Safety of Rapid Intravenous Administration of Valproic Acid

Introduction: Traditionally, intravenous (IV) valproic acid (VPA) is administered as a diluted infusion at ≤ 20 mg/minute, potentially leading to delays in treatment with infusion times typically over one hour. Recent studies suggest undiluted intravenous push (IVP) VPA may achieve therapeutic levels faster without compromising safety. This study aims to evaluate safety and cost differences between IV infusion and IVP VPA administration.


Methods: A retrospective analysis was conducted in adult patients who received IV VPA between January 2023 and December 2024 for seizures, headaches, or as a continuation of maintenance therapy. Patients were grouped based on IV VPA administration route (infusion or IVP). VPA infusions were administered over 60 minutes and IVP was administered over 3-5 minutes. The primary outcomes included heart rate, mean arterial pressure (MAP), oxygen saturation, and respiration rate (RR) measured at baseline and post-administration times of 30 minutes, 60 minutes, and 4 hours of the first dose of administered VPA. Secondary outcomes included time to administration, incidence of extravasation, and cost.


Results: A total of 80 patients were included for analysis (Infusion n=40; IVP n=40). Indications for VPA use included seizures (Infusion 17.5%; IVP 17.5%), headache (Infusion 17.5%; IVP 10%), and continuation of maintenance regimen (Infusion 65%; IVP 72.5%). Median dose for both groups was 1000 mg [IQR 500-1500]. Primary outcomes showed no significant differences in changes in MAP, oxygen saturation, and RR at 30 minutes, 60 minutes, and 4 hours post-administration. Median time to administration was significantly shorter for IVP (48.5 vs. 72.5 mins, p=0.02). Bradycardia (HR < 55 bpm) did not occur in either group. Hypotension (MAP < 65) occurred in one patient in the IVP group. No extravasation requiring hyaluronidase administration occurred in either group. The infusion method incurred an added cost of $8.59 per dose derived from chemotherapeutic adaptors and gown used to compound the VPA infusion.


Conclusions: Administration of IVP VPA had similar safety compared to traditional infusion, with no significant differences in hemodynamic outcomes. IVP significantly reduced time to administration, suggesting a more efficient and cost-effective approach without compromising patient safety.