ISSN: 1524-4539 Copyright ? 2005 American Heart Association. All rights reserved. Print ISSN: 0009-7322. Online 72514 Circulation is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX DOI: 10.1161/CIRCULATIONAHA.105.166560 2005;112;84-88; originally published online Nov 28, 2005; Circulation Part 7.5: Postresuscitation Support http://circ.ahajournals.org/cgi/content/full/112/24_suppl/IV-84 located on the World Wide Web at: The online version of this article, along with updated information and services, is http://www.lww.com/static/html/reprints.html Reprints: Information about reprints can be found online at journalpermissions@lww.com Street, Baltimore, MD 21202-2436. Phone 410-5280-4050. Fax: 410-528-8550. Email: Permissions: Permissions & Rights Desk, Lippincott Williams & Wilkins, 351 West Camden http://circ.ahajournals.org/subsriptions/ Subscriptions: Information about subscribing to Circulation is online at by on February 21, 2006 circ.ahajournals.orgDownloaded from Part 7.5: Postresuscitation Support F ew randomized controlled clinical trials deal specifically with supportive care following cardio-pulmonary- cerebral resuscitation (CPCR) from cardiac arrest. Neverthe- less, postresuscitation care has significant potential to im- prove early mortality caused by hemodynamic instability and multi-organ failure and later mortality/morbidity resulting from brain injury. 1 This section summarizes our evolving understanding of the hemodynamic, neurologic, and metabol- ic abnormalities encountered in patients who are resuscitated from cardiac arrest. Initial objectives of postresuscitation care are to ● Optimize cardiopulmonary function and systemic perfu- sion, especially perfusion to the brain ● Transport the victim of out-of-hospital cardiac arrest to the hospital emergency department (ED) and continue care in an appropriately equipped critical care unit ● Try to identify the precipitating causes of the arrest ● Institute measures to prevent recurrence ● Institute measures that may improve long-term, neurolog- ically intact survival Improving Postresuscitation Outcomes Postresuscitation care is a critical component of advanced life support. Patient mortality remains high after return of spon- taneous circulation (ROSC) and initial stabilization. Ultimate prognosis in the first 72 hours may be difficult to determine, 2 yet survivors of cardiac arrest have the potential to lead normal lives. 3–5 During postresuscitation care providers should (1) optimize hemodynamic, respiratory, and neuro- logic support; (2) identify and treat reversible causes of arrest; and (3) monitor temperature and consider treatment for disturbances of temperature regulation and metabolism. The first sections below discuss initial stabilization and tempera- ture/metabolic factors that may be relevant to improving postresuscitation outcome, particularly in the critically ill survivor. Subsequent sections highlight organ-specific eval- uation and support. Return of Spontaneous Circulation The principal objective of postresuscitation care is the re- establishment of effective perfusion of organs and tissue. After ROSC in the out-of-hospital or in-hospital setting, the provider must consider and treat the cause of the arrest and the consequences of any hypoxemic/ischemic/reperfusion injury. In most cases the acidemia associated with cardiac arrest improves spontaneously when adequate ventilation and perfusion are restored. But restoration of blood pressure and improvement in gas exchange do not ensure survival and functional recovery. Significant myocardial stunning and hemodynamic instability can develop, requiring vasopressor support. Most postresuscitation deaths occur during the first 24 hours. 6,7 Ideally the patient will be awake, responsive, and breathing spontaneously. Alternatively the patient may initially be comatose but have the potential for full recovery after postresuscitation care. 3 Indeed, up to 20% of initially coma- tose survivors of cardiac arrest have been reported to have good 1-year neurologic outcome. 