Targeted Temperature Management for 48 vs 24 Hours and Neurologic Outcome After Out-of-Hospital Cardiac Arrest A Randomized Clinical Trial

IMPORTANCE International resuscitation guidelines recommend targeted temperature management (TTM) at 33 degrees C to 36 degrees C in unconscious patients with out-of-hospital cardiac arrest for at least 24 hours, but the optimal duration of TTM is uncertain. OBJECTIVE To determine whether TTM at 33 degrees C for 48 hours results in better neurologic outcomes compared with currently recommended, standard, 24-hour TTM. DESIGN, SETTING, AND PARTICIPANTS This was an international, investigator-initiated, blinded-outcome-assessor, parallel, pragmatic, multicenter, randomized clinical superiority trial in 10 intensive care units (ICUs) at 10 university hospitals in 6 European countries. Three hundred fifty-five adult, unconscious patients with out-of-hospital cardiac arrest were enrolled from February 16, 2013, to June 1, 2016, with final follow-up on December 27, 2016. INTERVENTIONS Patients were randomized to TTM(33 +/- 1 degrees C) for 48 hours (n = 176) or 24 hours (n = 179), followed by gradual rewarming of 0.5 degrees C per hour until reaching 37 degrees C. MAIN OUTCOMES AND MEASURES The primary outcome was 6-month neurologic outcome, with a Cerebral Performance Categories (CPC) score of 1 or 2 used to define favorable outcome. Secondary outcomes included 6-month mortality, including time to death, the occurrence of adverse events, and intensive care unit resource use. RESULTS In 355 patients who were randomized (mean age, 60 years; 295 [83%] men), 351 (99%) completed the trial. More patients in the 48-hour group had a favorable outcome, but this was not statistically significant. Six-month mortality was not different between the groups. Adverse events were more common in the 48-hour group than in the 24-hour group. There was no significant difference in the time to mortality (hazard ratio, 0.79; 95% CI, 0.54-1.15; P = .22). The median length of ICU stay (151 vs 117 hours; P < .001), but not hospital stay (11 vs 12 days; P = .50), was longer in the 48-hour group than in the 24-hour group. [GRAPHICS] CONCLUSIONS AND RELEVANCE In unconscious survivors from out-of-hospital cardiac arrest admitted to the ICU, targeted temperature management at 33 degrees C for 48 hours did not significantly improve 6-month neurologic outcome compared with targeted temperature management at 33 degrees C for 24 hours. However, the study may have had limited power to detect clinically important differences, and further research may be warranted.