, activation of proteases and oxygen radicals, or cell-death signaling pathways, the end result is the same for affected tissue.27,28 These processes can last from hours to even days after the insult.5 Thus, this period becomes the window of opportunity for treatment. The ischemic event disrupts many of the autoregulatory mechanisms of cerebral blood evidenced by both microcirculatory and macrocirculatory dysfunctions. On a microcirculatory level, ongoing ischemia may result even after ROSC, possibly secondary to a no-reflow phenomenon.29 This outcome is currently attributed to thrombus formation, though controversies surround the exact mechanisms involved.30 On the macrocirculatory level, variations in mean arterial pressure (MAP) fail to prompt the correct compensatory changes in cerebral blood flow.31,32 Initially after ROSC, the brain may, in fact, become hyperemic, leading to worsening edema and other reperfusion injuries.33 The clinical significance of each of these contributing injuries is not well categorized; however, these responses may cause as much damage to the patient as the pathology that led to the arrest. Etiology And Pathophysiology: Postcardiac Arrest Syndrome Any patient who experiences a period of cardiac arrest undergoes at least 2 pathologic processes. The first is the disease process that led to the arrest; the second is the body’s reaction to the period of arrest, or global hypoperfusion. During arrest, each of the body’s systems (whether initially in a state of poor health or not) suffers a great insult. A severely decreased provision of substrate in each organ system leads to a cascade of events designed to compensate for or ameliorate the sudden loss.24 Sudden April 2011 • EBMedicine.net Postcardiac Arrest Myocardial Injury The myocardium is as sensitive to global ischemic events as the brain. The emergency clinician may thus be dealing with both the cardiac pathology that led to the arrest and the myocardium’s response 3 Emergency Medicine Practice © 2011 to the ROSC. The heart may initially become hyperkinetic secondary to endogenous or exogenous catecholamines circulating in the body.34,35 Global hypokinesis with noted decreases in cardiac output and increases in end-diastolic filling pressures may also be observed.36,37 Fortunately, these effects are often transient, with the myocardium returning to its baseline status within 72 hours.38,39 During this period, the myocardium appears to remain responsive to exogenous catecholamines37; however, the peri-code period may be adversely affected by large doses of exogenous catecholamines, which may have subsequent effects on overall mortality outcomes. Rivers et al demonstrated that patients who had received more than 15 mg of epinephrine during the code had significantly lower cardiac index, systemic oxygen consumption, and systemic oxygen delivery, as well as increased systemic vascular resistance and 6-hour lactate levels.34 very similar to those seen in severe sepsis and septic shock.40,41 There is a release of inflammatory cytokines such as interleukin-6, tumor necrosis factor alpha, and endotoxins.42 Endothelial damage leads to activation of fibrin pathways and the potential for thrombi formation.43 This is especially deleterious in the microcirculation because the end organs and tissue beds are dependent upon this system for adequate perfusion; even after ROSC, tissue beds may continue to suffer from ischemic damage.44 Adrenal tissue is also known to suffer after periods of ischemia as measured by cortisol levels, which commonly decrease. Studies have shown that patients who died early from refractory shock had lower cortisol levels than did patients who died later from other causes such as neurologic issues.45 Separate from this septic-type response, the brain also appears to release several neurohormonal mediators secondary specifically to ischemia. Apoptosis appears to occur via several stages involving free radicals and subsequent peroxynitrite, CA2+-dependent protease calpain, accumulation of glutamate, and various phospholipases, as well as poly (ADP-ribose) polymerase.28 Following this model, several animal studies have demonstrated Systemic Ischemic Reperfusion Response As both the brain and heart suffer from a period of hypoperfusion, so does essentially every organ system. Whole-body oxygen deprivation causes an activation of immune and coagulation responses Table 1. Published Guidelines Specific To Therapeutic Hypothermia Organization Recommendations Task Force on Scandinavian Therapeutic Hypothermia Guidelines, Clinical Practice Committee, Scandinavian Society of Anaesthesiology and Intensive Care Medicine20 • http://onlinelibrary.wiley.com/doi/10.1111/j.1399-6576.2008.01881.x/pdf Use of Hypothermia After Cardiac Arrest, Canadian Association of Emergency Physicians, Critical Care Committee21 http://www.caep.ca/template.asp?id=37C951DE051A45979A9BDD0C 5715C9FE • • • • • Adult Advanced Life Support: Australian Resuscitation Council Guidelines 200622 • http://onlinelibrary.wiley.com/doi/10.1111/j.1742-6723.2006.00890.x/ abstract • 2010 American Heart Association Guidelines for CPR and Emergency Cardiovascular Care Science23 • Level I* evidence supports use of hypothermia after VF; therapy is also recommended for patients with ROSC after asystole and PEA Protocol should be standardized and initiated as soon as possible Evidence is insufficient to support recommendations on optimal target temperature, duration of cooling, and rewarming time. Patients with nonperfusing VT or VF and ROSC who remain unresponsive should undergo therapeutic hypothermia (Grade A**) Patients with asystole or PEA thought to be of cardiac origin and ROSC but who remain unconscious should be considered for therapeutic hypothermia (Grade D***) Patients under 18 years of age and pregnant women may benefit from this therapy, but its role is unproven; consideration in these populations should be on a case-by-case basis (Grade D***) Unconscious adult patients with ROSC after out-of-hospital cardiac arrest, when the initial rhythm was VF, should be cooled to 32°C (90°F) to 34°C (93°) for 12 to 24 hours Such cooling may also be beneficial in unconscious adult patients with ROSC after out-of-hospital cardiac arrest when the initial rhythm was not VF or after cardiac arrest in the hospital Therapeutic hypothermia should be considered for any patient who is unable to follow verbal commands after ROSC http://circ.ahajournals.org/content/vol122/18_suppl_3/ Abbreviations: PEA, pulseless electrical activity; RCT, randomized controlled trial; ROSC, return of spontaneous circulation; VF, ventricular fibrillation; VT, ventricular tachycardia. *Level I evidence: Large, randomized trials with clear-cut results; low risk of false-positive error or false-negative error. **Grade A: Consistent Level 1 evidence - systematic review [with homogeneity] of RCTs; individual RCT [with narrow confidence interval] studies. ***Grade D: Inconsistent or inconclusive studies of any level. Emergency Medicine Practice © 2011 4 EBMedicine.net • April 2011 that even mild hypothermia decreases the amount of apoptotic neuronal tissue by decreasing or inhibiting the cascade production of several of these neurospecific mediators.46-48 Equally important, these same models have demonstrated that inhibition of the cascade is most effective when it occurs early after the ischemic insult.46 sion. Although patients were able to reach the goal temperature by the time of intervention, the study was not sufficiently powered to show a statistically significant difference in infarct size though the current evidence suggests there is a difference.54 Another possible deterrent to therapeutic hypothermia in the patient with AMI is the risk of increased bleeding, as coagulopathy is a known side effect of subnormal body temperature. A prospective study in 2002 by Bernard et al demonstrated improvements in neurologic outcomes secondary to hypothermia in postcardiac arrest patients.15 The study did not demonstrate any significant difference in adverse events, such as major hemorrhage, in patients undergoing PCI or thrombolytic therapy who were randomly assigned to hypothermia or normothermia groups. Patients in both groups also received standard treatments such as antiplatelet and anticoagulation therapies.15 In a more recent study, Schefold et al prospectively observed that the combination of reperfusion strategies―including anticoagulation and thrombolysis―and hypothermia was not associated with an excessive risk of bleeding complications.55 Therefore, the evidence indicates that induced hypothermia can be safely used in conjunction with other major interventions for management of AMI. This finding will likely grow in importance considering the most recent ACLS guidelines, which recommend considering PCI for cardiac arrest survivors with concerns for non-STsegment elevation myocardial infarction (NSTEMI) as well as for patients with STEMI.56 This guidance may increase the number of patients who receive PCI after cardiac arrest and, therefore, the number of patients who receive hypothermia and PCI. Postcardiac arrest care in patients with a suspected PE may be complicated by the need to leave the emergency department (ED) for imaging studies. Fortunately, most of the cooling devices, both external and internal, are portable and can easily go to the radiology suite with the patient. If this is not possible, disconnecting the patient from the device for the relatively short period required to perform a computed tomography (CT) scan usually will not allow the patient’s temperature to rise more than 0.5°C to 1.0°C (1°F to 2°F). This increase may be of no consequence, and if the patient returns slightly above the goal range of 32°C (90°F) to 34°C (93°F), his or her temperature can be returned to the target by reinitiating the cooling system. A more concerning question related to postarrest care in patients with a suspected PE is the use of anticoagulation and thrombolytic therapies. Study data on the use of thrombolytic therapy for the treatment of PE during induced hypothermia are limited. There have, however, been case reports mentioning the use of thrombolytics for PE during hypothermia treatment. Hovland et al reported such a case in 2008, with no major bleeding complications.57 Differential Diagnosis: Disease Management Considerations The differential diagnosis of patients being considered for induced hypothermia is essentially the same as that for patients with cardiac arrest. This differential, though initially broad, narrows on the basis of the patient’s history and the physical examination findings. Much of this initial work-up, however, will likely take place during the initiation of the hypothermia care, and thus the workup of cardiac arrest parallels the cooling activities. It is important to note that the available data do not show that implementing hypothermia care causes significant delays in addressing the etiologies of cardiac arrest in terms of diagnosis or interventions. This issue was specifically addressed in a recent study by Batista et al, who found that cardiac reperfusion via catheterization was not delayed by administration of hypothermia care.49 The effect of hypothermia care on the timing of other diagnostic and interventional modalities has not been specifically addressed. Conversely, questions have also been raised about how the diagnosis and management of cardiac arrest as well as its underlying pathology might affect hypothermia care. For example, do certain diagnoses such as acute myocardial infarction (AMI), pulmonary embolism (PE), intracranial hemorrhage, and sepsis affect the initiation or continuation of induced hypothermia? With regard to percutaneous coronary intervention (PCI), recent evidence has shown that patients who receive concurrent hypothermia therapy do not experience worse outcomes than those patients who receive PCI alone.50-52 A randomized controlled trial by Dixon et al clearly showed that hypothermia was both safe and feasible when combined with PCI; however, they were unable to show that the size of the infarct was reduced, an outcome suggested by previous animal models.53 Additionally, the investigators were unable to meet goal temperature at the time of reperfusion. Batista et al demonstrated that induction of hypothermia and a concomitant PCI was