IMPORTANCE: Therapeutic hypothermia may increase survival with good neurologic outcome after cardiac arrest. Trans-nasal evaporative cooling is a method used to induce cooling, primarily of the brain, during cardiopulmonary resuscitation (ie, intra-arrest). OBJECTIVE: To determine whether prehospital trans-nasal evaporative intra-arrest cooling improves survival with good neurologic outcome compared with cooling initiated after hospital arrival. DESIGN, SETTING, AND PARTICIPANTS: The PRINCESS trial was an investigator-initiated, randomized, clinical, international multicenter study with blinded assessment of the outcome, performed by emergency medical services in 7 European countries from July 2010 to January 2018, with final follow-up on April 29, 2018. In total, 677 patients with bystander-witnessed out-of-hospital cardiac arrest were enrolled. INTERVENTIONS: Patients were randomly assigned to receive trans-nasal evaporative intra-arrest cooling (n = 343) or standard care (n = 334). Patients admitted to the hospital in both groups received systemic therapeutic hypothermia at 32°C to 34°C for 24 hours. MAIN OUTCOMES AND MEASURES: The primary outcome was survival with good neurologic outcome, defined as Cerebral Performance Category (CPC) 1-2, at 90 days. Secondary outcomes were survival at 90 days and time to reach core body temperature less than 34°C. RESULTS: Among the 677 randomized patients (median age, 65 years; 172 [25%] women), 671 completed the trial. Median time to core temperature less than 34°C was 105 minutes in the intervention group vs 182 minutes in the control group (P < .001). The number of patients with CPC 1-2 at 90 days was 56 of 337 (16.6%) in the intervention cooling group vs 45 of 334 (13.5%) in the control group (difference, 3.1% [95% CI, -2.3% to 8.5%]; relative risk [RR], 1.23 [95% CI, 0.86-1.72]; P = .25). In the intervention group, 60 of 337 patients (17.8%) were alive at 90 days vs 52 of 334 (15.6%) in the control group (difference, 2.2% [95% CI, -3.4% to 7.9%]; RR, 1.14 [95% CI, 0.81-1.57]; P = .44). Minor nosebleed was the most common device-related adverse event, reported in 45 of 337 patients (13%) in the intervention group. The adverse event rate within 7 days was similar between groups. CONCLUSIONS AND RELEVANCE: Among patients with out-of-hospital cardiac arrest, trans-nasal evaporative intra-arrest cooling compared with usual care did not result in a statistically significant improvement in survival with good neurologic outcome at 90 days. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01400373.

Department of Anesthesiology and Intensive Care Norrtälje Hospital Norrtälje Sweden

Department of Emergency Medicine University Hospital of Freiburg Faculty of Medicine University of Freiburg Freiburg Germany

Department of Intensive Care Erasme Hospital Université Libre de Bruxelles Brussels Belgium

Department of Medicine Center for Resuscitation Science Karolinska Institute Solna Sweden

Department of Physiology and Pharmacology Karolinska Institute and Perioperative Medicine and Intensive Care Karolinska University Hospital Stockholm Sweden

Emergency Department and SAMU Centre Hospitalier Régional Universitaire de Lille Lille France

Emergency Department St Maria Hospital Halle Belgium

Emergency Department University Hospitals of Leuven Leuven Belgium

Emergency Medical Services of the Hradec Kralove Region Czech Republic

Empresa Pública de Emergencias Sanitarias Almería Andalucía Spain

School of Health and Social Work University of Hertfordshire Hertfordshire United Kingdom

Sistema d'Emergències Mèdiques Barcelona Catalunya Spain

JAMA. 2019 May 7;321(17):1673-1675. doi: 10.1001/jama.2019.4253. PubMed

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Strategies of Advanced Airway Management in Out-of-Hospital Cardiac Arrest during Intra-Arrest Hypothermia: Insights from the PRINCESS Trial

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ClinicalTrials.gov
NCT01400373