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Biomedical subjects

G Rupani

Publications and source records attributed to G Rupani.

13 recordsLinked to original sources

Differential acute tolerance development to effects of nitrous oxide in humans.

The analgesic, subjective, and psychomotor effects of 0, 10, 20, 30, and 40% nitrous oxide in oxygen were studied in 10 volunteers to determine if acute tolerance developed differentially to these variables. In this prospective, randomized, crossover, double-blind study, volunteers inhaled either placebo (100% oxygen) or one of the aforementioned doses of nitrous oxide for 120 min. During this period, volunteers immersed their non-dominant forearm, for 3 min, in ice-cold water at 25, 70 and 115 min from the onset of the inhalation. At other prescribed time intervals throughout the session, mood and psychomotor performance were assessed. Subjects reported less pain intensity from the cold-water stimulus and reported the pain bothered them less as a function of increasing nitrous oxide dose; in addition, this analgesia was significantly less as the inhalation period progressed (i.e., acute tolerance). Some subjective effects of nitrous oxide that could be considered hedonic in nature (elation, drug liking) also showed evidence of acute tolerance. In contrast, other subjective effects and the psychomotor-impairing effects of nitrous oxide did not change significantly during the inhalation period (i.c., no acute tolerance). The differential acute tolerance observed in this study suggests that different effects of nitrous oxide may be mediated by different neurochemical substrates.

Adult↗

Lack of acute tolerance development to the subjective, cognitive, and psychomotor effects of nitrous oxide in healthy volunteers.

A crossover, double-blind trial was conducted using eleven healthy volunteers to determine whether and the degree to which acute drug tolerance occurred to the subjective, cognitive, and psychomotor effects of a range of subanesthetic nitrous oxide doses (0, 10, 20, 30, and 40%). There was little evidence of acute drug tolerance to the subjective measures or to the cognitive/psychomotor impairing effects of nitrous oxide at any of the concentrations tested over the course of the 120-min inhalation.

Administration, Inhalation↗

Propofol at conscious sedation doses produces mild analgesia to cold pressor-induced pain in healthy volunteers.

STUDY OBJECTIVE: To determine whether subanesthetic doses of propofol have analgesic effects in healthy volunteers. DESIGN: Prospective, double-blind, placebo-controlled, randomized, crossover trial. SETTING: Human psychomotor performance laboratory within our anesthesia and critical care department. SUBJECTS: 12, non-drug abusing volunteers, aged 22 to 38 years. INTERVENTIONS: Five drug conditions were used in which a loading injection was followed by a 20-minute infusion period: placebo [saline (Intralipid)] injection, Intralipid infusion; propofol 0.125 mg/kg injection, propofol 12.5 mcg/kg/min infusion; propofol 0.25 mg/kg injection, propofol 25 mcg/kg/min infusion; propofol 0.5 mg/kg injection, propofol 50 mcg/kg/min infusion; fentanyl 1.4 mcg/kg injection (positive control), Intralipid infusion. Five minutes into the infusion period and 115 minutes after the infusion period was terminated, subjects immersed their forearms in ice-cold water for three minutes while pain assessments were recorded. MEASUREMENTS AND MAIN RESULTS: Propofol at the two higher doses during part of the first immersion produced a significant reduction (p < 0.05) in pain intensity and bothersomeness ratings. However, relative to fentanyl, the analgesia was mild. Propofol did not affect any ratings on the 15-item short-form McGill Pain Questionnaire, whereas fentanyl reduced 10 of the ratings. CONCLUSION: Our laboratory results are consistent with the commonly accepted clinical practice of supplementing propofol with an opioid in conscious sedation procedures to provide a satisfactory level of pain relief.

Adult↗

Midazolam does not influence intravenous fentanyl-induced analgesia in healthy volunteers.

The effects of saline and intravenous midazolam (0.5, 1, and 2 mg per 70 kg) in combination with intravenous fentanyl (0.1 mg/70 kg) were examined on pain induced by a cold pressor test. Healthy volunteers (six females, six males) were enrolled in a prospective, double-blind, randomized, crossover trial in which mood and psychomotor performance were also examined. Five minutes and 135 min postinjection subjects immersed their forearm in ice cold water for 3 min while assessments of pain were recorded. During the first immersion, subjects reported significantly lower pain intensity and bothersomeness ratings after having been injected with fentanyl, relative to the saline condition, but the addition of midazolam neither increased nor decreased pain reports. During the second immersion (approximately 2.5 h postinjection) pain ratings did not differ between the drug and saline conditions. Mood-altering and psychomotor-impairing effects of the drug combination were dose related. We conclude that midazolam at the doses and route of administration tested neither potentiates nor decreases the analgesia produced by fentanyl in a cold-pressor pain assay.

Adult↗

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 sessions. 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.

Adult↗

Flumazenil may attenuate some subjective effects of nitrous oxide in humans: a preliminary report.

