Time- and Dose-Dependent Effects of Desflurane in Sensitized Airways.

BACKGROUND: Although the bronchodilatory actions of volatile anesthetics, such as halothane, isoflurane, and sevoflurane, have been well documented in previous studies, the properties of desflurane remain controversial. The aim of this study was to investigate the effects of desflurane at different concentrations and durations in an ovalbumin-sensitized guinea pig model of airway hyper-responsiveness. METHODS: Ovalbumin-sensitized animals (n = 176) were randomly assigned to 5 groups according to the minimum alveolar concentration (MAC) of desflurane they received: 0.0, 0.5, 1.0, 1.5, and 2.0 MAC. Total lung resistance in vivo, airway smooth muscle tension in vitro, and intracellular cyclic adenosine monophosphate (AMP) levels were measured to evaluate the effects of desflurane. RESULTS: In 5 sensitized groups, total lung resistance increased from baseline to peak at approximately 8 minutes and then decreased slowly until about 17 minutes with extended administration of desflurane. Desflurane dose-dependently increased total lung resistance with or without incremental doses of acetylcholine and reduced muscle tension with increasing concentrations of carbacholine. Cyclic AMP levels were increased by desflurane: at the 60-minute time point, cyclic AMP concentrations (means ± SD) with 0.5 MAC (1.96 ± 0.40) and 1.0 MAC (2.11 ± 0.50) desflurane were higher than those at the 8-minute time point (1.11 ± 0.23 and 1.32 ± 0.32). CONCLUSIONS: Desflurane exerted time- and dose-dependent effects and could be used at 0.5 and 1.0 MAC concentrations without significant bronchoconstriction in ovalbumin-sensitized guinea pigs. Cyclic AMP-mediated airway smooth muscle relaxation might be one mechanism by which desflurane induces bronchodilation.

Phosphodiesterase 4 inhibitor roflumilast improves the bronchodilative effect of sevoflurane in sensitized airways.

BACKGROUND: Although phosphodiesterase 4 inhibitors and the volatile anesthetic sevoflurane are known to have independent bronchodilator properties, the combined administration of these two agents may have the potential to exert an additive or synergistic bronchodilator effect. The authors tested this hypothesis and investigated the common site of this combined relaxation effect in a model of airway hyperresponsiveness with ovalbumin-sensitized guinea pigs. METHODS: Ovalbumin-sensitized animals (n = 138) were randomized into six groups: sensitized, sevoflurane, rolipram1.0, roflumilast1.0, sevoflurane/rolipram1.0, and sevoflurane/roflumilast1.0. Total lung resistance in vivo, airway smooth muscle tension in vitro, and intracellular cyclic adenosine monophosphate levels were measured to evaluate the relaxation effect. RESULTS: Among the six sensitized groups, total lung resistance was higher in the order of sensitized > sevoflurane > rolipram 1.0 > roflumilast1.0 > sevoflurane/rolipram1.0 > sevoflurane/roflumilast1.0, with an increase in acetylcholine concentration. Compared with the other five groups, the muscle tensions in the sevoflurane/roflumilast1.0 group were significantly lower at carbacholine doses of 10, 10, and 10 M; the cyclic adenosine monophosphate concentrations (means ± SD) in the sevoflurane/rolipram1.0 (1.61 ± 0.34) and sevoflurane/roflumilast1.0 (1.50 ± 0.20) groups were higher than that in the sensitized (0.52 ± 0.15) and sevoflurane (1.12 ± 0.32) groups. CONCLUSIONS: The combined use of phosphodiesterase 4 inhibitors with the volatile anesthetic sevoflurane had an additive bronchodilator effect in ovalbumin-sensitized guinea pigs. The concurrent increase in cyclic adenosine monophosphate levels in sensitized airway smooth muscle might be a mechanism of this combined relaxation effect.

Synergic bronchodilator effects of a phosphodiesterase 3 inhibitor olprinone with a volatile anaesthetic sevoflurane in ovalbumin-sensitised guinea pigs.

