Severe Valproic Acid Intoxication is Associated with Atrial Tachycardia: Secondary Detoxication by Hemoperfusion

Abstract

Valproic acid is an anticonvulsant drug which is associated with serious toxicity including fatal outcome in case of severe intoxication. Secondary detoxication by hemodialysis or hemoperfusion has been employed successfully in valproic acid intoxication. Cardiac arrhythmias have only been described rarely in valproic acid intoxication in humans.
We report on a 15 year-old boy with severe valproic acid intoxication (valproic acid plasma level on admission: 1 150 mg/l) who presented with coma, hypernatremia and atrial tachycardia. The patient was successfully treated with hemoperfusion and intensive supportive care without implementation of a specific antiarrhythmic therapy. We conclude that patients with severe valproic acid intoxication may benefit from secondary detoxication. In addition to generally known symptoms valproic acid intoxication may also be associated with cardiac arrhythmias.

Zusammenfassung

Im Rahmen einer Intoxikation mit Valproat kann es zu lebensbedrohlichen Komplikationen kommen. Die Behandlung einer schweren Valproat-Intoxikation beinhaltet intensiv-medizinische Maßnahmen; eine sekundäre Giftelimination kann mittels Hämodialyse, Hämofiltration, Hämodiafiltration oder Hämoperfusion erfolgen. Kardiale Rhythmusstörungen beim Menschen durch Valproat-Intoxikationen wurden in der Literatur bisher sehr selten beschrieben.
Wir berichten über einen 15-jährigen Jungen mit einer schweren Valproat-Intoxikation (Valproatspiegel im Plasma bei Aufnahme: 1 150 mg/l). Initial war der Patient komatös, hypernatriämisch und zeigte im EKG eine atriale Tachykardie. Unter intensivmedizinischer Therapie sowie einer sekundären Giftelimination mittels Hämoperfusion trat eine rasche Besserung des klinischen Zustandes ein. Die atriale Tachykardie sistierte ohne eine spezifische antiarrhythmische Therapie. Der Patient konnte ohne neurologische Folgeschäden entlassen werden.

Key words

Valproic acid - intoxication - children - atrial tachycardia - hemoperfusion

Schlüsselwörter

Valproat - Intoxikation - Kinder - atriale Tachykardie - Hämoperfusion

References

• 1 Azarbayjani F, Danielsson B R. Pharmacologically induced embryonic dysrhythmia and episodes of hypoxia followed by reoxygenation: A common teratogenic mechanism for antiepileptic drugs?.  Teratology. 1998;  57 117-126
• 2 Bradley D J, Fischbach P S, Law I H, Serwer G A, Dick M. The clinical course of multifocal atrial tachycardia in infants and children.  J Am Coll Cardiol. 2001;  38 401-408
• 3 Connacher A A, Macnab M SP, Moody J P, Jung R T. Fatality due to massive overdose of sodium valproate.  Scott Med J. 1987;  32 85-86
• 4 Farrar H C, Herold D A, Reed M D. Acute valproic acid intoxication: Enhanced drug clearance with oral-activated charcoal.  Crit Care Med. 1993;  21 299-301
• 5 Franssen E J, van Essen G G, Portman A T, de Jong J, Go G, Stegeman C A, Uges D RA. Valproic acid toxicokinetics: serial hemodialysis and hemoperfusion.  Ther Drug Monit. 1999;  21 289-292
• 6 Gram L, Bentsen K D. Valproate: an updated review.  Acta Neurol Scand. 1985;  72 129-139
• 7 Gurland H, Samtleben W, Lysaght M J, Winchester J F. Extracorporeal blood purification techniques: Plasmapheresis and hemoperfusion. In: Jacob C, Kjellstrand CM, Koch KM, Winchester JF (eds). Replacement of renal function by dialysis. 4th ed. Kluwer Academic Publishers, Dordrecht 1996
• 8 Ishikuro H, Matsuo N, Matsubara M, Ishihara T, Takeyama N, Tanaka T. Valproic acid overdose and L-carnitine therapy.  J Anal Toxicol. 1996;  20 55-58
• 9 Johnson L Z, Martinez I, Fernandez, Davis C P, Kasinath B S. Successful treatment of valproic acid overdose with hemodialysis.  Am J Kidney Dis. 1999;  33 786-789
• 10 Klotz U, Antonin K H. Pharmacokinetics and bioavailabiltiy of sodium valproate.  Clin Pharmcol Ther. 1977;  21 736-743
• 11 Maurer H H, Kraemer T, Kratzsch C. What is the appropriate analytical strategy for effective management of intoxicated patients?. In: Balikova M, Navakova E (eds). Proceedings of the 39th International TIAFT Meeting in Prague, 2001. Charles University, Czeck Republic 2002; 61-75
• 12 McCord J, Borzak S. Multifocal atrial tachycardia.  Chest. 1998;  113 203-209
• 13 Minari M, Maggiore U, Tagliavini D, Rotelli C, Cabassi A, David S, Fiaccadori E. Severe acute valproic acid intoxication successfully treated with hemodiafiltration without hemoperfusion.  Ann Emerg Med. 2002;  39 204-205
• 14 Montero F J. Naloxone in the reversal of coma induced by sodium valproate.  Ann Emerg Med. 1999;  33 357-358
• 15 Murphy J V, Groover R V, Hodge C. Hepatotoxic effects in a child receiving valproate and carnitine.  J Pediat. 1994;  124 318-320
• 16 Von Mühlendahl K E. Vergiftungen im Kindesalter. 4. Aufl. Thieme, Stuttgart 2003
• 17 Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. American Academy of Clinical Toxicology; European Association of Poison Centres and Clinical Toxicologists.  J Toxicol Clin Toxicol. 1999;  37 731-751
• 18 Richens A. Pharmacokinetics and efficacy of epylim in patients receiving long-term therapy with other antiepileptic drugs. In: Legg NJ (ed). Clinical and pharmacological aspects of sodium valproate (epylim) in the treatment of epilepsy. MCS Consultant, United Kingdom 1976; 78-88
• 19 Scher D L, Asura E L. Multifocal atrial tachycardia: mechanisms, clinical correlate, and treatment.  Am Heart J. 1989;  118 574-580
• 20 Spiller H A, Krenzelok E P, Klein-Schwartz W, Winter M L, Weber J A, Sollee D R, Bangh S A, Griffith J R. Multicenter case series of valproic acid ingestion: serum concentrations and toxicity.  J Toxicol Clin Toxicol. 2000;  38 755-760
• 21 Tank J E, Palmer B F. Simultaneous “in series” hemodialysis and hemoperfusion in the management of valproic acid overdose.  Am J Kidney Dis. 1993;  22 341-344