Ionised Hypocalcaemia as a Compounding Factor in Refractory Seizures During Opioid-benzodiazepine Withdrawal: A Case Report

Concurrent opioid and benzodiazepine dependence is common in clinical practice, and abrupt cessation of either agent can independently precipitate withdrawal seizures that are frequently refractory to standard treatment. Ionised hypocalcaemia is a less widely recognised and potentially reversible contributor to seizure threshold lowering in this setting, and can be overlooked when only total serum calcium is measured. Hereby, the authors present a case report of a 28-year-old male with a 6-to-7-year history of polysubstance dependence, involving codeine-containing cough syrup, alprazolam, tobacco, gutkha, and intermittent methamphetamine use, in whom this compounding metabolic factor was identified during combined opioid-benzodiazepine withdrawal. He presented to the Emergency Department with altered sensorium and cluster tonic-clonic seizures approximately 48 hours after abrupt cessation of all substances. On arrival, the Glasgow Coma Scale (GCS) was 7 of 15, and arterial blood gas analysis showed a critically low ionised calcium of 0.56 mmol/L (reference range 1.12 to 1.32 mmol/L), while total serum calcium checked the following day was normal (10.4 mg/dL), illustrating that total calcium can be misleadingly reassuring when ionised calcium is critically low. Six further cluster seizures occurred in the Emergency Department despite prior benzodiazepine loading at a referring hospital, and management required intravenous sodium valproate, lorazepam, naloxone for diagnostic clarification of possible opioid co-ingestion, thiamine, intravenous calcium gluconate correction, and intensive-care-level monitoring with neurology and psychiatry co-management. Seizure frequency decreased progressively, with improvement in sensorium and correction of ionised calcium, and the patient was discharged on a structured benzodiazepine taper together with naltrexone for relapse prevention. The present case illustrates that combined opioid and benzodiazepine withdrawal can produce seizures resistant to initial benzodiazepine monotherapy, and that severe ionised hypocalcaemia should be actively sought and corrected as a potential contributing factor in withdrawal-associated seizures, particularly when radiological and cerebrospinal fluid evaluation are not feasible and other causes cannot be fully excluded.