not associated with an increase in the number of adverse events or with a significant delay in time to reperfusion.49 Götberg et al looked at mild hypothermia with a goal temperature of less than 35°C (95°F) performed during reperfusion therapy.54 They reported a 38% reduction in infarct size on magnetic resonance imaging (MRI) scans after reperfuApril 2011 • EBMedicine.net 5 Emergency Medicine Practice © 2011 Without direct evidence, we are left to extrapolate opinions from the studies of the use of thrombolytics for AMI. Intracranial hemorrhage presents challenges similar to those raised in the discussion of PE. As stated earlier, patient transport for CT with or without the cooling device in tow is both feasible and unlikely to cause any significant variations in the patient’s temperature. Although known significant bleeding or intracranial hemorrhage was previously discussed as a relative contraindication to the initiation of hypothermia, intracranial bleeding is not necessarily a reason to discontinue hypothermia care once started. Several studies investigating the use of hypothermia for neurologic protection after devastating neurologic events have shown great promise.58-62 A randomized controlled trial by Todd et al specifically addressed the care of aneurysmal subarachnoid hemorrhage (SAH) after surgical intervention. Although no significant benefit was observed in the hypothermic group, there were no significant increases in morbidity or mortality.60 On the basis of the available data, the decision to continue hypothermia care if the patient is subsequently found to have SAH may be reasonable. These issues should be discussed with the appropriate specialists. Sepsis is another etiology of cardiac arrest; however, it is not the easiest diagnosis to make. Many of the markers used to identify severe sepsis and septic shock are the markers of inflammation that are also elevated in postresuscitative syndrome.40-42,63 The patient history is essential in localizing the infection. Unfortunately, the initial presentation of cardiac arrest often comes with a limited history. If the available information does point to either severe sepsis or septic shock, induced hypothermia may be contraindicated. This determination is predicated on the known side effect of hypothermia decreasing the immune response. Early studies into hypothermia showed that patients in deep hypothermia (less than 30°C [86°F]) or cooled for more than 24 hours were more prone to developing infections.16,64-66 In counterpoint, if current theories about many of the deleterious effects of sepsis being secondary to overactivation of the patient’s immune system are correct, it is tempting to extrapolate from animal data on immunosuppression during sepsis and assume that suppression by induced hypothermia may actually be of benefit.67-70 Unfortunately, to date, no clinical trials of specific anti-inflammatory agents in patients with severe sepsis have shown significant benefits,71,72 nor have the data on hypothermia suggested its utility solely as an immunosuppressive agent in sepsis. Thus, the effects of hypothermia on neurologic outcome after a cardiac arrest with septic etiology are unknown. For now, enough evidence does not exist to recommend sepsis as an absolute Emergency Medicine Practice © 2011 contraindication to hypothermia care; if hypothermia care has been implemented before the identification of sepsis as the cause of a cardiac arrest, it is reasonable to continue the therapy. Prehospital Care Extrapolating from animal studies, the more quickly therapeutic hypothermia is induced after ROSC, the better the outcome.6,73 It therefore is not surprising that some EMS systems have moved towards implementing field initiation of hypothermia. Wake Forest EMS in North Carolina and the entire New York City EMS system have started field initiation of hypothermia intra-arrest. Although data on the effectiveness of this strategy are still emerging, these locales have shown that such therapy is possible in the field. Both services use small, vehicle-powered coolers to keep bags of saline at refrigerator temperature (ie, 4°C [39°F]). Additionally, EMS providers must review current treatment protocols that may interfere with hypothermia, such as the use of paralytics during rapid sequence intubation, as these medications may subsequently alter the initial neurologic examination findings. Another prehospital issue that has emerged is the transport of patients to designated cardiac arrest centers. The management of postcardiac arrest patients requires skilled staff, coordination between multiple services, and the availability of advanced services such as catheterization laboratories. Centers with more experience using hypothermia protocols may also care for these patients more effectively. Similar to their policies regarding patients with stroke and STEMI, some EMS systems are transporting their postcardiac arrest patients to these advanced centers, bypassing closer hospitals (eg, Arizona and New York City have adopted this strategy). For the prehospital provider and medical control personnel, choosing a facility to receive patients with an out-of-hospital cardiac arrest now involves several interventional considerations. The 2010 iteration of the American Heart Association’s Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care recommend transportation to facilities capable of PCI for patients with cardiac arrest from possible acute coronary syndrome if the facility can be reached within an appropriate time.56 For more information on the 2010 ACLS Guidelines, see the March 2011 issue of EM Practice Guidelines Update at www.ebmedicine.net/ACLS. The guidelines also recommend inducing hypothermia care in appropriate postcardiac arrest patients.23 Because a potential conflict exists between centers that have varying services available, these issues are best addressed prior to implementing a treatment protocol. 6 EBMedicine.net • April 2011 Emergency Department Evaluation tions required for hypothermia care. Additionally, if the patient has not clearly expressed wishes concerning end-of-life care, it falls to the emergency clinician to evaluate whether he or she would benefit from the therapy. Although end-of-life care may suggest advanced age, there are no specific recommendations based solely on age. Neurologic condition is a primary outcome metric; therefore, if the patient has a poor baseline status regardless of age, initiation of hypothermia care may be futile. Protection of neurologic function is a primary goal of induced hypothermia; therefore, a baseline mental status must be established before initiation of treatment. If the postcardiac arrest patient returns to near full mental status, sits up, opens his or her eyes, and begins interacting with the surroundings, hypothermia care would not be expected to confer much benefit, and any improvement would be impossible to measure from such a high-functioning baseline. On the other end of the spectrum, the comatose patient with no response to painful stimuli, no brainstem reflexes, or no independent respirations has a defined baseline from which efforts may be gauged and would qualify for entry into the induced hypothermia protocol. A Glasgow Coma Scale (GCS) score of 3 is not necessarily a marker of dismal prognosis.80 Most patients are between the extremes of fully awake and profoundly comatose, so a short and focused neurologic examination must be performed. This evaluation should consist of determining the GCS score and conducting tests of basic brainstem function. Certainly, the physical examination for a patient in cardiac arrest must be extensive and thorough. If patients are able to follow commands, hypothermia is contraindicated; if they are responsive to voice but not able to follow commands (GCS motor score < 6), most centers will still induce. Corneal, pupillary, and oculocephalogyric (doll’s eye sign) reflexes should be tested. Assessment of overbreathing is made easier by temporarily lowering the ventilator rate to 6 to 8 breaths per Inclusion criteria for use of induced hypothermia at the author’s facility are listed in Table 2. The criteria focus on the timing of patient presentation and the patient’s clinical status and overall baseline health. Of note, the patient must be postcardiac arrest. This criterion is included to acknowledge that any nonperfusing rhythm is eligible. Initially, studies on induced hypothermia focused on patients who were in ventricular fibrillation or pulseless ventricular tachycardia.11,15 This constraint has given way to acceptance as candidates those patients with any nonperfusing rhythm.73-79 Timing issues are central to induced hypothermia care. The benefit of hypothermia has been shown to be significant in animal and humans if started within 6 hours of ROSC.11,12 After this period, there appears to be no significant benefit. The amount of time that the patient is in arrest is also significant. The best evidence shows that a time 30 minutes from arrest to ROSC is optimal for seeing benefit from therapeutic hypothermia; however, the possibility of benefit when ROSC occurs at 35 or even 45 minutes is unclear.11 Since unwitnessed arrests are impossible to time, and even witnessed arrests may be difficult to accurately recount, the author’s facility notes the “start” time of the arrest as the beginning of medical intervention, ie, the arrival of the code team or EMS provider. Other clinical inclusion criteria are measures of the patient’s circulatory status and mental status. Although mild to moderate hypothermia does not significantly worsen the patient’s hemodynamics, the inability to maintain a MAP of at least 65 mm Hg is a relative contraindication to hypothermia. This is a detail best worked out with the facility’s intensivist staff, as it is not specifically addressed in the literature. Table 3 shows exclusion criteria for inducing hypothermia at the author’s facility. There are absolute criteria and several relative contraindications. A primary tenet of the list is known advanced directives that are in contrast to the aggressive interven- Table 3. Exclusion Criteria For Induced Hypothermia Table 2. Inclusion Criteria For Induced Hypothermia (Must Have All) • • • • • • • • • • Postcardiac arrest status (any rhythm as a cause of arrest is eligible) ROSC < 30 minutes from EMS/code team arrival Time at induction < 6 hours from ROSC Comatose status (patient does not follow commands) MAP ≥ 65 mm Hg (may include use of vasopressor drugs) • • DNR advanced directive, MOLST, poor baseline status, or terminal disease Traumatic etiology for the arrest Active bleeding or known intracranial bleeding (relative) Cryoglobulinemia (relative) Pregnancy (relative; consider obstetrician/gynecologist consultation) Recent major surgical procedure (relative) Severe sepsis/septic shock as cause of arrest (relative) Abbreviations: EMS, emergency medical services; MAP, mean arterial pressure; ROSC, return of spontaneous circulation. Abbreviations: DNR, do not resuscitate; MOLST, medical orders for life-sustaining treatment. Used with permission, Elmhurst Hospital Center, New York, NY. Used with permission, Elmhurst Hospital Center, New York, NY. April 2011 • EBMedicine.net 7 Emergency Medicine Practice © 2011 minute. Evidence has shown that in the time immediately after cardiac arrest, routine assessments of neurologic functions such as spontaneous breathing and fixed dilated pupils do not hold reliable prognostic value.80 Thus, these examinations should not be used to determine whether the patient will benefit from the therapy, but rather to establish a baseline from which improvement can be measured. Any medications administered may affect neurologic findings and thus should be documented; however, the use of these medications should not render the patient ineligible for therapy. Blood gas results are affected by hypothermia secondary to alterations in laboratory analysis of the sample. Most blood gas analyzers will change the temperature of the sample to normothermia. The partial pressures of gasses are directly proportional to their temperature based on Boyle’s Law. Thus, the laboratory results will show the CO2 and O2 values as increased from their in vivo values. Consequent lowering of the pH will occur. In general, the partial pressure values will be falsely elevated