Protein phosphorylation in intact pig leukocytes.

The phosphorylation of proteins in intact pig polymorphonuclear leukocytes loaded with H3(32)PO4 was investigated by two-dimensional gel electrophoresis and subsequent autoradiography. The incorporation of 32P into at least 17 proteins began to increase and into one to decrease, relative to resting cells, upon exposure of the cells to phorbol 12-myristate 13-acetate. These changes in the autoradiographic patterns were accompanied by changes in the protein patterns obtained by staining with Coomassie brilliant blue, including the appearance, the acidic shift and the increase or decrease of the intensity of the spots. Among these proteins, Mr = 64 000, 31 000, 22 000, 21 000, 18 000 and 13 000 proteins were correlated well with the superoxide anion production of the cells in respect to the time-courses and the dose-responses. By taking the effects of EGTA into consideration, the phosphorylation of Mr 64 000 and 21 000 proteins, of which the latter was identified as the light chain of myosin, seemed to be involved in the signal-transmission mechanism of the induction of the NADPH oxidase responsible for the 'respiratory burst'. These two proteins were also phosphorylated in the cells stimulated by NaF or oil droplets opsonized with IgG.

Phosphorylation of myosin light chain in intact pig leukocytes stimulated by phorbol 12-myristate 13-acetate.

Phosphorylation of myosin light chain was investigated in intact pig polymorphonuclear leukocytes. The labeling of the myosin light chain (Mr = 21000) was increased by exposure of the cells to phorbol 12-myristate 13-acetate. Two-dimensional gel electrophoresis revealed three forms of Mr = 21000 light chain, of which two were phosphorylated. The phosphorylation of the myosin light chain was inhibited by neither N-(6-aminohexyl)-5-chloro-1-naphthalene sufonamide nor trifluoperazine, suggesting that calmodulin is not involved in the phosphorylation.

Calcium channel antagonist induced inhibition of superoxide production in human neutrophils. Mechanisms independent of antagonizing calcium influx.

Three calcium channel antagonists, verapamil, diltiazem and nisoldipine, inhibited superoxide production in human neutrophils that were stimulated by phorbol 12-myristate 13-acetate (PMA) in a buffered saline lacking calcium. Concentrations of these drugs giving 50% control activity (IC50) were 0.3, 0.45 and 0.01 mM respectively. This inhibition was also observed in the presence of ethylene glycol bis (beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA) and was not reversed by the addition of calcium. This suggests that calcium channel antagonists inhibited superoxide production independently of extracellular calcium. These calcium channel antagonists inhibited the mobilization of membrane-associated calcium, and protein phosphorylation probably catalyzed by C-kinase, both of which are thought to be involved in the signal transmission for the induction of superoxide production. Calcium channel antagonists also inhibited NADPH oxidase, responsible for superoxide production, with IC50 = 0.5, 3 and more than 0.08 mM, respectively, for verapamil, diltiazem and nisoldipine. The results indicate that calcium channel antagonists inhibit superoxide production by affecting not only the catalytic activity by also the activation of NADPH oxidase. Inhibition of superoxide production by calcium channel antagonists suggests that these antagonists do not affect cell functions merely by affecting calcium influx.

Carbon tetrachloride increases sinusoidal efflux of reduced and oxidized glutathione in rats.

To elucidate the significance of the changes in plasma glutathione concentrations associated with carbon tetrachloride (CCl4)-induced liver damage, the changes in the concentrations of reduced (GSH) and oxidized glutathione (GSSG) in plasma as well as in the liver were investigated in rats. In the liver, the concentration of GSH decreased, and that of GSSG increased 24 hr after the intraperitoneal administration of CCl4. In the right atrial plasma, the concentration of both GSH and GSSG increased. The GSH/GSSG ratio in the plasma decreased as did that in the liver. The net sinusoidal efflux of GSH and GSSG from the liver was calculated by subtracting their concentrations in plasma of the infrahepatic inferior vena cava from those of the suprahepatic inferior vena cava. The net efflux of GSH and GSSG started to increase as early as 3-6 hr after CCl4 administration, and reached a plateau 6 and 24 hr after CCl4 administration, respectively. On the other hand, an elongation of prothrombin time and leakage of alanine aminotransferase reached a maximum 24 and 48 hr after CCl4 administration, respectively. Vacuolization in the centri-lobular region and inflammatory infiltration started 3 and 6 hr after CCl4 administration, respectively, and progressed for 48 hr. These results suggest that CCl4 induced an increase in plasma concentrations of GSH as well as GSSG by increasing their efflux from the liver, and that the changes in plasma glutathione status might be a useful and sensitive marker for CCl4-induced liver damage.

