Abstract

Background: Early initiation of hypothermia has shown to be important to reduce brain injuries in experimental cardiac arrest models. The aim of this study was to investigate the association between time to initiate cooling and neurological intact survival in patients with out-of-hospital cardiac arrest (OHCA). Methods: A secondary analysis of prospectively collected data from the PRINCESS trial (NCT01400373) including 677 OHCA patients randomized to transnasal evaporative intra-arrest cooling or standard advanced life support and cooling started subsequent to hospital arrival. Time to randomization was used a proxy measurement for time to initiate cooling. An early treatment group was defined as patients randomized by the EMS <20 minutes from the time of the cardiac arrest. Propensity scores were used to find matching patients in the control group. Patients with initial shockable rhythms were analyzed as a predefined subgroup. The primary outcome was good neurologic outcome, Cerebral Performance Category (CPC) 1-2 at 90 days. Secondary outcome was complete recovery (CPC 1). Results: In total 406 patients were randomized <20 minutes from the cardiac arrest and were propensity score matched (1:1). In the propensity score matched analysis the proportion of patients with CPC 1-2 was 21.7% in the intervention and 17.2% in the control group, odds ratio (OR) 1.33, 95% confidence interval (CI) 0.80-2.21, p=0.273. In patients with initial shockable rhythm (79 intervention, 79 control) the difference in CPC 1-2 was 48.1% versus 32.0%, OR 2.05, 95%CI 1.00-4.21, p=0.0498. The proportion of patients with complete neurologic recovery, CPC 1, was 19.7% in the intervention and 13.3% in the control group, OR 1.60, 95% CI 0.92-2.79, p=0.097. In patients with initial shockable rhythm the proportion with CPC 1 was 45.6% versus 24.6%, OR 2.81, 95% CI 1.23-6.42, p=0.014. Conclusions: In this ancillary study of OHCA patients receiving intra-arrest cooling, there were differences in survival with good neurologic outcome and in complete neurological recovery in favor of early intra-arrest cooling patient group compared to standard care. These differences were statistically significant in the subgroup of patients with initial shockable rhythms.

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