Effect of intra-arrest trans-nasal evaporative cooling in out-of-hospital cardiac arrest: a pooled individual participant data analysis

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 post hoc pooled analysis of individual data from two randomized trials including 851 patients who eventually received the allocated intervention and with available outcome ("as-treated" analysis). 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.

Results: 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 526 patients with initial non-shockable rhythms, favourable neurological outcome was in 10/259 (3.8%) in the intervention and 13/267 (4.9%) in the control group (RR 0.88 [CIs 0.52-1.29]; p = 0.67); survival and complete neurological recovery were also similar between groups. No significant benefit was observed for the intervention in the entire population.

Conclusions: 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. Future studies are needed to confirm the potential benefits of this intervention in this subgroup of patients.

Keywords: Cardiac arrest; Hypothermia; Intra-arrest; Outcome; Randomized clinical trial.

Fig. 1

Flow chart of the subjects included in this analysis, according to the intention-to-treat (ITT) or “as-treated” approach. TNEC = trans-nasal evaporative cooling; CPR = cardiopulmonary resuscitation; DNAR = do not actively resuscitate

Fig. 2

Pooled analyses of favourable neurological outcome (CPC 1–2) at hospital discharge in all included patients and in the subgroup of patients with shockable and non-shockable rhythm. PRINCE (13) and PRINCESS (14)

Fig. 3

Pooled analyses of complete neurological outcome (CPC 1) at hospital discharge in all included patients and in the subgroup of patients with shockable and non-shockable rhythm. PRINCE (13) and PRINCESS (14)