Impact of Therapeutic Hypothermia During Cardiopulmonary Resuscitation on Neurologic Outcome: A Systematic Review and Meta-analysis

Abstract Background: Therapeutic cooling initiated during cardiopulmonary resuscitation (intra arrest therapeutic hypothermia, IATH) provided diverging effect on neurological outcome of out-of-hospital cardiac arrest (OHCA) patients depending on the initial cardiac rhythm and the cooling methods used. Methods: We performed a systematic search of PubMed, EMBASE and the CENTRAL databases using established Medical Subject Headings (MeSH) terms for IATH and OHCA. Only studies comparing IATH to standard in-hospital targeted temperature management (TTM – control group) were selected. We used the revised Cochrane RoB-2 and the Newcastle-Ottawa scale tool to assess risk of bias of each study. Primary outcome was favorable neurological outcome (FO); secondary outcomes included return of spontaneous circulation (ROSC) rate and overall survival to hospital discharge. Two authors independently assessed the validity of included human studies and extracted data regarding characteristics of the studied cohorts and main outcomes. Results: Out of 20950 studies, 8 studies (n=3493 patients, including 4 randomized trials, RCTs) were included in the final analysis. When compared to controls, the use of IATH was not associated with improved favorable neurological outcome (OR 0.96 [95% CIs 0.68-1.37]; p= 0.84), increased ROSC rate (OR 1.11 [95% CIs 0.83-1.49]; p= 0.46) or survival to hospital discharge (OR 0.91 [95% CIs 0.73-1.14]; p= 0.43). Significant heterogeneity among studies was observed only for the analysis of ROSC rate ( I 2 =69%). Trans-nasal evaporative cooling and cold fluids were explored in two RCTs each and no significant differences were observed on neurological outcome. However, trans-nasal evaporative cooling was associated with a higher probability of favorable neurological outcome when compared to controls in patients with an initial shockable rhythm (OR 1.62 [95% CI 1.00-2.64]; p=0.05]. Conclusions: In this meta-analysis, IATH was not associated with improved neurological outcome when compared to standard in-hospital TTM. However, there are considerable outcome differences depending on the methods used and the studied population that need to be explored in future trials. Clinical Trial Registration: PROSPERO (CRD42019130322)