Targeted Temperature Management for Cardiac Arrest Due to Non-shockable Rhythm: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Targeted temperature management (TTM) is recommended in adult patients following cardiac arrest (CA) with any rhythm. However, as to non-shockable (NSR) CA, high-quality evidence of TTM supporting its practices remains uncertain. Thus, we aimed to conduct a systematic review and meta-analysis with randomized controlled trials (RCTs) to explore the efficacy and safety of TTM in this population. Methods: We searched PubMed, Embase, and Cochrane library databases for potential trials from inception through Aug 25, 2021. RCTs evaluating TTM for CA adults due to NSR were included, regardless of the timing of cooling initiation. Outcome measurements were mortality and good neurological function. We used the Cochrane bias tools to evaluate the quality of the included studies. Heterogeneity, subgroup analyses, and sensitivity analysis were investigated to test the robustness of the primary outcomes. Results: A total of 14 RCTs with 4,009 adults were eligible for the final analysis. All trials had a low to moderate risk of bias. Of the included trials, six compared NSR patients with or without TTM, while eight compared pre-hospital to in-hospital TTM. Pooled data showed that TTM was not associated with improved mortality (Risk ratio [RR] 1.00; 95% CI, 0.944-1.05; P = 0.89, I-2 = 0%) and good neurological outcome (RR 1.18; 95% CI 0.90-1.55; P = 0.22, I-2 = 8%). Similarly, use of pre-hospital TTM resulted in neither an improved mortality (RR 0.99, 95% CI 0.97-1.03; I-2 = 0%, P = 0.32) nor favorable neurological outcome (RR 1.13, 95% CI 0.93-1.38; I-2 = 0%, P = 0.22). These results were further confirmed in the sensitivity analyses and subgroup analyses. Conclusions: Our results showed that using the TTM strategy did not significantly affect the mortality and neurologic outcomes in CA survival presenting initial NSR.