Pathological Case of the Month: Sudden Death in a Child as a Result of Pancreatitis During Valproic Acid Therapy

Abstract

Valproic acid is a widely used drug in the treatment of epilepsy and, compared to other anticonvulsant drugs, is considered safe. The most common side effects of valproic acid ingestion or therapy are transient nausea, vomiting, abdominal cramps, and diarrhea. Most of these complaints are mild. However, more serious adverse reactions can occur such as hepatotoxicity and pancreatitis. It has been proposed that, whenever possible, valproic acid not be used in the younger child, the child with a severe seizure disorder or other neurological disorders, mental retardation, developmental delay, organic brain disease, congenital abnormalities, or the child who is taking multiple anticonvulsant drugs, as these factors may increase the likelihood of hepatotoxicity and/or pancreatitis. In the present report, we describe a fatal case of acute hemorrhagic pancreatitis in a four and a half-year-old Hispanic female child who was receiving valproic acid in combination with another anticonvulsant drug for control of focal seizures. The patient also received the macrolide antibiotic azithromycin. For pediatricians and forensic pathologists valproic acid-induced pancreatitis can be a challenging diagnosis which must not be mistaken for abdominal trauma. We discuss the workup of the patient and differential diagnosis.

Fatal valproate overdose in a newborn baby

“…However, intoxication with VPA may lead to leucopenia, thrombocytopenia, hepatotoxicity, acute pancreatitis, respiratory and renal failure, encephalopathy, coma, brain edema, and sometimes may be fatal. [1][2][3][4][5] Although some side effects of VPA are not dose-dependent, toxic effects are associated with daily doses above 1800 mg and blood levels above 100 g/mL. 6 Children younger than two years who are treated with VPA are at significant risk (1:800) for developing an idiosyncratic, potentially fatal hepatotoxic syndrome.…”

Antiepileptic drugs: Role in paediatric poisoning

“…[41][42][43] The development of pancreatitis has been described, including fatal cases. 44 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. 45 Possible laboratory intoxication signs include metabolic acidosis, hyperosmolarity, hypernatraemia, hypocalcaemia and hyperammonaemia.…”