topiramate and Coma

Topics: Adult; Anticonvulsants; Coma; Diffusion Magnetic Resonance Imaging; Epilepsy; Fructose; Glasgow Coma Scale; Heat Stroke; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Tomography, X-Ray Computed; Topiramate

Topics: Analgesics; Anticonvulsants; Coma; Drug Interactions; Female; Fructose; Humans; Middle Aged; Sodium Oxybate; Topiramate

Topiramate is primarily renally eliminated and requires dosage adjustment based upon renal function. While there is data to suggest drug removal during intermittent hemodialysis (IHD), little is known regarding its clearance and dosing during continuous renal replacement therapy (CRRT).. We describe a 59-year-old man with refractory status epilepticus who was started on continuous venovenous hemodiafiltration (CVVHDF) for acute renal failure while receiving topiramate with a series of serum concentrations to assess for removal during CVVHDF.. Our data suggest clinically important amounts of topiramate are removed by CRRT, and higher topiramate dosage may be needed for these patients instead of the current recommended 50% of normal dosage. Unfortunately, there is no antiepileptic drug dosing recommendation when used during CRRT due to the paucity of data. This case highlights a need for research evaluating the effect of CRRT on AED elimination in order to optimize therapy for seizure control.

Topics: Anticonvulsants; Coma; Drug Resistance; Electroencephalography; Fatal Outcome; Fructose; Glasgow Coma Scale; Hemofiltration; Humans; Kidney Function Tests; Male; Middle Aged; Status Epilepticus; Topiramate

Topiramate is used to treat a variety of neurologic and psychiatric diseases due to its benign safety profile. Data regarding the toxicity and toxicokinetics of topiramate in acute overdose are limited. A case of massive, acute ingestion resulting in the highest reported topiramate level is presented, including toxicokinetic evaluation. A 37-year-old woman presented with coma unresponsive to naloxone following topiramate ingestion. She had normal vital signs without respiratory depression. She was intubated for airway protection, given 3.5 mg lorazepam IV for facial and neck muscle twitching, and transferred to our facility. No additional sedation was required for 18 h on the ventilator. Following mental status improvement, the patient was extubated. Confusion, dysarthria, and imbalance resolved over the next 2 days. Nonanion gap metabolic acidosis persisted for 3 days. Peak serum topiramate level was 356.6 microg/ml (reference range, 5-20 microg/ml). Massive topiramate ingestion led to prolonged coma with normal vital signs and nonanion gap metabolic acidosis. Coma of this severity has not been previously reported. Serum half-life, which has not been studied after overdose, was 16 h. Despite the large ingestion and significant presenting symptoms, the patient recovered fully with supportive intensive care alone. Massive acute topiramate ingestion may lead to nonanion gap metabolic acidosis and prolonged coma which resolves with intensive supportive care. Toxicokinetic data following large, suicidal ingestion of topiramate were similar to previously published pharmacokinetic information.

Topics: Acidosis; Adult; Anticonvulsants; Bipolar Disorder; Blood Gas Analysis; Coma; Critical Care; Drug Overdose; Female; Fructose; Gas Chromatography-Mass Spectrometry; Humans; Hypnotics and Sedatives; Lorazepam; Respiration, Artificial; Topiramate