Pharmacodynamics of phenobarbital anesthesia and pentylenetetrazol-induced maximal seizures in a rat model of neoplastic spinal cord compression

Abstract

The purpose of this investigation was to determine whether paraplegia induced by neoplastic cord compression affects the pharmacodynamics of phenobarbital general anesthesia or of pentylenetetrazol (PTZ)-induced convulsions. Paraplegic rats harboring a thoracolumbar epidural tumor, or an identical hindlimb tumor mass, received an i.v. infusion of phenobarbital until the onset of anesthesia. At that point, the phenobarbital concentrations in the CSF and serum were measured. Similarly, PTZ was infused until the onset of maximal seizures. It was found that changes related to systemic tumor growth and newly developed paraplegia due to neoplastic spinal cord compression did not attenuate the pharmacodynamics of phenobarbital. However, sustained paraplegia of 4 days' duration reduced CNS sensitivity to the hypnotic action of the barbiturate as evidenced by the higher cerebrospinal fluid phenobarbital concentration required to induce anesthesia (170 +/- 31 vs 125 +/- 20 mg/L; P < 0.05). On the other hand, sustained paraplegia did not affect brain threshold concentration for PTZ-induced seizures.