JOURNAL ARTICLE

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

Joo Suk Oh, Jinka Tulasi, Ren Xiaodan, William C Stacey, Robert W Neumar
Critical Care Medicine 2017, 45 (11): e1149-e1156
28857853

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.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
28857853
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"