BACKGROUND AND OBJECTIVE: Phosphodiesterase 3 (PDE3) inhibitors and sevoflurane are both known to have bronchodilator properties and the combination of these two agents may be synergistic. We tested this hypothesis in a model of airway hyperresponsiveness using ovalbumin-sensitised guinea pigs. METHODS: Animals were randomised into five groups: control, sevoflurane, sevoflurane/theophylline, sevoflurane/milrinone and sevoflurane/olprinone. Total lung resistance (RL) and dynamic lung compliance (CL) were recorded and the dose-response curves for acetylcholine (Ach) of RL and CL were used to evaluate the bronchodilator effect. RESULTS: The dose-response curve for Ach of RL was elevated that for and CL was depressed significantly in the ovalbumin-sensitised animals compared to normal control guinea pigs. Among the five sensitised groups, RL was higher in the order of control > sevoflurane > sevoflurane/theophylline > sevoflurane/milrinone > sevoflurane/olprinone with increasing Ach concentration. Sevoflurane/olprinone treatment attenuated the bronchoconstriction induced by the highest dose of Ach with RL being significantly lower (0.318 ± 0.056 cmH2O ml(-1) s(-1)) than those observed in the control group (0.437 ± 0.061 cmH2O ml(-1) s(-1)), sevoflurane group (0.378 ± 0.052 cmH2O ml(-1) s(-1)) and in the sevoflurane/theophylline group (0.374 ± 0.073 cmH2O ml(-1) s(-1)). CONCLUSION: Combined use of PDE inhibitors with a volatile anaesthetic had a synergic bronchodilator effect in ovalbumin-sensitised guinea pigs. A greater bronchodilator effect can be obtained by using the selective PDE3 inhibitor olprinone with the volatile anaesthetic sevoflurane.

Beta-1 selective adrenergic antagonist landiolol and esmolol can be safely used in patients with airway hyperreactivity.

This study was undertaken to clarify the effects of esmolol and landiolol, beta-1 selective adrenergic antagonists, on hyperreactive airways in both ovalbumin-sensitized guinea pigs and asthmatic patients. In the animal study, asthma was induced by ovalbumin. After control acetylcholine responses for total pulmonary resistance (Raw) and dynamic lung compliance (Cdyn) were obtained, the animals received propranolol, esmolol, or landiolol, and the same protocol was again performed. Sixty inpatients with coronary risk factors and asthma were enrolled in the human study. Under propofol anesthesia, the patients received saline, esmolol, or landiolol. To assess intubation-induced bronchoconstriction, the presence of wheezing was determined. The dose-response curves of Raw and Cdyn to acetylcholine were significantly elevated and declined in the ovalbumin-sensitized model compared with those in the control group. Neither esmolol nor landiolol had any effect on the acetylcholine-induced response curve in these sensitized animals. However, propranolol significantly enhanced Raw and reduced Cdyn in this model. Tracheal intubation increased the incidence of wheezing in asthmatic patients. However, there was no significant difference in the incidence of wheezing among these groups. The ultra-short-acting beta-1 selective adrenergic antagonists esmolol and landiolol can be safely used perioperatively in patients with airway hyperreactivity.

Guideline-oriented perioperative management of patients with bronchial asthma and chronic obstructive pulmonary disease.

Increased airway hyperresponsiveness is a major concern in the perioperative management of patients with bronchial asthma and chronic obstructive pulmonary disease. Guidelines using evidence-based medicine are continually being updated and published regarding the diagnosis, treatment, and prevention of these respiratory disorders. Perioperative management in these patients involves: (1) adequate control of airway hyperresponsiveness, including detection of purulent sputum and infection before surgery; (2) evidence-based control of anesthesia; and (3) the aggressive use of beta-2 adrenergic stimulants and the systemic administration of steroids for the treatment of acute attacks. Good preoperative control, including the use of leukotriene antagonists, can reduce the incidence of life-threatening perioperative complications. Awareness of recent guidelines is thus important in the management of patients with airway hyperresponsiveness. This review covers the most recent guidelines for the perioperative management of patients with bronchial asthma and chronic obstructive pulmonary disease.