Effects of sevoflurane and isoflurane on electrocorticographic activities in patients with temporal lobe epilepsy.

To compare the neuroexcitatory effects of sevoflurane and isoflurane, we recorded electrocorticograms (ECoG) during wakefulness and during sevoflurane and isoflurane anesthesia in six patients with temporal lobe epilepsy (TLE). These patients had subdural grid electrodes chronically implanted in the temporal region. During sevoflurane anesthesia at 1.5 minimum alveolar concentration (MAC) of the combination with 67% nitrous oxide (N2O), a marked increase in interictal paroxysmal activities was observed in four patients. Two patients had a slight increase in paroxysmal activities. Activated areas were widely distributed, not being confined to the ictal onset zone of spontaneous seizures. However, isoflurane anesthesia at 1.5 MAC of the combination with 67% N2O was associated with less increased paroxysmal activity. While the neuroexcitatory properties of sevoflurane proved greater than those of isoflurane, the widespread irritative response to sevoflurane administration was not helpful in localizing the epileptogenic area.

Anesthetic management of children with moyamoya disease.

A review of the surgical and postoperative records of 127 revascularization procedures performed on 82 children with Moyamoya disease was done to evaluate changes we made in anesthetic management in response to perioperative complications. From 1982 to 1996, out of 82 children who underwent revascularization surgery at our hospital, five developed perioperative complications. One developed circulatory instability during surgery; the cause seemed to be a depth of anesthesia insufficient for preventing surgical stress. To rectify this problem, an increased dose of fentanyl was used to improve the maintenance of anesthesia. Four patients developed cerebral infarction during the early postoperative period due, in part, to inadequate management of postoperative pain. We began to administer supplemental doses of meperidine to patients after they emerged from anesthesia to provide better control of postoperative pain. Our review confirmed the effectiveness of these measures. The data suggest that during the perioperative management of children with Moyamoya disease, close attention should be paid to balancing the patients' anesthetic state against surgical stress and providing adequate postoperative analgesia.

Effect of coronary artery bypass grafting with gastroepiploic artery on gastric intramucosal pH and systemic inflammation.

BACKGROUND: The purpose of this study was to investigate the effect of coronary arterial bypass grafting (CABG) with gastroepiploic artery (GEA) on gastric intramucosal pH and systemic inflammation. DESIGN: retrospective study. SETTING: University hospital. PARTICIPANTS: 22 patients underwent CABG. INVESTIGATIONS: the GEA group (n=13) received CABG with the GEA graft. The non-GEA group (n=9) received conventional CABG without the GEA graft. MEASUREMENTS: gastric intramucosal pH (pHi) and carbon dioxide tension (PrCO(2)) were assessed by capnometric air tonometry. The difference between PrCO(2) and PaCO(2), PCO(2)-gap, was also determined. Systemic inflammatory responses were evaluated by serum interleukin-6 (IL-6) and leucocyte counts. Hemodynamics, oxygen delivery index (DO(2)I) and uptake index (VO(2)I) were monitored with catheters in the radial and pulmonary arteries (thermodilution). RESULTS: The duration of aortic cross-clamping and cardiopulmonary bypass was similar in both groups. Both groups did not show any significant difference in gastric pHi, PCO(2)-gap, systemic inflammation and hemodynamics. CONCLUSIONS: Our findings suggest that CABG using the GEA graft does not disturb gastric mucosal perfusion, and that laparotomy for the GEA graft does not aggravate systemic oxygen demand-supply imbalance or systemic inflammatory responses induced by hypothermic CPB. CABG with the GEA graft does not seem to pose an additional risk and is a safe technique compared with conventional CABG with regard to pHi and systemic inflammation.

