November 04, 2025

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No Significant Benefit Of Moderate Hypothermia Versus Mild Hypothermia In Comatose Survivors: JAMA

Study on Target Temperature in Cardiac Arrest Survivors

Study on Target Temperature in Cardiac Arrest Survivors

According to a recent study in JAMA, a target temperature of 31 °C did not significantly reduce the rate of death or poor neurologic outcome at 180 days versus a target temperature of 34 °C in comatose survivors of out-of-hospital cardiac arrest.

Comatose survivors of out-of-hospital cardiac arrest have been shown to experience high rates of death and severe neurologic injury. Current guidelines recommend targeted temperature management at 32 °C to 36 °C for 24 hours. However, few studies have suggested a potential benefit of targeting lower body temperature.

Against the above background, a team of researchers led by Michel Le May from the University of Ottawa Heart Institute, Ottawa, Ontario, Canada, aimed to determine whether moderate hypothermia (target temperature of 31 °C) compared with mild hypothermia (target temperature of 34 °C) improves clinical outcomes in comatose survivors of out-of-hospital cardiac arrest.

For this purpose, the researchers designed a single-center, double-blind, randomized, clinical superiority trial (The CAPITAL CHILL Randomized Clinical Trial) in a tertiary cardiac care center in eastern Ontario, Canada. It enrolled a total of 389 patients with out-of-hospital cardiac arrest between August 4, 2013, and March 20, 2020.

Patients were randomly assigned to temperature management with a target body temperature of 31 °C (n = 193) or 34 °C (n = 196) for a period of 24 hours.

The primary outcome was all-cause mortality or poor neurologic outcome at 180 days. Neurologic outcome was assessed using the Disability Rating Scale, with poor neurologic outcome defined as a score greater than 5 (range, 0-29, with 29 being the worst outcome [vegetative state]). There were 19 secondary outcomes, including mortality at 180 days and length of stay in the intensive care unit.

Of 367 patients included in the primary analysis (mean age, 61 years; 69 women [19%]), 366 (99.7%) completed the trial.

Key Findings from the Study

  • The primary outcome occurred in 89 of 184 patients (48.4%) in the 31 °C group and in 83 of 183 patients (45.4%) in the 34 °C group (risk difference, 3.0%; relative risk, 1.07).
  • Of the 19 secondary outcomes, 18 were not statistically significant. Mortality at 180 days was 43.5% and 41.0% in patients treated with a target temperature of 31 °C and 34 °C, respectively.
  • The median length of stay in the intensive care unit was longer in the 31 °C group (10 vs 7 days).
  • Among adverse events in the 31 °C group vs the 34 °C group, deep vein thrombosis occurred in 11.4% vs 10.9%, and thrombus in the inferior vena cava occurred in 3.8% and 7.7%, respectively.

"A target temperature of 31 °C did not significantly reduce the rate of death or poor neurologic outcome at 180 days in comatose survivors of out-of-hospital cardiac arrest, compared with a target temperature of 34 °C," wrote the authors. "However, the study may have been underpowered to detect a clinically important difference."

Reference

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):1494–1503. doi:10.1001/jama.2021.15703

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