BACKGROUND: The aim of this study was to assess whether hypothermia increased survival and improved functional outcome when compared with normothermia in out-of-hospital cardiac arrest (OHCA) patients with similar characteristics than in previous randomized studies showing benefits for hypothermia. METHODS: Post hoc analysis of a pragmatic, multicenter, randomized clinical trial (TTM-2, NCT02908308). In this analysis, the subset of patients included in the trial who had similar characteristics to patients included in one previous randomized trial and randomized to hypothermia at 33 °C or normothermia (i.e. target < 37.8 °C) were considered. The primary outcome was survival at 6 months; secondary outcomes included favorable functional outcome at 6 months, defined as a modified Rankin scale of 0-3. Time-to-death and the occurrence of adverse events were also reported. RESULTS: From a total of 1891 included in the TTM-2 study, 600 (31.7%) were included in the analysis, 294 in the hypothermia and 306 in the normothermia group. At 6 months, 207 of the 294 patients (70.4%) in the hypothermia group and 220 of the 306 patients (71.8%) in the normothermia group had survived (relative risk with hypothermia, 0.96; 95% confidence interval [CI], 0.81 to 1.15; P = 0.71). Also, 198 of the 294 (67.3%) in the hypothermia group and 202 of the 306 (66.0%) in the normothermia group had a favorable functional outcome (relative risk with hypothermia, 1.03; 95% CI, 0.87 to 1.23; P = 0.79). There was a significant increase in the occurrence of arrythmias in the hypothermia group (62/294, 21.2%) when compared to the normothermia group (43/306, 14.1%-OR 1.49, 95% CI 1.05-2.14; p = 0.026). CONCLUSIONS: In this study, hypothermia at 33 ̊C did not improve survival or functional outcome in a subset of patients with similar cardiac arrest characteristics to patients in whom benefit from hypothermia was shown in prior studies.

• MeSH
• Cardiopulmonary Resuscitation methods   statistics & numerical data   MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Hypothermia, Induced * methods   statistics & numerical data   MeSH
• Treatment Outcome MeSH
• Out-of-Hospital Cardiac Arrest * therapy   mortality   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH

Background: Several biochemical markers in blood correlate with the magnitude of brain injury and may be used to predict neurological outcome after cardiac arrest. We present a protocol for the evaluation of prognostic accuracy of brain injury markers after cardiac arrest. The aim is to define the best predictive marker and to establish clinically useful cut-off levels for routine implementation. Methods: Prospective international multicenter trial within the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial in collaboration with Roche Diagnostics International AG. Samples were collected 0, 24, 48, and 72 hours after randomisation (serum) and 0 and 48 hours after randomisation (plasma), and pre-analytically processed at each site before storage in a central biobank. Routine markers neuron-specific enolase (NSE) and S100B, and neurofilament light, total-tau and glial fibrillary acidic protein will be batch analysed using novel Elecsys® electrochemiluminescence immunoassays on a Cobas e601 instrument. Results: Statistical analysis will be reported according to the Standards for Reporting Diagnostic accuracy studies (STARD) and will include comparisons for prediction of good versus poor functional outcome at six months post-arrest, by modified Rankin Scale (0-3 vs. 4-6), using logistic regression models and receiver operating characteristics curves, evaluation of mortality at six months according to biomarker levels and establishment of cut-off values for prediction of poor neurological outcome at 95-100% specificities. Conclusions: This prospective trial may establish a standard methodology and clinically appropriate cut-off levels for the optimal biomarker of brain injury which predicts poor neurological outcome after cardiac arrest.

• Publication type
• Journal Article MeSH