Extended Cooling No Better Than Shorter Duration After Cardiac Arrest

Extending the duration of therapeutic hypothermia beyond a few hours did not improve neurological outcomes in comatose survivors of out-of-hospital cardiac arrest (OHCA), addressing the longstanding question of whether longer cooling provides additional neuroprotection, according to a large, adaptive-design randomized trial published in JAMA.¹

“No clinical strategy has implemented therapeutic hypothermia in comatose survivors of OHCA in a manner that consistently demonstrates efficacy despite extensive preclinical research identifying the mechanisms underlying hypothermic neuroprotection in global cerebral ischemia,” the researchers wrote. “The results of the current study demonstrate that increasing cooling duration, as performed and evaluated in this trial in broadly representative and inclusive cohorts of patients after OHCA, does not improve outcomes.”

The ICECAP trial (NCT04217551), conducted by the Strategies to Innovate Emergency Care Clinical Trials Network at 71 US hospitals, enrolled 1158 adults with OHCA between June 2020 and June 2025. Patients were cooled to 33°C and randomized using a response-adaptive allocation algorithm to cooling durations ranging from 6 to 72 hours. However, enrollment stopped before any patients were assigned to the 60- or 72-hour groups after a prespecified interim analysis. The trial separately evaluated patients with nonshockable (n = 883) and shockable (n = 275) presenting rhythms to account for differences in injury severity.

Duration Made No Difference

The primary outcome was a weighted modified Rankin Scale score at 90 days, reflecting both survival and degree of neurological recovery. In the nonshockable rhythm cohort, the posterior probability that 6 hours was the shortest duration achieving the best attainable neurological outcome was 0.51; in the shockable rhythm cohort, it was 0.49.

In neither group did the duration-response curve trend upward with longer cooling, and the trial met a prespecified interim stopping rule because the predefined threshold for identifying the shortest optimal cooling duration had been reached. Secondary neuropsychological testing using the National Institutes of Health Toolbox Cognition Battery showed no meaningful differences across cooling durations.

Overall 90-day mortality was 74.4% (81.3% in the nonshockable cohort; 52.0% in the shockable cohort), with no differences in mortality observed across cooling durations. The most common study-defined adverse event was neurological worsening. Despite the sobering mortality figures, the authors noted that the approximately 20% survival rate among patients with nonshockable rhythms is more encouraging than commonly assumed, given the common perception that these patients rarely survive.

The findings add to a series of trials evaluating temperature management strategies after cardiac arrest, including studies comparing 33°C vs 36°C targets and hypothermia with fever-prevention strategies, none of which demonstrated the superiority of alternative temperature management approaches over existing practice. Nationally, only about 10% of adults who experience emergency medical services-treated OHCA survive to hospital discharge, underscoring the continued need for effective post-arrest therapies.²

However, the authors cautioned that ICECAP's inclusive eligibility criteria, while strengthening generalizability, also resulted in a higher-than-expected proportion of patients with nonshockable rhythms, reducing the number of neurologically intact survivors available to inform the duration-response curve.¹ They also noted that restricting enrollment to patients who reached target temperature within 4 hours may have inadvertently selected patients with more severe neurological injury who were easier to cool because of impaired thermoregulation.

The findings support shorter, standardized hypothermia durations rather than prolonged cooling regimens, which require additional intensive care unit resources and nursing time and may increase the risk of complications such as infection or coagulopathy without demonstrated neurological benefit. Care management teams overseeing post-arrest and neurocritical care pathways may want to revisit utilization criteria that assume extended cooling improves outcomes and instead emphasize consistent implementation of evidence-based temperature management and standardized neuroprognostication practices, both of which remain central to contemporary resuscitation guidelines.

“Among comatose survivors of out-of-hospital cardiac arrest treated with therapeutic hypothermia at 33°C, increasing cooling duration did not improve neurological outcomes,” the researchers wrote. “Duration of therapeutic hypothermia should not be routinely extended in comatose survivors of cardiac arrest.”

References

1. Meurer WJ, Yeatts SD, Geocadin RG, et al. Duration of therapeutic hypothermia after out-of-hospital cardiac arrest: the ICECAP randomized clinical trial. JAMA. Published online August 5, 2026. doi:10.1001/jama.2026.10247
2. 2025 heart disease and stroke statistics update fact sheet. American Heart Association. January 27, 2025. Accessed August 4, 2026. https://www.heart.org/en/-/media/PHD-Files-2/Science-News/2/2025-Heart-and-Stroke-Stat-Update/2025-Statistics-At-A-Glance.pdf