8 The pathway to the best hospital postresuscitation care of all initial survivors is not completely known, but there is increasing interest in identi- fying and optimizing practices that can improve outcome. 9 Regardless of the patient’s initial status, the provider should support adequate airway and breathing, administer supple- mentary oxygen, monitor the patient’s vital signs, establish or verify existing intravenous access, and verify the function of any catheters in place. The clinician should assess the patient frequently and treat abnormalities of vital signs or cardiac arrhythmias and request studies that will further aid in the evaluation of the patient. It is important to identify and treat any cardiac, electrolyte, toxicologic, pulmonary, and neurologic precipi- tants of arrest. The clinician may find it helpful to review the H’s and T’s mnemonic to recall factors that may contribute to cardiac arrest or complicate resuscitation or postresuscitation care: hypovolemia, hypoxia, hydrogen ion (acidosis), hyper-/ hypokalemia, hypoglycemia, hypothermia; toxins, tamponade (cardiac), tension pneumothorax, thrombosis of the coronary or pulmonary vasculature, and trauma. For further informa- tion see Part 10: “Special Resuscitation Situations.” After initial assessment and stabilization of airway, venti- lation, and circulation, transfer the patient to a special care unit for observation, continuous monitoring, and further therapy. Personnel with appropriate training and resuscitation equipment must accompany the patient during transport to the special care unit. Temperature Regulation Induced Hypothermia Both permissive hypothermia (allowing a mild degree of hypothermia H1102233°C [91.5°F] that often develops spontane- ously after arrest) and active induction of hypothermia may play a role in postresuscitation care. In 2 randomized clinical trials (LOE 1 3 ; LOE 2 4 ) induced hypothermia (cooling within minutes to hours after ROSC) resulted in improved outcome in adults who remained comatose after initial resuscitation from out-of-hospital ventricular fibrillation (VF) cardiac ar- rest. Patients in the study were cooled to 33°C (91.5°F) 3 or to the range of 32°C to 34°C (89.6°F to 93.2°F) 4 for 12 to 24 hours. The Hypothermia After Cardiac Arrest (HACA) study 3 included a small subset of patients with in-hospital cardiac arrest. (Circulation. 2005;000:IV-84-IV-88.) ? 2005 American Heart Association. This special supplement to Circulation is freely available at http://www.circulationaha.org DOI: 10.1161/CIRCULATIONAHA.105.166560 IV-84 A third study (LOE 2) 10 documented improvement in metabolic end points (lactate and O 2 extraction) when coma- tose adult patients were cooled after ROSC from out-of- hospital cardiac arrest in which the initial rhythm was pulseless electrical activity (PEA)/asystole. In the HACA 3 and Bernard 4 studies, only about 8% of patients with cardiac arrest were selected for induced hypo- thermia (ie, patients were hemodynamically stable but coma- tose after a witnessed arrest of presumed cardiac etiology). This highlights the importance of identifying the subset of patients who may most benefit. Although the number of patients who may benefit from hypothermia induction is limited at present, it is possible that with more rapid and controlled cooling and better insights into optimal target temperature, timing, duration, and mechanism of action, such cooling may prove more widely beneficial in the future. 11 A recent multicenter study in asphyxiated neonates showed that hypothermia can be beneficial in another select population. 12 Complications associated with cooling can include coagu- lopathy and arrhythmias, particularly with an unintentional drop below target temperature. Although not significantly higher, cases of pneumonia and sepsis increased in the hypothermia-induction group. 3,4 Cooling may also increase hyperglycemia. 4 Most clinical studies of cooling have used external cooling techniques (eg, cooling blankets and frequent applications of ice bags) that may require a number of hours to attain target temperature. More recent studies 13 suggest that internal cool- ing techniques (eg, cold saline, endovascular cooling cathe- ter) can also be used to induce hypothermia. Providers should continuously monitor the patient’s temperature during cooling. 