by 5 mm Hg, and the pH falsely lowered by 0.012 for every 1°C below 37°C (approximately every 2°F below 98.6°F). Drug metabolism is generally dependent on enzyme processes that are frequently temperature-dependent and become slower during hypothermia.84 The half-life of most drugs will increase, therefore prolonging the duration of action of the medications. As a general rule, lower dosing will be mandated for most metabolized medications. Likewise, infusion rates may require adjustment. In certain circumstances, bolus dosing may be safer and easier to manage for drugs that are infused and titrated under normal conditions. Cardiac arrhythmias are frequently seen during the hypothermia process, but intervention is rarely required.16,85,86 During mild hypothermia, bradycardia is common, and the patient’s peripheral resistance may also rise by approximately 10 mm Hg. These combined effects may lower overall cardiac output. Typical hemodynamic strategies are aimed at maximizing cardiac output and, therefore, tissue perfusion. Hypothermia therapy may thus seem counterproductive in postresuscitative care. Fortunately, lowering of cardiac output is often matched by an overall decrease in whole-body metabolism, such that the lower demand for substrate is met by a lower supply from cardiac output.16 In most situations, the small changes in heart rate, MAP, and cardiac output caused by the hypothermia Diagnostic Studies Induced hypothermia affects all aspects of physiology. Many of the physiologic changes that occur either require no specific response or are easily dealt with using simple intervention and monitoring techniques. Induced hypothermia is frequently associated with changes in metabolic, liver function, and hematologic profiles. Volume changes occur as a result of cold diuresis, and there may be changes in drug metabolism. (See Table 4.) Platelet function and coagulation are both adversely affected by hypothermia. Mild platelet dysfunction begins at temperatures below 35°C (95°F), whereas coagulation changes will be seen only at temperatures of 33°C (91°F) and below.81,82 In very mild hypothermia (ie, temperatures above 35°C [95°F]), no increased bleeding will be seen. None of the studies analyzing outcomes of hypothermia in patients with known or discovered intracranial hemorrhage showed any significant increase in bleeding61,62,74; however, because even mild coagulopathy or platelet dysfunction may be deleterious to the multiple-trauma patient, hypothermia is contraindicated in this situation. Desmopressin has been shown to reverse the platelet dysfunction induced by hypothermia.83 Table 4. Common Laboratory Changes Associated With Induced Hypothermia16 Value Chemistry Blood gas Change Correction/Intervention Potassium, magnesium Check frequently and replace as needed to maintain values in normal range Bicarbonate Monitor along with blood gas values; replacement is generally unnecessary Amylase, AST, ALT Monitoring only CO2 Mathematically correct for changes in temperature, as the reported values are likely obtained by altering the temperature of the laboratory sample O2 pH Hematology WBC Monitoring only PT/PTT Usually none; however, may give correction factors if severe bleeding or discovery of occult bleeding such as intracranial hemorrhage Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; PT, prothrombin time; PTT, partial thromboplastin time; WBC, white blood cell. Emergency Medicine Practice © 2011 8 EBMedicine.net • April 2011 care are negligible. Severe, life-threatening arrhythmias generally occur at temperatures below 30°C (86°F) and are thus avoided during mild to moderate hypothermia.14 The common ECG changes seen are PR, QT, and QRS prolongations. (See Table 5.) Severe arrhythmias may be atrial fibrillation and ventricular fibrillation. Even though these dysrhythmias are typically not seen during mild to moderate hypothermia, their development is a contraindication to the continuation of the therapy. If life-threatening arrhythmias develop, any hypothermia treatment should be discontinued and the patient slowly warmed. near the body’s core (ie, in the axilla and groin and around the head).88 Although readily available and easy to set up, these systems do not allow for strict control; maintaining a setting for 24 hours is technically challenging and often results in wide variations in temperature.89 A more practical approach may be to initially cool the body with ice packs while another system is set up to maintain the temperature. Commercially available external systems generally offer the added benefit of a thermostat system (for monitoring the patient’s core temperature) that maintains the temperature within a narrow range. The Blanketrol® II and III hyper/hypothermia systems (Cincinnati Sub-Zero Products, Inc., Cincinnati, Ohio) are essentially a set of blankets that circulate water. The water temperature is controlled via a bedside unit. This system features a temperature input that allows feedback from a probe placed within the patient. The water temperature is then adjusted as needed to maintain the chosen body temperature. The same principles of external cooling are used with pad systems that circulate temperature-controlled water and wrap around certain parts of the body. Examples include the CoolBlueTM Surface Pad System (Innercool Therapies, San Diego, California) and the Arctic Sun 5000 Targeted Temperature ManagementTM system (Medivance Inc., Louisville, Colorado). These systems also provide feedback through a temperature probe placed on or within the body. In general, the water-circulating external contact devices have a cooling rate of 1°C to 2°C per hour (Fahrenheit not listed for device).16 If a patient starts out at approximately normal body temperature, cooling may take up to several hours. Other modalities, however, may be used in addition to the external devices to shorten induction time. Treatment The use of hypothermia as a therapy is divided into 3 phases: induction, maintenance, and rewarming. During the induction phase, the patient’s body temperature is taken from the presenting state to the goal temperature. During the maintenance phase, the patient’s temperature is held steady at goal, generally for a period of 24 hours from the time of initiation of induction. The rewarming phase begins at the end of this period, as the body is slowly returned to a normothermic state. The process of induced hypothermia results in a cold diuresis that must be taken into consideration during patient management. In a patient who may already require fluid resuscitation as a consequence of the pre-arrest pathology, this additional diuresis will be counterproductive. Treatment is simply the replacement of ongoing losses. The author recommends strict intake and output monitoring, with subsequent 1:1 replacement of all urinary losses in addition to any ongoing fluid resuscitation as directed by hemodynamic monitoring protocols. See “Critical Care Basics,” page 12. Internal Cooling Systems Internal systems are, most commonly, intravascular devices. A simple example of this type of cooling is the infusion of cold saline, which offers the distinct advantage of a rapid decrease in temperature of approximately 2°C to 4°C (3.5°F to 7°F) per hour.16,88,90 Saline infusion may also be used in conjunction with other Cooling Systems Cooling systems are typically either external or internal devices. External systems involve cool objects that are placed next to the skin,16 while internal systems are largely intravascular in nature, and the heat exchange takes place within the circulatory system of the patient rather than on the external body surface. In addition, a relatively new third approach exists, involving delivery of coolant to the nasopharyngeal passages. This device, the RhinoChillTM (BeneChill, Inc., San Diego, California), has been shown to be feasible, safe, and effective in the prehospital environment.87 Table 5. Common Cardiac Changes Parameter Cardiac activity MAP Cardiac output External Cooling Systems External systems are the most common systems for cooling the body. On the most basic level, exposure, cold air, cold water immersion, and ice can be used to both cool and maintain temperature. Ice packs are economical and work to induce cooling when placed April 2011 • EBMedicine.net Heart rate ECG PR interval QRS duration QT interval Atrial or ventricular fibrillation Abbreviations: ECG, electrocardiogram; MAP, mean arterial pressure. 9 Emergency Medicine Practice © 2011 Clinical Pathway For The Application Of Therapeutic Hypothermia YES Patient with cardiac arrest followed by ROSC? ROSC within 30-60 minutes of start of code (arrival of EMS if in the field)? Initiation of hypothermia within 6 hours of ROSC (Class I)? NO NO Continue with standard postresuscitative care NO Continue with standard postresuscitative care YES Patient deemed a candidate after a quick review of baseline mental and functional status and goals of care (per patient and/or family wishes)? YES Conduct focused examination to establish comatose state and baseline neurologic function • GCS (does not portend prognosis) (Class II) • Brainstem reflexes Initiate induction phase of cooling Hypothermia Protocol Induction phase • Reach goal of 32°C-34°C within 1 hour (Class I) • Set up chosen devices Temperature maintenance device Temperature monitoring device • Monitor for shivering Critical Care Basics • Establish central venous access • Conduct arterial pressure monitoring • Manage mechanical ventilation Maintenance Phase • Assess for shivering Evaluate need for analgesia and sedation (recommend paralysis only as needed) • Assess for changes in laboratory values with correction of electrolyte levels • Monitor in/outs; maintain euvolemia Address Inciting Pathology • Radiologic assessments CT scan Angiography • Cardiac interventions PCI Thrombolysis • Stroke interventions tPA (intra-arterial as needed) Aneurysm surgical procedure • Medications None contraindicated during hypothermia l l l l l l l l l l Rewarming phase • Rewarm approximately 0.5°C (1°F) per hour (Class I) • Assess for electrolyte shifts, particularly potassium • Assess mental status and neurologic function Abbreviations: CT, computed tomography; EMS, emergency medical services; GCS, Glasgow Coma Scale; PCI, percutaneous coronary intervention; ROSC, return of spontaneous circulation; tPA, tissue plasminogen activator. See Class of Evidence descriptions on page 11. Emergency Medicine Practice © 2011 10 EBMedicine.net • April 2011 systems. Additionally, crystalloids are ubiquitous in the clinical arena. Storage of several liters in a cooling unit will provide an easily accessible and inexpensive method to immediately begin cooling a patient. Commercially available intravascular systems use a catheter-based heat exchange process. For example, CoolLine®, CoolGard 3000 and Fortius CatheterTM systems (Zoll Medical Corporation, Chelmsford, Massachusetts) circulate cooled fluid within balloons, whereas the Celsius Control SystemTM (Innercool Therapies, San Diego, California) uses metal-based catheters that are in direct contact with the bloodstream. These systems have the ability to rapidly cool the patient and then accurately maintain the temperature at a set point with minimal variations; however, they require an invasive and potentially time-consuming procedure. Intravascular devices may also increase the risk of venous thrombosis, although the limited data that exist show an increased risk after several days and not necessarily within the first 24 hours of use.91-93 transition from normothermia to goal temperature; therefore, there may be an advantage to reaching the goal temperature as quickly as possible. Several modalities are available for rapid induction, ranging from low-cost methods such as the administration of cooled crystalloid and devices that allow controlled immersion to more invasive methods such as intravascular thermal exchange devices. Each device has certain advantages and disadvantages, and their use will most often be dependent upon the resources available at the time. At the author’s institution, iced saline is used for induction, and a surface blanket machine is used for continued maintenance while the patient remains in the ED. Alternatively, induction can be achieved with iced saline and maintenance provided by ice bags placed in the