Time to intra-arrest therapeutic hypothermia in out-of-hospital cardiac arrest patients and its association with neurologic outcome: a propensity matched sub-analysis of the PRINCESS trial

PURPOSE: To study the association between early initiation of intra-arrest therapeutic hypothermia and neurologic outcome in out-of-hospital cardiac arrest. METHODS: A prespecified sub-analysis of the PRINCESS trial (NCT01400373) that randomized 677 bystander-witnessed cardiac arrests to transnasal evaporative intra-arrest cooling initiated by emergency medical services or cooling started after hospital arrival. Early cooling (intervention) was defined as intra-arrest cooling initiated < 20 min from collapse (i.e., ≤ median time to cooling in PRINCESS). Propensity score matching established comparable control patients. Primary outcome was favorable neurologic outcome, Cerebral Performance Category (CPC) 1–2 at 90 days. Complete recovery (CPC 1) was among secondary outcomes. RESULTS: In total, 300 patients were analyzed and the proportion with CPC 1–2 at 90 days was 35/150 (23.3%) in the intervention group versus 24/150 (16%) in the control group, odds ratio (OR) 1.92, 95% confidence interval (CI) 0.95–3.85, p = .07. In patients with shockable rhythm, CPC 1–2 was 29/57 (50.9%) versus 17/57 (29.8%), OR 3.25, 95%, CI 1.06–9.97, p = .04. The proportion with CPC 1 at 90 days was 31/150 (20.7%) in the intervention group and 17/150 (11.3%) in controls, OR 2.27, 95% CI 1.12–4.62, p = .02. In patients with shockable rhythms, the proportion with CPC 1 was 27/57 (47.4%) versus 12/57 (21.1%), OR 5.33, 95% CI 1.55–18.3, p = .008. CONCLUSIONS: In the whole study population, intra-arrest cooling initiated < 20 min from collapse compared to cooling initiated at hospital was not associated with improved favorable neurologic outcome. In the subgroup with shockable rhythms, early cooling was associated with improved favorable outcome and complete recovery. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-06024-3) contains supplementary material, which is available to authorized users.