3,4 In summary, providers should not actively rewarm hemo- dynamically stable patients who spontaneously develop a mild degree of hypothermia (H1102233°C [91.5°F]) after resusci- tation from cardiac arrest. Mild hypothermia may be benefi- cial to neurologic outcome and is likely to be well tolerated without significant risk of complications. In a select subset of patients who were initially comatose but hemodynamically stable after a witnessed VF arrest of presumed cardiac etiology, active induction of hypothermia was beneficial. 3,4,13 Thus, unconscious adult patients with ROSC after out-of- hospital cardiac arrest should be cooled to 32°C to 34°C (89.6°F to 93.2°F) for 12 to 24 hours when the initial rhythm was VF (Class IIa). Similar therapy may be beneficial for patients with non-VF arrest out of hospital or for in-hospital arrest (Class IIb). Hyperthermia After resuscitation, temperature elevation above normal can create a significant imbalance between oxygen supply and demand that can impair brain recovery. Few studies (with either frequent use of antipyretics or “controlled normother- mia” with cooling techniques) have directly examined the effect of temperature control immediately after resuscitation. Because fever may be a symptom of brain injury, it may be difficult to control it with conventional antipyretics. Many studies of brain injury in animal models, however, show exacerbation of injury if body/brain temperature is increased during or after resuscitation from cardiac arrest. 14–17 More- over, several studies have documented worse neurologic outcome in humans with fever after cardiac arrest (LOE 3) 18 and ischemic brain injury (LOE 7 extrapolated from stroke victims 18 ). Thus, the provider should monitor the patient’s temperature after resuscitation and avoid hyperthermia. Glucose Control The postresuscitation patient is likely to develop electrolyte abnormalities that may be detrimental to recovery. Although many studies have documented a strong association between high blood glucose after resuscitation from cardiac arrest and poor neurologic outcomes (LOE 4 21,22 ; LOE 5 9,22–26 ; LOE 6 27 ), they did not show that control of serum glucose level alters outcome. A prospective randomized study by van den Berghe (LOE 1) 28 did show that tight control of blood glucose using insulin reduced hospital mortality rates in critically ill patients who required mechanical ventilation. The study did not specifi- cally focus on postresuscitation patients, but the effect of blood glucose control on outcome is compelling. The study documented not only improved survival but decreased mor- tality from infectious complications, a common problem in the postresuscitation setting. In comatose patients, signs of hypoglycemia are less apparent, so clinicians must monitor serum glucose closely to avoid hypoglycemia when treating hyperglycemia. On the basis of findings of improved outcomes in critically ill patients when glucose levels are maintained in the normal range, it is reasonable for providers to maintain strict glucose control during the postresuscitation period. Additional study is needed, however, to identify the precise blood glucose concentration that requires insulin therapy, the target range of blood glucose concentration, and the effect of tight glucose control on outcomes of patients after cardiac arrest. Organ-Specific Evaluation and Support After ROSC patients may remain comatose or have decreased responsiveness for a variable period of time. If spontaneous breathing is absent or inadequate, mechanical ventilation via an endotracheal tube or other advanced airway device may be required. Hemodynamic status may be unstable with abnor- malities of cardiac rate, rhythm, systemic blood pressure, and organ perfusion. Clinicians must prevent, detect, and treat hypoxemia and hypotension because these conditions can exacerbate brain injury. Clinicians should determine