Hypothermia versus normothermia after out-of-hospital cardiac arrest: A systematic review and meta-analysis of randomized controlled trials

Abstract

Background: The current guidelines recommend targeted temperature management (TTM) as part of the post-resuscitation care for comatose patients following out-of-hospital cardiac arrest. These recommendations are based on the weak evidence of benefit seen in the early clinical trials. Recent large multicentered trials have failed to show a meaningful clinical benefit of hypothermia, unlike the earlier studies. Thus, to fully appraise the available data, we sought to perform this systematic review and meta-analysis of randomized controlled trials. Methods: We searched four databases for randomized controlled trials comparing therapeutic hypothermia (32–34 °C) with normothermia (≥36 °C with control of fever) in adult patients resuscitated after out-of-hospital cardiac arrest. Independent reviewers did the title and abstract screening, full-text screening, and extraction. The primary outcome was mortality six months after cardiac arrest, and secondary outcomes were neurological outcomes and adverse effects. Relevance for patients: Six randomized controlled trials were included in this review. There was no significant difference between the hypothermia and normothermia groups in mortality till 6 months follow up after out-of-hospital cardiac arrest (OR 0.88, 95% CI 0.67–1.16; n = 3243; I2 = 51%), or favorable neurological outcome (OR 1.31, 95% CI 0.93–1.84; n = 3091; I2 = 68%). Rates of arrhythmias were notably higher in the hypothermia group than the normothermia group (OR 1.43, 95% CI 1.20–1.71; n = 3029; I2 = 4%). However, odds for development of pneumonia showed no significant differences across two groups (OR 1.13, 95% CI 0.98–1.31; n = 3056; I2 = 22%). Therefore, targeted hypothermia with a target temperature of 32–34 °C does not provide mortality benefit or better neurological outcome in patients resuscitated after the out-of-hospital cardiac arrest when compared with normothermia.