Clarification of anesthesia standards and guidelines.

Understanding and complying with the guidelines of the American Society of Anesthesiologists will help ensure high-quality patient care, increase levels of patient safety, and minimize medico-legal risk. The author discusses important standards and guidelines for the administration of general anesthesia and sedation/analgesia in the office-based setting and compares the requirements of the different accrediting organizations. (Aesthetic Surg J 2001;21:573-575.).

Subjective, psychomotor, cognitive, and analgesic effects of subanesthetic concentrations of sevoflurane and nitrous oxide.

BACKGROUND: Sevoflurane is a volatile general anesthetic that differs in chemical nature from the gaseous anesthetic nitrous oxide. In a controlled laboratory setting, the authors characterized the subjective, psychomotor, and analgesic effects of sevoflurane and nitrous oxide at two equal minimum alveolar subanesthetic concentrations. METHODS: A crossover design was used to test the effects of two end-tidal concentrations of sevoflurane (0.3% and 0.60%), two end-tidal concentrations of nitrous oxide (15% and 30%) that were equal in minimum alveolar concentration to that of sevoflurane, and placebo (100% oxygen) in 12 healthy volunteers. The volunteers inhaled one of these concentrations of sevoflurane, nitrous oxide, or placebo for 35 min. Dependent measures included subjective, psychomotor, and physiologic effects, and pain ratings measured during a cold-water test. RESULTS: Sevoflurane produced a greater degree of amnesia, psychomotor impairment, and drowsiness than did equal minimum alveolar concentrations of nitrous oxide. Recovery from sevoflurane and nitrous oxide effects was rapid. Nitrous oxide but not sevoflurane had analgesic effects. CONCLUSIONS: Sevoflurane and nitrous oxide produced different profiles of subjective, behavioral, and cognitive effects, with sevoflurane, in general, producing an overall greater magnitude of effect. The differences in effects between sevoflurane and nitrous oxide are consistent with the differences in their chemical nature and putative mechanisms of action.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Our laboratory results do not support the long-held belief that barbiturates are "antanalgesic" or hyperalgesic, at least for cold-pressor-induced pain.

Modulating effects of a cold water stimulus on opioid effects in volunteers.

The purpose of this study was to characterize the effect of a painful stimulus on morphine and butorphanol effects in healthy non-drug abusing volunteers. Thirteen subjects with no history of opiate dependence participated in a randomized, placebo-controlled, double-blind, crossover trial in which each subject received saline, 2 mg/70 kg butorphanol, and 10 mg/70 kg morphine, IV, in each of two conditions, periodic forearm immersions into either ice-cold water (2 degrees C) or into warm water (37 degrees C). Both opioids reduced self-reported ratings of pain intensity, indicative of analgesia. Several of the subjective effects of morphine were attenuated either during or in between cold-water immersions, including visual analog scale ratings of "coasting (spaced out)," "high (drug "high")," "sleepy (drowsy, tired)," and "lightheaded". In contrast, some of butorphanol's subjective effects were increased by the cold-water manipulation. Morphine impaired psychomotor performance during one of the warm-water immersions, but not during the cold-water immersions. Psychomotor impairment induced by butorphanol was not affected by water temperature. This study provides evidence that opioid effects can be modulated by a painful stimulus in humans.

The effects of alcohol history on the reinforcing, subjective and psychomotor effects of nitrous oxide in healthy volunteers.

The purpose of this study was to characterize the reinforcing, subjective and psychomotor effects of nitrous oxide in healthy volunteers with different alcohol histories. Subjects were divided into two groups: light drinkers (n = 9) and moderate drinkers (n = 10). A choice procedure was used in which subjects first sampled placebo and a given concentration of nitrous oxide, and then chose between the two. Nitrous oxide concentration varied across the four-session experiment from 10-40%. Besides choice, subjective and psychomotor effects served as dependent measures. The majority of subjective effects of nitrous oxide, and its psychomotor-impairing effects, did not vary as a function of drinking group. However, a Wilcoxon rank sum test showed that the median number of times moderate drinkers chose nitrous oxide (three) was significantly higher than the median number of times light drinkers chose nitrous oxide (one). This study provides suggestive evidence that the reinforcing effects of nitrous oxide are modulated by alcohol history.

The reinforcing effects of brief exposures to nitrous oxide in healthy volunteers.

The reinforcing and subjective effects of brief (about 1.5 min) exposures to nitrous oxide, ranging from inspired concentrations of 20-80% in oxygen, were examined in 11 healthy volunteers. A choice procedure was used in which during each of four sessions, subjects first sampled a given concentration of nitrous oxide and placebo oxygen, and then chose between the two. 20, 40, 60 and 80% nitrous oxide were chosen by five, four, three, and three subjects, respectively--these choice levels did not exceed that of chance. All concentrations had psychoactive effects, and in general, concentration-related subjective effects were found. We conclude that in a medical setting, nitrous oxide inhaled in a manner similar to that when used recreationally in a naturalistic setting, does not function as a reinforcer across a wide range of concentrations, in subjects with a modest lifetime history of psychoactive drug use.

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.

The effects of a cold-water immersion stressor on the reinforcing and subjective effects of fentanyl in healthy volunteers.

The reinforcing and subjective effects of fentanyl, an opioid analgesic, were tested in ten healthy volunteers without histories of drug abuse, as a function of the temperature of a water bath in which the volunteers' forearms were immersed. The temperatures were body-temperature (37 degrees C), moderately cold (10 degrees C), and very cold (2 degrees C). A discrete-trial choice procedure was used in which, in each session, volunteers sampled 50 micrograms of fentanyl (delivered as a bolus via an infusion pump) and saline, and then on three successive trials, chose between the two. Volunteers then had to immerse their non-dominant forearm in the water bath 5 min after a drug delivery. Fentanyl was chosen on 77% of choice occasions in the 10 degrees C and 2 degrees C water conditions, which was significantly different from chance levels, and on 60% of choice occasions in the 37 degrees C water condition, which did not differ from chance levels. Several subjective effects of fentanyl were also modulated by the temperature of the water bath. We conclude that in the context of a painful stimulus, 50 micrograms of fentanyl functions as a reinforcer in non-drug abusers.