the baseline postarrest status of each organ system and support organ function as needed. The remainder of this chapter focuses on organ-specific measures that should be provided in the immediate postresus- citation period. Respiratory System After ROSC patients may exhibit respiratory dysfunction. Some patients will remain dependent on mechanical ventila- tion and will need an increased inspired concentration of oxygen. Providers should perform a full physical examination and evaluate the chest radiograph to verify appropriate Part 7.5: Postresuscitation Support IV-85 endotracheal tube depth of insertion and identify cardiopul- monary complications of resuscitation. Providers should ad- just mechanical ventilatory support based on the patient’s blood gas values, respiratory rate, and work of breathing. As the patient’s spontaneous ventilation becomes more efficient, the level of respiratory support may be decreased until spontaneous respiration returns. If the patient continues to require high inspired oxygen concentrations, providers should determine if the cause is pulmonary or cardiac and direct care accordingly. Debate exists as to the length of time patients who require ventilatory support should remain sedated. To date there is little evidence to guide therapy. One observational study (LOE 3) 29 found an association between use of sedation and development of pneumonia in intubated patients during the first 48 hours of therapy. The study, however, was not designed to investigate sedation as a risk factor for either pneumonia or death in patients with cardiac arrest. At this time there is inadequate data to recommend for or against the use of a defined period of sedation or neuromuscular block- ade after cardiac arrest (Class Indeterminate). Use of neuro- muscular blocking agents should be kept to a minimum because these agents preclude thorough neurologic assess- ments during the first 12 to 72 hours after ROSC. 2 Sedation may be necessary to control shivering during hypothermia. If shivering continues despite optimal sedation, neuromuscular blockade may be required in addition to deep sedation. Ventilatory Parameters Sustained hypocapnea (low PCO 2 ) may reduce cerebral blood flow. 30–31 After cardiac arrest, restoration of blood flow results in an initial hyperemic blood flow response that lasts 10 to 30 minutes, followed by a more prolonged period of low blood flow. 32,33 During this latter period of late hypoperfu- sion, a mismatch between blood flow (oxygen delivery) and oxygen requirement may occur. If the patient is hyperventi- lated at this stage, cerebral vasoconstriction may further decrease cerebral blood flow and increase cerebral ischemia and ischemic injury. There is no evidence that hyperventilation protects the brain or other vital organs from further ischemic damage after cardiac arrest. In fact, Safar et al 34 provided evidence that hyperventilation may worsen neurologic outcome. Hyperven- tilation may also generate increased airway pressures and augment intrinsic positive end-expiratory pressure (so-called “auto PEEP”), leading to an increase in cerebral venous and intracranial pressures. 35,36 Increases in cerebral venous pres- sure can decrease cerebral blood flow and increase brain ischemia. In summary, no data supports targeting a specific arterial PaCO 2 level after resuscitation from cardiac arrest. But data extrapolated from patients with brain injury supports venti- lation to normocarbic levels as appropriate. Routine hyper- ventilation is detrimental (Class III). Cardiovascular System Both the ischemia/reperfusion of cardiac arrest and electrical defibrillation can cause transient myocardial stunning and dysfunction 37 that can last many hours but may improve with vasopressors. 38 Cardiac biomarker levels may be increased in association with global ischemia caused by absent or de- creased coronary blood flow during cardiac arrest and CPR. Increased cardiac biomarkers may also indicate acute myo- cardial infarction as the cause of cardiac arrest. Hemodynamic instability is common after cardiac arrest, and early death due to multi-organ failure is associated with a persistently low cardiac index during the first 24 hours after resuscitation (LOE 5). 