Biomedical subjects
J M Klafta
Publications and source records attributed to J M Klafta.
The effect of sevoflurane and desflurane on upper airway reactivity.
BACKGROUND: Although bronchial reactivity can be assessed by changes in airway resistance, there is no well-accepted measure of upper airway reactivity during anesthesia. The authors used the stimulus of endotracheal tube cuff inflation and deflation to assess changes in airway reactivity in patients anesthetized with sevoflurane and desflurane. METHODS: Sixty-four patients classified as American Society of Anesthesiologists physical status I or II participated in this randomized, double-blind study. Patients were anesthetized with either sevoflurane or desflurane at 1.0 and 1.8 minimum alveolar concentration (MAC). The trachea was stimulated by inflating the endotracheal tube cuff. A blinded observer assessed the severity of patient response to the stimulus and changes in hemodynamic variables. The process was repeated at the second MAC treatment condition. RESULTS: At 1.0 MAC, patients anesthetized with desflurane had a more intense response and a greater likelihood of significant coughing and associated hemodynamic changes (both at P < 0.05). At 1.8 MAC, sevoflurane and desflurane both suppressed clinically significant responses to tracheal stimulation. Interrater reliability was excellent for this measure of upper airway reactivity (P < 0.001). CONCLUSIONS: The assessment of the cough response to tracheal stimulation by endotracheal tube cuff inflation is a reliable and clinically meaningful measure of upper airway reactivity. At 1.0 MAC, sevoflurane is superior to desflurane for suppressing moderate and severe responses to this stimulus.
Bronchial injury: An avoidable complication during bronchial intubation.
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The practice of using sevoflurane inhalation induction for emergency cesarean section and a parturient with no intravenous access.
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Effects of information 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 (N2O) in healthy volunteers who were given different amounts of information regarding the drugs they were being administered in the experiment. A choice procedure was used in which subjects first sampled a placebo and a given concentration of N2O and then chose between the two. N2O concentration varied across the four-session experiment from 10-40%. Besides choice, subjective and psychomotor effects served as dependent measures. In the INFORMED group (n = 11), subjects were told at the beginning of each sampling trial what concentration of N2O they were inhaling or whether they were inhaling 100% oxygen (placebo). They were also informed about the prototypic effects of N2O (e.g. tingling or numbing, euphoria, dysphoria) and oxygen (e.g. no discernible effects). In the NON-INFORMED group (n = 11), subjects were only told at the beginning of each sampling trial that the drugs they would be inhaling came from one of six classes of drugs. Thirty percent N2O was chosen by a significantly higher proportion of subjects than expected by chance in the INFORMED group, but not in the NON-INFORMED group. Further, the probability of choosing 20-40% N2O was higher in the INFORMED group than in the NON-INFORMED group. Subjective effects of N2O were not affected by the information manipulation. Psychomotor performance at the highest N2O concentration tested (40%) was impaired to a greater extent in the NON-INFORMED than in the INFORMED group. We conclude that the reinforcing effects of N2O, and perhaps the impairing effects, can be modulated by telling subjects beforehand that they are inhaling N2O and what effects they might be expected to experience from the drug.
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.
Three sudden postoperative respiratory arrests associated with epidural opioids in patients with sleep apnea.
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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.
Emergent lung separation for management of pulmonary artery rupture.
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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.
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.
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.
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.
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 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.
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.
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.
Measuring end-tidal CO2 during intentional rebreathing.
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