Target cooling temperatures in cardiac arrest – should we just focus on avoiding fever instead?

Prior trials of out-of-hospital cardiac arrest of presumed cardiac etiology have demonstrated improved survival and neurologic function when patients are treated with therapeutic hypothermia. Questions remain as to the optimal target temperature for therapeutic hypothermia. In this international study of patients with out-of-hospital cardiac arrest, 950 patients were randomly assigned to therapeutic hypothermia at a target temperature of either 33°C or 36°C. Treating physicians were aware of the patient’s assignment and all therapies to achieve targets were at the treating center’s discretion. Mean follow-up was 256 days and the primary outcome was death with secondary outcomes including assessments of neurological recovery. No benefit was observed with treatment to target temperature of 33°C. Compared to patients treated to 36°C, patients treated to 33°C had similar mortality (hazard ratio, 1.06; 95% CI, 0.89 to 1.28; P=0.51) and neurologic recovery (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78) Pre-specified sub-group analyses also failed to demonstrate statistically significant differences between the two target temperatures.

Conclusions:

In this study of patients suffering out-of-hospital cardiac arrest, there was no benefit seen in cooling to a target of 33°C as opposed 36°C. This study raises questions as to the benefits of hypothermia in cardiac arrest. It may be that patient cooling results in avoidance of fever and thereby improves outcomes, rather than cooling itself providing patient benefit.

Summarized by Steven M. Bradley and Hussain Contractor

  • Nielsen N, 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 and Friberg H. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med. 2013 Dec 5;369(23):2197-206.