Lichtor Jl

Awakening, clinical recovery, and psychomotor effects after desflurane and propofol anesthesia.

We compared postanesthetic and residual recovery of desflurane versus propofol anesthesia.Twenty volunteers were anesthetized for 1 h at 1-wk intervals with either propofol (induction) plus desflurane (1.25 minimum alveolar anesthetic concentration) in O2 (PD), propofol plus desflurane in N2 O-O2 (PDN), propofol plus propofol infusion with N2 O-O2 (PPN), or desflurane (induction) plus desflurane in O2 (DD). Awakening and clinical recovery were measured. Psychomotor skills (attention, coordination, reactive skills, and memory) were tested before and 1, 3, 5, and 7 h after anesthesia. Awakening was fastest in Group PDN. At 1 h after anesthesia, the subjects given desflurane for maintenance (PD, PDN, and DD) performed significantly (P < 0.05-0.01) better in several psychomotor tests compared with those whose anesthesia was maintained with propofol (PPN). However, subjects met criteria for home readiness as fast after PPN as after PDN anesthesia (mean times +/- SE until fitness for discharge were 126 +/- 20, 81 +/- 14, 70 +/- 7, and 106 +/- 14 min after PD, PDN, PPN, and DD, respectively). Awakening and early psychomotor recovery for as long as 1 h after anesthesia is faster after desflurane than after propofol, but there was no difference in time to home readiness or in residual effects thereafter between propofol and desflurane with N2 O in O2. (Anesth Analg 1996;83:721-5)

Propofol at a subanesthetic dose may have abuse potential in healthy volunteers.

We conducted a study in which the rewarding effects of propofol were assessed in humans, using a discrete-trials choice procedure. Normal healthy volunteers (n = 12) were exposed in a blind fashion to acute bolus injections of 0.6 mg/kg of propofol twice and to a similar volume of Intralipid® twice. Then, for the next three sessions, subjects chose which drug (identified by a color code) they wished to receive. We defined propofol choosers if individuals chose propofol two or three times, and nonchoosers if they chose propofol once or not at all. By using a χ2 goodness-of-fit test of a random choice model, the choice distribution differed significantly from a random choice distribution (P < 0.005). Six subjects were choosers: four subjects chose propofol on all three choice occasions and two subjects chose the drug on 2/3 occasions (referred to hereafter as propofol choosers). Six subjects were nonchoosers: five subjects chose Intralipid® on all three choice occasions, and one subject chose Intralipid® twice (referred to hereafter as propofol nonchoosers). During sampling sessions, propofol choosers reported pleasant acute effects and no unpleasant residual effects, whereas propofol non-choosers reported either unpleasant acute subjective effects and/or residual effects from propofol. We conclude that 1) propofol may be rewarding (reinforcing) in some individuals without a history of drug abuse, and 2) further abuse liability testing is needed with this drug.

The subjective, behavioral and cognitive effects of subanesthetic concentrations of isoflurane and nitrous oxide in healthy volunteers

A prospective, crossover, double-blind trial was conducted in nine healthy volunteers in which the subjective, psychomotor and memory effects of isoflurane (0.0, 0.3 and 0.6%) and nitrous oxide (N2O) (0, 20 and 40%) were examined. Dependent measures included visual analog scales and a standardized drug effects inventory (subjective effects), reaction time and eye-hand coordination (e.g., psychomotor performance), and immediate and delayed free recall (memory). There were some similarities in subjective effects between the two inhaled drugs (e.g., increased ratings of “drunk” and “spaced out”), but isoflurane had effects which N2O did not have. Isoflurane but not N2O increased visual analog scale ratings of “confused,” “sedated,” and “carefree,” and decreased ratings of “in control of thoughts” and “in control of body.” An odor was detected with isoflurane and it was disliked. Psychomotor performance was more grossly impaired during isoflurane inhalation than during N2O inhalation. Psychomotor recovery from both agents was rapid and complete so that 5 min after the inhalation period had ceased, performance had returned to baseline levels. Both isoflurane and nitrous oxide impaired immediate and delayed free recall. The feasibility of using isoflurane in conscious sedation procedures is discussed.

