The effects of flumazenil on sleepiness, task performance and nocturnal sleep after anesthesia with midazolam.

The purpose of the present study was to clarify the changes in psychophysiological functions after anesthesia with midazolam (intravenous (i.v.) benzodiazepine anesthetic) and to examine the ability of flumazenil (benzodiazepine antagonist) to prevent the adverse effects of anesthesia with midazolam. Clinical dose of midazolam (0.1 mg/kg i.v.) was administered to seven healthy volunteers and either flumazenil (0.3 mg i.v.) or saline was injected at the end of the anesthesia. After anesthesia with midazolam, subjective sleepiness and euphoria increased significantly, but these changes were not observed when flumazenil was administered. In addition, sleep latency was prolonged and sleep efficiency decreased significantly after midazolam anesthesia with and without flumazenil. Slow wave sleep decreased significantly only by co-administration of flumazenil.

Effects of pranlukast, a leukotriene receptor antagonist, on airway inflammation in mild asthmatics.

To determine the anti-inflammatory actions of pranlukast, a cysteinyl leuklotriene receptor antagonist, we measured exhaled nitric oxide (NO) concentrations and eosinophil ratio in induced sputum of three groups of mild asthmatics (n = 30): treated with bronchodilators alone, with bronchodilators and inhaled steroid (beclomethasone dipropionate; 400 microg/day), and bronchodilators and pranlukast (450 mg/day). Pranlukast (450 mg/day) reduced the eosinophil ratio in the induced sputum significantly (p < 0.01) without a major effect on the concentration of exhaled NO. Pranlukast also increased values of peak expiratory flow significantly (p < 0.05). Pranlukast may be useful for mild asthmatics, in part through its ability to suppress eosinophilic airway infiltration.

Effects of esophageal acid perfusion on airway hyperresponsiveness in patients with bronchial asthma.

STUDY OBJECTIVES: The effects of gastroesophageal reflux on airway hyperresponsiveness in patients with bronchial asthma have yet to be studied in significant detail. The purpose of the present study was to determine how esophageal acid perfusion could change airway responsiveness in patients with bronchial asthma. PATIENTS AND INTERVENTIONS: In seven patients with bronchial asthma (mean +/- SD age, 55.1 +/- 6.4 years; four women and three men), esophageal pH was monitored by a pH meter and airway responsiveness was evaluated by aerosol inhalation of methacholine, during esophageal perfusion through an esophageal tube filled with either saline solution or 0. 1N hydrochloric acid (HCl), the order of which was selected at random, in 1-week intervals. Spirometry was also performed during esophageal pH monitoring. RESULTS: A significant decrease in the geometric mean of airway sensitivity or the concentration of methacholine causing a 35% fall in respiratory conductance was observed during esophageal HCl perfusion compared with that of saline solution perfusion (p < 0.01 or p < 0.003), although no significant changes were observed in vital capacity, FEV(1), peak expiratory flow, respiratory resistance, or slope of respiratory conductance during the periods of saline solution and HCl perfusion. CONCLUSION: We concluded that an increase in airway hyperresponsiveness was induced when HCl stimulated the esophagus in patients with bronchial asthma. These results suggest that esophageal reflux is one of the important factors that aggravate asthmatic status.

[Dyspnea attack due to hysteria after general anesthesia].

A 30-year-old female was scheduled for an expander insertion of the breast under local anesthesia. Thirty minutes after infiltration anesthesia with lidocaine and bupivacaine mixture, she suffered from dyspnea. She was intubated and transferred to our hospital. As her vital signs were stable and consciousness was clear, she was extubated in the emergency room. However, she was reintubated at night and ventilated mechanically for two days. Three months later, breast expander insertion was performed under general anesthesia. After extubation, dyspnea attack occurred and midazolam was injected. Seven months later, the reconstruction of TRAM flap was performed under general anesthesia and continuous subcutaneous injection of morphine was used for the postoperative analgesia. After extubation, she was sedated deeply and dyspnea attack did not occur. A month later, she was scheduled for the debridment and the resuture. Then, dyspnea attack occurred in the ward at night. The apnea monitor was attached to her in recovery room after extubation following the operation of debridment and resuture. Dyspnea attack appeared and was diminished with midazolam injection. We diagnosed her as hysteria with CMI and MMPI psychologic tests.