[Perioperative evaluation of a kit for simplified measurement of blood theophylline concentration (Accumeter Theophylline)].

BACKGROUND: We investigated the perioperative usefulness of a kit for simplified measurement of blood theophylline concentration (BTC), Accumeter theophylline (Nikken Chemicals Co.) in asthmatic patients. METHODS: Study 1) BTCs were measured by Accumeter at the beginning of surgery in asthmatic patients who had been medicated with oral theophylline. Study 2) BTCs were corrected during anesthesia in asthmatic patients who showed lower BTCs (<8 microg x g ml(-1)) at the beginning of surgery. Study 3) Theophylline was administered to asthmatic patients who had not been medicated with theophylline, and calculated and measured BTCs were compared. RESULTS: Study 1) Measured BTC at the begin- ning of surgery was 8.2 +/- 3.1 microg x ml(-1) (mean +/- SD), and 14 of 31 patients (45%) showed lower BTC. Patients who smoked showed a significantly lower BTC than that of non-smoking patients (P=0.04). Study 2) Five of 10 patients showed lower BTC at the beginning of surgery, but BTC had increased significantly at the end of surgery after i.v. administration of theophylline. Study 3) There was no significant linear correlation between calculated and measure BTCs after i.v. administration of theophylline (R2=0.25, n=10). Although the mean was near zero (0.05) by limits of agreement, 2 SD was large (2.53). There was no patient who showed wheezing during the study. CONCLUSIONS: It is important to monitor BTCs perioperatively in asthmatic patients, and Accumeter theophylline is a simple and useful device for management of BTC.

Changes in concentrations of free propofol by modification of the solution.

UNLABELLED: Because free propofol is thought to be responsible for pain on injection, we investigated the changes in concentrations of free propofol by modifying two kinds of propofol products in a medium- and long-chain triglyceride (MCT/LCT) emulsion and in an LCT emulsion. The techniques used in this study were 1) mixing 2% lidocaine (10:1), 2) mixing 5% dextrose in acetated Ringer's solution to reduce pH (10:1), and 3) changing the temperature to 4 degrees , 20 degrees , and 36 degrees C. The propofol preparations were dialyzed for 24 h, and the receptor medium was analyzed using high-performance liquid chromatography. The concentration of free propofol in propofol MCT/LCT was significantly smaller by 30% than that in propofol LCT. Neither mixing lidocaine nor cooling reduced the concentrations of free propofol in both products, but the concentrations were reduced by a decrease in pH and by an increase in temperature. Because mixing lidocaine can induce instability in an emulsion of propofol and warming can rapidly induce microbial growth, injection of lidocaine before propofol administration is recommended to reduce the pain on injection. The concentrations of free propofol in propofol MCT/LCT were significantly smaller (by approximately 30%-45%) than those in propofol LCT during any situation in this study. IMPLICATIONS: Neither mixing lidocaine nor cooling reduced the concentrations of free propofol in both products but the concentrations were reduced by a decrease in pH and by an increase in temperature. Propofol medium- and long-chain triglycerides had significantly smaller concentrations by approximately 30%-45% than those in propofol long-chain triglycerides during any situation in this study.

[Assessment of the quality of information on departments/divisions of anesthesiology available on the World Wide Web].

BACKGROUND: The quality of health information available in the World Wide Web is an important issue, but no review of the quality of such information has been performed. METHODS: We investigated the quality of information available on the World Wide Web regarding departments/divisions of anesthesiology in 82 specific functioned hospitals in Japan. RESULTS: Eighty-eight percent of the hospitals have their own web site for anesthesiology. Although only general clinical information was available on 64-71% of the web sites, detailed information on clinical results and members having diploma of the board was available on 11-26% of the sites. Regarding education, only 4% of the sites provided information on contents of lectures, whereas 75% of the sites have pages for medical students. CONCLUSIONS: Departments/divisions of anesthesiology, especially in specific functioned hospitals, should recognize an important role of web pages for medical consumers (= e-patient) and renew their web sites appropriately and opportunely.