patient’s groin and axilla. Although this method is almost cost-free, it has been associated with poorer temperature control and possibly increased complication rates.89 Temperature blankets can be placed as soon as the patient has achieved ROSC and is stable enough to be manipulated. Once the device is fully connected and the probe is in place, the goal temperature is set and the machine is allowed to begin cooling the patient. These blankets may be placed before other necessary procedures such as CT, and even invasive interventions such as PCI may be performed with most devices in place. Use of external systems alone may result in a prolonged induction phase. Rapid temperature reduction is achieved with the administration of cooled (4°C [39°F]) normal saline (or other crystalloid/colloid based on the clinical scenario). In many situations, the patient benefits from maximization of volume status through fluid resuscitation. With use of this method alone, temperature reduction of approximately 2.5°C to 3.5°C (4.5°F to 6°F) per hour has been observed.94 Thus, a normothermic patient can be cooled from 37°C (98.6°F) to 33.5°C (92°F), Cooling System Summary To summarize, cooling systems can be placed into 2 basic categories, external and internal. Within each of these categories, there are low-cost and essentially “do-it-yourself” options to expose the patient to precooled items that are readily available in the clinical environment. These methods offer the advantage of a low cost but have the disadvantage of lack of control. Alternatively, each category includes a variety of technologically advanced systems. The greatest advantage of advanced cooling technologies is their capability to react to the patient’s temperature and alter the exposing medium to maintain body temperature at a set point. Induction Induction should be the shortest of the 3 phases. The majority of adverse effects occur during the Class Of Evidence Definitions Each action in the clinical pathways section of Emergency Medicine Practice receives a score based on the following definitions. Class I • Always acceptable, safe • Definitely useful • Proven in both efficacy and effectiveness Level of Evidence: • One or more large prospective studies are present (with rare exceptions) • High-quality meta-analyses • Study results consistently positive and compelling Class II • Safe, acceptable • Probably useful Level of Evidence: • Generally higher levels of evidence • Non-randomized or retrospective studies: historic, cohort, or case control studies • Less robust RCTs • Results consistently positive Class III • May be acceptable • Possibly useful • Considered optional or alternative treatments Level of Evidence: • Generally lower or intermediate levels of evidence • Case series, animal studies, consensus panels • Occasionally positive results Indeterminate • Continuing area of research • No recommendations until further research Level of Evidence: • Evidence not available • Higher studies in progress • Results inconsistent, contradictory • Results not compelling Significantly modified from: The Emergency Cardiovascular Care Committees of the American Heart Association and represen- tatives from the resuscitation councils of ILCOR: How to Develop Evidence-Based Guidelines for Emergency Cardiac Care: Quality of Evidence and Classes of Recommendations; also: Anonymous. Guidelines for cardiopulmonary resuscitation and emergency cardiac care. Emergency Cardiac Care Committee and Subcommittees, American Heart Association. Part IX. Ensuring effectiveness of communitywide emergency cardiac care. JAMA. 1992;268(16):2289-2295. This clinical pathway is intended to supplement, rather than substitute for, professional judgment and may be changed depending upon a patient’s individual needs. Failure to comply with this pathway does not represent a breach of the standard of care. Copyright © 2011 EB Practice, LLC d.b.a. EB Medicine. 1-800-249-5770. No part of this publication may be reproduced in any format without written consent of EB Practice, LLC d.b.a. EB Medicine. April 2011 • EBMedicine.net 11 Emergency Medicine Practice © 2011 which is within the goal range of 32°C (90°F) to 34°C (93°F) in 1 hour. Combined with additional devices, this method can achieve induction more expediently. Studies demonstrating the effectiveness of cooled fluids in therapeutic hypothermia have used an initial goal of 30 mL/kg and an infusion rate of approximately 100 mL/min.95-97 For the average adult, this regimen requires approximately 2 L as a maximum initial infusion. Depending on the size and type of catheter used, this rate may be best accomplished by using a pressure bag. The 2 L therefore should be delivered in approximately 20 minutes. It may take several additional minutes to reach maximal temperature effect. If the patient is still not below 34°C (93°F) after the initial maximum dose, we recommend waiting 15 minutes for the temperatures to equilibrate. If the goal is still not reached after this period, additional boluses of 250 mL of cooled fluid may be given every 10 minutes until the patient’s core temperature is less than 34°C (93°F). Conversely, if the patient reaches a temperature less than 34°C (93°F) at any time before the completion of the maximal fluid dose, the cooled fluids can be discontinued. If further fluid is needed, room temperature saline may be given from this point. Many temperature control systems have a monitoring probe. Regardless of the actual configuration of the device, evidence suggests that the most efficient placement during the induction phase is within the esophagus.16 This placement offers the earliest feedback on the patient’s true core temperature. Both bladder and rectal placements of the probe are certainly easier and effective to a point; however, there may be a lag between the patient’s true core temperature and the rectal temperature, which can lead to a delay in the machine sensing whether the patient is at a desired temperature. Although the monitoring capabilities of the cooling systems vary, the evidence suggests that, given a choice, esophageal placement is ideal. Within the esophagus, the best placement of the probe is behind the right atrium. This site is landmarked externally as approximately 4 cm cephalad to the xiphoid process. The probe can be measured before insertion and a notation made of the probe before placement. If the probe cannot be placed in the esophagus, it should be inserted in the rectum to approximately 5 cm. Assuming the patient is intubated and has vascular access, once the temperature blankets are applied, all of the necessary systems are in place for hypothermia therapy. Further procedures will be necessary as part of the standard approach to a critically ill patient and are discussed in the following section. control methods alone. If the methodology up to this point has overshot the goal and the patient’s temperature subsequently drops below 32°C (90°F) (although not below 30°C [86°F]), no drastic warming measures are necessary. Most surface devices, if set to automatic mode, will begin to warm the patient in order to attain the set temperature. If the temperature rises above 34°C (93°F), there will be a shift back into “induction” mode. In these cases, it is recommended to give additional 250-mL boluses of cooled fluid every 10 minutes until a temperature of less than 34°C (93°F) is reached. Critical Care Basics Regardless of whether postcardiac arrest patients are treated with induced hypothermia care, they are still critically ill and will benefit from invasive monitoring and aggressive management. Table 6 lists recommended monitoring devices and procedures for each patient. In general, access to the head, neck, and arms is not inhibited by any of the systems used in induced hypothermia. Although hypothermia has adverse effects on basic hemodynamic parameters such as heart rate and blood pressure, the goals of resuscitation for postcardiac arrest patients are similar to the goals used in the care of the severely septic patient. Taking into account that the etiology of the cardiac arrest may have continuing deleterious effects on the patient’s homeostasis, the pathophysiology of the disorder parallels that of severe sepsis and septic shock. The effects of inflammatory mediators and cascades that occur secondary to the initial insults lead to many of the same homeostatic disruptions seen in sepsis. The current recommendations therefore support a similar strategy of hemodynamic optimization, by ensuring adequate tissue perfusion through maintenance of perfusion pressure and cardiac output.2 The hemodynamic goal in treating these parallel pathologies is adequate tissue perfusion and thus substrate delivery. Ensuring tissue perfusion involves maintaining adequate perfusion pressure and adequate cardiac output. Cardiac output is further dependent upon preload, afterload, inotropy, and heart rate. Assessment of these efforts via specific monitoring devices provides ongoing feedback for further adjustments and prognosis. Table 6. Procedures Recommended For Hemodynamic Monitoring Maintenance Phase • • • • Once a core temperature of less than 34°C (93°F) is reached, the patient is in the maintenance phase. This phase can be managed with blanket or surface Emergency Medicine Practice © 2011 12 Full sterile neck line with central venous pressure monitoring Full sterile arterial line Foley catheter with hourly urine monitoring Orogastric tube on suction EBMedicine.net • April 2011 Perfusion pressure at the tissue bed is dependent on the MAP. Studies of shock and sepsis show that a MAP of at least 65 mm Hg is generally adequate to maintain perfusion of vital organs, including the heart itself.98 Injury to the brain may cause an increase in intracranial pressure. A higher MAP may be theoretically beneficial by maintaining adequate cerebral perfusion pressure. Studies of postcardiac arrest have shown no worse outcome for patients with a MAP as high as 90 to 100 mm Hg.15,78 If the patient is hypertensive during the postresuscitation period, it is suggested that the allowable upper limit of MAP is 100 mm Hg, based on these same data. No specific agents are recommended for control of MAP in the patient undergoing hypothermia therapy. Norepinephrine is often used as a firstchoice pressor and vasopressin as a second-line agent. For hypertensive patients, nitroglycerin may be used. These choices are based in part on evidence of adequate outcomes with these agents for shock in general99 and in part on the author’s experience and comfort with their use in a variety of clinical experiences. Of note, any pressor or vasodilator agent has specific use requirements and side effect profiles that dictate its applicability in certain clinical scenarios and treatment environments. Adequacy of preload cannot be assessed through a single measurement; several tools should be used simultaneously to obtain the best estimation of the patient’s preload status. Measurement of central venous pressure (CVP) has been used in early goal-directed sepsis therapy100; however, evidence has shown that it is most useful when low and that interpretation of CVP becomes less helpful when the initial values are within the normal range.101,102 Therefore, if a normal CVP value is 8 to 10 mm Hg, the further the patient’s reading is below this mark, the more likely the need for preload support. Additional evaluations include sonographic assessment of respiration changes in inferior vena cava (IVC) diameter,103 pulse pressure variation,104 passive leg raise, and simple bedside echocardiography. The combination of these assessments should guide decisions regarding volume replacement. If the patient is already at goal temperature, room temperature isotonic fluids should be used in aliquots of 200 to 500 mL, followed by reassessment of these same clinical parameters. The final division in the tissue perfusion scheme is ensuring adequate cardiac output by the adequacy of inotropy. Cardiac output is a combination of stroke volume and heart rate. Stroke volume is affected by the aforementioned preload and afterload and is dependent upon the intrinsic ability of the heart to pump (inotropy). Cardiac output can be further affected by manipulating inotropy, thus allowing the heart rate to be solely a compensatory mechanism that is best managed intrinsically. In