• Taeyun Kim, Michael G Paine, He Meng, Ren Xiaodan, Jacob Cohen, Tulasi Jinka, Huiyong Zheng, James A Cranford, and Robert W Neumar.
• Department of Emergency Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, United States; Department of Emergency Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; Department of Emergency Medicine, Gyeongsang National University Hospital, Republic of Korea.
• Resuscitation. 2016 Oct 1; 107: 94-101.

AimPost-cardiac arrest hypothermic-targeted temperature management (HTTM) improves outcomes in preclinical cardiac arrest studies. However, inadequate understanding of the mechanisms and therapeutic windows remains a barrier to optimization. We tested the hypothesis that combined intra- and post-cardiac arrest HTTM provides a synergistic outcome benefit compared to either strategy alone.MethodsRats subjected to 8-min asphyxial cardiac arrest were block randomized to 4 treatment groups (n=12/group): NTTM) normothermic-targeted temperature management; 1-24 HTTM) HTTM initiated 1h post-ROSC and maintained for 24h; Intra-1 HTTM) HTTM initiated at CPR onset and maintained for 1h; and Intra-24 HTTM) HTTM initiated at CPR onset and maintained for 24h. HTTM was induced by nasopharyngeal cooling and maintained using an automated temperature regulation system. Target temperature range was 36.5-37.5°C for NTTM and 32.0-34.0°C for HTTM. Post-arrest neurologic function score (NFS) was measured daily, and rats surviving 72h were euthanized for histological analysis of neurodegeneration.ResultsTarget brain temperature was achieved 7.8±3.3min after initiating intra-arrest cooling. The survival rate was 42%, 50%, 50%, and 92% in the NTTM, 1-24 HTTM, Intra-1 HTTM, and Intra-24 HTTM groups, respectively (p<0.05, Intra-24 group vs. all other groups). The rate of survival with good neurologic function (NFS≥450) was 33% in the Intra-24 HTTM group vs. 0% in all other groups (mid p<0.05). Hippocampal CA1 sector neurodegeneration was significantly reduced in the Intra-24 HTTM group compared to all other groups (p<0.05).ConclusionCombined intra- and post-cardiac arrest HTTM has greater outcome benefits than either strategy alone.Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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