Therapeutic Hypothermia and Neurological Outcomes After Adult Cardiac Arrest: A Meta-Analysis With Trial Sequential Analysis

Background:Cardiac arrest (CA) is associated with poor neurological outcomes.The neuroprotective role of therapeutic hypothermia (TH) remains controversial.We hypothesized that TH would be associated with a higher likelihood of favorable neurological outcome at hospital discharge. Material/Methods:PubMed, Embase, and the Cochrane Library were searched through August 2025.Randomized controlled trials (RCTs) and cohort studies comparing hypothermia (32-34 °C) with controlled normothermia (36-38 °C) were included.The primary outcome was favorable neurological outcome at hospital discharge, defined as a Cerebral Performance Category (CPC) score of 1-2 or a modified Rankin Scale (mRS) score of 0-3.Secondary outcomes were favorable neurological outcome at 180-day follow-up, hospital mortality, and adverse events.Pooled estimates were calculated using the Mantel-Haenszel method, with fixed-or random-effects models applied according to heterogeneity, with pre-specified subgroup analyses.Trial sequential analysis (TSA) was performed for the primary outcome to assess the robustness of the pooled estimates. Results:Ten RCTs and 19 cohort studies involving 33 696 patients were included.In RCTs, TH was associated with a higher likelihood of favorable neurological outcome at hospital discharge (RR = 1.40; 95% CI, 1.10-1.77;I 2 = 47%).No significant improvement was observed in neurological outcomes at 180-day follow-up.A small borderline reduction in hospital mortality was observed in the hypothermia group (RR = 0.9268; 95% CI, 0.8620-0.9963;P = 0.04).TSA indicated insufficient randomized evidence.TH was associated with more arrhythmia, while other adverse events were similar.Subgroup analyses showed no significant interaction by initial rhythm.Observational studies suggested better neurological outcomes and lower mortality with TH but showed substantial heterogeneity.Conclusions:TH may be associated with better neurological outcomes at hospital discharge after CA, but TSA indicated that the current randomized evidence remains insufficient to confirm a definitive benefit.No significant improvement was observed in neurological outcomes at 180-day follow-up.A small borderline reduction in hospital mortality was observed, while no demonstrated subgroup interaction was identified by initial rhythm.Further adequately powered RCTs are needed to clarify patient selection and optimize hypothermic temperature control strategies.