Pankaj Thapar

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.

Objective and subjective impairment from often-used sedative/analgesic combinations in ambulatory surgery, using alcohol as a benchmark

Impairment caused by different sedative/analgesic combinations commonly used in ambulatory settings was compared to that of alcohol at blood alcohol concentrations (BACs) higher than or equal to 0.10%. Impairment was measured via subjective (mood) and objective (psychomotor performance) assays. Twelve healthy human volunteers (10 males and 2 females; age range 21-34 yr) participated in this prospective, double-blind, randomized, cross-over study. Each subject was exposed to five drug conditions across 5 wk. Each of the following drug conditions were adjusted for body weight (per 70 kg): fentanyl 50 micro gram and propofol 35 mg (FP), fentanyl 50 micro gram and midazolam 2 mg (FM), fentanyl 50 micro gram, midazolam 2 mg, and propofol 35 mg (FMP), alcohol 56 g (orally administered), and placebo (PLC). With the exception of alcohol, the other drugs were administered via the intravenous route. Tests for psychomotor performance, subjective effects, and short-term memory were done at baseline, and at different intervals until 240 min postinjection. Psychomotor impairment caused by alcohol at 15 min postingestion (at a BAC of 0.11% +/- 0.03% [mean +/- SE]) was used as a benchmark with which impairment caused by other sedative/analgesic combinations was compared. All the study drug combinations produced impairment (i.e., impairment greater than that seen with PLC), similar to that observed with alcohol at a BAC of 0.11%. We have demonstrated that some sedative/analgesic drug combinations used in anesthesia for ambulatory procedures produce impairment similar to or greater than that observed with a large dose of alcohol. (Anesth Analg 1995;80:1092-8)

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. (Anesth Analg 1995;80:521-5)

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)

Effects of marijuana history on the subjective, psychomotor, and reinforcing effects of nitrous oxide in humans

An experiment using marijuana users and non-users was conducted to assess whether the reinforcing, subjective, or psychomotor effects of nitrous oxide were influenced by a subjects drug history. Subjects in the first four sessions sampled 40% nitrous oxide in oxygen and 100% oxygen (placebo), and then over the next three sessions, chose which agent they wished to inhale. Choice distributions between the two groups did not differ significantly, and nitrous oxide choice rates were less than 50% in both groups. However, a history of marijuana use appeared to intensify some of the subjective effects induced by nitrous oxide inhalation.

Decreased mivacurium constant infusion requirements with defasciculating doses of pancuronium

This study was designed to verify a technique in which the pharmacologic profile of mivacurium infusions could be altered by small doses of pancuronium to reduce the infusion requirement without altering the subsequent recovery kinetics.Thirty ASA physical status I or II patients were randomized into two groups in a blinded fashion. One group was administered pancuronium 10 micro g/kg followed by pancuronium 2.5 micro g [centered dot] kg-1 [centered dot] h-1 thereafter. The control group was given identical volumes of saline. Subsequently, all patients were given an initial bolus of mivacurium, and anesthesia was maintained using a nitrous oxide/alfentanil technique. When the thenar electromyogram response to supramaximal train-of-four stimulation returned to 5% of baseline, a mivacurium infusion was begun in both groups, and the infusion rate required to maintain the electromyographic response at 1%-10% of baseline was determined. At the conclusion of the procedure, the infusion was terminated and the recovery profile ascertained. The mivacurium infusion requirement for the group receiving the pancuronium supplementation was 2.77 +/- 1.38 micro g [centered dot] kg-1 [centered dot] min-1 (mean +/- SD), which represented a 49% decrease compared with the group that used mivacurium alone which required an infusion rate of 5.43 +/- 1.85 micro g [centered dot] kg-1 [centered dot] min-1. No statistically significant difference was found in the recovery profiles of the two groups when the infusion was terminated. We conclude that the addition of a small amount of pancuronium decreased the required mivacurium infusion rate by nearly 50% without affecting the spontaneous recovery when terminating the infusion. (Anesth Analg 1997;84:668-71)

Assessing recovery after day-case surgery

Abstract With an increasing number of complex operations being performed in ambulatory settings, proper assessment of recovery from anaesthesia is necessary. Strict guidelines should be established for discharging patients. These criteria include stable vital signs, ability to walk unaided, minimal nausea or vomiting, pain that can be controlled by oral analgesics, and an escort home. Patients should be warned to refrain from driving for at least 24 hours after anaesthesia.

Using Alcohol as a Standard to Assess the Degree of Impairment Induced by Sedative and Analgesic Drugs Used in Ambulatory Surgery

Background There is a need for a standard by which to compare the degree of subjective and behavioral impairment caused by anesthetic drugs, because anesthesiologists may not be able to gauge how extreme or important a statistically significant change in psychomotor functioning is. This study examined the psychomotor and subjective effects of alcohol at blood concentrations equal or greater than 0.10% as a standard with which to compare those effects caused by sedative and analgesic agents commonly used in ambulatory surgery. Methods Twelve healthy human volunteers (11 men and 1 nonpregnant woman), with an average age of 28 yr (range 24–34 yr) and an average alcohol consumption of four drinks per week, were selected in this institutional review board‐approved study. Each subject was exposed to five drug conditions (70 mg/70 kg propofol intravenously, 2 mg/70 kg midazolam intravenously, 50 micro gram/70 kg fentanyl intravenously, 0.8 g/kg alcohol orally, and placebo orally and intravenously) in a double‐blind randomized fashion over five weekly sessions. Testing was done at baseline and at different intervals until 240 min after drug administration. Testing included psychomotor performance (Maddox Wing, eye‐hand coordination, auditory reaction time test, and digit symbol substitution test), subjective effects (strength of drug effect scale, drug liking scale, and visual analog scale), and short‐term memory. Psychomotor performance was used as an index of objective impairment, and mood was used as an index of subjective impairment. Results After consumption of the alcoholic beverage, a blood alcohol level of 0.11 plus/minus 0.003% (mean plus/minus SE) was obtained at 15 min after injection. The study drugs not only produced statistically significant impairment (i.e., impairment greater than that seen with placebo) but also, at one or more times after injection, produced impairment similar to that observed with alcohol at a blood alcohol concentration of 0.11%. Midazolam produced a similar degree of impairment to that of alcohol for a longer duration than did fentanyl and propofol. Conclusions This study provides evidence that degree of impairment caused by sedative and analgesic drugs used in ambulatory surgery is similar to that obtained with a dose of alcohol that produces a blood alcohol concentration of 0.11%. We suggest that anesthesiologists can use alcohol as a standard by which to assess degree of impairment produced by drugs used for sedation/analgesia.