Hostname: page-component-cd9895bd7-p9bg8 Total loading time: 0 Render date: 2024-12-23T12:33:21.846Z Has data issue: false hasContentIssue false
  • English
  • Français

Systematic review of randomized controlled trials of therapeutic hypothermia as a neuroprotectant in post cardiac arrest patients

Published online by Cambridge University Press:  21 May 2015

Ka Wai Cheung ,
Robert S. Green  and
Kirk D. Magee
Ka Wai Cheung
Affiliation:
Department of Emergency Medicine, Division of Critical Care Medicine, Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, NS
Robert S. Green*
Affiliation:
Department of Emergency Medicine, Division of Critical Care Medicine, Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, NS Department of Internal Medicine, Division of Critical Care Medicine, Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, NS
Kirk D. Magee
Affiliation:
Department of Emergency Medicine, Division of Critical Care Medicine, Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, NS
*
Division of Critical Care, Queen Elizabeth II Health Sciences Centre, Dalhousie University, 1278 Tower Rd., Rm. 349, Bethune Building, Halifax NS B3H 2Y9

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
Objective:

Several randomized controlled trials have suggested that mild induced hypothermia may improve neurologic outcome in comatose cardiac arrest survivors. This systematic review of randomized controlled trials was designed to determine if mild induced hypothermia improves neurologic outcome, decreases mortality, or is associated with an increased incidence of adverse events.

Data sources:

The following databases were reviewed: Cochrane Controlled Trials Register (Issue 4, 2005), MEDLINE (January 1966 to November 2005), EMBASE (1980 to November 2005), CINAHL (1982 to November 2005) and Web of Science (1989 to November 2005). For each included study, references were reviewed and the primary author contacted to identify any additional studies.

Study selection:

Studies that met inclusion criteria were randomized controlled trials of adult patients (>18 years of age) with primary cardiac arrest who remained comatose after return of spontaneous circulation. Patients had to be randomized to mild induced hypothermia (32°C-34°C) or normothermia within 24 hours of presentation. Only studies reporting pre-determined outcomes including discharge neurologic outcome, mortality or significant treatment-related adverse events were included. There were no language or publication restrictions.

Data synthesis:

Four studies involving 436 patients, with 232 cooled to a core temperature of 32°C-34°C met inclusion criteria. Pooled data demonstrated that mild hypothermia decreased inhospital mortality (relative ratio [RR] 0.75; 95% confidence interval [CI], 0.62-0.92) and reduced the incidence of poor neurologic outcome (RR 0.74; 95% CI, 0.62-0.84). Numbers needed to treat were 7 patients to save 1 life, and 5 patients to improve neurologic outcome. There was no evidence of treatment-limiting side effects.

Conclusions:

Therapeutically induced mild hypothermia decreases in-hospital mortality and improves neurologic outcome in comatose cardiac arrest survivors. The possibility of treatment-limiting side effects cannot be excluded.

Keywords

cardiac arrestinduced hypothermiasystematic review
Type
Education • Éducation
Information
Canadian Journal of Emergency Medicine , Volume 8 , Issue 5 , September 2006 , pp. 329 - 337
Copyright
Copyright © Canadian Association of Emergency Physicians 2006

