The effect of mild induced hypothermia on outcomes of patients after cardiac arrest: a systematic review and meta-analysis of randomised controlled trials

Introduction: Mild induced hypothermia (MIH) is believed to reduce mortality and neurological impairment after out-of-hospital cardiac arrest. However, a recently published trial demonstrated that hypothermia at 33 degrees C did not confer a benefit compared with that of 36 degrees C. Thus, a systematic review and meta-analysis of randomised controlled trials (RCTs) was made to investigate the impact of MIH compared to controls on the outcomes of adult patients after cardiac arrest. Methods: We searched the following electronic databases: PubMed/MEDLINE, the Cochrane Library, Embase, the Web of Science, and Elsevier Science (inception to December 2014). RCTs that compared MIH with controls with temperature >34 degrees C in adult patients after cardiac arrest were retrieved. Two investigators independently selected RCTs and completed an assessment of the quality of the studies. Data were analysed by the methods recommended by the Cochrane Collaboration. Random errors were evaluated with trial sequential analysis. Results: Six RCTs, including one abstract, were included. The meta-analysis of included trials revealed that MIH did not significantly decrease the mortality at hospital discharge (risk ratio (RR) = 0.92; 95 % confidence interval (CI), 0.82-1.04; p = 0.17) or at 6 months or 180 days (RR = 0.94; 95 % CI, 0.73-1.21; p = 0.64), but it did reduce the mortality of patients with shockable rhythms at hospital discharge (RR = 0.74; 95 % CI, 0.59-0.92; p = 0.008) and at 6 months or 180 days. However, MIH can improve the outcome of neurological function at hospital discharge (RR = 0.80; 95 % CI, 0.64-0.98; p = 0.04) especially in those patients with shockable rhythm but not at 6 months or 180 days. Moreover, the incidence of complications in the MIH group was significantly higher than that in the control group. Finally, trial sequential analysis indicated lack of firm evidence for a beneficial effect. Conclusion: The available RCTs suggest that MIH does not appear to improve the mortality of patients with cardiac arrest while it may have a beneficial effect for patients with shockable rhythms. Although MIH may result in some adverse events, it helped lead to better outcomes regarding neurological function at hospital discharge. Large-scale ongoing trials may provide data better applicable to clinical practice.