Post–Cardiac Arrest Syndrome

Abstract

HomeCirculationVol. 118, No. 23Post–Cardiac Arrest Syndrome Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReview ArticlePDF/EPUBPost–Cardiac Arrest SyndromeEpidemiology, Pathophysiology, Treatment, and Prognostication A Consensus Statement From the International Liaison Committee on Resuscitation (American Heart Association, Australian and New Zealand Council on Resuscitation, European Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Asia, and the Resuscitation Council of Southern Africa); the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; and the Stroke Council Robert W. Neumar, MD, PhD, Jerry P. Nolan, FRCA, FCEM, Christophe Adrie, MD, PhD, Mayuki Aibiki, MD, PhD, Robert A. Berg, MD, FAHA, Bernd W. Böttiger, MD, DEAA, Clifton Callaway, MD, PhD, Robert S.B. Clark, MD, Romergryko G. Geocadin, MD, Edward C. Jauch, MD, MS, Karl B. Kern, MD, Ivan Laurent, MD, W.T. LongstrethJr, MD, MPH, Raina M. Merchant, MD, Peter Morley, MBBS, FRACP, FANZCA, FJFICM, Laurie J. Morrison, MD, MSc, Vinay Nadkarni, MD, FAHA, Mary Ann Peberdy, MD, FAHA, Emanuel P. Rivers, MD, MPH, Antonio Rodriguez-Nunez, MD, PhD, Frank W. Sellke, MD, Christian Spaulding, MD, Kjetil Sunde, MD, PhD and Terry Vanden Hoek, MD Robert W. NeumarRobert W. Neumar Search for more papers by this author , Jerry P. NolanJerry P. Nolan Search for more papers by this author , Christophe AdrieChristophe Adrie Search for more papers by this author , Mayuki AibikiMayuki Aibiki Search for more papers by this author , Robert A. BergRobert A. Berg Search for more papers by this author , Bernd W. BöttigerBernd W. Böttiger Search for more papers by this author , Clifton CallawayClifton Callaway Search for more papers by this author , Robert S.B. ClarkRobert S.B. Clark Search for more papers by this author , Romergryko G. GeocadinRomergryko G. Geocadin Search for more papers by this author , Edward C. JauchEdward C. Jauch Search for more papers by this author , Karl B. KernKarl B. Kern Search for more papers by this author , Ivan LaurentIvan Laurent Search for more papers by this author , W.T. LongstrethJrW.T. LongstrethJr Search for more papers by this author , Raina M. MerchantRaina M. Merchant Search for more papers by this author , Peter MorleyPeter Morley Search for more papers by this author , Laurie J. MorrisonLaurie J. Morrison Search for more papers by this author , Vinay NadkarniVinay Nadkarni Search for more papers by this author , Mary Ann PeberdyMary Ann Peberdy Search for more papers by this author , Emanuel P. RiversEmanuel P. Rivers Search for more papers by this author , Antonio Rodriguez-NunezAntonio Rodriguez-Nunez Search for more papers by this author , Frank W. SellkeFrank W. Sellke Search for more papers by this author , Christian SpauldingChristian Spaulding Search for more papers by this author , Kjetil SundeKjetil Sunde Search for more papers by this author and Terry Vanden HoekTerry Vanden Hoek Search for more papers by this author Originally published23 Oct 2008https://doi.org/10.1161/CIRCULATIONAHA.108.190652Circulation. 2008;118:2452–2483Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: October 23, 2008: Previous Version 1 I. Consensus ProcessThe contributors to this statement were selected to ensure expertise in all the disciplines relevant to post–cardiac arrest care. In an attempt to make this document universally applicable and generalizable, the authorship comprised clinicians and scientists who represent many specialties in many regions of the world. Several major professional groups whose practice is relevant to post–cardiac arrest care were asked and agreed to provide representative contributors. Planning and invitations took place initially by e-mail, followed a series of telephone conferences and face-to-face meetings of the cochairs and writing group members. International writing teams were formed to generate the content of each section, which corresponded to the major subheadings of the final document. Two team leaders from different countries led each writing team. Individual contributors were assigned by the writing group cochairs to work on 1 or more writing teams, which generally reflected their areas of expertise. Relevant articles were identified with PubMed, EMBASE, and an American Heart Association EndNote master resuscitation reference library, supplemented by hand searches of key papers. Drafts of each section were written and agreed on by the writing team authors and then sent to the cochairs for editing and amalgamation into a single document. The first draft of the complete document was circulated among writing team leaders for initial comment and editing. A revised version of the document was circulated among all contributors, and consensus was achieved before submission of the final version for independent peer review and approval for publication.II. BackgroundThis