the past, measurements of cardiac output and inotropy involved the use of pulmonary artery catheters, with subsequent measurements and calculations. Mixed venous oxygen saturation measured from a central venous catheter placed in the superior vena cava can be used as a surrogate marker. As blood moves through the capillary bed, oxygen is removed by processes of cellular transport and simple diffusion. If cardiac output is below the baseline level, oxygen uptake is increased by the tissues as compensation. When returned to the venous side, this blood will be less saturated. A saturation of 70% has been shown to correlate with adequate tissue perfusion and thus adequate cardiac output.105,106 Cost-Effective Strategies For Therapeutic Hypothermia • Therapeutic hypothermia is unlikely to add significantly to the overall cost of caring for patients in acute situations and offers significant benefits in decreasing disability (with its inherent costs). • Cooling machines and supplies are the only significant added costs of therapeutic hypothermia. The machines range in price, and few data on head-to-head comparisons support the benefit of one machine or type over another. Thus, financial constraints are not an evidence-based hindrance to applying this therapy. • Many EDs and hospitals already stock temperature control equipment as a way of treating pathologic hyperthermia and hypothermia. Many of these machines and modalities are easily adapted to the purpose of inducing, or asApril 2011 • EBMedicine.net sisting with maintenance of, hypothermia. • Ice and cooled saline are already available in hospitals and therefore represent no real costs for this therapy. These less expensive measures may be more difficult to regulate, however, and require more vigilance by emergency clinicians in terms of monitoring patients. • Total costs need not be absorbed by one department or specialty within the hospital system. Cardiac arrest can occur in-hospital or out-ofhospital, and subsequent care is likely to involve many different hospital services, making application of this therapy a multidisciplinary effort. The allocation of resources, particularly personnel, may thus be shared among multiple services and departments. 13 Emergency Medicine Practice © 2011 In the postcardiac arrest state, as in the septic state, inflammatory cytokines and other mediators also act as cardiodepressants. Evidence shows that a global dysfunction may occur after ROSC from cardiac arrest, regardless of the etiology. This global dysfunction is generally transitory and is not associated with decreased coronary flow (ie, ischemia).26 To overcome this in vivo depression of cardiac activity, inotropes such as dobutamine may be considered. An echocardiogram should be performed to further define the extent of dysfunction and the response to pharmacologic interventions, as well as to evaluate for more invasive assistance such as intra-aortic balloon pumps. Recent literature regarding the treatment of septic shock supports the use of lactate clearance as a marker of adequate tissue perfusion.107 Unfortu- nately, this option has not been studied specifically during hypothermia therapy. If this value is taken into account when the patient’s hemodynamic status is evaluated, it should be kept in mind that hypothermia may cause lactate levels to rise during the induction period.14 Thus, after the goal temperature is reached, a new baseline serum lactate assay should be obtained to serve as the starting point from which to evaluate tissue perfusion. Shivering Response During the initial stages of induced hypothermia, efforts are focused on implementation of cooling and ongoing care of the critically ill patient. Once the therapy is initiated, the emergency clinician must remain vigilant in ensuring that all facets of care are addressed. Shivering is by far the most insidious and counterproductive adverse effect of the hypo- Risk Management Pitfalls For Therapeutic Hypothermia (Continued on page 15) 1. “A patient has arrived from a nursing home with ROSC after being found unresponsive during the morning shift change. The patient is nonverbal and noninteractive, with little apparent cognitive ability secondary to a prior stroke. Am I obligated to induce hypothermia?” This practice is not the standard of care at this time; thus, the emergency clinician reserves the right to decide on a case-by-case basis which patients may or may not benefit from this therapy. The emergency clinician reserves the right to decide when clinical and/or extraclinical factors (such as resource allocation) make the application impractical. 4. “I’m called to the bedside by the nurse because the most recent ECG of a patient receiving therapeutic hypothermia appears to have a lot of artifact that she can’t seem to get rid of. On close inspection, the patient appears to have a fine tremor. The nurse asks if I would like to administer another dose of paralytic.” Paralysis should be used only as a last resort for shivering control, as masking seizure activity may result in worsening of neurologic status despite any benefits gained by therapeutic hypothermia. Sedation and analgesia should be used first. 2. “I was treating a patient with chest pain and a very concerning history when she suddenly arrested. After several minutes, we were able to bring her back. An ECG taken after the arrest showed lateral wall myocardial infarction. I activated the cath team, but should I have waited until the patient was cooled before letting her go for the procedure?” Treating a patient with induced hypothermia should not delay or inhibit the application of any other emergent procedures or investigations (eg, cardiac catheterization, surgical intervention, interventional radiology) related to the underlying pathology of cardiac arrest. Most times, the interventions can be performed simultaneously. 5. “While working medical control for my local EMS system, I received a call about a patient postcardiac arrest with ROSC. The EMS providers stated that they had been training to perform hypothermia and asked if they should begin therapy before my assessment of the patient.” Emergency medical services are a vital part of the hypothermia care paradigm, as the therapy has been shown to be more effective when 3. “As an emergency clinician, I’m excited about the prospect of having an additional therapy Emergency Medicine Practice © 2011 for my postcardiac arrest patients. I have all of the tools in my ED and would like to get started right away. What else do I need to do?” Therapeutic hypothermia is a multidisciplinary treatment modality; before initiation of any hypothermia protocol, all potential services that may be caring for the patients should be involved in the discussion. These services may include neurology, intensive care medicine, emergency medicine, and EMS. 14 EBMedicine.net • April 2011 thermic process. The shivering response is seen at a core temperature of approximately 35.5°C (96°F).108 Initially, the body responds to cooling by increasing sympathetic tone, causing peripheral vasoconstriction. As the body continues to cool, however, the same sympathetic stimulation leads to increased production of heat through shiver mechanisms. This shivering leads to an increase in metabolism, oxygen consumption, excess work of breathing, heart rate, and general stresslike response.109,110 Each of these reactions may be detrimental to the goals of hypothermia; however, the greatest detriment is the generation of heat, which directly counteracts the entire focus of the therapy. Although shivering is most commonly seen during the induction phase, it can occur during any phase of the hypothermia process; thus, patients should be assessed every 15 minutes during treatment. The treatment of shivering focuses on proper sedation of the patient. An obvious “quick fix” to shivering is to paralyze the patient. No muscle movement essentially means that no heat is generated; however, the shivering response is centrally mediated.110 Simply turning off muscle movement does not hinder the central nervous system’s attempts to warm the body. Other stress responses that are detrimental to the overall goals of hypothermia will also be masked, rather than mitigated, by paralytics. Masking the level of possible seizure activity can be dangerous; therefore, sedation should be the primary intervention used against shivering.16 Many sedating and anesthetic medications are available in most EDs, though several choices have specific advantages in helping to mitigate shivering. Fentanyl citrate has a very rapid onset of action and short half-life, making it ideal for titration. It is Risk Management Pitfalls For Therapeutic Hypothermia (Continued from page 14) delivered early. The initial cooling process can be started easily in the field with ice or cooled saline. If the receiving emergency clinician does not feel that hypothermia care is warranted, then there is no obligation to continue it. 6. “The patient receiving therapeutic hypothermia suddenly went into atrial fibrillation. I decided to attempt cardioversion, and the first shock converted the patient to normal sinus rhythm. After several minutes, however, the atrial fibrillation returned. Then the patient’s blood pressure started falling.” The development of a life-threatening arrhythmia is a contraindication to hypothermia care. The patient should be rewarmed to normothermia. 9. “While beginning to rewarm the patient, I noticed a change in the T wave morphology on the monitor. A subsequent ECG showed peaked T waves. Did I miss renal failure in the patient?” A too-rapid rate of rewarming will cause severe electrolyte shifts, particularly hyperkalemia. The rate of rewarming should not exceed 1°C (2°F) per hour and ideally should be more toward 0.5°C (1°F) per hour. 7. “When using therapeutic hypothermia I continue to have difficulty maintaining a constant temperature. Every time I adjust the device or add saline to recool the patient, I end up overshooting my goal.” First and foremost, check the patient for shivering. Wide temperature swings are not the norm and may be a sign of occult or fine shivering. Second, consider a different placement for the particular feedback device. If possible, esophageal placement should be attempted. 10. “A patient who has undergone hypothermia care is neurologically devastated several days after rewarming. I am asked why it did not work.” Hypothermia care offers no guarantees. Efforts should be made to explain to providers and family that this therapy will increase the patient’s chances for attaining a good neurologic outcome; however, it is difficult to predict which patients will fully recover on the basis of the available data. 8. “After several hours of stability during therapeutic hypothermia, my patient became gradually more tachycardic. Although she was initially weaned from pressors, her blood pres- April 2011 • EBMedicine.net sure started falling again. I used ultrasound only to find her IVC had collapsed, and her heart was pumping vigorously.” Cold will cause a diuresis. Although all patients may require some form of maintenance fluid, hypothermic patients should have urine output monitored closely and subsequently matched in return. 