Title: Evaluation of the Safety and Tolerability of Intravenous Push Dose Valproic Acid
Authors’ names: Maryam Hashem, Kaitlyn Wallace, Olivia Morgan, Katleen Chester
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[email protected] Background: Valproic acid (VPA) is an antiseizure medication that inhibits voltage-gated sodium channels and gamma-aminobutyric acid (GABA) transaminase and enhances GABA synthesis. Multiple VPA formulations are commercially available, but intravenous (IV) administration is preferred when patients lack oral access or require emergent treatment. Grady Memorial Hospital (GMH) transitioned from IV VPA maintenance doses administered via IV piggyback (IVPB) at a rate of 6 mg/kg/minute to slow IV push (IVP) over 2 to 5 minutes, due to the fluid shortages following Hurricane Helene. The transition to IVP VPA was based on limited available evidence evaluating the safety and operational efficiency of this administration strategy. The objective of this study was to investigate the safety, tolerability, and operational efficiency of IVP VPA compared to IVPB VPA.
Methods: This was a single center, retrospective, observational study evaluating the safety, tolerability, and operational efficiency of IVP VPA maintenance doses (≤1500 mg) compared to IVPB from July 2024 to January 2025. Included patients were aged 18 years or older who received at least one dose of IV VPA. The primary outcome was the incidence of injection site reactions including injection site pain, discomfort, phlebitis, burning, infiltration, extravasation, or erythema. Secondary outcomes included number of doses received prior to a reaction, type of reaction, type of line medication was administered through, dispense location (central pharmacy or floor pyxis), and time from order verification to administration. Baseline characteristics such as age, gender, weight, location at the time of initial administration, and type of line were collected. Descriptive statistics were used to summarize baseline characteristics and outcoming using medians and interquartile ranges, or means and standard deviation, as appropriate. Continuous variables were compared using the Mann-Whitney U test, and categorical variables were compared using chi-square test.
Results: A total of 200 patients met inclusion criteria and were included in the analysis. Baseline characteristics were similar between groups, with no significant differences in age between the IVPB and IVP groups or weight. In the IVPB VPA cohort, there were a total of 1,338 administrations; only 2 administrations resulted in a reaction. In the IVP VPA cohort, there were a total of 1,068 administrations; 8 administrations resulted in a reaction. Infiltration was the most common reaction, occurring in 2 patients in the IVPB group and 5 patients in the IVP group (p-value=0.07). Burning occurred in two patients and erythema in one patient in the IVP group; neither finding was statistically significant (p-value=0.14 and 0.30, respectively). All patients continued to receive IV VPA after the initial reaction without a reported reoccurrence. Dispense location differed significantly between groups. All IVPB doses were prepared by the central pharmacy, whereas only 39% of IVP doses came from the pharmacy and 61% were dispensed from automated dispensing cabinets (p-value <0.001). The median time from pharmacist verification to administration of the first maintenance dose was 85 minutes in the IVPB group and 78 minutes in the IVP group; however, this finding was not statistically significant (p-value = 0.168).
Conclusion: Injection site reactions were low overall. Implementation of IVP VPA did not result in a significant increase in injection site reactions when compared to IVPB VPA for maintenance doses, indicating that the switch to IVP for maintenance dosing is a safe and efficient practice.