scientific statement outlines current understanding and identifies knowledge gaps in the pathophysiology, treatment, and prognosis of patients who regain spontaneous circulation after cardiac arrest. The purpose is to provide a resource for optimization of post–cardiac arrest care and to pinpoint the need for research focused on gaps in knowledge that would potentially improve outcomes of patients resuscitated from cardiac arrest.Resumption of spontaneous circulation (ROSC) after prolonged, complete, whole-body ischemia is an unnatural pathophysiological state created by successful cardiopulmonary resuscitation (CPR). In the early 1970s, Dr Vladimir Negovsky recognized that the pathology caused by complete whole-body ischemia and reperfusion was unique in that it had a clearly definable cause, time course, and constellation of pathological processes.1–3 Negovsky named this state “postresuscitation disease.” Although appropriate at the time, the term “resuscitation” is now used more broadly to include treatment of various shock states in which circulation has not ceased. Moreover, the term “postresuscitation” implies that the act of resuscitation has ended. Negovsky himself stated that a second, more complex phase of resuscitation begins when patients regain spontaneous circulation after cardiac arrest.1 For these reasons, we propose a new term: “post–cardiac arrest syndrome.”The first large multicenter report on patients treated for cardiac arrest was published in 1953.4 The in-hospital mortality rate for the 672 adults and children whose “heart beat was restarted” was 50%. More than a half-century later, the location, cause, and treatment of cardiac arrest have changed dramatically, but the overall prognosis after ROSC has not improved. The largest modern report of cardiac arrest epidemiology was published by the National Registry of Cardiopulmonary Resuscitation (NRCPR) in 2006.5 Among the 19 819 adults and 524 children who regained any spontaneous circulation, in-hospital mortality rates were 67% and 55%, respectively. In a recent study of 24 132 patients in the United Kingdom who were admitted to critical care units after cardiac arrest, the in-hospital mortality rate was 71%.6In 1966, the National Academy of Sciences–National Research Council Ad Hoc Committee on Cardiopulmonary Resuscitation published the original consensus statement on CPR.7 This document described the original ABCDs of resuscitation, in which A represents airway; B, breathing; C, circulation; and D, definitive therapy. Definitive therapy includes not only the management of pathologies that cause cardiac arrest but also those that result from cardiac arrest. Post–cardiac arrest syndrome is a unique and complex combination of pathophysiological processes, which include (1) post–cardiac arrest brain injury, (2) post–cardiac arrest myocardial dysfunction, and (3) systemic ischemia/reperfusion response. This state is often complicated by a fourth component: the unresolved pathological process that caused the cardiac arrest. A growing body of knowledge suggests that the individual components of post–cardiac arrest syndrome are potentially treatable. The first intervention proved to be clinically effective is therapeutic hypothermia.8,9 These studies provide the essential proof of concept that interventions initiated after ROSC can improve outcome.Several barriers impair implementation and optimization of post–cardiac arrest care. Post–cardiac arrest patients are treated by multiple teams of providers both outside and inside the hospital. Evidence exists of considerable variation in post–cardiac arrest treatment and patient outcome between institutions.10,11 Therefore, a well-thought-out multidisciplinary approach for comprehensive care must be established and executed consistently. Such protocols have already been shown to improve outcomes at individual institutions compared with historical controls.12–14 Another potential barrier is the limited accuracy of early prognostication. Optimized post–cardiac arrest care is resource intensive and should not be continued when the effort is clearly futile; however, the reliability of early prognostication (<72 hours after arrest) remains limited, and the impact of emerging therapies (eg, hypothermia) on accuracy of prognostication has yet to be elucidated. Reliable approaches must be developed to avoid premature prognostication of futility without creating unreasonable hope for recovery or consuming healthcare resources inappropriately.The majority of research on cardiac arrest over the past half-century has focused on improving the rate of ROSC, and significant progress has been made; however, many interventions improve ROSC without improving long-term survival. The translation of optimized basic life support and advanced life support interventions into the best possible outcomes is contingent on optimal