Speed and Safety of IV Push Versus IV Piggyback Valproate Loading Doses: A Retrospective Cohort Study

Abstract

Background:

Delays in intravenous antiseizure medication (ASM) administration may worsen seizure outcomes. Intravenous push (IVP) administration reduces administration time for several ASMs, but evidence for IVP valproate loading is limited.

Objective:

To compare time from pharmacist verification to documented administration for IVP versus intravenous piggyback (IVPB) valproate loading doses and compare adverse event frequencies.

Methods:

This single-center retrospective study included adults from October 2023 to May 2025 who received an IV valproate loading dose (≥15 mg/kg). On August 15, 2024, institutional practice changed from IVPB valproate more than 60 minutes to undiluted IVP valproate at 500 mg/min. The primary outcome was time from pharmacist verification to loading dose administration. Secondary outcomes included order-to-administration time, adverse events, intensive care unit (ICU) admission, length of stay, and mortality.

Results:

One hundred thirty-one patients met the inclusion criteria (IVP, n = 60; IVPB, n = 71). Median (interquartile range [IQR]) age was 63 years (44-71), and 85 (65%) patients were male. Valproate indications were witnessed seizure in 92 (70.2%), suspected seizure in 29 (22.1%), and agitation/psychiatric in 10 (7.6%). Sixty-four (48.8%) patients received loading doses for status epilepticus. The median (IQR) loading dose was 28 (20-34.5) mg/kg. Median time to administration was 36 (95% CI, 22-52) minutes shorter with IVP than with IVPB (median [IQR], 28 [13-48] vs 63 [50-84] minutes; P < 0.001). Cardiovascular events occurred in 38.3% and 27.8% of IVP and IVPB patients (P = 0.27); sedation in 3.3% and 0% (P = 0.20); and valproate-associated adverse events in 6.7% and 1.4% (P = 0.18). No phlebitis or infiltration occurred.

Conclusion and Relevance:

Intravenous push valproate loading reduced time to administration without an observed increase in adverse events.