Changes in subjective sleepiness, subjective fatigue and nocturnal sleep after anaesthesia with propofol.

The purpose of this study was to clarify the changes in psycho-physiological functions after anaesthesia with propofol (PF). The subjects were seven healthy male volunteers and the duration of the anaesthesia was 1 h (14:00-15:00 h). The plasma concentration of PF immediately decreased after the anaesthesia. The subjective sleepiness and VAS (visual liner analogue scale) scores (i.e. effort to do something) increased significantly at 20 min after the anaesthesia. However, these changes were improved at 80 min after the anaesthesia. The sleep latency at the nocturnal sleep 8 h after the anaesthesia was prolonged significantly, but the other parameters including the distributions of stage 3 + 4 and the rapid eye movement 'REM' stage were not changed.

[Perioperative pulmonary embolism: a nationwide survey in Japan].

Pulmonary embolism is a leading cause of death and morbidity in the perioperative period. To obtain a contemporary overview of the epidemiology of acute pulmonary embolism, a questionnaire was mailed to anesthesia department chair-persons at 179 hospitals in Japan. The 158 cases were reported from the 88 hospitals. The cause of embolism was thromboembolism 127, gas 13, fat 9, amniotic fluid 4 and tumor 3. The mortality rate for patients with thromboembolism was high (29%). Dyspnea was the most frequent symptom (60%) and hypotension was the most frequent clinical sign (54%). The signs which suggested massive pulmonary embolism, such as hypotension, cyanosis (53%), syncope (39%) and cardiac arrest (29%) were frequently seen. Most of the pulmonary embolisms occurred during the operation and within 7 days after the operation. The high risk factors associated with thromboembolism were age, malignancy, obesity and the type of surgery performed. Treatment performed included anticoagulation 81%, catecholamine infusion 66%, thrombolysis 14%, surgical embolectomy 8% and extra-corporeal circulation 4%. This study indicates that the perioperative pulmonary embolism is still associated with high mortality and requires an immediate diagnosis and intensive therapy.

[Anesthetic management using extracorporeal circulation of a patient with severe tracheal stenosis by thyroid cancer].

A 64-year-old male with tracheal stenosis by thyroid cancer was scheduled for the emergency management of airway maintenance and total thyroidectomy. Dyspnea and orthopnea appeared suddenly on the admission for operation. Cervical CT and bronchial fiberscope examination revealed the trachea oppressed at the frontal neck by thyroid tumor. The trachea diameter was nearly 5 mm at the narrowest part. Therefore it seemed to be of high risk of perform tracheal intubation and tracheostomy. Extracorporeal circulation was adopted for the respiratory management at anesthesia induction. At first, the femoral artery and vein were cannulated with local anesthesia for cardiopulmonary bypass (CPB). After confirming CPB pump working, intravenous anesthetic agents were infused. Thyroid tumor was partially resected and tracheostomy was done under CPB. After the tracheostomy, a spiral tracheal tube was inserted. Anesthesia was maintained with sevoflurane and managed with controlled ventilation. Thereafter operation and anesthesia were uneventful. After the operation, pleural bloody effusion was noticed. Blood in effusion seemed to be due to the heparinization in extracorporeal circulation. We conclude that anesthetic management with extracorporeal circulation is one of useful methods for managing severe tracheal stenosis.

[Anesthetic management of a patient with Eaton-Lambert syndrome with chronic respiratory failure].

A 66-year-old male with colon cancer was scheduled for left hemicolectomy. He had a past history of respiratory failure due to chronic obstructive pulmonary disease (COPD). Anesthesia method chosen was general anesthesia with sevo-flurane combined with epidural anesthesia. Respiration was managed with assisted ventilation using laryngeal mask airway and muscle relaxation was obtained with suxamethonium chloride given intermittently. After the operation, he did not seem to have COPD because of the relation between arterial PCO2 and bicarbonate in the perioperative period. Therefore, after obtaining informed consent from this patient, we determined the relation between arterial and spinal fluid acid-base balance under acetazolamide administration. He was more sensitive to central respiratory response because his respiration increased following the decrease of spinal fluid bicarbonate. We further examined and diagnosed him as Eaton-Lambert syndrome by evoked electromyography and by Ca2+ channel antibody.

