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

BACKGROUND: 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. CASE PRESENTATION: 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. CONCLUSION: 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.