IMPORTANCE: International guidelines recommend body temperature control below 37.8 °C in unconscious patients with out-of-hospital cardiac arrest (OHCA); however, a target temperature of 33 °C might lead to better outcomes when the initial rhythm is nonshockable. OBJECTIVE: To assess whether hypothermia at 33 °C increases survival and improves function when compared with controlled normothermia in unconscious adults resuscitated from OHCA with initial nonshockable rhythm. DATA SOURCES: Individual patient data meta-analysis of 2 multicenter, randomized clinical trials (Targeted Normothermia after Out-of-Hospital Cardiac Arrest [TTM2; NCT02908308] and HYPERION [NCT01994772]) with blinded outcome assessors. Unconscious patients with OHCA and an initial nonshockable rhythm were eligible for the final analysis. STUDY SELECTION: The study cohorts had similar inclusion and exclusion criteria. Patients were randomized to hypothermia (target temperature 33 °C) or normothermia (target temperature 36.5 to 37.7 °C), according to different study protocols, for at least 24 hours. Additional analyses of mortality and unfavorable functional outcome were performed according to age, sex, initial rhythm, presence or absence of shock on admission, time to return of spontaneous circulation, lactate levels on admission, and the cardiac arrest hospital prognosis score. DATA EXTRACTION AND SYNTHESIS: Only patients who experienced OHCA and had a nonshockable rhythm with all causes of cardiac arrest were included. Variables from the 2 studies were available from the original data sets and pooled into a unique database and analyzed. Clinical outcomes were harmonized into a single file, which was checked for accuracy of numbers, distributions, and categories. The last day of follow-up from arrest was recorded for each patient. Adjustment for primary outcome and functional outcome was performed using age, gender, time to return of spontaneous circulation, and bystander cardiopulmonary resuscitation. MAIN OUTCOMES AND MEASURES: The primary outcome was mortality at 3 months; secondary outcomes included unfavorable functional outcome at 3 to 6 months, defined as a Cerebral Performance Category score of 3 to 5. RESULTS: A total of 912 patients were included, 490 from the TTM2 trial and 422 from the HYPERION trial. Of those, 442 had been assigned to hypothermia (48.4%; mean age, 65.5 years; 287 males [64.9%]) and 470 to normothermia (51.6%; mean age, 65.6 years; 327 males [69.6%]); 571 patients had a first monitored rhythm of asystole (62.6%) and 503 a presumed noncardiac cause of arrest (55.2%). At 3 months, 354 of 442 patients in the hypothermia group (80.1%) and 386 of 470 patients in the normothermia group (82.1%) had died (relative risk [RR] with hypothermia, 1.04; 95% CI, 0.89-1.20; P = .63). On the last day of follow-up, 386 of 429 in the hypothermia group (90.0%) and 413 of 463 in the normothermia group (89.2%) had an unfavorable functional outcome (RR with hypothermia, 0.99; 95% CI, 0.87-1.15; P = .97). The association of hypothermia with death and functional outcome was consistent across the prespecified subgroups. CONCLUSIONS AND RELEVANCE: In this individual patient data meta-analysis, including unconscious survivors from OHCA with an initial nonshockable rhythm, hypothermia at 33 °C did not significantly improve survival or functional outcome.

• MeSH
• Unconsciousness MeSH
• Adult MeSH
• Hypothermia * MeSH
• Cardiopulmonary Resuscitation * MeSH
• Humans MeSH
• Prognosis MeSH
• Aged MeSH
• Hypothermia, Induced * methods   MeSH
• Out-of-Hospital Cardiac Arrest * therapy   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH
• Comment MeSH

BACKGROUND: Trans-nasal evaporative cooling is an effective method to induce intra-arrest therapeutic hypothermia in out-of-hospital cardiac arrest (OHCA). The use of supraglottic airway devices (SGA) instead of endotracheal intubation may enable shorter time intervals to induce cooling. We aimed to study the outcomes in OHCA patients receiving endotracheal intubation (ETI) or a SGA during intra-arrest trans-nasal evaporative cooling. METHODS: This is a pre-specified sub-study of the PRINCESS trial (NCT01400373) that included witnessed OHCA patients randomized during resuscitation to trans-nasal intra-arrest cooling vs. standard care followed by temperature control at 33 °C for 24 h. For this study, patients randomized to intra-arrest cooling were stratified according to the use of ETI vs. SGA prior to the induction of cooling. SGA was placed by paramedics in the first-tier ambulance or by physicians or anesthetic nurses in the second tier while ETI was performed only after the arrival of the second tier. Propensity score matching was used to adjust for differences at the baseline between the two groups. The primary outcome was survival with good neurological outcome, defined as cerebral performance category (CPC) 1-2 at 90 days. Secondary outcomes included time to place airway, overall survival at 90 days, survival with complete neurologic recovery (CPC 1) at 90 days and sustained return of spontaneous circulation (ROSC). RESULTS: Of the 343 patients randomized to the intervention arm (median age 64 years, 24% were women), 328 received intra-arrest cooling and had data on the airway method (n = 259 with ETI vs. n = 69 with SGA). Median time from the arrival of the first-tier ambulance to successful airway management was 8 min for ETI performed by second tier and 4 min for SGA performed by the first or second tier (p = 0.001). No significant differences in the probability of good neurological outcome (OR 1.43, 95% CI 0.64-3.01), overall survival (OR 1.26, 95% CI 0.57-2.55), full neurological recovery (OR 1.17, 95% CI 0.52-2.73) or sustained ROSC (OR 0.88, 95% CI 0.50-1.52) were observed between ETI and SGA. CONCLUSIONS: Among the OHCA patients treated with trans-nasal evaporative intra-arrest cooling, the use of SGA was associated with a significantly shorter time to airway management and with similar outcomes compared to ETI.

• Keywords
• airway management, cardiac arrest, intra-arrest hypothermia,
• Publication type
• Journal Article MeSH

Background: Despite promising results, the role of intra-arrest hypothermia in out-of-hospital cardiac arrest (OHCA) remains controversial. The aim of this study was to assess the effects of trans-nasal evaporative cooling (TNEC) during resuscitation on neurological recovery in OHCA patients admitted alive to the hospital. Methods: A post hoc analysis of the PRINCESS trial, including only patients admitted alive to the hospital, either assigned to TNEC or standard of care during resuscitation. The primary endpoint was favorable neurological outcome (FO) defined as a Cerebral Performance Category (CPC) of 1-2 at 90 days. The secondary outcomes were overall survival at 90 days and CPC 1 at 90 days. Subgroup analyses were performed according to the initial cardiac rhythm. Results: A total of 149 patients in the TNEC and 142 in the control group were included. The number of patients with CPC 1-2 at 90 days was 56/149 (37.6%) in the intervention group and 45/142 (31.7%) in the control group (p = 0.29). Survival and CPC 1 at 90 days was observed in 60/149 patients (40.3%) vs. 52/142 (36.6%; p = 0.09) and 50/149 (33.6%) vs. 35/142 (24.6%; p = 0.11) in the two groups. In the subgroup of patients with an initial shockable rhythm, the number of patients with CPC 1 at 90 days was 45/83 (54.2%) in the intervention group and 27/78 (34.6%) in the control group (p = 0.01). Conclusions: In this post hoc analysis of admitted OHCA patients, no statistically significant benefits of TNEC on neurological outcome at 90 days was found. In patients with initial shockable rhythm, TNEC was associated with increased full neurological recovery.

• Keywords
• cardiac arrest, intra-arrest hypothermia, outcome, trans-nasal evaporative cooling,
• Publication type
• Journal Article MeSH