Combined intra- and post-cardiac arrest hypothermic-targeted temperature management in a rat model of asphyxial cardiac arrest improves survival and neurologic outcome compared to either strategy alone

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 1 h post-ROSC and maintained for 24 h; Intra-1 HTTM) HTTM initiated at CPR onset and maintained for 1 h; and Intra-24 HTTM) HTTM initiated at CPR onset and maintained for 24 h. 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 72 h were euthanized for histological analysis of neurodegeneration.ResultsTarget brain temperature was achieved 7.8 ± 3.3 min 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.