post–cardiac arrest care. This requires effective implementation of what is already known and enhanced research to identify therapeutic strategies that will give patients who are resuscitated from cardiac arrest the best chance for survival with good neurological function.III. Epidemiology of Post–Cardiac Arrest SyndromeThe tradition in cardiac arrest epidemiology, based largely on the Utstein consensus guidelines, has been to report percentages of patients who survive to sequential end points such as ROSC, hospital admission, hospital discharge, and various points thereafter.15,16 Once ROSC is achieved, however, the patient is technically alive. A more useful approach to the study of post–cardiac arrest syndrome is to report deaths during various phases of post–cardiac arrest care. In fact, this approach reveals that rates of early mortality in patients achieving ROSC after cardiac arrest vary dramatically between studies, countries, regions, and hospitals.10,11 The cause of these differences is multifactorial but includes variability in patient populations, reporting methods, and, potentially, post–cardiac arrest care.10,11Epidemiological data on patients who regain spontaneous circulation after out-of-hospital cardiac arrest suggest regional and institutional variation in in-hospital mortality rates. During the advanced life support phase of the Ontario Prehospital Advanced Life Support Trial (OPALS), 766 patients achieved ROSC after out-of-hospital cardiac arrest.17 In-hospital mortality rates were 72% for patients with ROSC and 65% for patients admitted to the hospital. Data from the Canadian Critical Care Research Network indicate a 65% in-hospital mortality rate for 1483 patients admitted to the intensive care unit (ICU) after out-of-hospital arrest.18 In the United Kingdom, 71.4% of 8987 patients admitted to the ICU after out-of-hospital cardiac arrest died before being discharged from the hospital.6 In-hospital mortality rates for patients with out-of-hospital cardiac arrest who were taken to 4 different hospitals in Norway averaged 63% (range 54% to 70%) for patients with ROSC, 57% (range 56% to 70%) for patients who arrived in the emergency department with a pulse, and 50% (range 41% to 62%) for patients admitted to the hospital.10 In Sweden, the 1-month mortality rate for 3853 patients admitted with a pulse to 21 hospitals after out-of-hospital cardiac arrest ranged from 58% to 86%.11 In Japan, 1 study reported that patients with ROSC after witnessed out-of-hospital cardiac arrest of presumed cardiac origin had an in-hospital mortality rate of 90%.19 Among 170 children with ROSC after out-of-hospital cardiac arrest, the in-hospital mortality rate was 70% for those with any ROSC, 69% for those with ROSC >20 minutes, and 66% for those admitted to the hospital.20 In a comprehensive review of nontraumatic out-of-hospital cardiac arrest in children, the overall rate of ROSC was 22.8%, and the rate of survival to discharge was 6.7%, which resulted in a calculated post-ROSC mortality rate of 70%.21The largest published in-hospital cardiac arrest database (the NRCPR) includes data from >36 000 cardiac arrests.5 Recalculation of the results of this report reveals that the in-hospital mortality rate was 67% for the 19 819 adults with any documented ROSC, 62% for the 17 183 adults with ROSC >20 minutes, 55% for the 524 children with any documented ROSC, and 49% for the 460 children with ROSC >20 minutes. It seems intuitive to expect that advances in critical care over the past 5 decades would result in improvements in rates of hospital discharge after initial ROSC; however, epidemiological data to date fail to support this view.Some variability between individual reports may be attributed to differences in the numerator and denominator used to calculate mortality. For example, depending on whether ROSC is defined as a brief (approximately >30 seconds) return of pulses or spontaneous circulation sustained for >20 minutes, the denominator used to calculate postresuscitation mortality rates will differ greatly.15 Other denominators include sustained ROSC to the emergency department or hospital/ICU admission. The lack of consistently defined denominators precludes comparison of mortality among a majority of the studies. Future studies should use consistent terminology to assess the extent to which post–cardiac arrest care is a contributing factor.The choice of denominator has some relationship to the site of post–cardiac arrest care. Patients with fleeting ROSC are affected by interventions that are administered within seconds or minutes, usually at the site of initial collapse. Patients with ROSC that is sustained for >20 minutes receive care during transport or in the emergency department before hospital admission. Perhaps it is more appropriate to look at mortality rates for out-of-hospital (or immediate