Late occurrence of diffuse cerebral swelling after intracerebral hemorrhage in a patient with the HELLP syndrome--Case report.

Hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome can occur at any time in the course of pregnancy and is associated with many complications including fatal stroke. A 37-year-old female presented with HELLP syndrome causing an intracerebral hematoma, which was treated by evacuation and mild hypothermia. Unexpected diffuse cerebral swelling occurred on the 15th day of the initially favorable postoperative course. Considerable impairment of consciousness persisted despite conservative therapy. Serial computed tomographic findings indicated delayed cerebral vasospasm as the cause of the swelling. Particularly careful management is required even beyond the first 2 weeks for patients with stroke as a complication of HELLP syndrome.

[Clinical trial of bradykinin-enhancing chemotherapy for a recurrent malignant glioma: a case report].

Patients with malignant glioma undergo a combined treatment with surgical resection, radiotherapy, and chemotherapy. Although those treatments usually show some restraining effects on the tumor, a relapse occurs in most of the patients within a few years. We have investigated the feasibility and safety of intra-arterial chemotherapy for malignant brain tumors by enhancing vascular permeability using intra-arterial bradykinin infusion. In 2001, The Committee of Ethics in Kyushu University approved our clinical trial of the bradykinin-enhancing chemotherapy for recurrent malignant gliomas. We here report the first case of our clinical trial. A 31-year-old man, who had undergone surgical resection followed by chemotherapy and irradiation for malignant progression of the left frontal astrocytoma over a period of 2 years, had a relapse of the tumor in the bilateral frontal lobes. After obtaining informed consent, bradykinin and carboplatin were infused through a microcatheter at the left A1 portion under general anesthesia. By dose escalation of bradykinin, the enhanced lesion in the bilateral frontal lobes diminished on magnetic resonance imaging after 3 trials with 3-week intervals, regardless of new lesions outside of the treated area. No neurological or physiological complication including myelosuppression was noted. Bradykinin-enhancing chemotherapy appeared to be effective and safe for malignant glioma. Because it was able to increase drug delivery to the tumor, it was possible to reduce the size of the dose of chemotherapeutic agent, which resulted in minimum complication.

[Effect of dibucaine on the association of protein kinase C with liposome].

The association of protein kinase C with membranes are thought to be a prerequisite for the activation of the enzyme. Dibucaine has been reported to inhibit the enzyme activity competitively with phosphatidylserine. We investigated the effect of dibucaine on the association of protein kinase C with liposome. Calcium and phorbol 12-myristate 13-acetate (PMA) independently and synergistically induced the association of rat brain protein kinase C with phosphatidylserine/phosphatidylcholine liposome. Although dibucaine inhibited the association induced by calcium alone, it did not affect the association induced by PMA alone. Dibucaine, however, inhibited the association which was induced synergistically by calcium and PMA. It was suggested that dibucaine did not always inhibit the association of protein kinase C with phospholipid membranes.

[Lack of communication between anesthesiologists and surgeons: comparison of questionnaire survey among anesthesiologists with that among surgeons concerning pre-anesthetic evaluation of surgical patients].

We conducted a survey to examine surgeons' opinions and criticisms of patient evaluations done by anesthesiologists prior to surgery. We sent questionnaires to 117 departments of general surgery in Japanese university hospitals. We received answers from 77% of the departments. We analyzed their answers, and compared the answers with those from a similar survey done in 1995 by Japan Society of Anesthesiology, one in which anesthesiologists were asked to evaluate themselves. Our most significant findings were as follows. (1) Although most of surgeons were satisfied with their own preanesthetic evaluation of their patients, 30% of the departments reported postponement of surgery due to the need of further examination during recent 2 months and the occurrence of peri-operative myocardial infarction during recent 2 years, (2) The 1995 survey indicated that 46 percent of anesthesiology departments had explained the major perioperative risk, but a half of the 46% had done so without discussing the risk with responsible surgeons. Furthermore, the present survey showed that only 17% of the surgery departments had been aware of such explanation done by anesthesiologists. (3) One-third of the anesthesiology departments did not document the text of the preanesthetic explanation to patients. In our opinion, the final responsibility for the patient's peri-operative care is primarily the surgeon's at present in Japan, although each specialist including the anesthesiologist and the cardiologist should share the responsibility. If the anesthesiologist explain the major peri-operative risk to the patient without first obtaining the surgeon's permission to do so, the patient may become confused about who is responsible for his or her care. It should be made clear to the patient what responsibility each doctor has. It is also important that all explanations given to a patient and the consent to anesthesia given by a patient be properly documented. Japanese anesthesiologists and surgeons need to work far more closely together with regard to pre-anesthetic evaluation and explaining patients about their peri-operative risk.