Safety and beneficial effect on body core temperature of a prewarmed plasma substitute--hydroxyethyl starch--during anesthesia.

PURPOSE: We investigated, first, the safety of use and stability of a plasma substitute-hydroxyethyl starch (HES)-kept in a warming cabinet for a long period, and then the effect on body core temperature of the prewarmed HES in patients during urological surgery. METHODS: In the first part of the study, HES colloid solutions (500 ml per pack; Hespander) were kept in a warming cabinet (40 degrees C) for 3 months and were tested for biological and chemical safety and stability. In the second part of the study, 1000 ml of HES at room temperature (control group; n = 10) or kept in a warming cabinet for a few days (warmed group; n = 10) was infused via a central venous catheter for 30 min in patients undergoing urological surgery under general anesthesia with lumbar epidural anesthesia. Esophageal temperature was monitored as the core temperature. HES fluid temperatures in the pack and at the end of a 1-m intravenous tube connected to the central venous catheter were also measured. RESULTS: The test of HES products warmed for 3 months passed all inspections performed during the study period. In the warmed group, the pack and intravenous tube temperatures of HES were still high at 15 min after infusion (37.1 degrees +/- 1.5 degrees C [mean +/- SD] and 34.8 degrees +/- 2.2 degrees C, respectively). Core temperature in the warmed group decreased significantly, by 0.34 degrees +/- 0.06 degrees C, but was significantly higher than that in the control group (by 0.84 degrees +/- 0.13 degrees C) after 30 min of the infusion. CONCLUSIONS: The use of HES products kept in a warming cabinet prior to surgery can maintain warm body temperature, easily, safely, and effectively.

Effects of oral atenolol on volatile anesthetic induction with sevoflurane in adults.

PURPOSE: To determine whether premedication with a beta-blocker can bring about a more rapid and smooth induction of anesthesia, we investigated the effect of oral premedication with atenolol on volatile anesthetic induction with sevoflurane by monitoring the cardiac output (CO) and bispectral (BIS) index. METHODS: Twenty-four patients undergoing general anesthesia with endotracheal intubation were randomly divided into two groups: a control group ( n = 12) and a beta-blocker group ( n = 12). Each patient in the beta-blocker group was premedicated with oral atenolol 25 mg 1 h before the induction of anesthesia. Anesthesia was induced by the repeated vital capacity technique with 5% sevoflurane and 66% nitrous oxide. The trachea was intubated 5 min after sevoflurane exposure. The CO and BIS index, as well as the induction time and specific side effects of induction (e.g., movement of limbs), were recorded. RESULTS: There were no significant differences in induction time and specific side effects between the groups. The downward-sloping part of the BIS index curve in the beta-blocker group (mean, 2.9 +/- 0.2) was significantly sharper than that in the control group (2.5 +/- 0.2), and the BIS index after induction of anesthesia was significantly lower in the beta-blocker group (21.0 +/- 2.2) than in the control group (24.2 +/- 2.0). CO in the beta-blocker group was significantly lower than in the control group during the study period. The hemodynamic changes caused by endotracheal intubation were inhibited in the beta-blocker group but not in the control group. CONCLUSION: Oral premedication with 25 mg of atenolol provides a more rapid decrease in BIS index and is recommended for use in stable volatile anesthetic induction with sevoflurane.

[Evaluation by undergraduate medical students of clinical clerkships in the Department of Anesthesiology].