References

1.World Health Organization. Cardiovascular Diseases — Prevention and Control. Geneva: The Organization; 2001.Google Scholar
2.Mayer, SA. Hypothermia for neuroprotection after cardiac arrest. Curr Neurol Neurosci Rep 2002;2:525–6.Google Scholar
3.Myerburg, RJ, Castellanos, A. Heart disease: a textbook of cardiovascular medicine. 5th ed. Philadelphia: W.B. Saunders; 1997.Google Scholar
4.Eisenberg, MS, Horwood, BT, Cummins, RO, et al. Cardiac arrest and resuscitation: a tale of 29 cities. Ann Emerg Med 1990; 19:179–86.CrossRefGoogle ScholarPubMed
5.Bernard, SA. Outcome from prehospital arrest in Melbourne, Australia. Emerg Med 1998;10:25–9.Google Scholar
6.Randomized clinical study of thiopental loading in comatose survivors of cardiac arrest. Brain Resuscitation Clinical Trial I Study Group. N Engl J Med 1986;314(7):397–403.CrossRefGoogle Scholar
7.A randomized clinical study of a calcium-entry blocker (lidoflazine) in the treatment of comatose survivors of cardiac arrest. Brain Resuscitation Clinical Trial II Study Group. N Engl J Med 1991;324(18):1225–31.Google Scholar
8.Roine, RO, Kaste, M, Kinnunen, A, et al. Nimodipine after resuscitation from out-of-hospital ventricular fibrillation. A placebo-controlled, double-blind, randomized trial. JAMA 1990;264: 3171–7.Google Scholar
9.Jastremski, M, Sutton-Tyrrell, K, Vaagenes, P, et al. Glucocorti-coid treatment does not improve neurological recovery following cardiac arrest. Brain Resuscitation Clinical Trial I Study Group. JAMA 1989;262:3427–30.Google Scholar
10.Chopp, M, Knight, R, Tidwell, CD, et al. The metabolic effects of mild hypothermia on global cerebral recirculation in the cat: a comparison to normothermia and hyperthermia. J Cereb Blood Flow Metab 1989;9:141–8.Google Scholar
11.Xue, D, Huang, ZG, Smith, KE, et al. Immediate or delayed mild hypothermia prevents focal cerebral infarction. Brain Res 1992; 587(1):66–72.Google Scholar
12.Bernard, S. Induced hypothermia in intensive care medicine. Anaesth Intensive Care 1996;24:382–8.CrossRefGoogle ScholarPubMed
13.Hegnauer, AH, D’Amato, HE. Oxygen consumption and cardiac output in the hypothermic dog. Am J Physiol 1954;178:138–42.CrossRefGoogle ScholarPubMed
14.Morimoto, Y, Kemmotsu, O, Kitami, K, et al. Acute brain swelling after out-of-hospital cardiac arrest: pathogenesis and outcome. Crit Care Med 1993;21:104–10.Google Scholar
15.Callaway, CW, Tadler, SC, Katz, LM, et al. Feasibility of external cranial cooling during out-of-hospital cardiac arrest. Resuscitation 2002;52:159–65.Google Scholar
16.Busto, R, Globus, MYT, Dietrich, WD, et al. Effect of mild hypothermia on ischemia-induced release of neurotransmitters and free fatty acids in rat brain. Stroke 1989;20:904–10.CrossRefGoogle ScholarPubMed
17.Biggar, WD, Bohn, DJ, Kent, G. Neutrophil circulation and release from bone marrow during hypothermia. Infect Immun 1983;40:708–12.Google Scholar
18.Bohn, DJ, Biggar, WD, Smith, CR, et al. Influence of hypothermia, barbiturate therapy, and intracranial pressure monitoring on morbidity and mortality after near drowning. Crit Care Med 1986;14:529–34.CrossRefGoogle ScholarPubMed
19.Yanagawa, Y, Ishihara, S, Norio, H, et al. Preliminary clinical outcome study of mild resuscitative hypothermia after out-of-hospital cardiopulmonary arrest. Resuscitation 1998;39:61–6.Google Scholar
20.Rohrer, MJ, Natale, AM. Effect of mild hypothermia on the coagulation cascade. Crit Care Med 1992;20:1402–5.Google Scholar
21.Valeri, CR, Feingold, H, Cassidy, G, et al. Hypothermia-induced reversible platelet dysfunction. Ann Surg 1987;205:175–81.Google Scholar
22.Landis, JR, Koch, GG. The measurement of observer agreement for categorical data. Biometrics 1977;33:159–74.Google Scholar