[Mycoplasma pneumonia found by the occurrence of atelectasis during the induction of anesthesia in a child with tetralogy of Fallot].

A 3-yr-old girl was scheduled to undergo surgical repair of tetralogy of Fallot. She had no sign or data indicating an infectious disease, other than a slight dry cough for a few days prior to the proposed operation. During the induction of anesthesia with nitrous oxide, oxygen and sevoflurane, transient moist rale was noticed with a precordial stethoscope. Her trachea was intubated without any difficulty after the administration of pancuronium, followed by a chest auscultation, which revealed vesicular sound bilaterally but no rale. However, a chest X-ray taken after the right subclavian vein catheterization showed a massive hypoaeration in the upper left pulmonary region. The presence of the right-to-left intracardiac shunt made it impossible to detect the occurrence of atelectasis by a decrease in SpO2. Fiberoptic bronchoscopy showed no obstruction of the bronchus and no hypersecretion initially, but physical therapy and humidification made it possible to aspirate intratracheal sputum. Because there seemed to be an imbalance between the relatively uneventful induction of anesthesia and the relative resistance of atelectasis to authentic therapies, the operation was postponed, and the antibody to mycoplasma pneumoniae was titrated. The titer in the serum was 1:80, and increased to 1:560 6 days later. Chest X-rays revealed normal lung condition 3 days later, and she was given erythromycin, 800 mg.day-1 for 2 weeks. We conclude that we should be alert to possible asymptomatic mycoplasma infection, which potentially makes patients susceptible to atelectasis during the perioperative period.

[Transient tracheal obstruction during surgical correction of scoliosis in a patient with Marfan's syndrome].

A 13-yr-old male with Marfan's syndrome underwent surgical correction of severe scoliosis. He had not manifested dyspnea previously in any position. Under anesthesia with thiamylal and vecuronium, his trachea was intubated with a reinforced endotracheal tube without any difficulty. Anesthesia was maintained with nitrous oxide and fentanyl, 8 micrograms.kg-1. The patient was placed in a prone position. Thirty min after the start of operation, when orthopedists compressed the thoracic vertebrae vertically, positive pressure ventilation became impossible abruptly, even with a high airway pressure. Three min later, ventilation became possible after cessation of compression and by mouth-to-tube insufflation. SpO2 monitored with a pulse oximeter recovered immediately from 61% to 99%. A capnogram showed a lengthy retardation of an inspiratory phase. Emergency fibreoptic bronchoscopy revealed that the trachea had been compressed vertically; the compression was reduced by moving the chest supporters laterally. After the apneic episode, the operation continued uneventfully, and he was discharged a month later. A severe deformity of the thorax due to severe scoliosis and weak tracheal tissue due to connective tissue defect caused partial tracheal compression before the surgery, and made his trachea susceptible to complete obstruction by vertical external compression on the thorax. Patients with Marfan's syndrome and scoliosis should have careful preoperative airway evaluation. The selection and positioning of endotracheal tubes should be done with care. During surgery, the patient's body position and the condition of the trachea should be checked frequently. Capnography and fiberoptic bronchoscopy seem to be mandatory for early detection of tracheal stenosis and prevention of tracheal obstruction.

[Annual study of perioperative mortality and morbidity for the year of 1999 in Japan: the outlines--report of the Japan Society of Anesthesiologists Committee on Operating Room Safety].

