What is the right temperature to cool post-cardiac arrest patients?

CITATION: Niklas Nielsen, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, Pellis T, Stammet P, Wanscher M, Wise MP, Åneman A, Al-Subaie N, Boesgaard S, Bro-Jeppesen J, Brunetti I, Bugge JF, Hingston CD, Juffermans NP, Koopmans M, Køber L, Langørgen J, Lilja G, Møller JE, Rundgren M, Rylander C, Smid O, Werer C, Winkel P, Friberg H. Targeted temperature management at 33 °C versus 36 °C after cardiac arrest. N Engl J Med. 2013;369:2197-206. doi: 10.1056/NEJMoa1310519 . Epub 2013 Nov 17. Pub Med PMID: 20089970.

BACKGROUND: Brain ischemia and reperfusion injury leading to tissue degeneration and loss of neurological function following return of spontaneous circulation after cardiac arrest (CA) is a well-known entity. Two landmark trials in 2002 showed improved survival and neurological outcome of comatose survivors of out-of-hospital cardiac arrest (OHCA) of presumed cardiac origin when the patients were subjected to therapeutic hypothermia of 32 to 34 °C for 12 to 24 hours. However, the optimal target temperature for these cohorts is yet to be established and also it is not clear whether strict fever management and maintaining near normal body temperature are alone sufficient to improve the outcome.

OBJECTIVE: The objective is to determine whether a hypothermic goal of a near-normal body temperature of 36 °C reduces all-cause mortality compared with a moderate hypothermia of 33 °C for the unconscious survivors of OHCA of presumed cardiac origin when subjected randomly to these different targeted temperatures.

DESIGN: A multicenter, international, open label, randomized controlled trial.

SETTING: Thirty-six ICUs in Europe and Australia participated in this study.

PARTICIPANTS: Unconscious adults (older than 18 years of age) who survived (Glasgow coma scale less than 8) OHCA due to presumed cardiac origin with subsequent persistent return of spontaneous circulation (more than 20 minutes without chest compressions).

INTERVENTION: The above participant cohorts were randomized to targeted body temperature of either 33 °C or 36 °C for 36 hours after the CA with gradual rewarming of both groups to 37 °C (hourly increments of 0.5 °C) after the initial 28 hours. Body temperatures in both the groups were then maintained below 37.5 °C for 72 hours after the initial 36 hours.

OUTCOMES: Primary outcome measure of all-cause mortality in both the groups at the end of the trial with the secondary outcome measure of all-cause mortality, composite neurological function as evaluated by cerebral performance category scale and modified ranking scale at the end of 180 days were studied.

RESULTS: Out of the 939 participants, all-cause mortality at the end of the trial was 50 % in the 33 °C group (225 of 466 patients) compared with 48 % in the 36 °C group (235 of 473 patients); the hazard ratio with a temperature of 33 °C was 1.06 (95 % confidence interval (CI) 0.89 to 1.28, P = 0.51). At the end of 180 days, 54 % of patients in the 33 °C group versus 52 % in the 36 °C group had died or had poor neurological outcome according to cerebral performance category (risk ratio 1.02, 95 % CI 0.88 to 1.16, P = 0.78) but the modified ranking scale at the end of 180 days was unchanged (52 %) in both groups (risk ratio 1.01, 95 % CI 0.89 to 1.14, P = 0.87).

CONCLUSIONS: Maintaining targeted lower normothermia of 36 °C had similar outcomes compared with induced moderate hypothermia of 33 °C for unconscious survivors of OHCA of presumed cardiac cause.