23.Clarke, M, Oxman, AD, eds. Cochrane reviewers’ handbook 4.2.0. Oxford: Update Software; 2003.Google Scholar
24.Jadad, AR, Moore, RA, Carroll, D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Cont Clin Trials 1996;17:1–12.Google Scholar
25.Higgins, JP, Thompson, SG, Deek, JJ, et al. Measuring inconsistency in meta-analyses. BMJ 2003;327:557–60.Google Scholar
26.Breslow, NE, Day, NE. Analysis of case-control studies. Statistical methods in cancer research. Lyon: International Agency for Research on Cancer; 1980.Google Scholar
27.Egger, M, Davey Smith, G, Schneider, M, et al. Bias in meta-analysis detected by a simple graphical test. BMJ 1997;325:629–34.CrossRefGoogle Scholar
28.Mori, K, Takeyama, Y, Itoh, Y, et al. Multivariate analysis of prognostic factors in survivors of out-of-hospital cardiac arrest with brain hypothermia therapy. Crit Care Med 2000;28:A168.Google Scholar
29.Hachimi-Idrissi, S, Corne, L, Ebinger, G, et al. Mild hypothermia induced by a helmet device: a clinical feasibility study. Resuscitation 2001;51:275–81.Google Scholar
30.Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest [published erratum appears in N Engl J Med 2002;346 (22):1756]. N Engl J Med 2002;346(8):549–56.Google Scholar
31.Bernard, SA, Gray, TW, Buist, MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557–63.CrossRefGoogle ScholarPubMed
32.Nolan, JP, Morley, MD, Vanden Hoek, TL, et al. Therapeutic hypothermia after cardiac arrest. An advisory statement by the advanced life support task force of the International Liaison Committee on Resuscitation. Resuscitation 2003;57:231–5.Google Scholar
33.Green, RS, Howes, D; on behalf of the CAEP Critical Care Committee. Hypothermic modulation of anoxic brain injury in adult survivors of cardiac arrest: a review of the literature and an algorithm for emergency physicians. Can J Emerg Med 2005;7(1):42–7.CrossRefGoogle Scholar
34.Canadian Association of Emergency Physicians (CAEP) and the CAEP Critical Care Committee. Guidelines for the use of hypothermia after cardiac arrest [position statement]. Can J Emerg Med 2006;8(2):106–8.CrossRefGoogle Scholar
35.Howes, D, Green, R, Gray, S, et al; for the Canadian Association of Emergency Physicians. Evidence for the use of hypothermia after cardiac arrest. Can J Emerg Med 2006;8(2):109–15.CrossRefGoogle ScholarPubMed
36.Abella, BS, Rhee, JW, Huang, KN, et al. L.B B. Induced hypothermia is underused after resuscitation from cardiac arrest: a current practice survey. Resuscitation 2005;64:181–6.Google Scholar
37.Callaway, CW. Improving neurologic outcomes after out-of-hospital cardiac arrest. Prehosp Emerg Care 1997;1:45–57.Google Scholar
38.Stiell, IG, Wells, GA, Field, B, et al. Ontario Prehospital Advanced Life Support Study Group. Advanced Cardiac Life Suppport in Out-of-Hospital Cardiac Arrest. N Engl J Med 2004;351:647–56.Google Scholar
39.Vaillancourt, C, Stiell, IG. Canadian Cardiovascular Outcomes Research Team. Cardiac arrest care and emergency medical services in Canada. Can J Cardiol 2004;20:1081–90.Google Scholar
40.Richmond, TS. Cerebral resuscitation after global brain ischemia: linking research to practice. AACN Clin Issues 1997;8(2):171–81.Google Scholar
41.Krause, GS, Kumar, K, White, BC, et al. Ischemia, resuscitation, and reperfusion: meachanisms of tissue injury and prospects for protection. Am Heart J 1986;111:768–80.Google Scholar
42.Attia, J, Cook, D. Prognosis in anoxic and traumatic coma. Crit Care Clin 1998;14:497–511.Google Scholar
43.Bulkley, GB. Reactive oxygen metabolites and reperfusion injury: Aberrant triggering of reticuloendothelial function. Lancet 1994;344:934–6.Google Scholar
