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

Abstract

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 °C had similar mortality and unfavorable neurological outcome (UO) rates as TTM at 36 °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 °C) on patients’ outcome. We performed a systematic literature search from 1 January 2014 to 4 December 2020 and identified nine retrospective studies (very low levels of certainty; high risk of bias), including 3799 patients, that evaluated TTM at 33 °C vs. TTM at 36 °C on the occurrence of UO (n = seven studies) and mortality (n = nine studies). TTM at 33 °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 0.65–0.99]; p = 0.04). 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.

Clinical Outcomes with Targeted Temperature Management (TTM) in Comatose Out-of-Hospital Cardiac Arrest Patients—A Retrospective Cohort Study

“…This result is in line with the result of the study carried out by Nielsen et al [ 4 ]. In recent years, two other studies have been carried out, one of which shows the same results [ 18 ]. In contrary, the HYPERION study showed a higher percentage of favorable neurologic outcomes among patients with a non-shockable cardiac arrest treated with mild hypothermia (33 °C) [ 19 ].…”

ERC-ESICM guidelines on temperature control after cardiac arrest in adults

“…[37][38][39] In one systematic review including nine of these observational studies (2014-2020) this was associated with worse neurological outcomes but no change in mortality. 40 Similarly, a recent analysis accounting for time trend and variation between 235 critical care units in United Kingdom found no significant change in crude mortality associated with the change in practice that followed the TTM publication. 39 All members of the We recommend continuous monitoring of core temperature in patients who remain comatose after ROSC from cardiac arrest (good practice statement).…”

ERC-ESICM guidelines on temperature control after cardiac arrest in adults

“…Observational evidence shows that after the publication of the TTM trial in 2013 the use of temperature control after cardiac arrest declined [37][38][39]. In one systematic review including nine of these observational studies (2014-2020) this was associated with worse neurological outcomes but no change in mortality [40]. Similarly, a recent analysis accounting for time trend and variation between 235 critical care units in United Kingdom found no significant change in crude mortality associated with the change in practice that followed the TTM publication [39].…”