Does Therapeutic Hypothermia Improve Outcomes in Comatose Survivors of OOH Cardiac Arrest?

Moderate hypothermia therapy (31°C) did not significantly reduce the rate of mortality or poor neurologic outcome compared with mild hypothermia therapy (34°C) in comatose survivors of out-of-hospital cardiac arrest, according to research published in JAMA.

For the study, researchers enrolled patients (N=389) for the CAPITAL CHILL Randomized Clinical Trial ( Identifier: NCT02011568) at a tertiary cardiac care center in Ontario, Canada between August 2013 and March 2020, with a final follow-up in October 2020. All patients had out-of-hospital cardiac arrest and remained comatose at the time of admission. Researchers randomly assigned patients to receive temperature management with either moderate hypothermia or mild hypothermia.

The primary outcome was all-cause mortality or poor neurologic outcome measured at 180 days after randomization, using the Disability Rating Scale (DRS). The primary outcome was reached in 48.4% of patients in the moderate hypothermia group and in 45.4% of patients in the mild hypothermia group (risk difference, 3.0% [95% CI, -7.2% to 13.2%]; relative risk [RR], 1.07 [95% CI, 0.86-1.33]; P =.56). All-cause mortality was 43.5% in the moderate group and 41.0% in the mild group (risk difference, 2.5% [95% CI, -7.6% to 12.6%]; RR, 1.06 [95% CI, 0.83-1.35]; P =.63). DRS scores greater than 5 were recorded for 8.7% in the moderate group and 7.4% in the mild group (risk difference, 1.3% [95% CI, -6.1% to 8.6%]; RR, 1.17 [95% CI, 0.47-2.91]; P =.74).

This study was limited by a small sample size based on a 15% absolute risk reduction. According to the researchers, these results may not be applicable to cardiac arrest of all etiologies.

“To our knowledge, this study is the first randomized clinical trial to evaluate the benefits of therapeutic hypothermia with a target temperature below 32°C,” the researchers stated. “This trial … should be interpreted alongside the TTM trial (33°C vs 36°C), the FROST-I trial (32°C vs 33°C vs 34°C), and the Time-Differentiated Therapeutic Hypothermia (TTH48) trial (24 hours vs 48 hours of target temperature at 33°C), all of which have reported neutral results. One important consideration is that there may not be a single, optimal target temperature for all patients with cardiac arrest, as the treatment effect of therapeutic hypothermia could be modulated by several clinical variables.”


Le May M, Osborne C, Russo J, et al. Effect of moderate vs mild therapeutic hypothermia on mortality and neurologic outcomes in comatose survivors of out-of-hospital cardiac arrest: the CAPITAL CHILL randomized clinical trial. JAMA. 2021;326(15):1494-