RESPIRATORY DRIVE DURING STATUS EPILEPTICUS AND ITS TREATMENT - COMPARISON OF DIAZEPAM AND LORAZEPAM

In order to examine the respiratory effects of tonic-clonic seizures and their treatment with i.v. diazepam or lorazepam, we utilized a spontaneously breathing piglet seizure model. A tracheostomy, arterial catheter, and epidural electrodes were inserted and pigs were maintained under ketamine anesthesia. After baseline recordings, seizures were induced with a pentylenetetrazol (PTZ) bolus and a 20 min infusion (5-6 mg/kg/min). After 10 min of PTZ infusion, randomly assigned animals received diazepam (D; N = 7; 0.5 mg/kg), lorazepam (L; N = 7; 0.2 mg/kg), or 0.9% saline (C; N = 7; controls) by rapid peripheral vein injection. Minute ventilation (V-e), P-a(CO2), and the pressure change in response to airway occlusion at end-expiration (P-0.1) were measured at standard intervals. All groups had comparable increases in respiratory drive during untreated seizures. Changes in V-e and P-0.1 were reduced to at or below baseline values in groups D and L, but not C, from 2 to 45 min after treatment (P < 0.05). No significant changes were observed in P-a(CO2) after either intervention. Following anticonvulsants, the cumulative duration of seizures was significantly reduced in I, and D groups, compared to C (P < 0.05). We conclude that increases in respiratory drive occur during tonic-clonic seizures induced with PTZ. Amelioration of seizure activity with Iorazepam or diazepam results in a reduction in respiratory drive, but not respiratory failure, in this tracheostomized model.