44.White, BC, Sullivan, JM, DeGracia, DJ, et al. Brain ischaemia and reperfusion: molecular mechanisms of neuronal injury. J Neurol Sci 2000;179:1–33.Google Scholar
45.Negovsky, VA. Postresuscitation disease. Crit Care Med 1988;16:942–6.Google Scholar
46.Laptook, AR, Corbett, RJ, Sterett, R, et al. Quantitative relationship between brain temperature and energy utilization rate measured in vivo using 31P and 1H magnetic resonance spectroscopy. Pediatr Res 1995;38:919–25.Google Scholar
47.Michenfelder, JD, Milde, JH. The relationship among canine brain temperature, metabilism, and function during hypothermia. Anesthesiology 1991;75:130–6.Google Scholar
48.Nandate, K, Vuylsteke, A, Crosbie, AE, et al. Cerebrovascular cytokine responses during coronary artery bypass surgery: specific production of interleukin-8 and its attenuation by hypothermic cardiopulmonary bypass. Anesth Analg 1999;89:823–8.Google Scholar
49.Xiao, F, Safar, P, Alexander, H. Peritoneal cooling for mild hypothermia after cardiac arrest in dogs. Resuscitation 1995;30:51–9.CrossRefGoogle ScholarPubMed
50.Sterz, F, Safar, P, Tisherman, SA, et al. Mild hypothermic cardiopulmonary resuscitation improves outcome after prolonged cardiac arrest in dogs. Crit Care Med 1991;19:379–89.Google Scholar
51.Brader, E, Jehle, D, Safar, P. Protective head cooling during cardiac arrest in dogs [abstract]. Ann Emerg Med 1985;14:510.Google Scholar
52.Marion, DW, Leonov, Y, Ginsberg, M, et al. Resuscitative hypothermia. Crit Care Med 1996;24(suppl.):S81-9.Google Scholar
53.Weinrauch, V, Safar, P, Tisherman, SA, et al. Beneficial effect of mild hypothermia and detrimental effect of deep hypothermia after cardiac arrest in dogs. Stroke 1992;23:1454–62.Google Scholar
54.Kuboyama, K, Safar, P, Radovsky, A, et al. Delay in cooling negates the beneficial effect of mild resuscitative cerebral hypothermia after cardiac arrest in dogs: a prospective, randomized study. Crit Care Med 1993;21:1348–58.Google Scholar
55.Illievich, UM, Zornow, MH, Choi, KT, et al. Effects of hypothermic metabolic suppression on hippocampal glutamate concentrations after transient global cerebral ischemia. Anesth Analg 1994;78:905–11.CrossRefGoogle ScholarPubMed
56.Hicks, SD, DeFranco, DB, Callaway, CW. Hypothermia during reperfusion after asphyxial cardiac arrest improves functional recovery and selectively alters stress-induced protein expression. J Cereb Blood Flow Metab 2000;20:520–30.CrossRefGoogle ScholarPubMed
57.Leonov, Y, Sterz, F, Safar, P, et al. Mild cerebral hypothermia during and after cardiac arrest improves neurologic outcome in dogs. J Cereb Blood Flow Metab 1990;10:57–70.Google Scholar
58.Bernard, SA, Jones, BM, Horne, MK. Clinical trial of induced hypothermia in comatose survivors of out-of-hospital cardiac arrest. Ann Emerg Med 1997;30:146–53.Google Scholar
59.Shirai, S, Yokoi, H, Kimura, T, et al. Mild hypothermia for brain resuscitation after cardiac arrest. Circulation 2002;106:2011S.Google Scholar
60.Schubert, A. Side effects of mild hypothermia. J Neurosurg Anesthesiol 1995;7:139–47.Google Scholar
61.Pulsinelli, WA, Waldman, S, Rawlinson, D, et al. Moderate hyperglycemia augments ischemic brain damage: a neuropathologic study in the rat. Neurology 1982;32:1239–46.Google Scholar
62.Michenfelder, JD, Theye, RA. The effects of anesthesia and hypothermia on canine cerebral ATP and lactate during anoxia produced by decapitation. Anesthesiology 1970;33:430–9.Google Scholar
63.Holzer, M, Bernard, SA, Hachimi-Idrissi, S, et al.; for the Collaborative Group on Induced Hypothermia for Neuroprotection After Cardiac Arrest. Hypothermia for neuroprotection after cardiac arrest: systematic review and individual patient data meta-analysis. Crit Care Med 2005;33:41Google Scholar