6,39 Thus, after resuscitation clinicians should evaluate the patient’s electrocardiogram, radiographs, and laboratory analyses of serum electrolytes and cardiac biomarkers. Echocardiographic evaluation within the first 24 hours after arrest is useful to guide ongoing management. 5,40 One large case series (LOE 5) 6 of patients resuscitated following out-of-hospital cardiac arrest documented signifi- cant early but reversible myocardial dysfunction and low cardiac output, followed by later vasodilation. The hemody- namic instability responded to fluid administration and vaso- active support. 6 Invasive monitoring may be necessary to measure blood pressure accurately and to determine the most appropriate combination of medications to optimize blood flow and distribution. The provider should titrate volume administration and vasoactive (eg, norepinephrine), inotropic (eg, dobutamine), and inodilator (eg, milrinone) drugs as needed to support blood pressure, cardiac index, and systemic perfusion. The ideal target blood pressure or hemodynamic parameters associated with optimal survival have not been established. Both cardiac arrest and sepsis are thought to involve multi-organ ischemic injury and microcirculatory dysfunc- tion. Goal-directed therapy with volume and vasoactive drug administration has been effective in improving survival from sepsis. 41 The greatest survival benefit is due to a decreased incidence of acute hemodynamic collapse, a challenge also seen in the postresuscitation setting. Data extrapolated from a study of goal-directed therapy for sepsis (LOE 1 41 for sepsis; LOE 7 [extrapolated] for cardiac arrest) suggests that provid- ers should try to normalize oxygen content and oxygen transport. Relative adrenal insufficiency may develop following the stress of cardiac arrest, but the use of early corticosteroid supplementation in such patients to improve either hemody- namics or outcome is unproven and requires further evaluation. 42 Although sudden cardiac arrest may be precipitated by cardiac arrhythmia, it is unclear if antiarrhythmics are bene- ficial or detrimental in the postresuscitation period. Thus, there is insufficient evidence to recommend for or against prophylactic administration of antiarrhythmic drugs to pa- tients who have survived cardiac arrest from any cause. It may be reasonable, however, to continue an infusion of an antiarrhythmic drug that was associated with ROSC (Class Indeterminate). Also, given the cardioprotective effects of H9252-blockers in the context of ischemic heart disease, the use of H9252-blockers in the postresuscitation setting seems prudent if there are no contraindications. 9 IV-86 Circulation December 13, 2005 Central Nervous System A healthy brain and a functional patient are the primary goals of cardio-pulmonary-cerebral resuscitation. Following ROSC, after a brief initial period of hyperemia cerebral blood flow is reduced (the “no-reflow phenomenon”) as a result of microvascular dysfunction. This reduction occurs even when cerebral perfusion pressure is normal. 43,44 Neurologic support for the unresponsive patient should include measures to optimize cerebral perfusion pressure by maintaining a normal or slightly elevated mean arterial pressure and reducing intracranial pressure if it is elevated. Because hyperthermia and seizures increase the oxygen requirements of the brain, providers should treat hyperther- mia and consider therapeutic hypothermia. Witnessed sei- zures should be promptly controlled and maintenance anti- convulsant therapy initiated (Class IIa). Because of a paucity of data, routine seizure prophylaxis is a Class Indeterminate recommendation at present. Prognostic Factors The period after resuscitation is often stressful to medical staff and family members as questions arise about the patient’s ultimate prognosis. Ideally a clinical assessment, laboratory test, or biochemical marker would reliably predict outcome during or immediately after cardiac arrest. Unfortu- nately no such predictors are available. Determination of prognosis based on initial physical examination findings can be difficult, and coma scores may be less predictive than individual motor and brainstem reflexes found in the first 12 to 72 hours after arrest. 