From the Guidelines
The recommended loading dose of valproic acid is 20 to 30 mg/kg at a rate of 40 mg/min. This dose is based on the most recent and highest quality study available, which suggests that valproate is effective in treating status epilepticus after benzodiazepine administration as a second-line agent, with fewer adverse effects compared to phenytoin or fosphenytoin 1. The dose of 20 to 30 mg/kg is also supported by other studies, such as Chen et al 1, which demonstrated that valproate controlled seizures within 1 hour in 88% of patients with refractory convulsive status epilepticus.
When administering a loading dose of valproic acid, it is essential to monitor for potential side effects, including:
- Dizziness
- Thrombocytopenia
- Liver toxicity
- Hyperammonemia
The pharmacokinetics of valproic acid, including high protein binding and hepatic metabolism, support the use of a loading dose to quickly achieve therapeutic serum concentrations 1. Patients with hepatic impairment may require lower loading doses due to decreased drug clearance.
Key considerations for valproic acid loading dose administration include:
- Rate of administration: 40 mg/min
- Potential for adverse effects: monitor closely for dizziness, thrombocytopenia, liver toxicity, and hyperammonemia
- Hepatic impairment: consider lower loading doses due to decreased drug clearance.
From the Research
Valproic Acid Load Dose
- The valproic acid load dose can vary depending on the patient's body mass and the desired change in serum level.
- A study published in 1999 2 found that the mean dose administered was 1420 +/- 440 mg (19.4 +/- 5.4 mg/kg).
- Another study from 1999 3 reported a dose range of 21-28 mg/kg (mean 24.2 mg/kg) for rapid infusion of valproate to achieve high therapeutic levels.
- A more recent study from 2023 4 used a 30 mg/kg VPA loading dose for patients with generalized convulsive status epilepticus.
- The dose of valproic acid can also be influenced by the type of seizure and the patient's response to treatment, as noted in a study from 1998 5 which used a bolus dose of 15 mg/kg body weight followed by a continuous infusion of 1 mg/kg/h for 24 h.