(1373) Valproic Acid Serum Levels in ICU Patients: A Retrospective Evaluation

Introduction: Valproic acid (VPA) is a narrow therapeutic index drug most commonly used to treat seizure and mood disorders. Guidelines recommend targeting total levels between 50-100 mg/L for seizure disorders and 50-125 mg/L for bipolar disorder. Currently at our health system, there is no guidance on how to monitor either free or total VPA levels.

Methods: A multi-site, retrospective chart review was conducted from August 1, 2021 to July 31, 2022. Patients who received a VPA dose during an ICU admission were included in the study for evaluation. Data was collected on the patient’s age, gender, therapy details, VPA dosage, medication administration, lab results, and medical history. Trough levels were assessed for appropriate timing. Patients with supratherapeutic levels were evaluated for signs of toxicity.

Results: Four hundred and eight patients were included in this study. Of these patients, 87 (21%) patients had supratherapeutic levels. There were 41 supratherapeutic total levels and 92 supratherapeutic free levels in these patients. In terms of toxicities in patients with supratherapeutic levels, 33 (38%) patients had hyperammonemia, 17 (20%) had elevated AST/ALT, 21 (24%) had thrombocytopenia, and 12 (14%) had hyperbilirubinemia. When considering patient populations where there would be concern for discordant free versus total levels, there were 42 (48%) patients with hypoalbuminemia, 46 (52%) patients with hyperuremia, and 54 (62%) patients with altered renal function. Lastly, 20 (23%) patients had their doses adjusted after a supratherapeutic lab resulted, with an average time to dose change of 10 hours (SD 12).

Conclusions: While there were 133 supratherapeutic levels, only 20 of those were acted upon. This may suggest that the majority of these supratherapeutic levels were not drawn appropriately. The most common toxicity was hyperammonemia though the relatively low rate of toxicity occurrences in patients with supratherapeutic levels also implies most labs were incorrectly drawn. In sum, this data suggests there is an opportunity to optimize monitoring of VPA by providing clear guidance on when to appropriately draw VPA levels, especially, when a free level would be indicated