2 In a meta-analysis (LOE 1) 44 bilateral absence of cortical response to median nerve somatosensory-evoked potentials predicted poor outcome in normothermic patients who were comatose for at least 72 hours after hypoxic-ischemic insult. A case report 46 also documents the usefulness of this evalu- ation. Therefore, median nerve somatosensory-evoked poten- tials measured 72 hours after cardiac arrest can be used to predict neurologic outcome in patients with hypoxic-anoxic coma. A recent meta-analysis (LOE 1) of 11 studies involving 1914 patients 2 documented 5 clinical signs that were found to strongly predict death or poor neurologic outcome, with 4 of the 5 predictors detectable at 24 hours after resuscitation: ● Absent corneal reflex at 24 hours ● Absent pupillary response at 24 hours ● Absent withdrawal response to pain at 24 hours ● No motor response at 24 hours ● No motor response at 72 hours An electroencephalogram performedH1102224 to 48 hours after resuscitation has also been shown to provide useful predictive information (LOE 5 47–50 ) and can help define prognosis. Other Complications Sepsis is a potentially fatal postresuscitation complication. 51 Patients with sepsis will benefit from goal-directed therapy. Renal failure 52 and pancreatitis, while often transient, should be diagnosed and evaluated. 3,53 Summary The postresuscitation period is often marked by hemodynam- ic instability as well as laboratory abnormalities. This is also a period for which promising technological interventions such as controlled therapeutic hypothermia are being evalu- ated. Every organ system is at risk during this time, and patients may ultimately develop multi-organ dysfunction. A complete discussion of this topic is beyond the scope of this chapter. The goal of the postresuscitation period is to manage the patient’s vital signs and laboratory abnormalities and support organ system function to increase the likelihood of intact neurologic survival. References 1. Safar P. Resuscitation from clinical death: pathophysiologic limits and therapeutic potentials. Crit Care Med. 1988;16:923–941. 2. Booth CM, Boone RH, Tomlinson G, Detsky AS. Is this patient dead, vegetative, or severely neurologically impaired? Assessing outcome for comatose survivors of cardiac arrest. JAMA. 2004;291:870–879. 3. Hypothermia After Cardiac Arrest Study Group. Mild therapeutic hypo- thermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346:549–556. 4. Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002;346:557–563. 5. Bunch TJ, White RD, Gersh BJ, Meverden RA, Hodge DO, Ballman KV, Hammill SC, Shen WK, Packer DL. Long-term outcomes of out-of- hospital cardiac arrest after successful early defibrillation. N Engl J Med. 2003;348:2626–2633. 6. Laurent I, Monchi M, Chiche JD, Joly LM, Spaulding C, Bourgeois B, Cariou A, Rozenberg A, Carli P, Weber S, Dhainaut JF. Reversible myocardial dysfunction in survivors of out-of-hospital cardiac arrest. J Am Coll Cardiol. 2002;40:2110–2116. 7. Negovsky VA. The second step in resuscitation—the treatment of the ‘post-resuscitation disease.’ Resuscitation. 1972;1:1–7. 8. A randomized clinical study of cardiopulmonary-cerebral resuscitation: design, methods, and patient characteristics. Brain Resuscitation Clinical Trial I Study Group. Am J Emerg Med. 1986;4:72–86. 9. Skrifvars MB, Pettila V, Rosenberg PH, Castren M. A multiple logistic regression analysis of in-hospital factors related to survival at six months in patients resuscitated from out-of-hospital ventricular fibrillation. Resuscitation. 2003;59:319–328. 10. Hachimi-Idrissi S, Corne L, Ebinger G, Michotte Y, Huyghens L. Mild hypothermia induced by a helmet device: a clinical feasibility study. Resuscitation. 2001;51:275–281. 