Abstracts

Rationale: Valproic acid (VPA) is a broad spectrum anti-epileptic drug (AED) commonly used in the treatment of status epilepticus (SE) in the Intensive care unit (ICU). VPA is highly bound (90%) to proteins in the blood and is primarily metabolized in the liver. Renal failure is not uncommon in critically ill patients with SE. Continuous renal replacement therapy (CRRT) is an emerging modality in the management of renal failure. Although, no dosage adjustments are necessary in renal impairment, there is no acceptable data on dosing adjustments for patients undergoing CRRT. Methods: Case report: We describe a 35-year-old female with refractory non-convulsive SE secondary to anoxic injury as a result of a period of pulseless electrical activity. The patient was initially treated with Lacosamide, Levetiracetam, Vigabatrin and VPA. At a dose of 1,500 mg of VPA every twelve hours, her serum VPA level was 33.8 ug/ml. Scheduled Phenobarbital as well as continuous infusions of Propofol and Ketamine were also used briefly without any benefit. She subsequently developed severe acidosis, hyperkalemia, and her urine output acutely declined. CRRT was initiated at Sustained low-efficiency dialysis settings. Prior to initiation of CRRT the patient received a bolus of 3000 mg of VPA and the dose was adjusted to 3000 mg every eight hours. Three serum VPA levels while on CRRT were reported as undetectable. Therefore, VPA was discontinued. Clobazam, Pregabalin, and Topiramate were initiated during CRRT which continued for a total of 7 days. 1 day after CRRT was stopped VPA was restarted at 2000 mg every twelve hours. The subsequent serum VPA level was 72.2 ug/ml. 2 days later the SE resolved. The patient was discharged to a long term care facility. Results: We report that CRRT resulted in a substantial clearance of serum VPA. Conclusions: We observed that clinically significant amounts of VPA were removed by CRRT despite increase in dose. Although CRRT theoretically provides a relatively constant and predictable drug clearance when compared to intermittent hemodialysis, numerous factors are involved in determining the rate of clearance for a particular drug. We speculate that VPA may have been completely dialyzed during CRRT at Sustained low-efficiency dialysis settings. Further studies on higher doses of VPA with corresponding interval serum levels are required to establish guidelines on dosing. Alternatively, choosing filters with different pore size, permeability, surface area may be more effective while treatment with AEDs. Interestingly the SE resolved 2 days after discontinuing the CRRT which may have theoretically raised serum levels of the newer added AEDs further suggesting that CRRT may be removing clinically significant amounts of AEDs. This report underscores need for sophisticated research on pharmacokinetic properties of VPA and other AEDs in patients undergoing CRRT.