Targeted Hypothermia vs Targeted Normothermia in Survivors of Cardiac Arrest: A Systematic Review and Meta-Analysis of Randomized Trials

Background: The role of targeted hypothermia in patients with coma after cardiac arrest has been challenged in a recent randomized clinical trial. Methods: We performed a computerized search of MEDLINE, EMBASE, and Cochrane databases through July 2021 for randomized trials evaluating the outcomes of targeted hypothermia vs normothermia in patients with coma after cardiac arrest with shockable or non-shockable rhythm. The main study outcome was mortality at the longest reported follow-up. Results: The final analysis included 8 randomized studies with a total of 2927 patients, with a weighted follow-up period of 4.9 months. The average targeted temperature in the hypothermia arm in the included trials varied from 31.7°C to 34°C. There was no difference in long-term mortality between the hypothermia and normothermia groups (56.2% vs 56.9%, risk ratio [RR] 0.96; 95% confidence interval [CI], 0.87-1.06). There was no significant difference between hypothermia and normothermia groups in rates of favorable neurological outcome (37.9% vs 34.2%, RR 1.31; 95% CI, 0.99-1.73), in-hospital mortality (RR 0.88; 95% CI, 0.77-1.01), bleeding, sepsis, or pneumonia. Ventricular arrhythmias were more common among the hypothermia vs normothermia groups (RR 1.36; 95% CI, 1.17-1.58; P = .42). Sensitivity analysis, excluding the Targeted Hypothermia vs Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial, showed favorable neurological outcome with hypothermia vs normothermia (RR 1.45; 95% CI, 1.17-1.79). Conclusion: Targeted temperature management was not associated with improved survival or neurological outcomes compared with normothermia in comatose patients after cardiac arrest. Further studies are warranted to further clarify the value of targeted hypothermia compared with targeted normothermia.