Analgesic and psychomotor effects of thiopental at subanesthetic concentrations in human volunteers.

Abstract

Studies of the effects of barbiturates on the modulation of pain have produced mixed results. In a prospective, double-blind, randomized, placebo-controlled trial, we studied the effects of thiopental at presumed steady-state, "conscious sedation" levels on cold-pressor-induced pain in 12 healthy volunteers. Five drug conditions were used, each condition consisting of an injection (either drug or placebo) with a 20-min infusion and a 160-min recovery period. The conditions were placebo (saline), thiopental targeted to three effect-site concentrations, and fentanyl (1.4 micrograms/kg), as a positive control to verify test sensitivity to analgesic drugs. The three thiopental concentrations were modeled (STANPUMP) to achieve effect-site concentrations of 5, 7.5, and 10 micrograms/ml using a bolus and a three-step continuous infusion. Five minutes into the infusion period and 115 min after the infusion period was terminated, subjects immersed their forearms in ice cold water for 3 min while pain and behavioral assessments were recorded. Thiopental at the highest dose produced a significant reduction (P < 0.05) in self-reported pain intensity both at 5 min into the infusion period and at 115 min after termination of the infusion. Fentanyl reduced pain intensity during the first immersion only. Thiopental changed subjects' moods and psychomotor performance in a dose-related fashion. Our laboratory results do not support the long-held belief that barbiturates are "antanalgesic" or hyperalgesic, at least for cold-pressor-induced pain.