Effect of Trans-Nasal Evaporative Intra-arrest Cooling on Functional Neurologic Outcome in Out-of-Hospital Cardiac Arrest The PRINCESS Randomized Clinical Trial
Abstract
IMPORTANCE Therapeutic hypothermia may increase survival with good neurologic outcome after cardiac arrest. Trans-nasal evaporative cooling is amethod 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 trialwas 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 degrees C to 34 degrees C for 24 hours. MAIN OUTCOMES AND MEASURES The primary outcomewas 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 degrees 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 degrees 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.