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

Importance Comatose survivors of out-of-hospital cardiac arrest experience high rates of death and severe neurologic injury. Current guidelines recommend targeted temperature management at 32 degrees C to 36 degrees C for 24 hours. However, small studies suggest a potential benefit of targeting lower body temperatures. Objective To determine whether moderate hypothermia (31 degrees C), compared with mild hypothermia (34 degrees C), improves clinical outcomes in comatose survivors of out-of-hospital cardiac arrest. Design, Setting, and Participants Single-center, double-blind, randomized, clinical superiority trial carried out in a tertiary cardiac care center in eastern Ontario, Canada. A total of 389 patients with out-of-hospital cardiac arrest were enrolled between August 4, 2013, and March 20, 2020, with final follow-up on October 15, 2020. Interventions Patients were randomly assigned to temperature management with a target body temperature of 31 degrees C (n = 193) or 34 degrees C (n = 196) for a period of 24 hours. Main Outcomes and Measures 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. Results Among 367 patients included in the primary analysis (mean age, 61 years; 69 women [19%]), 366 (99.7%) completed the trial. The primary outcome occurred in 89 of 184 patients (48.4%) in the 31 degrees C group and in 83 of 183 patients (45.4%) in the 34 degrees C group (risk difference, 3.0% [95% CI, 7.2%-13.2%]; relative risk, 1.07 [95% CI, 0.86-1.33]; P = .56). 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 degrees C and 34 degrees C, respectively (P = .63). The median length of stay in the intensive care unit was longer in the 31 degrees C group (10 vs 7 days; P = .004). Among adverse events in the 31 degrees C group vs the 34 degrees 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. Conclusions and Relevance In comatose survivors of out-of-hospital cardiac arrest, a target temperature of 31 degrees C did not significantly reduce the rate of death or poor neurologic outcome at 180 days compared with a target temperature of 34 degrees C. However, the study may have been underpowered to detect a clinically important difference. This randomized trial assesses the effect of therapeutic hypothermia at target temperatures of 31 degrees C vs 34 degrees C for 24 hours on all-cause mortality or poor neurologic outcome at 180 days among comatose survivors of out-of-hospital cardiac arrest. Question Does moderate hypothermia (target temperature of 31 degrees C) compared with mild hypothermia (target temperature of 34 degrees C) reduce the rate of death or poor neurologic outcome in comatose survivors of out-of-hospital cardiac arrest? Findings In this randomized clinical trial that included 367 adults with out-of-hospital cardiac arrest, 180-day all-cause mortality or poor neurologic outcome among those randomized to receive hypothermia treatment at 31 degrees C vs 34 degrees C was 48.4% vs 45.4%, respectively. This difference was not statistically significant. Meaning In comatose survivors of out-of-hospital cardiac arrest, a target temperature of 31 degrees C did not significantly reduce the rate of death or poor neurologic outcome at 180 days compared with a target temperature of 34 degrees C.

Automated summary

This study compared the clinical outcomes of comatose survivors of out-of-hospital cardiac arrest with target temperatures of 31 degrees C and 34 degrees C, and found that there was no significant difference in all-cause mortality or poor neurologic outcome between the two groups.