Sedation and Recovery of Psychomotor Function After Intravenous Administration of Various Doses of Midazolam and Diazepam

&NA; A placebo‐controlled, double‐blind, crossover trial in 11 healthy male volunteers compared clinical sedation and psychomotor function after intravenous injection of midazolam (0.05, 0.1, or 0.15 mg/kg), diazepam (0.15 or 0.3 mg/kg), or placebo (saline). The depth of sedation was estimated at 5‐10‐min intervals during the first hour after injection. A comprehensive battery of psychomotor tests was used to collect objective data of psychomotor performance before drug injection and 1, 3, 5, and 7 h after injection. Midazolam (0.15 mg/kg) produced the highest scores of sedation and most impairment of psychomotor performance. In most tests, the maximal psychomotor effects seen after 0.3 mg/kg of diazepam did not reach those of 0.1 mg/kg of midazolam. Although the strongest psychomotor effects were induced by midazolam, these effects disappeared sooner than those of diazepam. By 5 h after injection, 0.3 mg/kg of diazepam showed the highest scores of psychomotor impairment. The authors conclude that at least four times as much diazepam as midazolam is needed to produce equally severe psychomotor impairment. That the residual effects of midazolam terminate sooner than those of diazepam probably accounts for the occasional underestimation of the potency of midazolam in clinical practice.

The acute and residual effects of subanesthetic concentrations of isoflurane/nitrous oxide combinations on cognitive and psychomotor performance in healthy volunteers.

A blind, randomized, cross-over trial was conducted to determine the degree of psychomotor/cognitive impairment and the recovery profile produced by combinations of subanesthetic concentrations of isoflurane and nitrous oxide in healthy volunteers. In the experiment, subjects (n = 10) inhaled 100% oxygen-placebo, 30% nitrous oxide in oxygen, and 0.2% and 0.4% isoflurane in oxygen, alone, and in combination with 30% nitrous oxide, in different seesions. Dependent measures included psychomotor and cognitive performance. Impairment was profound with the combination of inhaled anesthetics, and from an analysis of control conditions (the anesthetics alone), it appeared that isoflurane produced more impairment than did nitrous oxide. The time course of recovery was extremely rapid, with subjects returning to control-level functioning 5 min after cessation of the drug inhalation. The drug combination of isoflurane and nitrous oxide appears to be a promising candidate for conscious sedation procedures, although its analgesic and mood-altering effects need to be studied more systematically. (Anesth Analg 1996;82:153-7)

Subjective, behavioral and physiological responses to intravenous meperidine in healthy volunteers

Meperidine is a mu opiate agonist that is frequently used to treat pain. We examined in healthy volunteers (N=10) the effects of intravenous meperidine (0, 0.25, 0.5, and 1.0 mg/kg) on mood and psychomotor performance. A randomized, placebo-controlled, crossover design was used in which subjects were injected with meperidine or saline in a double-blind fashion. Subjects completed several subjective effects questionnaires commonly used in abuse liability testing studies before drug injection and at periodic intervals for up to 5 h after drug injection. Subjects also completed several psychomotor tests. Meperidine produced a constellation of subjective effects in a dose-related fashion, including increases in ratings of “sedated,” “coasting or spaced out” and “feel drug effect” ratings. Many of the drugs subjective effects persisted up to 4 or 5 h after administration of the 1.0 mg/kg dose. Drug liking ratings assessed on a visual analog scale were increased after meperidine injection in about half of the subjects (P=0.09). Eye-hand coordination was affected slightly by meperidine but other indices of psychomotor functioning were unaffected. Miosis increased in a dose-related fashion. Other physiological parameters, such as vital signs, were not affected by meperidine. We conclude that meperidine in healthy volunteers has robust and long-lasting effects on mood, but may have weaker effects on psychomotor performance.

