Objective: Valproic acid (VPA) is a broad-spectrum antiepileptic drug that is now used commonly for several other neurological and psychiatric indications. Manifestations of acute valproic acid toxicity reflect both exaggerated therapeutic effects and impaired intermediary metabolism (1). Central Nervous System depression is the most common finding, although rarely hepatotoxicity and hyperammonemia have been reported in acute overdose setting. L-carnitine is an amino acid derivative that is an essential cofactor in the β-oxidation of fatty acids. A few observations suggest that L-carnitine supplementation may increase the β-oxidation of VPA, thereby limiting cytosolic ω-oxidation and the production of toxic metabolites that are involved in liver toxicity and ammonia accumulation (2). Case series: From January 2011 to September 2013, 21 patients with acute VPA intoxication were admitted to our Clinical Toxicology Unit. In addition to gastrointestinal decontamination and supportive management, 9 patients required L-carnitine supplementation due to hyperammonemia or severe intoxication (VPA plasma level > 450 mg/L or reported ingestion of more than 400 mg/kg). All patients were treated with loading dose of 100 mg/kg i.v. (up to 6 g) over 30 minutes, followed by 15 mg/kg every 4 hours over 10-30 minutes (3). No side effect were observed. Median length of hospital stay was 6 days and within the fourth day ammonia and VPA plasma levels went back in range. One patient reported life threatening cardiac arrhythmias probably sustained by VPA induced quinidine-like effect and needed temporary intracavitary cardiac pacing. None of our patients experienced any sequelae. Conclusions: Our experience shows that early parenteral L-carnitine supplementation speeds up the decrease of ammonia and VPA plasmatic levels in acute poisoning. The lack of significant adverse effects and the relatively affordable cost strongly suggest the use of L-carnitine in severe VPA poisoning, in order to treat or even prevent hyperammonemia and improve clinical outcome. (1) Sztajnkrycer M. Valproic acid toxicity: overview and management. Clin Toxicol 2002; 40: 789-801. (2) Lheureux P, Hantoson P. Carnitine in the treatment of valproic acid-induced toxicity. Clin Toxicol 2009;47:101-111 (3) L-Carnitine in Hoffman R et al. Goldfrank's Manual of Toxicologic Emergencies. 2007:411-413

L-carnitine supplementation in the treatment of acute valproic acid overdoses / Maria Sili; Arianna Dilaghi; Arianna Totti; Brunella Occupati; Pistelli Alessandra; Guido Mannaioni. - In: CLINICAL TOXICOLOGY. - ISSN 1556-3650. - STAMPA. - 52:(2014), pp. 316-316.

L-carnitine supplementation in the treatment of acute valproic acid overdoses

MANNAIONI, GUIDO
2014

Abstract

Objective: Valproic acid (VPA) is a broad-spectrum antiepileptic drug that is now used commonly for several other neurological and psychiatric indications. Manifestations of acute valproic acid toxicity reflect both exaggerated therapeutic effects and impaired intermediary metabolism (1). Central Nervous System depression is the most common finding, although rarely hepatotoxicity and hyperammonemia have been reported in acute overdose setting. L-carnitine is an amino acid derivative that is an essential cofactor in the β-oxidation of fatty acids. A few observations suggest that L-carnitine supplementation may increase the β-oxidation of VPA, thereby limiting cytosolic ω-oxidation and the production of toxic metabolites that are involved in liver toxicity and ammonia accumulation (2). Case series: From January 2011 to September 2013, 21 patients with acute VPA intoxication were admitted to our Clinical Toxicology Unit. In addition to gastrointestinal decontamination and supportive management, 9 patients required L-carnitine supplementation due to hyperammonemia or severe intoxication (VPA plasma level > 450 mg/L or reported ingestion of more than 400 mg/kg). All patients were treated with loading dose of 100 mg/kg i.v. (up to 6 g) over 30 minutes, followed by 15 mg/kg every 4 hours over 10-30 minutes (3). No side effect were observed. Median length of hospital stay was 6 days and within the fourth day ammonia and VPA plasma levels went back in range. One patient reported life threatening cardiac arrhythmias probably sustained by VPA induced quinidine-like effect and needed temporary intracavitary cardiac pacing. None of our patients experienced any sequelae. Conclusions: Our experience shows that early parenteral L-carnitine supplementation speeds up the decrease of ammonia and VPA plasmatic levels in acute poisoning. The lack of significant adverse effects and the relatively affordable cost strongly suggest the use of L-carnitine in severe VPA poisoning, in order to treat or even prevent hyperammonemia and improve clinical outcome. (1) Sztajnkrycer M. Valproic acid toxicity: overview and management. Clin Toxicol 2002; 40: 789-801. (2) Lheureux P, Hantoson P. Carnitine in the treatment of valproic acid-induced toxicity. Clin Toxicol 2009;47:101-111 (3) L-Carnitine in Hoffman R et al. Goldfrank's Manual of Toxicologic Emergencies. 2007:411-413
2014
Maria Sili; Arianna Dilaghi; Arianna Totti; Brunella Occupati; Pistelli Alessandra; Guido Mannaioni
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/864513
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