Dataset Information

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 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.

SUBMITTER: Nordberg P

PROVIDER: S-EPMC6506882 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Mild therapeutic hypothermia (TH), or targeted temperature management, improves survival and neurological outcomes in patients after out-of-hospital cardiac arrest (OHCA). International guidelines strongly support initiating TH for all eligible individuals presenting with OHCA; however, the timing of cooling initiation remains uncertain. This systematic review and meta-analysis was conducted with all available randomised controlled trials (RCTs) included to explore the efficacy and safety of initiating pre-hospital TH in patients with OHCA. METHODS:The MEDLINE and Cochrane databases were searched from inception to October 2017. Inclusion criteria for full-text review included RCTs comparing pre-hospital TH with no pre-hospital TH after cardiac arrest, patients > 14 years of age with documented cardiac arrest from any rhythm, and outcome data that included survival to hospital discharge and temperature at hospital arrival. Results of retrieved studies were compared through meta-analysis using random effects modelling. RESULTS:A total of 10 trials comprising 4220 patients were included. There were no significant differences between the two arms for the primary outcome of neurological recovery (risk ratio [RR] 1.04, 95% CI 0.93-1.15) or the secondary outcome of survival to hospital discharge (RR 1.01, 95% CI 0.92-1.11). However, there was a significantly lower temperature at hospital arrival in patients receiving pre-hospital TH (mean difference - 0.83, 95% CI - 1.03 to - 0.63). Pre-hospital TH significantly increased the risk of re-arrest (RR 1.19, 95% CI 1.00 to 1.41). No survival differences were observed among subgroups of patients who received intra-arrest TH vs post-arrest TH or who had shockable vs non-shockable rhythms. CONCLUSIONS:Pre-hospital TH after OHCA effectively decreases body temperature at the time of hospital arrival. However, it does not improve rates of survival with good neurological outcome or overall survival and is associated with increased rates of re-arrest.

Project description:ImportanceThere is wide variability among emergency medical systems (EMS) with respect to transport to hospital during out-of-hospital cardiac arrest (OHCA) resuscitative efforts. The benefit of intra-arrest transport during resuscitation compared with continued on-scene resuscitation is unclear.ObjectiveTo determine whether intra-arrest transport compared with continued on-scene resuscitation is associated with survival to hospital discharge among patients experiencing OHCA.Design, setting, and participantsCohort study of prospectively collected consecutive nontraumatic adult EMS-treated OHCA data from the Resuscitation Outcomes Consortium (ROC) Cardiac Epidemiologic Registry (enrollment, April 2011-June 2015 from 10 North American sites; follow-up until the date of hospital discharge or death [regardless of when either event occurred]). Patients treated with intra-arrest transport (exposed) were matched with patients in refractory arrest (at risk of intra-arrest transport) at that same time (unexposed), using a time-dependent propensity score. Subgroups categorized by initial cardiac rhythm and EMS-witnessed cardiac arrests were analyzed.ExposuresIntra-arrest transport (transport initiated prior to return of spontaneous circulation), compared with continued on-scene resuscitation.Main outcomes and measuresThe primary outcome was survival to hospital discharge, and the secondary outcome was survival with favorable neurological outcome (modified Rankin scale <3) at hospital discharge.ResultsThe full cohort included 43?969 patients with a median age of 67 years (interquartile range, 55-80), 37% were women, 86% of cardiac arrests occurred in a private location, 49% were bystander- or EMS-witnessed, 22% had initial shockable rhythms, 97% were treated by out-of-hospital advanced life support, and 26% underwent intra-arrest transport. Survival to hospital discharge was 3.8% for patients who underwent intra-arrest transport and 12.6% for those who received on-scene resuscitation. In the propensity-matched cohort, which included 27?705 patients, survival to hospital discharge occurred in 4.0% of patients who underwent intra-arrest transport vs 8.5% who received on-scene resuscitation (risk difference, 4.6% [95% CI, 4.0%- 5.1%]). Favorable neurological outcome occurred in 2.9% of patients who underwent intra-arrest transport vs 7.1% who received on-scene resuscitation (risk difference, 4.2% [95% CI, 3.5%-4.9%]). Subgroups of initial shockable and nonshockable rhythms as well as EMS-witnessed and unwitnessed cardiac arrests all had a significant association between intra-arrest transport and lower probability of survival to hospital discharge.Conclusions and relevanceAmong patients experiencing out-of-hospital cardiac arrest, intra-arrest transport to hospital compared with continued on-scene resuscitation was associated with lower probability of survival to hospital discharge. Study findings are limited by potential confounding due to observational design.

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