11. Nolan JP, Morley PT, Hoek TL, Hickey RW. Therapeutic hypothermia after cardiac arrest: an advisory statement by the Advancement Life Support Task Force of the International Liaison Committee on Resusci- tation. Resuscitation. 2003;57:231–235. 12. Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, Fanaroff AA, Poole WK, Wright LL, Higgins RD, Finer NN, Carlo WA, Duara S, Oh W, Cotten CM, Stevenson DK, Stoll BJ, Lemons JA, Guillet R, Jobe AH. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005;353: 1574–1584. 13. Bernard S, Buist M, Monteiro O, Smith K. Induced hypothermia using large volume, ice-cold intravenous fluid in comatose survivors of out-of- hospital cardiac arrest: a preliminary report. Resuscitation. 2003;56:9–13. 14. Hickey RW, Kochanek PM, Ferimer H, Alexander HL, Garman RH, Graham SH. Induced hyperthermia exacerbates neurologic neuronal his- tologic damage after asphyxial cardiac arrest in rats. Crit Care Med. 2003;31:531–535. 15. Dietrich WD, Busto R, Halley M, Valdes I. The importance of brain temperature in alterations of the blood-brain barrier following cerebral ischemia. J Neuropathol Exp Neurol. 1990;49:486–497. 16. Dietrich WD, Busto R, Valdes I, Loor Y. Effects of normothermic versus mild hyperthermic forebrain ischemia in rats. Stroke. 1990;21: 1318–1325. 17. Kim Y, Busto R, Dietrich WD, Kraydieh S, Ginsberg MD. Delayed postischemic hyperthermia in awake rats worsens the histopathological Part 7.5: Postresuscitation Support IV-87 outcome of transient focal cerebral ischemia. Stroke. 1996;27: 2274–2280; discussion 2281. 18. Zeiner A, Holzer M, Sterz F, Schorkhuber W, Eisenburger P, Havel C, Kliegel A, Laggner AN. Hyperthermia after cardiac arrest is associated with an unfavorable neurologic outcome. Arch Intern Med. 2001;161: 2007–2012. 19. Hajat C, Hajat S, Sharma P. Effects of poststroke pyrexia on stroke outcome: a meta-analysis of studies in patients. Stroke. 2000;31: 410–414. 20. Mullner M, Sterz F, Binder M, Schreiber W, Deimel A, Laggner AN. Blood glucose concentration after cardiopulmonary resuscitation influences functional neurological recovery in human cardiac arrest sur- vivors. J Cereb Blood Flow Metab. 1997;17:430–436. 21. Langhelle A, Tyvold SS, Lexow K, Hapnes SA, Sunde K, Steen PA. In-hospital factors associated with improved outcome after out-of- hospital cardiac arrest: a comparison between four regions in Norway. Resuscitation. 2003;56:247–263. 22. Calle PA, Buylaert WA, Vanhaute OA. Glycemia in the post-resuscitation period. The Cerebral Resuscitation Study Group. Resuscitation. 1989; 17(suppl):S181–S188; discussion S199–S206. 23. Mackenzie CF. A review of 100 cases of cardiac arrest and the relation of potassium, glucose, and haemoglobin levels to survival. West Indian Med J. 1975;24:39–45. 24. Longstreth WT Jr, Diehr P, Inui TS. Prediction of awakening after out-of-hospital cardiac arrest. N Engl J Med. 1983;308:1378–1382. 25. Longstreth WT Jr, Inui TS. High blood glucose level on hospital admission and poor neurological recovery after cardiac arrest. Ann Neurol. 1984;15:59–63. 26. Longstreth WT Jr, Copass MK, Dennis LK, Rauch-Matthews ME, Stark MS, Cobb LA. Intravenous glucose after out-of-hospital cardiopulmonary arrest: a community-based randomized trial. Neurology. 1993;43: 2534–2541. 27. Sheldon RA, Partridge JC, Ferriero DM. Postischemic hyperglycemia is not protective to the neonatal rat brain. Pediatr Res. 1992;32:489–493. 28. van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R. Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001;345: 1359–1367. 29. Rello J, Diaz E, Roque M, Valles J. Risk factors for developing pneumonia within 48 hours of intubation. Am J Respir Crit Care Med. 1999;159:1742–1746. 30. Ausina A, Baguena M, Nadal M, Manrique S, Ferrer A, Sahuquillo J, Garnacho A. Cerebral hemodynamic changes during sustained hypocap- nia in severe head injury: can hyperventilation cause cerebral ischemia? Acta Neurochir Suppl. 1998;71:1–4. 31. Yundt KD, Diringer MN. The use of hyperventilation and its impact on cerebral ischemia in the treatment of traumatic brain injury. Crit Care Clin. 1997;13:163–184. 