A cool side effect of valproic acid administration: Single dose-induced hypothermia

Thermoregulatory derangements secondary to valproic acid (VPA) administration, specifically hypothermia, have been reported throughout the literature, but a handful of times. This case report describes a 28-year-old male presenting status-post multiple tonic-clonic seizures, treated for persistent seizure activity refractory to benzodiazepines with valproic acid (VPA), levetiracetam, and fosphenytoin. After just over an hour, the patient's core temperature fell from 36.8 °C to 34.9 °C. Temperatures were repeated for confirmation, no further doses of VPA were administered, and the patient's temperature returned to normal over the next 7 h with the use of warming blankets. Levetiracetam and fosphenytoin were continued with no further reported development of hypothermia during the patient's admission. After reviewing other potential causes, a thorough drug database review was performed that found VPA to be the only medication administered with published reports of inducing hypothermia. The mechanism of thermoregulatory derangement associated with VPA is not clearly defined and much of the evidence surrounds alterations in gamma-aminobutyric acid (GABA) activity in animal studies. To our knowledge, this case report is the first reported case of VPA-induced hypothermia following a single dose in the emergency department and offers the potential that prompt return to normothermia is likely following discontinuation of the offending agent.