Induced Hypothermia in Patients with Cardiac Arrest and a Non-shockable Rhythm: Meta-analysis and Trial Sequential Analysis

Background: Controversy surrounds utilization of induced hypothermia (IHT) in comatose cardiac arrest (CA) survivors with a non-shockable rhythm.

Methods: We conducted a meta-analysis and trial sequential analysis (TSA) comparing IHT with no IHT approaches in patients with CA and a non-shockable rhythm. The primary outcome of interest was favorable neurological outcomes (FNO) defined using the Cerebral Performance Category (CPC) score of 1 or 2. Secondary endpoints were survival at discharge and survival beyond 90 days.

Results: A total of 9 studies with 10,386 patients were included. There was no difference between both groups in terms of FNO (13% vs. 13%, RR 1.34, 95% CI 0.96-1.89, p = 0.09, I² = 88%), survival at discharge (20% vs. 22%, RR 1.09, 95% CI 0.88-1.36, p = 0.42, I² = 76%), or survival beyond 90 days (16% vs. 15%, RR 0.92, 95% CI 0.61-1.40, p = 0.69, I² = 83%). The TSA showed firm evidence supporting the lack of benefit of IHT in terms of survival at discharge. However, the Z-curves failed to cross the conventional and TSA (futility) boundaries for FNO and survival beyond 90 days, indicating lack of sufficient evidence to draw firm conclusions regarding these outcomes.

Conclusion: In this meta-analysis of 9 studies, the utilization of IHT was not associated with a survival benefit at discharge. Although the meta-analysis showed lack of benefit of IHT in terms of FNO and survivals beyond 90 days, the corresponding TSA showed high probability of type-II statistical error, and therefore more randomized controlled trials powered for these outcomes are needed.