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

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: Prospective, randomized, experimental study. SETTING: University research institution. SUBJECTS: Male Long Evans rats. 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: 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 < 0.05). Survival with good neurologic function, neurodegeneration, expression of HSP70, phosphorylation of Akt and Erk1/2 were not significantly different between hypothermic-targeted temperature management and hypothermic-targeted temperature management + valproic acid. The prevalence of seizures during the first 72-hour postcardiac arrest was significantly lower with hypothermic-targeted temperature management + valproic acid compared to hypothermic-targeted temperature management and normothermic-targeted temperature management (p = 0.01). CONCLUSIONS: High-dose valproic acid combined with hypothermic-targeted temperature management prevents postcardiac arrest seizures and improves survival. It remains to be determined if the mechanism of seizure prevention is through the antiepileptic effect of valproic acid or direct neuroprotection. Overall, the combination of high-dose valproic acid and hypothermic-targeted temperature management remains a promising strategy to improve cardiac arrest outcomes.

Variability of Post-Cardiac Arrest Care Practices Among Cardiac Arrest Centers: United States and South Korean Dual Network Survey of Emergency Physician Research Principal Investigators.

There is little consensus regarding many post-cardiac arrest care parameters. Variability in such practices could confound the results and generalizability of post-arrest care research. We sought to characterize the variability in post-cardiac arrest care practice in Korea and the United States. A 54-question survey was sent to investigators participating in one of two research groups in South Korea (Korean Hypothermia Network [KORHN]) and the United States (National Post-Arrest Research Consortium [NPARC]). Single investigators from each site were surveyed (N = 40). Participants answered questions based on local institutional protocols and practice. We calculated descriptive statistics for all variables. Forty surveys were completed during the study period with 30 having greater than 50% of questions completed (75% response rate; 24 KORHN and 6 NPARC). Most centers target either 33°C (N = 16) or vary the target based on patient characteristics (N = 13). Both bolus and continuous infusion dosing of sedation are employed. No single indication was unanimous for cardiac catheterization. Only six investigators reported having an institutional protocol for withdrawal of life-sustaining therapy (WLST). US patients with poor neurological prognosis tended to have WLST with subsequent expiration (N = 5), whereas Korean patients are transferred to a secondary care facility (N = 19). Both electroencephalography modality and duration vary between institutions. Serum biomarkers are commonly employed by Korean, but not US centers. We found significant variability in post-cardiac arrest care practices among US and Korean medical centers. These practice variations must be taken into account in future studies of post-arrest care.