Targeted temperature management after cardiac arrest. A systematic review and meta-analysis of animal studies

Animal studies are an important knowledge base when information from clinical trials is missing or conflicting. The goal of this systematic review and meta-analysis was to investigate the effect of conventional targeted temperature management (TTM) between 32-36 °C in animal cardiac arrest models, and to estimate the influence of effect modifiers on the pooled effect of TTM.We searched Medline and Scopus from inception to May 2020 for randomised controlled animal trials assessing the effect of conventional TTM versus normothermia on neurologic outcome after cardiac arrest. We extracted data on study characteristics, study quality data, neurologic outcome, mortality, and potential effect modifiers.We retrieved 1635 studies, 45 studies comprising data of 981 animals met the inclusion criteria. Risk of bias was high in 17 studies and moderate in 28 studies. We undertook random-effects meta-analyses and meta-regression analyses to calculate the pooled effect and the influence of effect modifiers. There was a strong beneficial effect of TTM as compared to normothermia on neurologic outcome (standardised mean difference of 1.4 [95% CI -1.7 to -1.1; I2 = 75%]). Faster cooling rates, lower target temperature of TTM within the range of 32-36 °C, and shorter duration of cooling were independently associated with an increasing effect size of TTM.This systematic review of animal cardiac arrest studies showed a consistent favourable effect of postresuscitation TTM as compared to normothermia on neurologic outcome that increased with lower target temperatures.