Abstracts

Rationale: In cases of refractory status epilepticus the ketogenic diet represents an alternative, non-pharmacologic approach to treatment. Its use has been associated with cessation of seizures in Febrile-Induced Refractory Status Epilepticus in children within days of achieving ketosis. Patients with refractory status epilepticus are typically treated with multiple anticonvulsant agents and/or anesthetic agents. In some cases, the concomitant treatments may interfere with the development of ketosis, thereby potentially limiting the utility of ketogenic diet treatment in this setting. Methods: Case report illustrating this effect. A 5 year old boy was admitted in refractory status epilepticus following a febrile illness 2 weeks prior. On admission in burst-suppression on EEG he was on a midazolam infusion, pentobarbital, levetiracetam, oxcarbazepine and intravenous immunoglobulin. Fosphenytoin had been discontinued due to lack of efficacy. Investigations for viral, metabolic, neuroimmunologic etiologies were all negative. Following failure of plasmapheresis and isoflurane to improve control, the ketogenic diet was initiated at a 4:1 ratio. Pentobarbital, discontinued during plasmapheresis, was reinstituted due to seizure recurrence. Plasma betahydroxybutyrate remained <0.6 mmol/L and no ketonuria was detected after 8 days. His respiratory exchange ratio was 1.0, and on blood testing glucose and insulin were high, all suggesting carbohydrate/glucose as the main metabolic fuel and therefore inadvertent glucose administration or unexpected gluconeogenesis. Examination of the medication regimen revealed a high intake of propylene glycol, the solvent/excipient for pentobarbital, and potential substrate for gluconeogenesis. Following withdrawal of pentobarbital in favor of phenobarbital (completed day 21), resulting in a decreased intake of propylene glycol, ketogenesis was established with the expected fall in respiratory exchange ratio to 0.7 and an elevation in plasma anion gap (AG) and betahydroxybutyrate (BHB). Results: The Figure shows the time course in withdrawal of the source of propylene glycol (g/day) during weaning of pentobarbital infusion and the associated rise in serum AG and BHB. This patient achieved seizure control with ketosis and the ketogenic diet and other anticonvulsant medications. Conclusions: In cases of refractory status epilepticus, the ketogenic diet may offer an alternative approach to treatment. Many such cases are on a complex regimen of anticonvulsant medications, often including pentobarbital. Depending on the doses required, large amounts of the solvent propylene glycol may be administered, effectively preventing ketogenesis by providing substrate for the physiologically preferred gluconeogenesis. This little known interaction should be considered in this setting when patients are unexpectedly unable to generate ketosis despite high diet ratios.