Evaluation of levocarnitine, lactulose, and combination therapy for the treatment of valproic acid-induced hyperammonemia in critically ill patients

Critically ill patients treated with valproic acid are at risk for hyperammonemic encephalopathy. Both levocarnitine and lactulose, either alone or in combination, have been used for the treatment of hyperammonemia associated with valproic acid, however they have not been directly compared in the literature. The aim of this study was to compare the effect of levocarnitine, lactulose, and combination therapy for the treatment of valproic acid-induced hyperammonemia in critically ill patients. This was a retrospective, system-wide, cohort study of critically ill patients who received valproic acid and levocarnitine, lactulose, or combination therapy from January 1, 2012 to October 31, 2019. The primary outcome of the study was the change in ammonia level from baseline to the lowest point within the first 48 h of treatment. Secondary outcomes included the change in ammonia levels within the first 7 days, the incidence of a clinically significant reduction, ICU length of stay, hospital length of stay, and hospital mortality. A total of 371 charts were reviewed and 114 patients (levocarnitine [n = 15], lactulose [n = 72], and combination [n = 27]) were included. No difference in the primary outcome was observed (levocarnitine [11umol/L] vs. lactulose [20 umol/L] vs. combination [23 umol/L], p = 0.605). The incidence of a clinically significant reduction in ammonia levels at 48 h did not differ between groups, nor did mortality. In critically ill patients with valproic acid-induced hyperammonemia, there was no significant difference in the reduction in ammonia levels in the first 48 h of treatment between levocarnitine, lactulose, and combination therapy. •Hyperammonemia is a potentially devastating adverse effect of valproic acid therapy.•Critically ill patients may be at increased risk for hyperammonemia.•Treatment with lactulose and/or levocarnitine is common in clinical practice.•Lactulose and levocarnitine resulted in a similar decrease in ammonia levels.