Effect of dopamine content in rat brain striatum on anesthetic requirement: an in vivo microdialysis study.

This study investigated the changes in anesthetic requirement caused by administration of two different concentrations (0.1 microM and 1. 0 microM/h) of dopamine into the rat striatum. During the measurement of minimum alveolar concentration (MAC), each dopamine solution was continuously injected directly into rat striatum by microdialysis technique. During perfusion of the lower dose, MAC did not change. During the higher dose of dopamine, MAC decreased by approximately 30%.

[Accuracy of measuring nitric oxide by the chemiluminescence: effect of measuring chamber pressure].

There are two ways of measuring nitric oxide (NO) by chemiluminescence; one reduces pressure in the NO reaction chamber, and the other does not. Devices with a reduced pressure chamber tend to be more accurate, but can be bulky and cumbersome to use. Devices without reduced pressure chamber can be useful because of their smaller size and short warm-up time. We compared the accuracy of two methods by measuring delivered gas concentrations after changing ventilatory parameters. The values of nitric dioxide (NO2) measured varied more widely than those of NO. NO2 measurements were particularly variable with changes in humidity. We consider the accuracy of NO measured by the chemiluminescence devices to be accurate for clinical monitor, but the accuracy of NO2 measurement must be improved to make NO therapy safer.

[Propofol anesthesia for a patient with insulinoma].

We experienced the anesthetic management of a 47-year-old woman with insulinoma. Removal of the tumor was performed under propofol, nitrous oxide, and epidural anesthesia. We tried the continuous infusion of glucose to maintain normal blood glucose level and to avoid intraoperative hypoglycemic event. The blood glucose and immunoreactive insulin (IRI) level were measured intermittently. After the removal of the insulinoma, the IRI level decreased rapidly to the normal range. In this case, neither hyperglycemic nor hypoglycemic episode was observed. The perioperative course was uneventful. Propofol has not been shown to significantly affect the release of insulin and glucose regulation. This case suggests that under the condition of continuous glucose infusion and blood glucose monitoring, propofol is an useful anesthetic agent for a patient with insulinoma.

[Respiratory management after closure of a bronchial-fistula with an omental pedicled gastric flap].

A 56-year-old female, after closure of a bronchial-fistula with an omental pedicle gastric flap, underwent controlled ventilation for two weeks in order to stabilize the flap. We suspended the administration of vecuronium once a day and examined the plasma concentration of vecuronium when a twitch response appeared. During the two weeks of ventilation, plasma concentration of vecuronium was maintained at low doses by adjusting the daily dose of vecuronium infusion. However, the suspended period of vecuronium infusion was prolonged gradually and the patient care such as tracheal suction and position changing became restricted. In addition, we have to care for the infection and a mental injury.

[Comparative study on the efficacy of ritipenem acoxil and cefotiam hexetil in chronic lower respiratory tract infections by the double-blind method].

To objectively evaluate the efficacy, safety and usefulness of the newly developed penem oral antibiotic, ritipenem acoxil (RIPM-AC), against chronic lower respiratory tract infections, we conducted a multi-center double-blind comparative study using cefotiam hexetil (CTM-HE) as a control drug. RIPM-AC was orally administered at 200 mg, and CTM-HE at 400 mg, t.i.d. for 14 days, in principle. The results were as follows: The total number of patients enrolled in this trial was 202, of which 151 cases (RIPM-AC group: 75, CTM-HE group: 76) were evaluable for clinical efficacy. 1. The clinical efficacy rates (excellent+good) were 85.3% (64/75) in the RIPM-AC group and 80.3% (61/76) in the CTM-HE group. There was no significant difference between the two groups, hence the clinical equivalency of RIPM-AC to CTM-HE was demonstrated. 2. In the patients enrolled in the evaluation of clinical efficacy, the eradication rates of the causative organisms were 50.0% (13/26) in the RIPM-AC group and 75.0% (18/24) in the CTM-HE group, with no significant difference between the two groups. 3. Side effects were noted in 10 cases (11.0%) of the RIPM-AC group and 10 cases (10.9%) of the CTM-HE group. Abnormal laboratory test findings were observed in 8 cases(9.5%) of the RIPM-AC group and in 14 cases (16.7%) of the CTM-HE group. There were no significant differences between the two groups in the incidence of side effects and abnormal laboratory test findings. In the safety evaluation, RIPM-AC was judged to be safe in 73 cases (80.2%) and CTM-HE in 71 cases (77.2%), with no significant difference. 4. The usefulness rates (markedly useful+useful) were 79.5% (62/78) in the RIPM-AC group and 76.9% (60/78) in the CTM-HE group. There was no significant difference between the two groups. Since RIPM-AC showed clinical efficacy similar to those of CTM-HE and posed no particular safety problems, it is expected to be a useful antibiotic for the treatment of chronic lower respiratory tract infections.