15 Emergency Medicine Practice © 2011 Disposition known to be effective in reducing pain and respiratory discomfort. The sensation of temperature is mitigated through similar pathways as pain; thus, blunting the opioid receptors decreases the sensation of hypothermia and therefore shivering. In a recent systematic review, Chamorro et al analyzed sedation regimens used during hypothermia protocols in the intensive care unit and found that fentanyl was the most common opioid used.111 We recommend maximizing the dose before the addition of other agents to achieve both sedation control and shivering control. Agents that may be added are magnesium,112,113 meperidine,114 propofol,115 dexmedetomidine,116 ketamine, and/ or benzodiazepine regimens. Regardless of the preferred regimen, sedation should be maximized before paralytics are used. If paralytics are necessary to control shivering, they should be given in bolus doses, as the maximal effects of sedation may be enough to keep the shivering from returning once the paralytic has been metabolized. Continuous electroencephalographic monitoring has been used in some centers to check for nonconvulsive status epilepticus. If paralytics are used, the author strongly recommends this modality to ensure that seizure activity does not go unrecognized and therefore untreated. All patients undergoing induced hypothermia are admitted to a critical care setting. Depending upon specific hospital resources, any or all parts of a hypothermia protocol can be administered in the ED or the intensive care unit. Both induction and maintenance may be completed in the ED; however, completion of these tasks should not delay transfer of the patient to a critical care setting, where advanced care can be given as needed. Rewarming In its simplest form, rewarming will occur naturally if the cooling devices are removed and the body is simply allowed to return to its own set temperature; however, several studies have shown that this technique may be associated with additional and unforeseen complications secondary to a too-rapid rise in temperature.118-121 We recommend that the same device be used for maintenance and rewarming. By gradually raising the set point and continuing to actively control shivering, emergency clinicians can achieve slow and controlled warming with minimal adverse effects. Once the patient’s temperature is at 36°C (97°F), passive warming should be permitted, since shivering is less likely to occur.108 Similar to the cooling process, the rewarming process can cause rapid shifts of electrolyte levels between intracellular and extracellular spaces. Specifically, levels of certain electrolytes such as potassium may rise quickly instead of decreasing quickly, as occurs with cooling.122 Hyperkalemia is a dangerous side effect of warming. Frequent blood draws during the rewarming period as well as a slow and controlled rate of rewarming will minimize rapid changes in electrolyte levels. If a warming program is not available, the set point of the device should be changed hourly in appropriate increments until a core temperature of 36°C (97°F) is reached. From this point on, the patient may be allowed to return to his or her own homeostatic temperature set point. Hyperthermia should be treated similarly as in any critical care patient and may be particularly detrimental to a patient with central neurologic injury. It may even become necessary to continue using the same cooling methods in order to maintain normothermia. Controversies There are essentially 2 arguments against therapeutic hypothermia. The first concerns the relative lack of supporting evidence. The evidence provided in this review, as well as that analyzed in more formal meta-analyses, has shown improved neurologic outcomes with this therapy.117 This said, these results are based on a relatively small number of patients.12 Thus, the criticism remains that the evidence upon which this intervention is based is small and stems mostly from a single study protocol that addressed only one pathology, cardiac arrest from ventricular fibrillation. The second issue with therapeutic hypothermia is its lack of generalizability. As mentioned above, most of the evidence comes from a trial involving patients with cardiac arrest with ventricular fibrillation. Only 8% of patients screened for inclusion in the HACA trial were accepted.12 Because the data come from such a limited sample, they may not be applicable to individual practices, especially given that cardiac arrest is a relatively rare event within emergency medicine. Considering that this therapy may be applied to only a few patients, the issue then becomes cost and resource allocation. There certainly are low-cost ways to induce hypothermia, including use of ice and cold saline; however, some of the available technologies are relatively expensive. Emergency Medicine Practice © 2011 Summary As with any new intervention, hypothermia therapy may appear at first impression to be a time-intensive, labor-intensive, and resource-intensive undertaking that is beyond the scope and expectations of most EDs. Most of the techniques described previously, however, are already part of emergency practice. Emergency medicine has seen a growth in both 16 EBMedicine.net • April 2011 run at approximately 100 mL per minute. After 15 minutes and 1700 mL of cold saline, the temperature probe reading was 33.9°C (92°F), and the cooled saline infusion was discontinued. During the induction phase, a triplelumen central venous catheter was placed under full sterile conditions with ultrasound guidance into the patient’s right internal jugular vein. A sterile right radial arterial line and orogastric and Foley catheters were placed. At this point, the patient’s vital signs were pulse rate, 107 beats per minute; BP, 110/52 mm Hg (MAP, 71 mm Hg) (norepinephrine infusion); respiratory rate, 21 breaths per minute (greater than ventilator setting of 16); O2 saturation, 96% on 50% FiO2, and a temperature of 33.4°C (92°F). An initial CVP reading from the central line gave a value of 8 cm H2O, which is below the threshold for volume resuscitation; however, a decision was made to conduct several other investigations of the preload status. On ultrasound examination, the IVC was measured at 1.3 cm and nearly reached full collapse upon administration of a pressurized ventilated breath. After a passive leg raise technique was used, the patient’s MAP increased slightly, as did the CVP. An ultrasound probe on the IVC concomitantly showed an increase in diameter, with less collapse upon pressurized ventilation. A 500-mL bolus of normal saline was initiated, after which the patient’s hemodynamic status improved, and his temperature was well maintained at 32.9°C (91°F). Shivering was noted; a fentanyl drip was started for sedation, and the shivering stopped. After several hours in the ED, the patient was moved to the ICU. After 24 hours of induced hypothermia, the patient was rewarmed. The machine was reset at increasing temperatures of 0.5°C (1°F) over an hour. When Mr. I.C. reached a temperature of 36°C (97°F), the temperature blankets were removed, and sedation was discontinued. The patient progressed well over the rest of his hospital course. During the next several days, Mr. I.C. regained consciousness, followed commands, and breathed spontaneously. He was liberated from the ventilator on day 3 of his hospital stay. On day 7, the patient was discharged to home, having regained his baseline mental status and was without residual deficit. A 1-month follow-up appointment found the patient continuing to do well, having resumed most of his daily functions and having returned to work. the number of critically ill patients treated in the ED and the duration of treatment pending critical care bed availability, a development that has made use of ventilator management, sterile central access, sedation medications, and fluid resuscitation more common. The only addition to established practice required by induced hypothermia is performance of these tasks while the patient is being cooled. The only additional equipment required is the cooling device itself. All of the other interventions are easily set up using equipment that is already available; for example, cold saline can be prepared ahead by simply refrigerating part of the department’s stock. Unfamiliarity may be the greatest hurdle to use of this therapy. Establishing a protocol similar to the examples presented in this review to facilitate the administration of the therapy is recommended. Any plans and protocols for use should be discussed with and agreed upon by other hospital staff who may be involved in further care of the patient. A unified and hospital-wide policy will help to smooth the implementation of this new therapy and will likely improve the outcomes. Case Conclusion Once the patient’s pulse was palpated, further investigation was undertaken. His first set of vitals included a pulse rate of 121 beats per minute; BP, 87/41 mm Hg (MAP, 53 mm Hg); respiratory rate, 12 breaths per minute (on ventilation); temperature, 36°C (97°F) (oral); and O2 saturation, 98% on 100% FiO2 via the ventilator. An initial ECG showed sinus tachycardia with significant Q waves noted inferiorly. The chest radiograph showed mild nonfocal congestion and no pneumothorax. A primary survey showed no obvious trauma or prior surgical scars, and the patient was unresponsive to deep sternal rub. Fluid therapy and an infusion of norepinephrine resulted in a BP reading of 97/52 mm Hg (MAP, 67 mm Hg). On neurologic examination, the patient had no eye-opening and decorticate motor response. The patient appeared to have no pupil or corneal reflexes; however, doll’s eye sign was present. The patient was being mechanically ventilated at a rate of 12 breaths per minute, but he was noted to be breathing at a rate of 16 to 18 breaths per minute (a noted change from the initial set of vital signs). His deep tendon reflexes were symmetric. A repeated physical examination revealed slightly improved vital signs (less tachycardia, but pressors still required to remain normotensive). No other remarkable physical examination features were noted. Mr. I.C. was rolled and placed between 2 cooling blankets. The blankets are designed to go directly against the skin, so there were no sheets or gowns covering him. The blankets were assembled to the machine, and a probe was placed in the patient’s esophagus; his core temperature was 36.4°C (97.5°F). Rapid cooling was facilitated with an infusion of cold saline at 5.5°C (42°F). 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(Retrospective; 272 patients) Valeri CR, MacGregor H, Cassidy G, et al. Effects of temperature on bleeding time and clotting time in normal male and female volunteers. Crit Care Med. 1995;23(4):698-704. (Prospective observation; 54 patients) Valeri CR, Feingold H, Cassidy G, et al. Hypothermiainduced reversible platelet dysfunction. Ann Surg. Emergency Medicine Practice © 2011 1987;205(2):175-181. (Animal model) 83. Ying CL, Tsang SF, Ng KF. The potential use of desmopressin to correct hypothermia-induced impairment of primary haemostasis--an in vitro study using PFA-100. Resuscitation. 2008;76(1):129-133. doi:10.1016/j.resuscitation.2007.07.009. (Bench research) 84. Tortorici MA, Kochanek PM, Poloyac SM. Effects of hypothermia on drug disposition, metabolism, and response: a focus of hypothermia-mediated alterations on the cytochrome P450 enzyme system. Crit Care Med. 2007;35(9):2196-2204. (Review) 85. Lewis ME, Al-Khalidi AH, Townend JN, et al. The effects of hypothermia on human left ventricular contractile function during cardiac surgery. J Am Coll Cardiol. 2002;39(1):102-108. (Prospective observational; 10 patients) 86. Mattheussen M, Mubagwa K, Van Aken H, et al. Interaction of heart rate and hypothermia on global myocardial contraction of the isolated rabbit heart. Anesth Analg. 1996;82(5):975981. (Animal model) 87. Castrén M, Nordberg P, Svensson L, et al. Intra-arrest transnasal evaporative cooling: a randomized, prehospital, multicenter study (PRINCE: Pre-ROSC IntraNasal Cooling Effectiveness). Circulation. 2010;122(7):729-736. doi:10.1161/ CIRCULATIONAHA.109.931691. (Prospective, randomized, controlled; 194 patients) 88. Larsson IM, Wallin E, Rubertsson S. Cold saline infusion and ice packs alone are effective in inducing and maintaining therapeutic hypothermia after cardiac arrest. Resuscitation. 2010;81(1):15-19. doi:10.1016/j.resuscitation.2009.09.012. (Prospective interventional; 38 patients) 89. Merchant RM, Abella BS, Peberdy MA, et al. Therapeutic hypothermia after cardiac arrest: unintentional overcooling is common using ice packs and conventional cooling blankets. Crit Care Med. 2006;34(12 suppl):S490-S494. doi:10.1097/01. CCM.0000246016.28679.36. (Prospective observational; 32 patients) 90. Kämäräinen A, Virkkunen I, Tenhunen J, et al. Induction of therapeutic hypothermia during prehospital CPR using ice-cold intravenous fluid. Resuscitation. 2008;79(2):205-211. doi:10.1016/j.resuscitation.2008.07.003. (Prospective interventional; 17 patients) 91. Prunet B, Lacroix G, Bordes J, et al. Catheter related venous thrombosis with cooling and warming catheters: two case reports. Cases J. 2009;2:8857. doi:10.1186/1757-1626-00020000008857. (Case report) 92. Simosa HF, Petersen DJ, Agarwal SK, et al. Increased risk of deep venous thrombosis with endovascular cooling in patients with traumatic head injury. Am Surg. 2007;73(5):461464. (Retrospective cohort; 11 patients) 93. Inderbitzen B, Yon S, Lasheras J, et al. Safety and performance of a novel intravascular catheter for induction and reversal of hypothermia in a porcine model. Neurosurgery. 