Life-threatening Valproate Overdose Successfully Treated with Haemodialysis

Abstract

Valproate (VPA) poisoning is an increasing clinical problem. The most common finding in VPA overdose is the depression of the central nervous system, which may progress to coma and death. This type of poisoning is difficult to treat, as no antidote exists. This report describes a case with a 16-year-old girl who poisoned herself with valproate. Initial treatment included naloxone, but she did not respond. She became comatose, with serum VPA concentration of 1320 µg mL -1. Three sessions of haemodialysis were performed, effectively eliminating VPA and decreasing the serum concentration. The patient regained consciousness and fully recovered. To our knowledge, this is the highest serum VPA concentration reported by now in children aged 16 or less. Haemodialysis has proved to be the treatment of choice for life-threatening acute VPA overdose in children. Me{trovi} J, et al. VALPROATE OVERDOSE TREATED WITH HAEMODIALYSIS Arh Hig Rada Toksikol 2008;59:295-298: Valproate (VPA) is used as sodium valproate to manage childhood refractory epilepsy, behavioural disorders, and migraines. Cases of VPA overdosing have been on the rise (1). The most common finding is the central nervous system depression, and management is mainly symptomatic and supportive, including activated charcoal and naloxone (2). Haemodialysis, haemoperfusion, or both, have also been reported (3, 4). Here we report a case of a 16-year-old girl with VPA-induced coma who was successfully treated with haemodialysis. KEY WORDS: central nervous system depressants, intensive care, thrombocytopenia, toxicity CASE PRESENTATIONA 16-year-old girl was admitted to the Emergency Department of the University Hospital Split eight hours after ingesting 75 g (882 mg kg -1 ) of VPA (enteric-coated formulation marketed as Apilepsin ® ) in attempted suicide. On admission, her vital signs were: blood pressure 130/70 mmHg, pulse 100 min -1 , and respiratory rate 25 min -1 and her Glasgow Coma Scale (GCS) score was 6. Initial blood analysis revealed serum VPA concentration of 1320 µg mL -1. Arterial blood gas analysis showed compensated metabolic acidosis, with an anion gap of 22.3 mmol L -1 . Complete blood count, electrolytes, creatinine, and liver enzymes were normal. Two doses of naloxone, 0.9 mg each, were given intravenously, but without notable improvement of her neurological status. Four hours after admission, she was in a deep coma (GCS 3). Breathing and circulation were stable, the patent airway was secured with the oropharyngeal (Guedel) airway, and there was no need for mechanical ventilation. Haemodialysis was considered the best possible therapeutic intervention at that moment, and the first session was immediately started through a double-lumen internal jugular vein using a NIPRO FB 130 TGA dialyser.

Antiepileptic drugs: Role in paediatric poisoning

“…In multicentre case series of VPA intoxications, patients presenting with a peak serum drug concentration over 450 μg/mL had a moderate/major adverse outcome, while patients showing a peak over 850 μg/mL were at risk of coma, acidosis, respiratory depression and aspiration . Possible laboratory intoxication signs include metabolic acidosis, hyperosmolarity, hypernatraemia, hypocalcaemia and hyperammonaemia …”

“…45 Possible laboratory intoxication signs include metabolic acidosis, hyperosmolarity, hypernatraemia, hypocalcaemia and hyperammonaemia. 40,46 Zonisamide Zonisamide (ZNS) is administered at a dose of 8 mg/kg/day. The therapeutic range is 10-40 mg/L, T max is 2-5 h, and T½ is 50-70 h. 7,17 ZNS poisonings in the literature are limited to single case reports, including a teenager who took an intentional overdose and developed non-anion gap metabolic acidosis, CNS depression and electrocardiogram changes.…”

Ağır Valproik Asit Zehirlenmesinde Kombine Tedavi

“…Valproik asit zehirlenmesinde hemodiyalizin faydalı olduğunu gösteren olgu sunumlarına ait az da olsa kanıtlar vardır (5,6). Valproik asit ile karbapenem grubu antibiyotikler arasındaki etkileşimin mekanizması net olmamakla birlikte, valproik asitin emilimi, dağılımı ve metabolizması üzerine etkili olduğu düşünülmektedir (7).…”