Development of a piglet model of status epilepticus: preliminary results.

Abstract

Ventilation frequently is impaired during prolonged clinical seizures and their treatment. In a pilot study, respiratory, metabolic, and hemodynamic variables were studied during induced seizures in a lightly anesthetized, spontaneously breathing piglet model. Weanling, mixed-breed domestic piglets. Piglets were instrumented with a tracheostomy, arterial catheter, and epidural electrodes. Conditions included hyperoxia, normothermia, and ketamine maintenance infusion throughout recordings. After baseline recordings, 2 mg/kg IV bicuculline was administered. For further model validation, piglets were randomized to infusions of diazepam (three), lorazepam (two), or saline (control; five) groups after ten minutes of untreated seizures. Integrated tidal volume, respiratory rate, PaCO2, pH, arterial pressure, rectal temperature, heart rate, and bipolar EEG waveforms were recorded and compared at intervals for 60 minutes. Vigorous tonic-clonic seizures occurred in all piglets, confirmed by sudden synchronization and large-amplitude EEG waveforms. Increases in heart rate, arterial pressure, tidal volume, respiratory rate, PaCO2, minute ventilation, and base deficit occurred in all piglets during seizures as compared with baseline. Five minutes after bicuculline was administered, increases in minute ventilation (4.5 +/- 0.4 L/min at baseline to 13 +/- 2.1 L/min) were accounted for by increases in both tidal volume and respiratory rate. More abrupt decreases in respiratory rate were observed in anticonvulsant-treated piglets as compared with controls. The duration of continuous seizure activity (12 +/- 1.0 minutes versus 21 +/- 3.3 minutes; P < .05) was reduced in anticonvulsant-treated piglets. Significant increases in ventilation occur during generalized seizures in tracheostomized piglets given bicuculline. Diazepam and lorazepam infusions ameliorate seizure activity and suppress increases in respiratory rate but not minute ventilation as compared with controls. Problems with this model included baseline variability, temperature instability, and that direct respiratory stimulation from the convulsant agent may have occurred.