Influence of valproate-induced hyperammonemia on treatment decision in an adult status epilepticus cohort

Status epilepticus (SE) is a neurological emergency in which immediate intervention is required to prevent permanent brain damage and death. Intravenous (IV) valproic acid (VPA) is often used for the treatment of SE. However, IV VPA frequently increases the blood ammonia level. In this study, we explore the impact of IV VPA-induced hyperammonemia (HA) on treatment management of SE and discuss the challenges related to this particular condition.

We used data from medical records of 31 adult patients (≥18 years) treated with IV VPA for SE at Oslo University Hospital between January 2006 and October 2019. Clinical and blood sample data and information about the influence of HA on treatment were collected. Correlations between ammonia levels and other continuous or categorical variables were tested using the Pearson's correlation coefficient. The Kruskal-Wallis H-test was used to analyze associations between different variables and treatment decisions.

Thirty of 31 patients had increased ammonia level during IV VPA treatment. In 16/30 patients, VPA was discontinued, and in 6/30 patients, the dose was reduced. We found a difference in the median peak ammonia level among the groups where VPA was discontinued (99 μmol/l), reduced (71 μmol/l), and continued (55.5 μmol/l) (P = 0.008). Also clinical status, measured by West Haven Criteria, varied among the groups where VPA was discontinued (3.5), reduced (2.5), and continued (2.0) (P = 0.01). Treatment decisions at peak ammonia were not associated with the level of liver enzymes and bilirubin.

Hyperammonemia had a substantial impact on further management. To date, no recommendations exist on how to manage VPA-induced HA in SE. We call for systematic prospective studies and evidence-based guidelines.