Effect of Trans-Nasal Evaporative Intra-arrest Cooling on Functional Neurologic Outcome in Out-of-Hospital Cardiac Arrest

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.

High Quality Targeted Temperature Management (TTM) After Cardiac Arrest

“…Similar results were obtained when cold fluids were administered during CPR (intra-arrest TTM), which theoretically should have even greater beneficial effects on the anoxic brain [18,19]. However, the use of intraarrest TTM using a trans-nasal device, which is a method able to primarily induce brain cooling during CPR, showed some potential benefits, in particular in OHCA victims with an initial shockable rhythm [20,21], suggesting that the method used to induce intra-arrest TTM may be determinant in maximizing brain protection and avoiding adverse effects.…”

Targeted Temperature Management for Treatment of Cardiac Arrest

“…The concept of achieving rapid prehospital cooling using an intranasal device that delivers a mixture of oxygen and a liquid coolant to the nasopharynx was investigated in the PRINCESS trial in patients with bystander witnessed OHCA. [44]. Although the median time to reach a target temperature less than 34°C was shorter with transnasal cooling device, survival with a favorable neurologic outcome did not differ significantly between groups (16.6% vs. 13.5%; P = 0.25).…”

Focus on cardiovascular management in critically ill patients

“…One of the differences between low-and high performing centres were the handling of targeted temperature management (TTM), including time to start of TTM. Interestingly, however, in the PRINCESS trial, an earlier start of TTM with early pre-hospital trans-nasal evaporative cooling did not result in improved neurological outcome after OHCA compared with cooling after hospital arrival [15]. TTM may, though, gain renewed popularity following the results of the HYPERION trial which suggested improved neurological outcome with moderate therapeutic hypothermia (33 °C) compared with targeted normothermia (37 °C) in comatose patients after cardiac arrest with non-shockable rhythm [16].…”