Respiratory dysfunction and fatal apnea during pilocarpine‐induced status epilepticus

OBJECTIVE: Status epilepticus (SE) is second only to sudden unexpected death in epilepsy as a cause of seizure-related mortality. The progression of respiratory dysfunction during experimental SE remains poorly characterized. We investigated how pilocarpine-induced SE affects respiration in mice. METHODS: We performed simultaneous plethysmographic, electroencephalographic, and electrocardiographic recordings in mice administered pilocarpine at 200, 240, or 280 mg/kg. We analyzed seizure progression, respiratory rate, ventilation, inspiratory/expiratory timing, and survival. RESULTS: Higher pilocarpine doses resulted in shorter latency to SE and increased mortality. Across all doses, respiratory frequency and ventilation increased from baseline through early and established SE. There were respiratory abnormalities during SE, apneustic respiration, and pathological sigh, each associated with prolonged inspiration and expiration compared to eupneic respiration. Abnormal respiratory events occurred with similar frequency in both fatal and surviving animals. Death occurred during established SE. The sequence of events leading to death was a severe seizure, ending with tonic extension followed by terminal apnea. Seizure activity continued after apnea onset, followed by electrocerebral silence. Cardiac rhythm persisted beyond brain inactivity, gradually slowing to terminal arrest. SIGNIFICANCE: Pilocarpine-induced SE leads to progressive, dose-dependent respiratory disturbances culminating in fatal apnea. These findings highlight the critical role of respiratory failure in SE-related death and underscore the need for real-time respiratory monitoring and early intervention during SE.