2002;50(2):364-370. (Animal model) 94. Polderman KH, Rijnsburger ER, Peerdeman SM, et al. Induction of hypothermia in patients with various types of neurologic injury with use of large volumes of ice-cold intravenous fluid. Crit Care Med. 2005;33(12):2744-2751. (Prospective interventional; 134 patients) 95. Virkkunen I, Yli-Hankala A, Silfvast T. Induction of therapeutic hypothermia after cardiac arrest in prehospital patients using ice-cold Ringerʼs solution: a pilot study. Resuscitation. 2004;62(3):299-302. doi:10.1016/j.resuscitation.2004.04.003. (Prospective observational; 13 patients) 96. Bernard S, Buist M, Monteiro O, et al. Induced hypothermia using large volume, ice-cold intravenous fluid in comatose survivors of out-of-hospital cardiac arrest: a preliminary report. Resuscitation. 2003;56(1):9-13. (Prospective interventional; 22 patients) 97. Rajek A, Greif R, Sessler DI, et al. Core cooling by central venous infusion of ice-cold (4 degrees C and 20 degrees 20 EBMedicine.net • April 2011 C) fluid: isolation of core and peripheral thermal compartments. Anesthesiology. 2000;93(3):629-637. (Prospective observational; 18 patients) 98. Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008;36(1):296-327. doi:10.1097/01. CCM.0000298158.12101.41. (Practice guidelines) 99. De Backer D, Biston P, Devriendt J, et al. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med. 2010;362(9):779-789. doi:10.1056/NEJMoa0907118. (Prospective, randomized, controlled; 1679 patients) 100. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368-1377. doi:10.1056/NEJMoa010307. (Prospective, randomized, controlled; 263 patients) 101. Jain RK, Antonio BL, Bowton DL, et al. Variability in central venous pressure measurements and the potential impact on fluid management. Shock. 2010;33(3):253-257. doi:10.1097/ SHK.0b013e3181b2bb22. (Prospective observational; 100 patients) 102. Otero RM, Nguyen HB, Huang DT, et al. Early goal-directed therapy in severe sepsis and septic shock revisited: concepts, controversies, and contemporary findings. Chest. 2006;130(5):1579-1595. doi:10.1378/chest.130.5.1579. (Review) 103. Keller AS, Melamed R, Malinchoc M, et al. Diagnostic accuracy of a simple ultrasound measurement to estimate central venous pressure in spontaneously breathing, critically ill patients. J Hosp Med. 2009;4(6):350-355. doi: 10.1002/jhm.503. (Prospective observational; 63 patients) 104. Muller L, Louart G, Bousquet PJ, et al. The influence of the airway driving pressure on pulsed pressure variation as a predictor of fluid responsiveness. Intensive Care Med. 2010;36(3):496-503. doi:10.1007/s00134-009-1686-y. (Prospective interventional; 57 patients) 105. Perner A, Haase N, Wiis J, et al. Central venous oxygen saturation for the diagnosis of low cardiac output in septic shock patients. Acta Anaesthesiol Scand. 2010;54(1):98-102. doi:10.1111/j.1399-6576.2009.02086.x. (Prospective observational; 56 patients) 106. Weinbroum AA, Biderman P, Soffer D, et al. Reliability of cardiac output calculation by the fick principle and central venous oxygen saturation in emergency conditions. J Clin Monit Comput. 2008;22(5):361-366. doi:10.1007/s10877-0089143-y. (Prospective observational; 15 patients) 107. Jones AE, Shapiro NI, Trzeciak S, et al. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010;303(8):739746. doi:10.1001/jama.2010.158. (Prospective, randomized, controlled; 300 patients) 108. Lopez M, Sessler DI, Walter K, et al. Rate and gender dependence of the sweating, vasoconstriction, and shivering thresholds in humans. Anesthesiology. 1994;80(4):780-788. (Prospective interventional; 16 patients) 109. Leslie K, Sessler DI. Perioperative hypothermia in the high-risk surgical patient. Best Pract Res Clin Anaesthesiol. 2003;17(4):485-498. (Review) 110. De Witte J, Sessler DI. Perioperative shivering: physiology and pharmacology. Anesthesiology. 2002;96(2):467-484. (Review) 111. Chamorro C, Borrallo JM, Romera MA, et al. Anesthesia and analgesia protocol during therapeutic hypothermia after cardiac arrest: a systematic review. Anesth Analg. 2010;110(5):1328-1335. doi:10.1213/ANE.0b013e3181d8cacf. (Systematic review) 112. Wadhwa A, Sengupta P, Durrani J, et al. Magnesium sulphate only slightly reduces the shivering threshold in April 2011 • EBMedicine.net humans. Br J Anaesth. 2005;94(6):756-762. doi:10.1093/bja/ aei105. (Prospective, randomized, controlled; 9 patients) 113. Zweifler RM, Voorhees ME, Mahmood MA, et al. Magnesium sulfate increases the rate of hypothermia via surface cooling and improves comfort. Stroke. 2004;35(10):2331-2334. doi:10.1161/01.STR.0000141161.63181.f1. (Prospective interventional; 22 patients) 114. Kimberger O, Ali SZ, Markstaller M, et al. Meperidine and skin surface warming additively reduce the shivering threshold: a volunteer study. Crit Care. 2007;11(1):R29. doi:10.1186/ cc5709. (Prospective interventional; 80 patients) 115. Matsukawa T, Kurz A, Sessler DI, et al. Propofol linearly reduces the vasoconstriction and shivering thresholds. Anesthesiology. 1995;82(5):1169-1180. (Prospective interventional; 5 patients) 116. Talke P, Tayefeh F, Sessler DI, et al. Dexmedetomidine does not alter the sweating threshold, but comparably and linearly decreases the vasoconstriction and shivering thresholds. Anesthesiology. 1997;87(4):835-841. (Prospective, randomized, interventional; 9 patients) 117. Cheung KW, Green RS, Magee KD. Systematic review of randomized controlled trials of therapeutic hypothermia as a neuroprotectant in post cardiac arrest patients. CJEM. 2006;8(5):329-337. (Systematic review) 118. Lavinio A, Timofeev I, Nortje J, et al. Cerebrovascular reactivity during hypothermia and rewarming. Br J Anaesth. 2007;99(2):237-244. doi:10.1093/bja/aem118. (Prospective observational; 118 patients) 119. Alam HB, Rhee P, Honma K, et al. Does the rate of rewarming from profound hypothermic arrest influence the outcome in a swine model of lethal hemorrhage? J Trauma. 2006;60(1):134-146. doi:10.1097/01.ta.0000198469.95292.ec. (Animal model) 120. Maxwell WL, Watson A, Queen R, et al. Slow, medium, or fast re-warming following post-traumatic hypothermia therapy? An ultrastructural perspective. J Neurotrauma. 2005;22(8):873-884. doi:10.1089/neu.2005.22.873. (Animal model) 121. Kawahara F, Kadoi Y, Saito S, et al. Slow rewarming improves jugular venous oxygen saturation during rewarming. Acta Anaesthesiol Scand. 2003;47(4):419-424. (Prospective, randomized, controlled; 100 patients) 122. Polderman KH, Peerdeman SM, Girbes AR. Hypophosphatemia and hypomagnesemia induced by cooling in patients with severe head injury. J Neurosurg. 2001;94(5):697-705. doi:10.3171/jns.2001.94.5.0697. (Prospective observational; 41 patients) CME Questions Take This Test Online! Current subscribers receive CME credit absolutely free by completing the following test. Monthly on line testing is now available for current and archived issues. Visit http://www.ebmedicine.net/CME Take This Test Online! today to receive your free CME credits. Each issue includes 4 AMA PRA Category 1 CreditsTM, 4 ACEP Category 1 credits, 4 AAFP Prescribed credits, and 4 AOA Category 2A or 2B credits. 21 Emergency Medicine Practice © 2011 1. Emergency medical services are critical in the care of a patient with an out-of-hospital cardiac arrest. They also contribute to hypothermia therapy in all of the following ways EXCEPT: a. Administering cooled saline by placing ice packs to start the cooling process b. Documenting the time frame of arrest as well as the presenting rhythms c. Controlling the patient’s airway with intubation d. Administering paralytic agents to treat shivering 4. Cardiac arrhythmias always require intervention. a. True b. False 5. The ideal placement for the temperature probe of common commercial cooling systems is where changes in core temperature can be sensed most quickly. What is the best anatomic location for probe placement? a. Rectum b. Axilla c. Oropharynx d. Esophagus e. Forehead 2. A patient is transported to the ED in cardiac arrest. Compressions have been in progress for approximately 15 minutes, starting immediately after EMS arrival. Return of spontaneous circulation is soon attained, and the patient is comatose, with a GCS score of 3. The first blood pressure reading is 64/22 mm Hg by arterial line. Pressors are initiated; however, after several liters of fluid, high-dose norepinephrine, and a vasopressin drip, the patient’s MAP is 55 mm Hg. Therapeutic hypothermia should not be initiated for which of the following reasons? a. The patient’s initial GCS score is a negative prognostic sign so soon after ROSC. b. Multiple vasopressors have failed to maintain a MAP greater than 65 mm Hg. c. The time from arrest to initiation of compressions cannot be established. d. The patient has an arterial line that may be a significant source of bleeding during cooling. e. The etiology of the arrest cannot be determined. 6. Which of the following procedures are contraindicated during therapeutic hypothermia? a. Arterial line placement b. Central venous catheter placement c. Thoracostomy d. Lumbar puncture e. None of the above 7. Although most common during the induction phase, shivering is possible during any period of therapeutic hypothermia. a. True b. False 8. Which of the following medications is effective at mitigating or terminating the shivering response? a. Magnesium b. Meperidine c. Fentanyl d. Propofol e. All of the above 3. Which of the following statements best describes alterations in blood gas readings caused by measurements at lower temperatures? a. The partial pressure of O2 will be falsely elevated, while the partial pressure of CO2 will be given accurately secondary to the decrease in overall metabolism. b. The partial pressure values will be falsely elevated by 5 mm Hg for every 1°C below 37°C. c. The partial pressure of CO2 will be falsely elevated, while the partial pressure of O2 will be given accurately secondary to the decrease in overall metabolism. d. The partial pressure values will be falsely elevated by 20 mm Hg for every 1°C below 37°C. e. All blood gas readings are accurate when reported at normal temperatures and do not require any correction. Emergency Medicine Practice © 2011 9. All of the following statements regarding the rewarming process are true EXCEPT: a. Passive rewarming is allowed once the patient’s temperature has reached 36°C (97°F). b. Rewarming may cause massive shifts of potassium out of cells, creating a dangerous level of hyperkalemia. c. Rewarming must take place at the relatively slow pace of no more than 1°C (2°F) per hour. d. After rewarming, hyperthermia poses no risk to the patient as he or she has already been exposed to the protective effects of the therapy. 22 EBMedicine.net • April 2011 Want 3 FREE issues added to your subscription? Receiving a FREE 3-issue extension on your Emergency Medicine Practice subscription is easy! Simply recommend Emergency Medicine Practice to a colleague and ask them to mention your name when they call to subscribe. 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Date of Original Release: April 1, 2011. Date of most recent review: March 10, 2011. Termination date: April 1, 2014. Accreditation: EB Medicine is accredited by the ACCME to provide continuing medical education for physicians. Credit Designation: EB Medicine designates this enduring material for a maximum of 4 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. ACEP Accreditation: Emergency Medicine Practice is approved by the American College of Emergency Physicians for 48 hours of ACEP Category 1 credit per annual subscription. AAFP Accreditation: Emergency Medicine Practice has been reviewed and is acceptable for up to 48 Prescribed credits per year by the American Academy of Family Physicians. AAFP Accreditation begins July 31, 2010. Term of approval is for 1 year from this date. Each issue is approved for 4 Prescribed credits. Credits may be claimed for 1 year from the date of each issue. 