32. Wolfson SK Jr, Safar P, Reich H, Clark JM, Gur D, Stezoski W, Cook EE, Krupper MA. Dynamic heterogeneity of cerebral hypoperfusion after prolonged cardiac arrest in dogs measured by the stable xenon/CT tech- nique: a preliminary study. Resuscitation. 1992;23:1–20. 33. Fischer M, Hossmann KA. No-reflow after cardiac arrest. Intensive Care Med. 1995;21:132–141. 34. Safar P, Xiao F, Radovsky A, Tanigawa K, Ebmeyer U, Bircher N, Alexander H, Stezoski SW. Improved cerebral resuscitation from cardiac arrest in dogs with mild hypothermia plus blood flow promotion. Stroke. 1996;27:105–113. 35. Gottfried SB, Rossi A, Milic-Emili J. Dynamic hyperinflation, intrinsic PEEP, and the mechanically ventilated patient. Crit Care Digest. 1986; 5:30–33. 36. Ligas JR, Mosiehi F, Epstein MAF. Occult positive end-expiratory pressure with different types of mechanical ventilators. J Crit Care. 1990;52:95–100. 37. Weaver WD, Cobb LA, Copass MK, Hallstrom AP. Ventricular defibril- lation: a comparative trial using 175-J and 320-J shocks. N Engl J Med. 1982;307:1101–1106. 38. Vasquez A, Kern KB, Hilwig RW, Heidenreich J, Berg RA, Ewy GA. Optimal dosing of dobutamine for treating post-resuscitation left ventric- ular dysfunction. Resuscitation. 2004;61:199–207. 39. Mullner M, Domanovits H, Sterz F, Herkner H, Gamper G, Kurkciyan I, Laggner AN. Measurement of myocardial contractility following suc- cessful resuscitation: quantitated left ventricular systolic function utilising non-invasive wall stress analysis. Resuscitation. 1998;39:51–59. 40. Spaulding CM, Joly LM, Rosenberg A, Monchi M, Weber SN, Dhainaut JF, Carli P. Immediate coronary angiography in survivors of out-of- hospital cardiac arrest. N Engl J Med. 1997;336:1629–1633. 41. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368–1377. 42. Ito T, Saitoh D, Takasu A, Kiyozumi T, Sakamoto T, Okada Y. Serum cortisol as a predictive marker of the outcome in patients resuscitated after cardiopulmonary arrest. Resuscitation. 2004;62:55–60. 43. Gisvold SE, Sterz F, Abramson NS, Bar-Joseph G, Ebmeyer U, Gervais H, Ginsberg M, Katz LM, Kochanek PM, Kuboyama K, Miller B, Obrist W, Roine RO, Safar P, Sim KM, Vandevelde K, White RJ, Xiao F. Cerebral resuscitation from cardiac arrest: treatment potentials. Crit Care Med. 1996;24(2 suppl):S69–S80. 44. del Zoppo GJ, Mabuchi T. Cerebral microvessel responses to focal ischemia. J Cereb Blood Flow Metab. 2003;23:879–894. 45. Zandbergen EG, de Haan RJ, Stoutenbeek CP, Koelman JH, Hijdra A. Systematic review of early prediction of poor outcome in anoxic- ischaemic coma. Lancet. 1998;352:1808–1812. 46. Rothstein TL. Recovery from near death following cerebral anoxia: a case report demonstrating superiority of median somatosensory evoked potentials over EEG in predicting a favorable outcome after cardiopul- monary resuscitation. Resuscitation. 2004;60:335–341. 47. Kaplan PW, Genoud D, Ho TW, Jallon P. Etiology, neurologic corre- lations, and prognosis in alpha coma. Clin Neurophysiol. 1999;110: 205–213. 48. Ajisaka H. Early electroencephalographic findings in patients with anoxic encephalopathy after cardiopulmonary arrest and successful resuscitation. J Clin Neurosci. 2004;11:616–618. 49. Bassetti C, Bomio F, Mathis J, Hess CW. Early prognosis in coma after cardiac arrest: a prospective clinical, electrophysiological, and bio- chemical study of 60 patients. J Neurol Neurosurg Psychiatry. 1996;61: 610–615. 50. Berkhoff M, Donati F, Bassetti C. Postanoxic alpha (theta) coma: a reappraisal of its prognostic significance. Clin Neurophysiol. 2000;111: 297–304. 51. Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G, Zim- merman JL, Vincent JL, Levy MM. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004;32:858–873. 52. Zeiner A, Sunder-Plassmann G, Sterz F, Holzer M, Losert H, Laggner AN, Mullner M. The effect of mild therapeutic hypothermia on renal function after cardiopulmonary resuscitation in men. Resuscitation. 2004; 60:253–261. 53. Mattana J, Singhal PC. Prevalence and determinants of acute renal failure following cardiopulmonary resuscitation. Arch Intern Med. 1993;153: 235–239. IV-88 Circulation December 13, 2005