Impact of therapeutic hypothermia during cardiopulmonary resuscitation on neurologic outcome: A systematic review and meta-analysis

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) 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 survival to hospital discharge.

Results: Out of 20,950 studies, 8 studies (n = 3493 patients, including 4 randomized trials, RCTs) were included in the final analysis. Compared to controls, the use of IATH was not associated with improved FO (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 (OR 0.91 [95% CIs 0.73-1.14]; p = 0.43). Significant heterogeneity among studies was observed for the analysis of ROSC rate (I² = 69%). Trans-nasal evaporative cooling and cold fluids were explored in two RCTs each and no differences were observed on FO, event when only patients with an initial shockable rhythm were analyzed (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, based on very low certainty of evidence.

Clinical trial registration: PROSPERO (CRD42019130322).