Which Target Temperature for Post-Anoxic Brain Injury? A Systematic Review from "Real Life" Studies

There is a persistent debate on the optimal target temperature to use during cooling procedures in cardiac arrest survivors. A large randomized clinical trial (RCT) including more than 900 patients showed that targeted temperature management (TTM) at 33 degrees C had similar mortality and unfavorable neurological outcome (UO) rates as TTM at 36 degrees C in out-of-hospital cardiac arrest patients with any initial rhythm. Since then, several observational studies have been published on the effects of changes in target temperature (i.e., from 33 to 36 degrees C) on patients' outcome. We performed a systematic literature search from 1 January 2014 to 4 December 2020 and identified ten retrospective studies (very low levels of certainty; high risk of bias), including 5509 patients, that evaluated TTM at 33 degrees C vs. TTM at 36 degrees C on the occurrence of UO (n = eight studies) and mortality (n = ten studies). TTM at 33 degrees C was associated with a lower risk of UO when studies assessing neurological outcome with the Cerebral Performance Categories were analyzed (OR 0.80 [95% CIs 0.72-0.98]; p = 0.03). No differences in mortality were observed within the two TTM strategies. These results suggest that an inappropriate translation of TTM protocols from large well-conducted randomized trials into clinical management may result in unexpected effects on patients' outcome. As for all newly commercialized drugs, epidemiological studies and surveillance programs with an adequate follow-up on large databases are necessary to understand how RCTs are implemented into medical practice.