A 3-year-old boy with lethargy, vomiting and elevated INR

A 3-year-old boy was brought to the emergency department by his parents with a 3-day history of lethargy, reduced appetite, and intermittent vomiting. He had become progressively sleepy over the past 24 hours and was difficult to rouse. He had been diagnosed with epilepsy at the age of 2 years and had been treated with levetiracetam 300 mg twice daily for one year. Two months ago, sodium valproate syrup 200 mg twice daily was added because of poor seizure control. Five days ago, he was diagnosed with acute otitis media and started on amoxicillin/clavulanate 250 mg three times daily. On examination, he was drowsy but rousable, no focal neurological signs, no meningism, temperature 37.2°C, heart rate 110 beats per minute, respiratory rate 24 per minute, blood pressure 90/60 mmHg. His abdomen was soft and non-tender, with no hepatosplenomegaly. There was no jaundice or rash. Blood tests showed normal renal function, ALT 150 U/L, AST 120 U/L, ALP 220 U/L, GGT 40 U/L, total bilirubin 18 umol/L, INR 2.1, platelet count 120 x 10^9/L, haemoglobin 11.5 g/dL, and white cell count 6.5 x 10^9/L. Serum ammonia was 48 umol/L (normal 15-40). The serum sodium valproate concentration was 120 mg/L (therapeutic range 50-100). Viral serology for hepatitis A, B, C, and Epstein-Barr virus was negative. Blood cultures were negative. Abdominal ultrasound was unremarkable. He was admitted to the paediatric ward. The sodium valproate was withheld, while levetiracetam and amoxicillin/clavulanate were continued. Over the next 72 hours, his level of consciousness improved, vomiting resolved, and his INR fell to 1.4. ALT decreased to 90 U/L. No rechallenge was performed.