BACKGROUND: Clerkships for undergraduate clinical training were introduced in Sapporo Medical University School of Medicine in 2002. METHODS: Questionnaire surveys by 5 steps Likert measure were conducted by asking the students about the evaluation of each department or division, and overall evaluation was obtained after the clerkships. The questionnaire consisted of 12 questions on 1) orientation; 2) learning chances and provision of teaching materials; 3) feedback, learning promotion and teaching attitude; 4) coordination of human relationship between medical staff and students; and 5) overall evaluation of teacher's physician. RESULTS: The average score for our department was 4.30 (mean, 6th grade of all 26 departments/divisions), and the scores on provision of medical practice (4.69) and the overall teacher's physician grading (4.65) were the best among the all departments/divisions. The evaluation gradings were rather low on chances for medical and health care interviews (3.59); physical examinations (3.83); and description of medical record (3.73). CONCLUSIONS: Reevaluation of the educational program in our department based on the results of the survey is essential for improvement of the program, and further provision of chances, especially for medical interviews, physical examinations and description of medical record is also needed for undergraduate students in the program.

Design of oxygen delivery systems influences both effectiveness and comfort in adult volunteers.

PURPOSE: The aim of this investigation was to compare the efficiency of four oxygen delivery systems in healthy volunteers. METHODS: The subjects received oxygen at flow rates of 3.0 and 5.0 L*min(-1) via a face mask, nasal cannulae, and two kinds of new open- and microphone-type oxygen delivery systems (OxyArm(TM) and Mike Cannula) in a random sequence, and values of partial arterial pressures of oxygen (PaO(2)) were measured. The comfort of these devices was also evaluated. RESULTS: A significant, oxygen flow dependent increase in PaO(2) was obtained with all devices tested. PaO(2) was significantly higher when the face mask was used [217.5 +/- 19.9 (mean +/- SD) mmHg at 5 L*min(-1)) than when the Mike Cannula was used (177.5 +/- 14.8 mmHg). The face mask was the least comfortable and OxyArm was the most comfortable among the devices tested. CONCLUSION: The results of our evaluation suggest that comfort and clinical performance should be considered when using oxygen delivery devices for patients who require oxygen supplementation.

[A case of pulmonary artery rupture due to pulmonary artery catheter malposition after the weaning of cardiopulmonary bypass].

An 80-year-old female with aortic regurgitation and angina was scheduled for aortic valve replacement and coronary artery bypass graft. After the induction of anesthesia, central venous catheter and pulmonary artery (PA) catheter were placed into the right internal jugular vein. At the weaning from cardiopulmonary bypass, we noticed pulmonary artery pressure (PAP) on the monitor indicating the PA catheter tip being wedged. Therefore, we pulled the PA catheter until the wedging PAP wave disappeared. However, immediately after repositioning of the PA catheter, massive fresh bleeding was found in the endotracheal tube. We estimated the cause of pulmonary bleeding was PA rupture due to malpositioned PA catheter because surgeons had not manipulated the PA during the operation. Soon after restarting the cardiopulmonary bypass, pulmonary bleeding was stopped. Examination with fiberoptic bronchoscope revealed no further bleeding and weaning from cardiopulmonary bypass was accomplished smoothly. Postoperative course was uneventful.

The infusion rate of most disposable, non-electric infusion pumps decreases under hypobaric conditions.

PURPOSE: To examine the delivery rates of four disposable, non-electric infusion pumps during hypobaric conditions. METHODS: Four models categorized by three different driving forces, one vacuum unit (Coopdech Syringector), one spring unit (Linear-fuser), and two elastomeric balloon-powered units (Multirate Infuser LV and Large DIB), were tested. Each infusion pump was placed in an airtight container, and the pressure in the container was decreased to 1,000, 900, and 800 hPa. The catheter tip of each pump was exposed either to atmospheric pressure (1,000 hPa) or to similar hypobaric conditions (800-1,000 hPa). RESULTS: Under normal atmospheric pressure, each pump showed an accurate delivery rate in the range of -2% to +8% of the set infusion rate (4.0-5.0 mL x hr(-1)). With the catheter tip exposed to atmospheric pressure, the infusion rate of each pump was reduced from 35% in the case of the Large DIB to 64% in the case of the Coopdech Syringector, depending on the magnitude of change in hypobaric pressure. When the pressure acting on the catheter tip was reduced to a level similar to that exerted on the pump body, infusion rate was reduced (by 19%-27%) in all three types of pump, and the Large DIB showed no significant difference in performance compared to normal atmospheric pressure. CONCLUSION: The infusion rates of disposable infusion pumps are reduced under hypobaric conditions. Even though we still do not know how the epidural pressure changes under hypobaric conditions, clinicians should be aware that the infusion rate of disposable infusion pumps is decreased under hypobaric conditions.

