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Intravenous use of valproic acid in status epilepticus is associated with high risk of hyperammonemia

Jonas Lind, Peter Nordlund
Seizure: the Journal of the British Epilepsy Association 2019, 69: 20-24

PURPOSE: The aim of the study was to examine the frequency of hyperammonemia secondary to valproic acid treatment in status epilepticus and to describe the characteristics of the patients.

METHODS: All patients with established status epilepticus during 2014 to 2016 at Ryhov County Hospital were identified in a retrospective case series. Clinical and laboratory findings were collected from electronic medical files and the Metavision database at the intensive care unit (ICU). Hyperammonemia was defined as a concentration of at least 50 μmol/L.

RESULTS: 11 of 40 patients developed hyperammonemia. These patients had a significantly longer stay at the ICU (12.6 vs 2.5 days) and at the hospital (22 vs 11 days). All patients with hyperammonemia were treated at the ICU and all received antibiotics. 12 patients were treated with intravenous valproic acid outside the ICU. Hyperammonemia was not related to Body Mass Index, time to initiation of therapy or laboratory abnormalities except anemia (Hemoglobin 104 vs 122 g/l). There was no difference in mortality between groups.

CONCLUSION: The risk of hyperammonemia is almost 40% in patients receiving intravenous valproic acid in the ICU setting. The underlying mechanisms are probably either individual susceptibility or high metabolic demands. A high vigilance should be recommended. These data require further research via prospective designs in which multiple variables are controlled to explore the effects of individual factors on treatment outcome.


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