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

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.

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

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.

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.

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