L-Arginine in the treatment of valproate overdose – five clinical cases. (21st April 2017)

• Record Type: Journal Article
• Authors: Schrettl, Verena; Felgenhauer, Norbert; Rabe, Christian; Fernando, Malkanthi; Eyer, Florian
• Is Part Of: Clinical toxicology. Volume 55:Number 4(2017)
• Page Start: 260
• Page End: 266
• Publication Date: 2017-04-21
• Subjects: l-Arginine -- N-acetylglutamate synthetase -- valproic acid -- hyperammonemia; Toxicology -- Periodicals; Toxicological emergencies -- Periodicals; 615.9
• DOI: 10.1080/15563650.2017.1284333
• Languages: English
• ISSNs: 1556-3650

Abstract

Abstract: Background: Valproic acid and its metabolites – particularly valproyl-CoA – are inhibitors of the enzyme N -acetylglutamate synthetase. The amino acidl -arginine can stimulate N -acetylglutamate synthetase activity and could be potentially used therapeutically to correct hyperammonemia caused by valproate therapy or overdose. Severely valproic-acid-poisoned patients are usually treated withl -carnitine or hemodialysis in order to decrease hyperammonemia. We herein report of five cases, in whichl -arginine was administered. Methods: Observational study on five cases. Patients with hyperammonemia (i.e., ammonia 80 > μg/dL) and symptoms consistent with valproate overdose (i.e., drowsiness, coma) were selected for treatment withl -arginine. Data was collected retrospectively. Results: l -Arginine decreased ammonia levels in a close temporal relation (case I ammonia in EDTA-plasma [μg/dL] decreased from 381 to 39; case II from 281 to 50; case III from 669 to 74; case IV from 447 to 56; case V from 202 to 60). In cases I and II, hemodialysis was performed andl -carnitine was given before the administration ofl -arginine. In case III, hemodialysis was performed after the administration ofl -arginine was already started. In cases IV and V, treatment withl -arginine was the sole measure to decrease ammonia levels in plasma. Conclusion: The results suggest thatl -arginine may be beneficial in selected cases of valproate overdose complicated by hyperammonemia.l -Arginine could extend our conventional treatment options for valproic acid overdose.