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In This Month’s Pediatric Emergency Medicine Practice An Evidence-Based Assessment Of Pediatric Endocrine Emergencies by Wesley Eilbert, MD, FACEP, FAAP Associate Professor of Emergency Medicine and Pediatrics, Assistant Chair for Pediatrics, Emergency Medicine Department Chief, Pediatric Emergency Medicine Division Medical Director, Pediatric Emergency Department, University of Florida Health Science Center, Jacksonville, FL Most emergency clinicians are quite comfortable treating diabetic ketoacidosis in children, but other rarer endocrine disorders in this population are likely to cause anxiety in even the most well-read ED clinician. In addition to their complex pathophysiologies, these disorders present with an array of nonspecific complaints — the most ominous of which is an altered mental status. This issue of Pediatric Emergency Medicine Practice reviews the diagnosis and manage ment of these uncommon disorders, which, if left untreated, can cause significant morbidity. 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Emergency Medicine Practice © 2011 24 EBMedicine.net • April 2011 Pt Name: MSSM ED Critical Care Induced Hypothermia Protocol Date: Time of Screening: : MRN: Place Sticker Your Name: Inclusion Criteria (Must have All) Exclusion Criteria � Post Cardiac Arrest (Any rhythm as cause of arrest is eligible) � ROSC < 30 min from EMS/Code Team Arrival � Time now <6 hrs from ROSC � Comatose (Does not follow commands) � MAP > 65 on no more than one vasopressor � Pt has DNR, MOLST, poor baseline status, or terminal disease � Active or Intracranial Bleeding � Traumatic etiology for arrest � Cryoglobulinemia � Pregnancy (Relative-Consider OB/Gyn consult) � Recent Major Surgery (Relative) � Severe Sepsis/Septic Shock as cause of Arrest (Relative) Neurologic Exam Eye Opening Spontaneous --------*� 4 Voice ----------------- � 3 Pain ------------------ � 2 None ----------------- � 1 Verbal Motor Oriented -------------*� 5 Obeys ----------------*� 6 Confused ------------*� 4 Localizes ------------ � 5 Inappropriate ------- � 3 Withdraws ---------- � 4 Sounds --------------- � 2 Decorticate ---------- � 3 None ----------------- � 1 Decerebrate --------- � 2 Intubated ------------ � 1 None ----------------- � 1 DTRs: Bicep L R Knee L R List any Sedatives or Paralytics On-Board at time of Exam: Brainstem Pupils React Corneal Spont. Resps Doll’s Eyes Toes L � yes � no � yes � no � yes � no � yes � no R If any Starred (*) Item is checked off on the neuro exam, the patient is ineligible for the protocol. Protocol •If there is a question regarding eligibility, discuss Case with the ICU Fellow or Attending : •Time of Discussion: If pt is deemed ineligible by ICU, list reason: •List Initial Arrest Rhythm: List Number of Minutes from Start of CPR to ROSC: •Send blood for: CMP, LFTs, Superstat I, Lactate, CBC, PT/PTT, CK/MB/Troponin, Lipase/Amylase •Completely expose patient and place cooling blanket above and below with nothing between blanket & skin. •Place temp probe in mid-esophagus (~4 cm above xiphoid via oral/nasal); if unable to place in esophagus, probe can be placed rectally (5 cm) •Hook both cooling blankets and the probe to the same blanketrol machine. •Set temperature to 33º C and Set the machine to “Auto Control”. : List Initial Patient Temperature: °C •List time Now (Starting Protocol): •If initial temperature is < 33º C, allow patient to warm to 33º C. •Begin opioids & sedation protocol (See page 3). Titrate to RASS Score -3/-4 (Ramsay Score 4/5 in the ICU). •Infuse refrigerated crystalloid, preferably through large bore, peripheral IV. Administer at ~100 ml per minute using pressure bag (evacuate air first). Maximum initial infusion is 30 cc/kg; if patient not < 34º C after this amount, wait 15 minutes before giving further 250 cc boluses Q 10 minutes. •Administer Tylenol 650 mg GT Q 6 hours unless pt has allergy. •If during induction, pt has shivering unrelieved by the above meds, Vecuronium 0.1 mg/kg x1 can be used : •Total Cold Crystalloid Infused: Time that Pt reaches 34º C: •If patient’s temperature rises above 34º C, infuse 250 cc boluses of cold crystalloid Q 10 min until <34º C. •Assess for shivering Q 15 minutes. If any signs of shivering, see the protocol on page 5. •Maintain temperature 32-34º C for 24 hours (ideal temperature is 33º C). •If significant bleeding or severe hemodynamic instability, consider rewarming. See ehced.org for protocol. : •Time of Rewarming: Reason Necessary: •Maintain MAP>80: Multiple Pressors and/or Dobutamine may be used during protocol, if fluid loading ineffective. Protocol provided by Scott D. Weingart, MD FACEP; Director, Division of ED Critical Care, Mount Sinai School of Medicine, New York, NY. Protected by Creative Commons BY-NC-SA 3.0 license. This protocol is for informational purposes only; check all recommendations and adapt to your individual institution. 4/3/09 Scan this worksheet when pt’s bed is ready and Give Original to ICU Resident MSSM ED Critical Care Post-ROSC Care Package Induction of Hypothermia See First Page Procedures • • • • Full sterile neck line with CVP monitoring Full sterile femoral arterial line (Axillary if femoral contraindicated/unsuccessful) Foley Catheter with hourly urine monitoring Orogastric Tube on suction Ventilation • • • • • • • • Place patient on AC Mode Set Vt to 8 ml/kg Ideal Body Weight (see last page) Set IFR to 60 lpm Set Initial rate to 18 bpm Set Initial O2 to 50% Titrate FiO2/PEEP to achieve corrected ABG Saturation 94-96%. Often pulse ox will not read well due to peripheral vasoconstriction Send an ABG, DO NOT INDICATE THE PATIENT’S TEMPERATURE ON THE ABG ORDER Hemodynamic Goals • Ensure Adequate Preload Assess by passive leg raise, pulse pressure variation, and echo. CVP may provide some indication if very low. Use normal saline, lactated ringers, or isolyte boluses. Use room temperature fluid if patient at goal temperature. Replace patient’s urine losses 1:1 • MAP > 65 at all times, MAP > 80 is preferred to augment cerebral perfusion Preferred initial pressor is norepinephrine, may add vasopressin if necessary If MAP is < 80 and CVP > 10 perform passive straight leg raise to assess fluid responsiveness. If MAP > 100, start nitroglycerin infusion • Corrected ScvO2 > 70 Can be measured by PreSEP catheter or central venous O2 saturation (send blood gas as mixed venous) If ScvO2 < 70 and HB < 7 (some would advocate <10 as trigger), transfuse patient If HB > 7, evaluate echocardiogram and consider inotropes vs. balloon pump/revascularization • Lactate Hypothermia will raise lactate levels and post-arrest patients will have high lactate. Send a baseline level after the patient achieves goal temperature. From this point on, the lactate should stay the same or drop. If lactate is increasing, the patient is under-resuscitated or seizing Cardiac Testing • Get EKG immediately upon arrival; at the start of hypothermia induction; and Q 1 hour for the first 4 hours • If possible, get a bedside transthoracic echo at the start of induction. In the ED, this should be performed by the emergency physician or cardiology. Look specifically for qualitative LV function, RV function, pericardial effusion/ tamponade, & gross valve function Protocol provided by Scott D. Weingart, MD FACEP; Director, Division of ED Critical Care, Mount Sinai School of Medicine, New York, NY. Protected by Creative Commons BY-NC-SA 3.0 license. This protocol is for informational purposes only; check all recommendations and adapt to your individual institution. 2 MSSM ED Critical Care Post-ROSC Care Package Sedation & Pain Control • • • • To gain the full benefits of hypothermia, it is imperative that the patient is adequately sedated Optimize fentanyl infusion rate first Add on propofol or dexmedetomidine if necessary Titrate to RASS Score -3/-4 (Ramsay Score of 4/5 if in the ICU) Richmond Agitation Sedation Scale (RASS) * Richmond Agitation Sedation Scale (RASS) Score Term Description +4 Combative Overtly combative, violent, immediate danger to staff +3 Very agitated Pulls or removes tube(s) or catheter(s); aggressive +2 Agitated Frequent non-purposeful movement, fights ventilator +1 Restless Anxious but movements not aggressive vigorous 0 Alert and calm -1 Drowsy Not fully alert, but has sustained awakening (eye-opening/eye contact) to voice (>10 seconds) -2 Light sedation Briefly awakens with eye contact to voice (<10 seconds) -3 Moderate sedation Movement or eye opening to voice (but no eye contact) -4 Deep sedation No response to voice, but movement or eye opening to physical stimulation -5 Unarousable No response to voice or physical stimulation Verbal Stimulation Physical Stimulation Procedure for RASS Assessment Labs1. &Observe Electrolytes patient • • • • • • • • • Send Superstat (ABGrestless, with Electrolytes) 4 hours, a. Patient isI alert, or agitated. and Lactate Q 1 hour for first (score 0 to +4)then Q 4 hours On2.arrival, send state CMP,patient’s CBC, Lytes, Lipase, Cardiac Enzymes, Type and Hold, & Pan-Cultures If not alert, namePT/PTT, and say to open eyes and look at speaker. Send CMP (complete metabolic panel) and CBC Q 4 hours b. Patient awakens with sustained eye opening and eye contact. (score –1) Send Cardiac Enzymes Q 6 hours Patient awakens with eye opening eyewith contact, but not sustained. (score –2) Keep c. Magnesium at high-normal at alland times aggressive IV repletion Replete Potassium if <movement 3.4 with IV KCl d. Patient has any in response to voice but no eye contact. (score –3) Keep iCal at high normal at all times 3. When no response to verbal stimulation, physically stimulate patient by Keep shaking Sodiumshoulder at least and/or 140 atrubbing all times, 150 is preferable sternum. Keep e. Glucose < 150 with Insulin Drip (preferred) or Subcutaneous Regular Insulin Patient has any movement to physical stimulation. (score –4) (score –5) f. Patient has no response to any stimulation. DVT Prophylaxis • If no contraindication, Heparin 5000 units subcutaneous Q 8 hours * Sessler CN, Gosnell M, Grap MJ, Brophy GT, O'Neal PV, Keane KA et al. The Richmond AgitationStress Ulcer Sedation Scale: Prophylaxis validity and reliability in adult intensive care patients. Am J Respir Crit Care Med 2002; 166:1338-1344. • Nexium 40 mg IVSS x 1 * Ely EW, Truman B, Shintani A, Thomason JWW, Wheeler AP, Gordon S et al. Monitoring sedation status over time in ICU patients: the reliability and validity of the Richmond Agitation Sedation Scale (RASS). VAP Prophylaxis JAMA 2003; 289:2983-2991. • Head of bed to 30° • Place in-line closed suction and perform aggressive pulmonary toilet Protocol provided by Scott D. Weingart, MD FACEP; Director, Division of ED Critical Care, Mount Sinai School of Medicine, New York, NY. Protected by Creative Commons BY-NC-SA 3.0 license. This protocol is for informational purposes only; check all recommendations and adapt to your individual institution. 3 MSSM ED Critical Care Post-ROSC Care Package Additional Testing • Consider Head CT if possible neurologic cause to arrest. Note: even an intracranial bleed is not a contra-indication to continuation of induced hypothermia. Consider letting the patient drift to 34°C and administration of dDAVP. • If there is a question of brain death, consider a CTA of the brain to assess for flow. • Consider CTA Chest if there is a strong suspicion of PE as the cause of arrest. Bedside dopplers by EP or sono technician may be a good first step • EEG if seizures (convulsive or non-convulsive) are suspected Revascularization for STEMI • PCI is preferred, consult with CPORT fellow/attending and CCU fellow. Hypothermia does not need to be discontinued for PCI. • If PCI is not available or will be delayed, thrombolysis should be administered. Thrombolysis can be given during hypothermia. CPR performed prior to ROSC should not stop reperfusion therapy. Use standard doses of Retevase. Consult with CPORT fellow/attending. Transport to radiology or ICU • Disconnect the hypothermia machine and leave the blankets and temperature probe in place. • If the patient returns to the ED, hook the machine back up. • If the patient’s temperture is >34.5, infuse 250 cc boluses of cold crystalloid Q 10 min until <34° C Protocol provided by Scott D. Weingart, MD FACEP; Director, Division of ED Critical Care, Mount Sinai School of Medicine, New York, NY. Protected by Creative Commons BY-NC-SA 3.0 license. This protocol is for informational purposes only; check all recommendations and adapt to your individual institution. 4