post-ROSC), emergency department, and ICU phases separately. A more physiological approach would be to define the phases of post–cardiac arrest care by time rather than location. The immediate postarrest phase could be defined as the first 20 minutes after ROSC. The early postarrest phase could be defined as the period between 20 minutes and 6 to 12 hours after ROSC, when early interventions might be most effective. An intermediate phase might be between 6 to 12 hours and 72 hours, when injury pathways are still active and aggressive treatment is typically instituted. Finally, a period beyond 3 days could be considered the recovery phase, when prognostication becomes more reliable and ultimate outcomes are more predictable (Figure). For both epidemiological and interventional studies, the choice of denominator should reflect the phases of post–cardiac arrest care that are being studied. Download figureDownload PowerPointFigure. Phases of post–cardiac arrest syndrome.Beyond reporting post–cardiac arrest mortality rates, epidemiological data should define the neurological and functional outcomes of survivors. The updated Utstein reporting guidelines list cerebral performance category (CPC) as a core data element.15 For example, examination of the latest NRCPR database report reveals that 68% of 6485 adults and 58% of 236 children who survived to hospital discharge had a good outcome, defined as CPC 1 (good cerebral performance) or CPC 2 (moderate cerebral disability). In one study, 81% of 229 out-of-hospital cardiac arrest survivors were categorized as CPC 1 to 2, although this varied between 70% and 90% in the 4 hospital regions.10 In another study, 75% of 51 children who survived out-of-hospital cardiac arrest had either pediatric CPC 1 to 2 or returned to their baseline neurological state.20 The CPC is an important and useful outcome tool, but it lacks the sensitivity to detect clinically significant differences in neurological outcome. The report of the recent Utstein consensus symposium on post–cardiac arrest care research anticipates more refined assessment tools, including tools that evaluate quality of life.16Two other factors related to survival after initial ROSC are limitations set on subsequent resuscitation efforts and the timing of withdrawal of therapy. The perception of a likely adverse outcome (correct or not) may well create a self-fulfilling prophecy. The timing of withdrawal of therapy is poorly documented in the resuscitation literature. Data from the NRCPR on in-hospital cardiac arrest indicate that “do not attempt resuscitation” (DNAR) orders were given for 63% of patients after the index event, and in 43% of these, life support was withdrawn.22 In the same report, the median survival time of patients who died after ROSC was 1.5 days, long before futility could be accurately prognosticated in most cases. Among 24 132 comatose survivors of either in- or out-of-hospital cardiac arrest who were admitted to critical care units in the United Kingdom, treatment was withdrawn in 28.2% at a median of 2.4 days (interquartile range 1.5 to 4.1 days).6 The reported incidence of inpatients with clinical brain death and sustained ROSC after cardiac arrest ranges from 8% to 16%.22,23 Although this is clearly a poor outcome, these patients can and should be considered for organ donation. A number of studies have reported no difference in transplant outcomes whether the organs were obtained from appropriately selected post–cardiac arrest patients or from other brain-dead donors.23–25 Non–heart-beating organ donation has also been described after failed resuscitation attempts after in- and out-of-hospital cardiac arrest,26,27 but these have generally been cases in which sustained ROSC was never achieved. The proportion of cardiac arrest patients dying in the critical care unit and who might be suitable non–heart-beating donors has not been documented.Despite variability in reporting techniques, surprisingly little evidence exists to suggest that the in-hospital mortality rate of patients who achieve ROSC after cardiac arrest has changed significantly in the past half-century. To minimize artifactual variability, epidemiological and interventional post–cardiac arrest studies should incorporate well-defined standardized methods to calculate and report mortality rates at various stages of post–cardiac arrest care, as well as long-term neurological outcome.16 Overriding these issues is a growing body of evidence that post–cardiac arrest care impacts mortality rate and functional outcome.IV. Pathophysiology of Post–Cardiac Arrest SyndromeThe high mortality rate of patients who initially achieve ROSC after cardiac arrest can be attributed to a unique pathophysiological process that involves multiple organs. Although prolonged whole-body ischemia initially causes global tissue and organ injury, additional damage occurs during and