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Original Investigation
Caring for the Critically Ill Patient
May 7, 2019

Effect of Trans-Nasal Evaporative Intra-arrest Cooling on Functional Neurologic Outcome in Out-of-Hospital Cardiac Arrest: The PRINCESS Randomized Clinical Trial

Author Affiliations
  • 1Department of Medicine, Center for Resuscitation Science, Karolinska Institute, Solna, Sweden
  • 2Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium
  • 3Emergency Medical Services of the Hradec Kralove Region, Czech Republic
  • 4Department of Anesthesiology and Intensive Care, Norrtälje Hospital, Norrtälje, Sweden
  • 5Emergency Department and SAMU, Centre Hospitalier Régional Universitaire de Lille, Lille, France
  • 6Emergency Department, St Maria Hospital, Halle, Belgium
  • 7Sistema d'Emergències Mèdiques, Barcelona, Catalunya, Spain
  • 8Empresa Pública de Emergencias Sanitarias, Almería, Andalucía, Spain
  • 9School of Health and Social Work, University of Hertfordshire, Hertfordshire, United Kingdom
  • 10Emergency Department, University Hospitals of Leuven, Leuven, Belgium
  • 11Department of Emergency Medicine, University Hospital of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
  • 12Department of Physiology and Pharmacology, Karolinska Institute, and Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden
JAMA. 2019;321(17):1677-1685. doi:10.1001/jama.2019.4149
Visual Abstract.
Visual Abstract.
Effect of Trans-Nasal Evaporative Intra-arrest Cooling on Functional Neurologic Outcome in Out-of-Hospital Cardiac Arrest
Effect of Trans-Nasal Evaporative Intra-arrest Cooling on Functional Neurologic Outcome in Out-of-Hospital Cardiac Arrest
Key Points

Question  Does cooling of the brain initiated during cardiopulmonary resuscitation improve survival with good neurologic outcome in patients with out-of-hospital cardiac arrest?

Findings  In this randomized clinical trial of 677 patients with out-of-hospital cardiac arrest, good neurologic outcome (Cerebral Performance Category 1-2) was 16.6% in the trans-nasal cooling group compared with 13.5% in the usual care group, a difference that did not reach statistical significance.

Meaning  Trans-nasal evaporative intra-arrest cooling did not result in a statistically significant improvement in survival with good neurologic outcome.

Abstract

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

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