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; I 2 = 51%), or favorable neurological outcome (OR 1.31, 95% CI 0.93–1.84; n = 3091; I 2 = 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; I 2 = 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; I 2 = 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.

Therapeutic Hypothermia Following Cardiopulmonary Arrest: A Systematic Review and Meta-Analysis with Trial Sequential Analysis

“…Clinically, favorable neurologic outcome is defined by the mRS or CPC scores, which describe the functionality of a patient after suffering a neurologic injury [16,17]. Similar to previous meta-analyses, our meta-analysis revealed no overall neurologic benefit of therapeutic hypothermia when compared to normothermia [18][19][20][21][22][23]. TSA of favorable neurologic outcome demonstrated the futility of therapeutic hypothermia compared to normothermia, suggesting further randomized controlled studies should likely not be conducted with this outcome.…”

The safety and efficacy of hypothermia combining mechanical thrombectomy or thrombolysis in the treatment of ischemic stroke: A systematic meta-analysis

“… 32 In addition, some other studies have shown different results, concluding that hypothermia does not improve patient outcomes, suggesting that more trials are needed in the future to determine the efficacy of clinical hypothermia treatment. 33 , 34 …”

Target temperature management versus normothermia without temperature feedback systems for out-of-hospital cardiac arrest survivors

“…The results of a recent comprehensive meta-analysis further indicated no differences in neurological or survival outcomes between targeted hypothermia (32-34 C) and normothermia (!36 C with fever control) for comatose OHCA patients. 23 The European Resuscitation Council-European Society of Intensive Care Medicine (ERC-ESCIM) guidelines still recommend TTM with a TFS. Active fever control with simple surface cooling using wet towels and ice can be considered in low-resource settings.…”

“…The results of a recent comprehensive meta-analysis further indicated no differences in neurological or survival outcomes between targeted hypothermia (32–34°C) and normothermia (≥36°C with fever control) for comatose OHCA patients. 23 …”