after reperfusion.28,29 The unique features of post–cardiac arrest pathophysiology are often superimposed on the disease or injury that caused the cardiac arrest, as well as underlying comorbidities. Therapies that focus on individual organs may compromise other injured organ systems. The 4 key components of post–cardiac arrest syndrome are (1) post–cardiac arrest brain injury, (2) post–cardiac arrest myocardial dysfunction, (3) systemic ischemia/reperfusion response, and (4) persistent precipitating pathology (Table 1). The severity of these disorders after ROSC is not uniform and will vary in individual patients based on the severity of the ischemic insult, the cause of cardiac arrest, and the patient’s prearrest state of health. If ROSC is achieved rapidly after onset of cardiac arrest, the post–cardiac arrest syndrome will not occur. Table 1. Post–Cardiac Arrest Syndrome: Pathophysiology, Clinical Manifestations, and Potential TreatmentsSyndromePathophysiologyClinical ManifestationPotential TreatmentsAMI indicates acute myocardial infarction; ACS, acute coronary syndrome; IABP, intra-aortic balloon pump; LVAD, left ventricular assist device; EMCO, extracorporeal membrane oxygenation; COPD, chronic obstructive pulmonary disease; CNS, central nervous system; CVA, cerebrovascular accident; PE, pulmonary embolism; and PCAS, post–cardiac arrest syndrome.Post–cardiac arrest brain injury• Impaired cerebrovascular autoregulation• Coma• Therapeutic hypothermia177• Seizures• Early hemodynamic optimization• Cerebral edema (limited)• Myoclonus• Postischemic neurodegeneration• Cognitive dysfunction• Airway protection and mechanical ventilation• Persistent vegetative state• Secondary Parkinsonism• Seizure control• Cortical stroke• Controlled reoxygenation (Sao2 94% to 96%)• Spinal stroke• Brain death• Supportive carePost–cardiac arrest myocardial dysfunction• Global hypokinesis (myocardial stunning)• Reduced cardiac output• Early revascularization of AMI171, 373• Hypotension• ACS• Dysrhythmias• Early hemodynamic optimization• Cardiovascular collapse• Intravenous fluid97• Inotropes97• IABP13,160• LVAD161• ECMO361Systemic ischemia/reperfusion response• Systemic inflammatory response syndrome• Ongoing tissue hypoxia/ischemia• Early hemodynamic optimization• Hypotension• Impaired vasoregulation• Cardiovascular collapse• Intravenous fluid• Increased coagulation• Pyrexia (fever)• Vasopressors• Adrenal suppression• Hyperglycemia• High-volume hemofiltration374• Impaired tissue oxygen delivery and utilization• Multiorgan failure• Temperature control• Infection• Glucose control223,224• Impaired resistance to infection• Antibiotics for documented infectionPersistent precipitating pathology• Cardiovascular disease (AMI/ACS, cardiomyopathy)• Specific to cause but complicated by concomitant PCAS• Disease-specific interventions guided by patient condition and concomitant PCAS• Pulmonary disease (COPD, asthma)• CNS disease (CVA)• Thromboembolic disease (PE)• Toxicological (overdose, poisoning)• Infection (sepsis, pneumonia)• Hypovolemia (hemorrhage, dehydration)Post–Cardiac Arrest Brain InjuryPost–cardiac arrest brain injury is a common cause of morbidity and mortality. In 1 study of patients who survived to ICU admission but subsequently died in the hospital, brain injury was the cause of death in 68% after out-of-hospital cardiac arrest and in 23% after in-hospital cardiac arrest.30 The unique vulnerability of the brain is attributed to its limited tolerance of ischemia and its unique response to reperfusion. The mechanisms of brain injury triggered by cardiac arrest and resuscitation are complex and include excitotoxicity, disrupted calcium homeostasis, free radical formation, pathological protease cascades, and activation of cell-death signaling pathways.31–33 Many of these pathways are executed over a period of hours to days after ROSC. Histologically, selectively vulnerable neuron subpopulations in the hippocampus, cortex, cerebellum, corpus striatum, and thalamus degenerate over a period of hours to days.34–38 Both neuronal necrosis and apoptosis have been reported after cardiac arrest. The relative contribution of each cell-death pathway remains controversial, however, and is dependent in part on patient age and the neuronal subpopulation under examination.39–41 The relatively protracted duration of injury cascades and histological change suggests a broad therapeutic window for neuroprotective strategies after cardiac arrest.Prolonged cardiac arrest can also be followed by fixed or dynamic failure of cerebral microcirculatory reperfusion despite adequate cerebral perfusion pressure (CPP).42,43 This impaired reflow can cause persistent ischemia and small infarctions in some brain regions. The cerebral microvascular occlusion that causes the no-reflow phenomenon has been attributed to intravascular thrombosis during cardiac arrest and