[A comparative study on the efficacies of ritipenem acoxil and cefotiam hexetil in bacterial pneumonia by the double-blind method].

To objectively evaluate the efficacy, safety and usefulness of the newly developed penem oral antibiotic, ritipenem acoxil (RIPM-AC), against bacterial pneumonia, we conducted a multi-center double-blind comparative study using cefotiam hexetil (CTM-HE) as the control drug. Both RIPM-AC and CTM-HE were orally administered at 200 mg t.i.d. for 14 days, in principle. The results were as follows: The total number of patients enrolled in this trial was 208, of which 152 cases (RIPM-AC group: 73, CTM-HE group: 79) were evaluable for clinical efficacy. 1. The clinical efficacy rates (excellent + good) were 91.8% (67/73) in the RIPM-AC group and 94.9% (75/79) in the CMT-HE group. There was no significant difference between the two groups, and the clinical equivalency of RIPM-AC to CTM-HE was demonstrated. 2. In the patients enrolled in the evaluation of clinical efficacy, the eradication rates of the causative organisms were 84.6% (22/26) in the RIPM-AC group and 91.7% (22/24) in the CTM-HE group, with no significant difference between the two groups. 3. Side effects were noted in 9 cases (9.6%) of the RIPM-AC group and 5 cases (4.9%) of the CTM-HE group. Abnormal laboratory test findings were observed in 23 cases (26.7%) of the RIPM-AC group and 15 cases (15.6%) of the CTM-HE group. There was no significant differences between the two groups in the incidence of side effects nor of abnormal laboratory test findings. In the safety evaluation, RIPM-AC was judged to be safe in 64 cases (68.1%) and CTM-HE in 82 cases (80.4%), with no significant difference. 4. The usefulness rates (markedly useful+useful) were 86.5% (64/74) in the RIPM-AC group and 92.5% (74/80) in the CTM-HE group. There was no significant difference between the two groups. Since RIPM-AC showed clinical efficacy similar to those of CTM-HE and posed no particular safety problems, it is expected to be a useful antibiotic for the treatment of bacterial pneumonia.

[Rapid diagnosis of adenoviral conjunctivitis by enzyme-linked immunosorbent assay (Adenoclone)].

We evaluated an enzyme-linked immunosorbent assay test (Adenoclone) for the rapid diagnosis of adenovirus infection in 589 cases of acute follicular conjunctivitis. Of 255 cases of adenoviral conjunctivitis proven by positive virus isolation. Adenoclone was positive in 51.0% by visual determination and 40.4% by spectrophotometry. Twenty-seven of 130 cases giving visually positive results were interpreted to be negative by spectrophotometry. In 334 adenovirus-negative cases, Adenoclone was negative in 99.1% and 99.4 by visual and spectrophotometric determination, respectively. Adenoclone was less sensitive in cases of adenovirus 3, 4 or 37, infections than in those of adenovirus 8, and also showed lower sensitivity in cases presenting mild conjunctivitis. Adenoclone is a rapid and easy test with high specificity but low sensitivity, and thus the test seems to be helpful in diagnosing adenoviral conjunctivitis.

[Differential reactivities of three kinds of carbon dioxide absorbents with sevoflurane].

