Association of Initial Illness Severity and Outcomes After Cardiac Arrest With Targeted Temperature Management at 36 °C or 33 °C.

Importance: It is uncertain what the optimal target temperature is for targeted temperature management (TTM) in patients who are comatose following cardiac arrest. Objective: To examine whether illness severity is associated with changes in the association between target temperature and patient outcome. Design, Setting, and Participants: This cohort study compared outcomes for 1319 patients who were comatose after cardiac arrest at a single center in Pittsburgh, Pennsylvania, from January 2010 to December 2018. Initial illness severity was based on coma and organ failure scores, presence of severe cerebral edema, and presence of highly malignant electroencephalogram (EEG) after resuscitation. Exposure: TTM at 36 °C or 33 °C. Main Outcomes and Measures: Primary outcome was survival to hospital discharge, and secondary outcomes were modified Rankin Scale and cerebral performance category. Results: Among 1319 patients, 728 (55.2%) had TTM at 33 °C (451 [62.0%] men; median [interquartile range] age, 61 [50-72] years) and 591 (44.8%) had TTM at 36 °C (353 [59.7%] men; median [interquartile range] age, 59 [48-69] years). Overall, 184 of 187 patients (98.4%) with severe cerebral edema died and 234 of 243 patients (96.3%) with highly malignant EEG died regardless of TTM strategy. Comparing TTM at 33 °C with TTM at 36 °C in 911 patients (69.1%) with neither severe cerebral edema nor highly malignant EEG, survival was lower in patients with mild to moderate coma and no shock (risk difference, -13.8%; 95% CI, -24.4% to -3.2%) but higher in patients with mild to moderate coma and cardiopulmonary failure (risk difference, 21.8%; 95% CI, 5.4% to 38.2%) or with severe coma (risk difference, 9.7%; 95% CI, 4.0% to 15.3%). Interactions were similar for functional outcomes. Most deaths (633 of 968 [65.4%]) resulted after withdrawal of life-sustaining therapies. Conclusions and Relevance: In this study, TTM at 33 °C was associated with better survival than TTM at 36 °C among patients with the most severe post-cardiac arrest illness but without severe cerebral edema or malignant EEG. However, TTM at 36 °C was associated with better survival among patients with mild- to moderate-severity illness.

Unsupervised learning of early post-arrest brain injury phenotypes.

INTRODUCTION: Trials may be neutral when they do not appropriately target the experimental intervention. We speculated multimodality assessment of early hypoxic-ischemic brain injury would identify phenotypes likely to benefit from therapeutic interventions. METHODS: We performed a retrospective study including comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA) by one of 126 emergency medical services or in-hospital arrest at one of 26 hospitals from 2011 to 2019. All patients were ultimately transported to a single tertiary center for care including standardized initial neurological examination, brain imaging and electroencephalography; targeted temperature management (TTM); hemodynamic optimization targeting mean arterial pressure (MAP) >80 mmHg; and, coronary angiography for clinical suspicion for acute coronary syndrome. We used unsupervised learning to identify brain injury phenotypes defined by admission neurodiagnostics. We tested for interactions between phenotype and TTM, hemodynamic management and cardiac catheterization in models predicting recovery. RESULTS: We included 1086 patients with mean (SD) age 58 (17) years of whom 955 (88%) were resuscitated from OHCA. Survival to hospital discharge was 27%, and 248 (23%) were discharged with Cerebral Performance Category (CPC) 1-3. We identified 5 clusters defining distinct brain injury phenotypes, each comprising 14% to 30% of the cohort with discharge CPC 1-3 in 59% to <1%. We found significant interactions between cluster and TTM strategy (P = 0.01), MAP (P < 0.001) and coronary angiography (P = 0.04) in models predicting outcomes. CONCLUSIONS: We identified patterns of early hypoxic-ischemic injury based on multiple diagnostic modalities that predict responsiveness to several therapeutic interventions recently tested in neutral clinical trials.