The interaction between alcohol and the residual effects of thiopental anesthesia.

BACKGROUND: During ambulatory surgery, barbiturates, such as thiopental, may impair psychomotor performance several hours after administration. It was hypothesized that if patients drink alcohol 4 h after thiopental injection, the increase in psychomotor impairment would be greater than that seen after alcohol ingestion alone. METHODS: Twelve healthy men volunteered to participate in a double-blind, placebo-controlled, crossover study with a Latin square design. On each testing day, the subjects received intravenous injections of either 5 mg/kg of 2.5% thiopental or an equal volume of saline for 30 s. Four hours after injection, the subjects consumed a beverage with or without 0.7 g/kg alcohol. Psychomotor performance and mood were assessed at five times: prior to injection, at 1 h and 3 h after injection, and at 1 h and 3 h after consumption of beverage. RESULTS: Both thiopental and alcohol had strong independent effects on the dependent measures in this study. In addition, body sway, one of the nine psychomotor tests used to assess impairment, was greater after thiopental and alcohol than after alcohol alone. Of eleven adjectives used to assess mood, lightheadedness was cited most frequently after a combination of thiopental and alcohol than after each alone. CONCLUSIONS: Based on our tests of performance and mood, an interaction between thiopental and alcohol is evident; in addition, the interaction between both drugs may exert deleterious effects on higher levels of central nervous system integration.

Assessing the behavioral effects and abuse potential of propofol bolus injections in healthy volunteers.

Propofol is a recently introduced intravenous anesthetic agent, commonly administered to surgical patients because it induces anesthesia smoothly (i.e., provides loss of consciousness rapidly and usually with no complications) and is associated with rapid recovery. Propofol has psychoactive effects that could be construed as pleasant, although little abuse liability testing has been done on this agent in humans. Accordingly, we examined various effects of this agent at different subanesthetic doses (0.2-0.6 mg/kg) in order to characterize this drug's abuse potential (for recreational use or potential for diversion). Using a double-blind, randomized, crossover design, healthy normal volunteers (N = 10) were injected intravenously with the drug or with placebo. Before the injection and for up to 1 h afterwards, mood (including drug liking), memory and psychomotor performance were assessed. Propofol impaired memory and psychomotor performance and produced changes in 10 of 20 VAS mood ratings. Although there was variability in self-reported drug liking, some subjects clearly liked the effects of propofol, especially at the two higher doses. At the debriefing interview held after completion of the study, five subjects said if they had to participate in one more session in which they were given a choice between being injected with the highest dose (0.6 mg/kg) or a placebo, they would choose propofol. These preliminary results suggest that this agent may have some potential for abuse/diversion and perhaps stricter accountability procedures should be established for this drug in settings where general anesthesia or conscious sedation procedures are done.

Reinforcing effects of extended inhalation of nitrous oxide in humans.

The subjective, psychomotor and reinforcing effects of nitrous oxide at subanesthetic doses (30% and 40% in oxygen) were determined in normal healthy volunteers using a choice paradigm. Thirty percent nitrous oxide was chosen no more often than oxygen (41.6% choice rate), indicating that, for most of the subjects tested, extended inhalation of this nitrous oxide concentration was no more reinforcing than oxygen inhalation. Forty percent nitrous oxide was chosen significantly less often than oxygen (22% choice rate), indicating that, for most of the subjects tested, extended inhalation of this nitrous oxide concentration was less reinforcing than oxygen. Nitrous oxide produced robust subjective effects (e.g., increased ratings of 'high,' 'tingling,' and 'dizzy'). Subjects who chose nitrous oxide reported pleasant subjective effects and liked it, while those who chose placebo reported unpleasant subjective effects and disliked it. Both concentrations of nitrous oxide impaired psychomotor performance in all subjects. The lack of reinforcing effects noted in the present study, given nitrous oxide's known abuse potential, is discussed.

Subjective and psychomotor effects of subanesthetic doses of propofol in healthy volunteers.

Propofol is increasingly being used in medical and surgical procedures in which conscious sedation of the patient is desired. The mood-altering and psychomotor effects of subanesthetic concentrations of propofol have not been well characterized. Therefore, we examined the effects of intravenous infusions of different subanesthetic doses of propofol on mood and psychomotor/cognitive performance in healthy volunteers (n = 10). A prospective, randomized, placebo-controlled, double-blind, crossover design was used in which subjects first were administered an intravenous loading dose of propofol or placebo (Intralipid) and then were infused over a 20-min period with a given dose of propofol or placebo. Each subject received placebo (Intralipid loading dose and infusion), low-dose propofol (0.08 mg/kg loading dose and 0.5 mg.kg-1.h-1 infusion), moderate-dose propofol (0.16 mg/kg loading dose and 1.0 mg.kg-1.h-1 infusion), and high-dose propofol (0.32 mg/kg loading dose and 2.0 mg.kg-1.h-1 infusion) in four sessions spaced approximately 1 week apart. Propofol induced changes in mood in a dose-related fashion. Some of these mood-altering effects lingered for as long as 30 min after termination of the infusion, but, in general mood had returned to baseline levels 1 h after termination of the infusion. Intralipid induced no changes in mood during the infusion period. Psychomotor functioning was impaired during, and anterograde amnesia was present after, the high-dose propofol infusion. These results suggest that propofol as a sedative has a spectrum of effects that are well-suited for ambulatory surgery (e.g., sedation, amnesia, and rapid and complete recovery).

Subjective and psychomotor effects of nitrous oxide in healthy volunteers.

The effects of nitrous oxide at subanesthetic doses (0%, 10%, 20%, and 40% in oxygen) on mood and psychomotor performance were determined in a group of 12 healthy volunteers (six males and six females). A randomized, placebo-controlled, double-blinded, crossover trial of five experimental sessions was used. Effects were measured before, during and after a 30-min inhalation period of the agent, using three subjective effects questionnaires (the Profile of Mood States, the Addiction Research Center Inventory, and the Visual Analogue Scale); and two psychomotor tests (auditory reaction time and Digit Symbol Substitution Test). In addition, an End-of-Session questionnaire, administered 60min after cessation of inhaling the agent, was used, which measured the subjects' reactions to the agent inhaled that day (i.e. peak concentration effect and concentration liking). The primary effects observed from nitrous oxide were confined to the inhalation of 20% and 40% concentrations. Subjects became more confused, sedated, high, dysphoric, and stimulated during inhalation of 40% nitrous oxide; fatigue, depression and anxiety increased after inhalation of 40% nitrous oxide had ceased. Significant or near-significant differences on several measures of subjective effects emerged between sexes. On the End-of-Session questionnaire, subjects' ratings of the peak effect of nitrous oxide were dose-related. There was individual variation in the degree to which subjects liked nitrous oxide: eight of the 12 subjects reported liking the 40% concentration, one was neutral, and three did not like it. Subjects' performance on the DSST was significantly impaired during inhalation of 40% nitrous oxide, but recovered soon after inhalation stopped. In summary, nitrous oxide had robust effects on mood, there appeared to be sex differences in the magnitude of subjective effects of nitrous oxide, and there was some variability in the extent to which subjects liked the anesthetic agent.