The differential reactivities of three kinds of carbon dioxide absorbents, Soda lime, Soda lime A, and Baralyme with sevoflurane were investigated. Sevoflurane was made to react with each carbon dioxide absorbents in a glass vial or in a closed system under administration of carbon dioxide. Glass vials were kept at 55 degrees C and 70 degrees C, and three kinds of carbon dioxide absorbents were compared regarding their reactivity under each temperature. In a closed system, we also monitored the temperature of glass container which was filled with each carbon dioxide absorbent. In a glass vial, the highest reactivity of sevoflurane was found with Baralyme. Although Soda lime A decomposed sevoflurane less than Baralyme or Soda lime in glass vial, the highest reactivity of sevoflurane in a closed system was found with Soda lime A. On the other hand, Soda lime A increased the temperature of glass container most. As increasing temperature tends to promote reaction, the possibility that the high temperature of the glass container contributes to the reactivity of sevoflurane with carbon dioxide absorbents exists. These results suggest that the highest reactivity of Soda lime A with sevoflurane was caused by the highest temperature of glass container although its chemical composition makes it most reactive with sevoflurane than the others.

The determination of a new inhalational anaesthetic, sevoflurane, using an internal standard, xenon, by gas chromatography/mass spectrometry/selected ion monitoring.

A novel determination method for a new inhalation anaesthetic, sevoflurane, in a closed circuit in the presence of carbon dioxide absorbents is investigated using gas chromatography/selected ion monitoring with xenon as an internal standard. The decrease rate of sevoflurane with soda lime was 0.22% +/- 0.158/h (mean +/- SD), while that with baralyme was 0.57% +/- 0.115/h (mean +/- SD).

The effect of halothane dose on striatal dopamine: an in vivo microdialysis study.

The relationship between a level of an anesthesia state and striatal dopamine concentration was investigated. The effect of halothane administration on dopamine level in rat striatal extracellular fluid was determined in tracheotomized rats, using an in vivo brain microdialysis method. The striatal dopamine was increased by halothane doses. The correlation coefficient between halothane and dopamine concentrations was 0.69.

[Solubility of desflurane (I-653), sevoflurane, isoflurane, and halothane in human blood].

The blood/gas partition coefficients for the new volatile anesthetic agent desflurane (I-653), sevoflurane, isoflurane, and halothane were determined, simultaneously, in 8 human volunteers to compare the solubilities of these agents in blood. The blood/gas partition coefficient for desflurane [0.49 +/- 0.03 (mean +/- SD)] was smallest, followed by sevoflurane (0.62 +/- 0.04), isoflurane (1.27 +/- 0.06), and halothane (2.46 +/- 0.09). Differences among the anesthetic agents were significant (P less than 0.001). The results of this study confirm that among these agents the solubility of desflurane in human blood is the smallest. The results suggest that the washin and washout of desflurane will be more rapid than that of sevoflurane, isoflurane, and halothane, and the washin and washout of sevoflurane will be more rapid than that of isoflurane and halothane.

[Reactivity of sevoflurane with carbon dioxide absorbents--comparison of soda lime and Baralyme].

The reactivity of sevoflurane with carbon dioxide absorbents, soda lime and Baralyme which are commercially available carbon dioxide absorbents, was studied. A closed circuit system which was made only for this investigation was set up without rubber. Sevoflurane 5% was circulated for 17 hours. The circulated gas was analyzed by gas chromatography (GC) and degradation products were identified by a gas chromatography-mass spectroscopy (GC-MS) as fluoromethyl 2-methoxy-2, 2-difluoro-1-(trifluoromethyl) ethyl ether, fluoromethyl 2-methoxy-2-fluoro-1-(trifluoromethyl) vinyl ether, and its isomer. These degradation products of sevoflurane from soda lime and Baralyme were the same substances. The rate of degradation by soda lime was 0.88% +/- 0.306, while that by Baralyme was 3.40% +/- 0.501. Baralyme decomposed sevoflurane about four times more than soda lime. There are two possible explanations for these results. One is the Baralyme contains more potassium hydroxide than soda lime. The other is that soda lime absorbs sevoflurane more because it contains more silica.