Subjective, behavioral, and physiologic responses to intravenous dezocine in healthy volunteers

Dezocine is an agonist-antagonist opiate that acts at the mu receptor, and is used for management of pain. Monkeys will readily press a lever to receive an injection of dezocine, and in former opiate addicts dezocine produces positive subjective effects similar to those of morphine. It is not clear, however, what its subjective effects are in people who do not have a history of opiate abuse. To answer this question, a within-subjects design was used in which 10 normal healthy volunteers (six men, four women) were injected with 0, 2.5, 5.0, and 10 mg/70 kg of dezocine in a double-blind fashion. Subjects completed several questionnaires (e.g., Addiction Research Center Inventory) commonly used in abuse liability testing before and at periodic intervals for up to 5 h after drug injection. We also assessed psychomotor performance (e.g., eye-hand coordination) and several physiologic measures (e.g., pupil size, respiration rate) at these times. Dezocine produced increases in ratings of drug liking (P < 0.001), as well as other subjective effects that might be considered as pleasant („good mood”, „drunken”, „coasting”, „happy” ratings) (all P < 0.05). At the same time, the drug had effects (increased dysphoria and sedation) that typically are not reported by addicts. Dezocine produced psychomotor impairment and miosis (constriction of the pupils) in a dose-dependent fashion. The observation that dezocine produces euphoria and increased drug-liking ratings in individuals without histories of drug abuse suggests that hospitals and surgicenters should have strict accountability procedures with this drug.

Examining the subjective, psychomotor and reinforcing effects of nitrous oxide in healthy volunteers: a dose-response analysis.

The present study examined the subjective, psychomotor and reinforcing effects of 10%, 20%, 30% and 40% nitrons oxide in oxygen in 16 healthy volunteers using a choice procedure in which sampling (e.g. 20% nitrous oxide and oxygen-placebo) and choice trials (e.g. 20% nitrous oxide vs. oxygen-placebo) were within the same session. Across the four-session study, nitrous oxide dose was varied. Nitrous oxide in a dose-related manner altered subjective effects (e.g. increased visual analog scale ratings of “high”, “stimulated” and “tingling”) and decreased performance on the Digit Symbol Substitution Test. 10%, 20%, 30% and 40% nitrous oxide were chosen over oxygen by 6, 7, 7 and 8 subjects, respectively. We conclude that nitrous oxide across a range of subanesthetic doses did not function as reinforcer in the majority of subjects tested.

Reinforcing effects of extended inhalation of a low nitrous oxide concentration in humans.

The reinforcing, subjective, and psychomotor effects of 30 min of inhalation of 20% nitrous oxide were determined in 12 healthy volunteers using a choice paradigm with 100% oxygen as placebo. Nitrous oxide was chosen on only 22% of choice occasions, indicating that, in general, this concentration did not function as a reinforcer. Nitrous oxide produced changes in mood, but had no effect on psychomotor performance. Three out of the 12 subjects chose nitrous oxide on at least two out of the three choice sessions, and during a poststudy debriefing interview, reported pleasant effects of the drug. The other nine subjects reported unpleasant acute effects of the drug (e.g., drowsiness) or residual (postsession) effects of the drug which, they said, influenced their drug choice. The present results are compared to those results obtained in a previous study in which higher concentrations of nitrous oxide (30 and 40%) also produced relatively low choice rates. The apparent lack of reinforcing effects of extended inhalation of nitrous oxide is discussed.

Alcohol after midazolam sedation: does it really matter?

Patients who arrive home several hours after ambulatory surgery may drink alcohol. The extent to which the residual effects of drugs used in ambulatory surgery interact with alcohol, perhaps potentiating alcohol effects, is not known. Accordingly, the purpose of this study was to determine whether intravenous midazolam had residual effects that would interact with alcohol consumed 4 h after the midazolam injection. Healthy male volunteers (n = 16) participated in a double-blind, randomized, placebo-controlled crossover trial. Subjects were studied four times successively with 1 wk between trials. On each test day the subjects randomly received by slow intravenous injection (30 s) either saline or 0.1 mg/kg of midazolam. Four hours after injection, the subjects consumed a beverage that either did or did not contain 0.7 g/kg of alcohol. Before and 1, 3, 5, and 7 h after injection (and before and 1 and 3 h after beverage consumption), psychomotor performance and mood were assessed. Whereas both midazolam and alcohol alone had effects on the dependent measures in this study, there were no significant interactions between the two drugs (i.e., potentiation of alcohol effects by midazolam or poten-tiation of midazolam by alcohol). We conclude that the effects of a short-acting benzodiazepine used in ambulatory surgery have probably dissipated by the time a patient arrives home, and that effects from alcohol ingested at home will probably not be influenced by the recent administration of a short-acting benzodiazepine such as midazolam.