Fatal heat stroke associated with topiramate therapy.

A 40-year-old man with diabetes and seizure disorder was found at home unresponsive and "very hot to touch" by his father 40 minutes before emergency medical services arrival. His usual medications included topiramate, divalproex sodium, and rosiglitazone/metformin. Paramedics administered oxygen, intravenous fluids, and naloxone. They did not witness or report seizure activity. Upon emergency department arrival, the patient was unresponsive (Glasgow Coma Scale 3), hypotensive (94/50 mm Hg), and tachypneic (32 breaths per minute), with a heart rate of 60 beats per minute and elevated rectal temperature peaking at 43.2°C. His skin was hot and dry, without rash; physical examination was otherwise normal. Laboratory studies revealed severe metabolic acidosis with acute renal failure and rhabdomyolysis. In spite of sedation, intubation, and aggressive cooling measures, the patient had cardiac arrest and died approximately 2 hours after arrival. Serum topiramate and valproate concentrations were within therapeutic ranges at 8.8 μg/mL (therapeutic 2-12) and 97 μg/mL (therapeutic 50-100), respectively.