Dankiewicz J, Cronberg T, Lilja G, et al. - Summarized by David L. Brown, MD This international investigator-initiated superiority trial screened unconscious patients > 18 years of age who had more than 20 consecutive minutes of spontaneous circulation after resuscitation following a presumed cardiac arrest or arrest of unknown cause from November 2017 to January 2020. Randomization was performed with a Web-based system involving permuted blocks of varying sizes and was stratified according to trial site. Health care professionals caring for the patients were not blinded to treatment assignment but those assessing neurologic prognosis, assessors of functional outcome and study administrators were unaware to treatment assignment. The intervention period began at randomization and lasted for 40 hours. The primary outcome was death from any cause at 6 months. The main secondary outcome was poor functional outcome defined as a score of 4-6 on the modified Rankin scale at 6 months. The sample size analysis estimated that 1862 patients would provide 90% power to detect a relative reduction of 15% in the risk of death in the hypothermia group. Data on the primary outcome were missing on 11 patients (<1%)-5 in the hypothermia group and 6 in the normothermia group. At 6 months 465 of 925 patients (50%) in the hypothermia group and 446 of 925 patients (48%) in the normothermia group had died (RR 1.04; 95% CI: 0.94-1.14, P=0.37). The effect of temperature intervention was consistent across all prespecified subgroups. At 6 months, 488 of 881 patients (55%) in the hypothermia group and 479 of 886 (55%) had a modified Rankin score of 4-6 (RR 1.00; 95% CI: 0.91-1.08). Arrhythmias resulting in hemodynamic compromise were more common in the hypothermia group (24% vs. 17%; P<0.001). Of note, 50% of patients in the normothermia group were cooled to treat fever.

The original trials of hypothermia published in the NEJM in 2002 changed practice with their reports that found hypothermia to be beneficial in OHCA. A meta-analysis published in 2011 found that the available trials at that time had a high risk of bias and random errors. The current trial has 5 times the sample size of the earlier trials. In addition, the supportive care of OHCA patients may have improved over the last 2 decades, negating any benefit of hypothermia. Thus, given these results, targeted hypothermia cannot be recommended for survivors of OHCA. It remains to be studied whether cooling to treat fever offers any benefit.