The repolarizing effects of volatile anesthetics on porcine tracheal and bronchial smooth muscle cells.

UNLABELLED: This study was conducted to determine the effects of volatile anesthetics (potent bronchodilators) on membrane potentials in porcine tracheal and bronchial smooth muscle cells. We used a current-clamp technique to examine the effects of the volatile anesthetics isoflurane (1.5 minimum alveolar anesthetic concentration [MAC]) and sevoflurane (1.5 MAC) on membrane potentials of porcine tracheal and bronchial (third- to fifth-generation) smooth muscle cells depolarized by a muscarinic agonist, carbachol (1 microM). The effects of volatile anesthetics on muscarinic receptor binding affinity were also investigated by using a radiolabeled receptor assay technique. The volatile anesthetics isoflurane and sevoflurane induced significant repolarization of the depolarized cell membranes in the trachea (from -19.8 to -23.6 mV and to -24.8 mV, respectively) and bronchus (from -24.7 to -29.3 mV and -30.4 mV, respectively) without affecting carbachol binding affinity to the muscarinic receptor. The repolarizing effect was abolished by a Ca(2+)-activated Cl(-) channel blocker, niflumic acid. These results indicate that volatile anesthetic-induced repolarization of airway smooth muscle cell membranes might be caused by a change in Ca(2+)-activated Cl(-) channel activity and that the different repolarized effects of the volatile anesthetics could in part contribute to the different effects of volatile anesthetics on tracheal and bronchial smooth muscle contractions. IMPLICATIONS: By use of a current-clamp technique, the volatile anesthetics isoflurane and sevoflurane repolarized porcine airway smooth muscle cell membranes depolarized by a muscarinic agonist. This effect might be caused mainly by change in Ca(2+)-activated Cl(-) channel activity, not in K(+) channel activity.

Usefulness of oral hypnotic premedication for volatile induction of anesthesia in adults.

PURPOSE: We investigated the effects of oral hypnotic premedication for smooth anesthetic induction and for the patient's comfort under anesthesia, using sevoflurane without nitrous oxide. METHODS: Adult patients were divided into four groups: control ( n= 12), triazolam (0.25 mg; n= 12), zopiclone (7.5 mg; n= 12), and clonidine (0.15 mg; n= 12) groups. Each premedication was given to each patient 1 h before the anesthesia. The patients breathed out to residual volume and then the anesthetic mask was fitted. The repeated vital capacity breathing technique was used, with 5% sevoflurane in 10 l.min(-1) oxygen. Induction time, specific induction side effects, and acceptability of this technique by the patients were recorded by an independent observer. RESULTS: Induction time in the premedicated groups ranged from 66 +/- 12 s (mean +/- SD) to 76 +/- 14 s, and these values were significantly shorter than that in the control group (92 +/- 16 s). The number of patients in whom adverse effects occurred during anesthetic induction was significantly greater in the control group (4 patients; 33%) than in the premedicated groups (1 patient each; 8%). Acceptability of the smell of sevoflurane was significantly higher in the premedicated groups (8-10 patients; 67%-83%) than in the control group (5 patients; 42%). CONCLUSION: Oral hypnotic premedications with either triazolam (0.25 mg), zopiclone (7.5 mg), or clonidine (0.15 mg) are recommended for smoother volatile anesthetic induction and for the patient's comfort in adults.