A Pooled Individual Participant Data Analysis of Trans-Nasal Cooling in Out-of-Hospital Cardiac Arrest

Abstract

Background: Randomized trials have shown that trans-nasal evaporative cooling initiated during CPR (i.e. intra-arrest) effectively lower core body temperature in out-of-hospital cardiac arrest patients. However, these trials may have been underpowered to detect significant differences in neurologic outcome, especially in patients with initial shockable rhythm. Methods: We conducted a pooled analysis of individual data from two randomised trials including 843 patients who eventually received the allocated intervention and with available outcome. Primary outcome was survival with favourable neurological outcome at hospital discharge (Cerebral Performance Category [CPC] of 1-2) according to the initial rhythm (shockable vs. non-shockable). Secondary outcomes included complete neurological recovery (CPC 1) at hospital discharge. Findings: Among the 325 patients with initial shockable rhythms, favourable neurological outcome was observed in 54/158 (34.2%) patients in the intervention and 40/167 (24.0%) in the control group (RR 1.43 [confidence intervals, CIs 1.01-2.02]). Complete neurological recovery was observed in 40/158 (25.3%) in the intervention and 27/167 (16.2%) in the control group (RR 1.57 [CIs 1.01-2.42]. Among the 518 patients with initial non-shockable rhythms, favourable neurological outcome was observed in 10/250 (4.0%) patients in the intervention and 13/267 (4.9%) in the control group (RR 0.82 [CIs 0.37-1.84]; complete neurological recovery was observed in 4/250 (1.6%) and 5/267 (1.9%) patients, respectively (RR 0.85 [CIs 0.23-3.15]. Interpretation: In this pooled analysis of individual data, intra-arrest cooling was associated with a significant increase in favourable neurological outcome in out-of-hospital cardiac arrest patients with initial shockable rhythms. No effects were observed in patients with initial non-shockable rhythms. Funding Statement: No funding has been received for this study. Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: Ethics and institutional committees in each participating country approved the study protocols and written consent was obtained from closest relative or a legal representative of each patient after hospital admission and, at a later stage, from each patient who showed neurological recovery. Both studies were conducted according to the requirements of the Declaration of Helsinki.