Seizure due to Lamotrigine Underexposure During High-Volume CRRT for Hyperammonaemia: A Case Report

Hyperammonaemic decompensation in urea cycle disorders (UCDs) is a medical emergency that requires prompt intervention. Continuous renal replacement therapy (CRRT) is an effective strategy for acute ammonia clearance, but it may significantly alter the pharmacokinetics of administered drugs.

A woman in her 40s with argininosuccinate lyase (ASL) deficiency and long-standing, well-controlled epilepsy treated with lamotrigine presented with a hyperammonaemic crisis and was treated with high-volume continuous venovenous haemodialysis (CVVHD). She developed a generalised tonic-clonic seizure shortly after cessation of CVVHD. Serum lamotrigine declined from 12.7 to 6.0 mg/L over approximately 12 h, corresponding to an apparent elimination half-life of 11.5 h. Lamotrigine was measurable in the effluent (2.9 mg/L), giving a saturation coefficient of 0.48 and an extracorporeal clearance of 38.4 mL/min during the high-volume phase. The seizure was attributed to the abrupt underexposure of lamotrigine in a previously seizure-free patient.

This case underscores the clinical significance of extracorporeal clearance of antiseizure medications during CRRT in patients with UCDs. Drug selection should consider both ammonia-modifying and dialysability profiles. Therapeutic drug monitoring and pre-emptive dose adjustment, or the addition of a second intravenously available agent, should be considered when high-volume dialysis is initiated in a patient receiving a dialysable antiseizure medication.