has been shown to be responsive to thrombolytic therapy in preclinical studies.44 The relative contribution of fixed no-reflow is controversial, however, and appears to be of limited significance in preclinical models when the duration of untreated cardiac arrest is <15 minutes.44,45 Serial measurements of regional cerebral blood flow (CBF) by stable xenon/computed tomography (CT) after 10.0 to 12.5 minutes of untreated cardiac arrest in dogs demonstrated dynamic and migratory hypoperfusion rather than fixed no-reflow.43,46 In the recent Thrombolysis in Cardiac Arrest (TROICA) trial, tenecteplase given to patients with out-of-hospital cardiac arrest of presumed cardiac origin did not increase 30-day survival compared with placebo (B.J.B., personal communication, February 26, 2008).Despite cerebral microcirculatory failure, macroscopic reperfusion is often hyperemic in the first few minutes after cardiac arrest because of elevated CPP and impaired cerebrovascular autoregulation.47,48 These high initial perfusion pressures can theoretically minimize impaired reflow.49 Yet, hyperemic reperfusion can potentially exacerbate brain edema and reperfusion injury. In 1 human study, hypertension (mean arterial pressure [MAP] >100 mm Hg) in the first 5 minutes after ROSC was not associated with improved neurological outcome, but MAP during the first 2 hours after ROSC was positively correlated with neurological outcome.50 Although resumption of oxygen and metabolic substrate delivery at the microcirculatory level is essential, a growing body of evidence suggests that too much oxygen during the initial stages of reperfusion can exacerbate neuronal injury through production of free radicals and mitochondrial injury (see section on oxygenation).51,52Beyond the initial reperfusion phase, several factors can potentially compromise cerebral oxygen delivery and possibly secondary injury in the hours to days after cardiac arrest. These include hypotension, hypoxemia, impaired cerebrovascular autoregulation, and brain edema; however, human data are limited to small case series. Autoregulation of CBF is impaired for some time after cardiac arrest. During the subacute period, cerebral perfusion varies with CPP instead of being linked to neuronal activity.47,48 In humans, in the first 24 to 48 hours after resuscitation from cardiac arrest, increased cerebral vascular resistance, decreased CBF, decreased cerebral metabolic rate of oxygen consumption (CMRO2), and decreased glucose consumption are present.53–56 Although the results of animal studies are contradictory in terms of the coupling of CBF and CMRO2 during this period,57,58 human data indicate that global CBF is adequate to meet oxidative metabolic demands.53,55 Improvement of global CBF during secondary delayed hypoperfusion using the calcium channel blocker nimodipine had no impact on neurological outcome in humans.56 These results do not rule out the potential presence of regional microcirculatory reperfusion deficits that have been observed in animal studies despite adequate CPP.43,46 Overall, it is likely that the CPP necessary to maintain optimal cerebral perfusion will vary among individual post–cardiac arrest patients at various time points after ROSC.Limited evidence is available that brain edema or elevated intracranial pressure (ICP) directly exacerbates post–cardiac arrest brain injury. Although transient brain edema is observed early after ROSC, most commonly after asphyxial cardiac arrest, it is rarely associated with clinically relevant increases in ICP.59–62 In contrast, delayed brain edema, occurring days to weeks after cardiac arrest, has been attributed to delayed hyperemia; this is more likely the consequence rather than the cause of severe ischemic neurodegeneration.60–62 No published prospective trials have examined the value of monitoring and managing ICP in post–cardiac arrest patients.Other factors that can impact brain injury after cardiac arrest are pyrexia, hyperglycemia, and seizures. In a small case series, patients with temperatures >39°C in the first 72 hours after out-of-hospital cardiac arrest had a significantly increased risk of brain death.63 When serial temperatures were monitored in 151 patients for 48 hours after out-of-hospital cardiac arrest, the risk of unfavorable outcome increased (odds ratio 2.3, 95% confidence interval [CI] 1.2 to 4.1) for every degree Celsius that the peak temperature exceeded 37°C.64 A subsequent multicenter retrospective study of patients admitted after out-of-hospital cardiac arrest reported that a maximal recorded temperature >37.8°C was associated with increased in-hospital mortality (odds ratio 2.7, 95% CI 1.2 to 6.3).10 Recent data demonstrating neuroprotection with therapeutic hypothermia further support the role of body temperature in the evolution of post–cardiac arrest brain injury.Hyperglycemia is common in p