Valproic Acid Combined With Postcardiac Arrest Hypothermic-Targeted Temperature Management Prevents Delayed Seizures and Improves Survival in a Rat Cardiac Arrest Model

Objectives: Objectives:High-dose valproic acid in combination with hypothermic-targeted temperature management has been reported to synergistically improve neurologic outcomes after cardiac arrest. This study investigated the potential synergistic mechanisms. Design: Design:Prospective, randomized, experimental study. Setting: Setting:University research institution. Subjects: Subjects:Male Long Evans rats. Intervention: Intervention:Rats resuscitated from asphyxial cardiac arrest were randomized to one of the three groups: normothermic-targeted temperature management (37°C ± 1°C), hypothermic-targeted temperature management (33° ± 1° × 24 hr + placebo infusion), hypothermic-targeted temperature management plus high-dose valproic acid (300 mg/kg IV × 1 initiated 5 min post return of spontaneous circulation and infused over 20 min) (hypothermic-targeted temperature management + valproic acid). Measurements and Main Results: Measurements and Main Results:Seventy-two-hour survival was significantly greater with hypothermic-targeted temperature management + valproic acid, compared to hypothermic-targeted temperature management and normothermic-targeted temperature management (p

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