Propofol in Subanesthetic Doses Terminates Status Epilepticus in an Experimental Model as First-Line Therapy.
Abstract number :
I.09
Submission category :
Year :
2000
Submission ID :
1142
Source :
www.aesnet.org
Presentation date :
12/2/2000 12:00:00 AM
Published date :
Dec 1, 2000, 06:00 AM
Authors :
Martin Holtkamp, Xong Tong, Matthew C Walker, Charite, Humboldt-Universitaet Berlin, Berlin, Germany; Dept of Clin Neurology, Queen Square, London, United Kingdom.
RATIONALE:_Status epilepticus is a life-threatenting condition refractory to first-line therapy in 40 % of cases. Barbiturates are well-established in the treatment of refractory SE, but there have also been reports on the success of non-barbiturate anesthetics such as propofol. This drug has advantageous pharmakokinetics with a rapid onset of action and no propensity to accumulate. There have, however, been very few studies evaluating the antiepileptic properties of propofol. METHODS:_In a well-characterized rat model, we induced self-sustaining status epilepticus (SSSE) by 2 hours electrical stimulation of the perforant path. Two minutes after the end of stimulation the animals were given an intraperitoneal bolus of propofol 50 mg/kg, diazepam 5 mg/kg, or phenytoin 50 mg/kg. In addition, other animals were treated after 3 hours of SSSE with propofol 50 mg/kg, diazepam 5 mg/kg, or pentobarbital 30 mg/kg. All animals were monitored clinically and electrophysiologically for 3 hours after drug injections. RESULTS:_Propofol (n=5) given 2 minutes after the end of stimulation terminated SSSE in all animals. At this stage diazepam (n=5) terminated SSSE in only 2 animals, with sedation levels similar to propofol. Phenytoin (n=5) administered 2 minutes after the end of stimulation did not stop SSSE in any animal. Even given 3 hours after the end of stimulation propofol (n=5) terminated SSSE in all animals as did pentobarbital (n=3); diazepam (n=4) at this stage stopped SSSE in 3 rats. Overall, after propofol injection animals were only minimally sedated with maintained auditory startle reflexes in 9 out of 10 animals; respiratory function and corneal reflexes were not impaired. CONCLUSIONS:_Our data demonstrate the strong antiepileptic properties of propofol in a rat model of refractory SSSE. We have not only shown that propofol after a single bolus is effective in refractory SE, but that it is an effective first-line therapy at subanesthetic doses. Propofol should thus be considered as a possible alternative to common first-line drugs, and clinical trials are warranted.