Two double-blind, randomized, crossover trials were conducted to study whether the benzodiazepine antagonist, flumazenil, would interact with the subjective and psychomotor effects of nitrous oxide in healthy volunteers. In both experiments, eight subjects inhaled 30% nitrous oxide in oxygen for 35 min and were challenged, 10 min into the inhalation, with flumazenil. Experiment 1 tested a range of flumazenil doses used clinically (0, 0.25, 0.5, and 1.0 mg/70 kg) whereas Experiment 2 tested a supraclinical flumazenil dose (0 and 5.0 mg/70 kg). Nitrous oxide increased mood ratings of "high," "drunk," and "tingling," and decreased psychomotor performance as assessed by the Digit Substitution Test. Flumazenil, at the supraclinical dose, significantly lowered the mood rating of "high." Decreases, though not significant (p < 0.10), were also obtained on the ratings "drunk," "elated," and "drug liking". Flumazenil, in both experiments, did not interact with the psychomotor effects of nitrous oxide. It appears that flumazenil, at a dose higher than that used clinically, may antagonize some of the subjective effects produced by nitrous oxide in humans.

Adult↗

A dose-response study of the effects of intravenous midazolam on cold pressor-induced pain.

The effects of intravenous midazolam (0.75, 1.5, and 3 mg/70 kg) were examined and compared to that of fentanyl (0.1 mg/70 kg; positive control) and saline on pain induced by a cold pressor test. Both sensory and affective components of the pain response were assessed, as there is some evidence that benzodiazepines reduce the affective component. Healthy volunteers (three females, nine males) were enrolled in a prospective, double-blind, randomized, cross-over trial in which mood and psychomotor performance were also examined. Five minutes and 135 min postinjection, subjects immersed their forearm in ice-cold water for 3 min while assessments of pain were recorded. During the first immersion, subjects reported significantly lower pain intensity and bothersomeness ratings after having been injected with fentanyl, relative to the saline and midazolam conditions, which did not differ significantly from each other. Fentanyl and midazolam had prototypical mood altering and psychomotor impairing effects. We conclude that midazolam in our laboratory setting at the doses and route of administration studied had no effects on either the sensory or affective components of the pain experience.

Adult↗

Clinical recovery and psychomotor function after brief anesthesia with propofol or thiopental.

Propofol, the new intravenous anesthetic agent, is generally used in outpatient anesthesia with expectations of fast recovery. We assessed recovery from anesthesia in a double-blind, crossover, controlled manner in 12 healthy volunteers using clinical tests during the first hour and several psychomotor tests 0.5, 1, 3, 5, and 7 h after brief anesthesia with propofol (2.5 mg/kg and 1.0 mg/kg 3 min later) or thiopental (5.0 mg/kg and 2.0 mg/kg 3 min later). Subjects were able to respond to command, sit, and stand steadily significantly faster (P less than 0.05) after propofol (time until standing steadily 33 +/- 7 min; mean +/- SD) when compared to thiopental anesthesia (time until standing steadily 62 +/- 29 min; mean +/- SD). Psychomotor performance remained significantly worse (P less than 0.05 to P less than 0.001) compared to control for 1 h after propofol and for 5 h after thiopental anesthesia. We conclude that the rapid and complete recovery makes propofol a suitable anesthetic for patients undergoing brief ambulatory surgery.

Adult↗

Sedation and recovery of psychomotor function after intravenous administration of various doses of midazolam and diazepam.

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.

Adult↗

Alcohol after sedation with i.v. midazolam-fentanyl: effects on psychomotor functioning.

Patients who arrive home several hours after outpatient surgery may drink alcohol. The extent to which residual drugs used in outpatient surgery interact with alcohol is not known. The purpose of this study was to determine if two i.v. drugs commonly used together in outpatient surgery, midazolam and fentanyl, have residual effects which would interact with alcohol drunk 4 h after injection. Twelve healthy male volunteers participated in a double-blind, randomized, placebo-controlled and cross-over study. Subjects were studied four times successively with a period of 1 week between trials. On each day of testing, the subjects received randomly, by slow i.v. injection (30 s), either saline followed immediately by saline, or midazolam 0.1 mg kg-1 followed immediately by fentanyl 2 micrograms kg-1. Four hours after the injection, the subjects consumed a beverage which either did or did not contain alcohol 0.7 g kg-1. Before and 1, 3, 5 and 7 h after injection (and before and 1 and 3 h after consumption of beverage), psychomotor performance and mood were assessed. While both the combination midazolam-fentanyl and alcohol had independent effects on the dependent measures in this study, there was no interaction between midazolam-fentanyl and alcohol (no potentiating of effects of alcohol by i.v. sedation). We conclude that the effects of benzodiazepines and opioids that are short-acting and used in outpatient surgery have probably dissipated by the time a patient arrives home, and that effects from alcohol ingested at home will probably not be affected by recent administration of these drugs.

Adult↗

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 potentiation 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.

Adult↗