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 N2O-O2 (PDN), propofol plus propofol infusion with N2O-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 N2O in O2.

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.

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.

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.

The effects of transnasal butorphanol on mood and psychomotor functioning in healthy volunteers.

Transnasal butorphanol is effective in relieving migraine and postoperative pain. The extent to which this drug preparation impacts on cognitive and psychomotor performance, as well as mood, has not been examined. Accordingly, the cognitive and psychomotor, subjective, and physiological effects of two clinically relevant doses of transnasal butorphanol (1 and 2 mg) were compared to that of placebo, and a common analgesic drug combination given for pain relief in ambulatory settings, 600 mg of acetaminophen and 60 mg of codeine, in healthy volunteers (n = 10). The larger transnasal butorphanol dose impaired psychomotor performance for up to 2 h, and produced subjective effects for up to 3 h. The smaller dose had no psychomotor-impairing effects, but had subjective effects (including increased ratings of "sleepy"). All three active drug conditions including miosis. These laboratory results suggest that patients should use caution when using the 1-mg dose of transnasal butorphanol, and should curtail certain activities if they administer the 2-mg dose of transnasal butorphanol for analgesia.

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% nitrous 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.

Adult clinical experience with sevoflurane and pharmaco-economic aspects.

This article has reviewed the physical-chemical properties and performance characteristics of sevoflurane. Both drugs provide a greater degree of control of anesthetic depth and a more rapid immediate recovery from anesthesia than is currently available with other inhaled agents because of their decreased solubility. Sevoflurane is currently in widespread clinical use in Japan and parts of Europe and the Americas. Compared to desflurane, sevoflurane has the additional advantage of being non-irritating to the airway; inhalation induction of anesthesia with sevoflurane is achieved rapidly and easily. The instability of sevoflurane with carbon dioxide absorbents and its in vivo biotransformation produce potentially toxic by-products. These by-products, including Compound A and fluoride have been extensively studied and although the possibility for iatrogenic sequella from sevoflurane exists, the likelihood of long-term toxicity appears quite low. Phase IV studies are indicated to determine the safety of administering sevoflurane: 1) to renally impaired patients, and 2) to any patient with fresh gas flows less than 2 liters per minute. Sevoflurane is otherwise very well tolerated and appears to offer the advantage of rapid and smooth induction and emergence from general anesthesia.

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.

Effects of a cold-water stressor on psychomotor and cognitive functioning in humans.

The effects of an acute stressful and painful stimulus, cold water, on psychomotor and cognitive functioning, was assessed in 14 healthy volunteers. Subjects immersed their forearm in ice-cold water (2-3 degrees C) and luke-warm water (37 degrees C) for 3 min, and during this time period a psychomotor or cognitive test was performed. These immersions were done over the course of two experimental sessions, spaced at least 2 days apart, with six trials in each session. Within each session, cold and warm water immersions alternated. Results indicated that flicker-from-fusion threshold from the critical flicker frequency test was higher in the cold-water condition than in the luke-warm-water condition, indicative of increased alertness from the cold stimulus. Short-term memory was attenuated, however, in the cold-water condition. Performance on other tests including those that required speed and/or concentration were not affected by the manipulation. Subjects rated the cold-water stimulus as painful and bothersome, and their blood pressure was significantly elevated by the stimulus. We conclude that a painful stimulus may affect psychomotor and/or cognitive functioning, but the relationship is somewhat complex and depends on the particular tests used.

Inhalational anesthetics: desflurane and sevoflurane.

This article reviews the physico-chemical properties and performance characteristics of the two new potent inhaled anesthetics, desflurane and sevoflurane. Both drugs provide a greater degree of control of anesthetic depth and a more rapid immediate recovery from anesthesia than is currently available with other inhaled agents because of their decreased solubility. Desflurane is currently in widespread clinical use in the United States and parts of Europe. Compared with sevoflurane, it has the additional advantage of being extremely resistant to degradation and biotransformation. However, its pungent odor and tendency to irritate the respiratory tract make it unsuitable for inhalational inductions, and it has been linked to CO production in CO2 absorbents. The sympathetic nervous system activation that occurs with desflurane limits its use in patients with cardiac disease. Otherwise, its hemodynamic and physiologic effects are similar to those seen with isoflurane. Studies of the economics of using desflurane are mixed, although it may offer the advantage of shorter postoperative recovery time. Sevoflurane is currently in widespread clinical use in Japan and parts of South America. The FDA Advisory Panel has recently recommended approval of sevoflurane in the United States, and we can expect the drug to be clinically available in the United States in the second quarter of 1995. Compared with desflurane, sevoflurane has the additional advantage of being nonirritating to the airway; inhalational induction of anesthesia with sevoflurane is achieved rapidly and easily. The instability of sevoflurane with CO2 absorbents and its in vivo biotransformation produce potentially toxic byproducts. These byproducts, including Compound A and fluoride, have been extensively studied, and although the possibility for iatrogenic sequelae from sevoflurane exists, the likelihood of long-term toxicity appears quite low. Phase IV studies are indicated to determine the safety of administering sevoflurane (1) to renally impaired patients and (2) to any patient with fresh gas flows less than 2 L/min. Sevoflurane is otherwise very well tolerated and appears to offer the advantage of rapid and smooth induction and emergence from general anesthesia.