Abstracts

Rationale: After 30-60 min, status epilepticus (SE) becomes refractory to treatment with benzodiazepines, and thus is associated with significant mortality and morbidity. Treatments for benzodiazepine-resistant SE include the use of anti-epileptic drugs, barbiturates and anesthetics. Using the lithium-pilocarpine model of SE, we compared the effectiveness of pentobarbital and propofol in terminating diazepam-resistant SE. Methods: Male, Sprague Dawley rats (n=52), implanted for electroencephalogram (EEG) recordings, were pretreated 18-24 h before pilocarpine treatment with lithium chloride (127 mg/kg). Scopolamine bromide (1 mg/kg) was administered 30 min prior to the injection of pilocarpine (50 mg/kg). Sixty minutes after the development of the first motor seizure, either vehicle, diazepam (10 mg/kg), propofol (100 mg/kg) or pentobarbital (30 mg/kg) was injected intraperitoneal. In a separate set of experiments, diazepam was given 15 min after the first motor seizure. Video-EEG data were collected for 24 h. The EEG data from 0-10 h after the administration of the test drug was band-pass filtered (20-70 Hz) and the power spectral density calculated and plotted over time. To compare across groups, the energy data were fit with an 8th order polynomial and statistical analyses were performed at different times after onset of SE (see Lehmkuhle et al., this meeting). Results: When administered at 15 min (n=7) after the first motor seizure, as expected, diazepam suppressed electrographic SE. Diazepam was consistently ineffective when given at 60 min (n=11), similar to vehicle (n=17). In contrast, both propofol (n=9) and pentobarbital (n=15), when given at 60 min, greatly reduced the mean power of the EEG. The effect was often detectable within 30 min, and was usually maximal at 2 h after administration. The effects of a single administration of propofol often lasted a few hours. Conclusions: At a time point when treatment with diazepam was ineffective in terminating SE, both propofol and pentobarbital were efficacious. Therefore, these animal data provide further evidence for the use of propofol and pentobarbital for the treatment of benzodiazepine-resistant SE. Supported by N01-4-2359 from NIH.