Anesthetic mortality and morbidity in Japan Society of Anesthesiologists (JSA) Certified Training Hospitals (CTH) for the year 1999 were reported as continuation of annual studies started in 1993. The JSA Committee on Operating Room Safety (CORS) sent confidential questionnaires to 774 CTH and received valid responses from 60.3% of hospitals. A total number of 793,840 anesthetics were documented. The respondents were asked to report all cases of cardiac arrests and other critical incidents (serious hypotension, serious hypoxemia and others), and their outcomes (death in operating room, death within 7 days, transfer to vegetative state and rescue without sequelae) as well as one principal cause for each incident from list of 52 items. They were also requested to submit the tabulation of patients by ASA physical status, age distribution, surgery sites and anesthetic methods. Analysis was made by total incidents under anesthesia/surgery, and also by incidents totally attributable to anesthetic management (AM), due to preoperative complications (PC), due to intraoperative pathological events (IP) and due to surgery (SG), with special reference to each of four tabulation groups and the whole group of patients. This paper focused analysis on all patients, as analyses with special reference to ASA physical status, age distribution, surgery sites and anesthetic methods were previously reported. Total incidence of cardiac arrest under anesthesia/surgery was 6.53 per 10,000 anesthetics. PC, IP and SG represented principal causes in 42.9%, 22.0% and 21.4% causes of total cardiac arrest cases, respectively. AM was noted as the principal cause in 12.0% of cases, with an incidence rate of 0.78 per 10,000. In 52 more detailed classification of principal causes, the most frequent cause of cardiac arrest was preoperative hemorrhagic shock, 20.3% of all cardiac arrests. The second cause was massive hemorrhage and/or hypovolemia due to surgical procedures (13.1%), and the third was intraoperative myocardial infarction/coronary ischemia/coronary spasm (9.5%). Prognoses of cardiac arrest cases declined due to PC: 71.1% of cardiac arrests died in the operating room or within 7 days after surgery and only 19.8% survived without sequelae. The best prognoses were found in cardiac arrest cases due to AM: 69.4% survived without sequelae and 12.9% died. The mortality rate post-cardiac arrest was 3.44 per 10,000 anesthetics, of those 0.10 due to AM, 0.57 due to IP, 1.99 due to PC and 0.76 due to SG. The mortality rate after critical incidents other than cardiac arrest such as severe hypotension and severe hypoxemia was 3.75, of those 0.03 due to AM, 0.28 due to IP, 2.31 due to PC and 1.13 due to SG. The final mortality rate attributable to anesthesia/surgery including deaths post-cardiac arrest and after other critical incidents was 7.19 per 10,000 anesthetics and very close to 7.18 [6.22, 8.13], that of mean [95% C.I.] in 1994-1998. The final mortality rate totally attributable to anesthesia was 0.13 per 10,000 anesthetics, which was significantly improved from 0.21 [0.15, 0.27], that of mean [95% C.I.] in 1994-1998. IP, PC and SG showed the final mortality rate of 0.84, 4.30 and 1.89, respectively. Five major causes of all critical incidents were massive hemorrhage due to surgical procedures (20.8%), preoperative hemorrhagic shock (10.7%), surgical technique (8.0%), inappropriate airway management (5.2%) and intraoperative myocardial infarction and coronary ischemia (4.5%). Drug overdose or selection error (3.9%) and overdose of main anesthetic (2.9%) as a result of human error occupied the 7th and 10th places. As far as anesthetic management to reduce mortality and morbidity related to anesthesia is concerned, we should increase vigilance to avoid human errors in addition to improving preanesthetic preparations and assessment of cardiovascular status as well as intraoperative management of cardiovascular events.

[Annual report of perioperative mortality and morbidity for the year 1999 with a special reference to anesthetic methods at Certificated Training Hospitals of Japanese Society of Anesthesiologists].

The Committee on Operating Room Safety of Japanese Society of Anesthesiologists (JSA) sends annually confidential questionnaires of perioperative mortality and morbidity to Certificated Training Hospitals of JSA. This report is on perioperative mortality and morbidity in 1999 with a special reference to anesthetic methods. Four hundred and sixty-seven hospitals reported the number of cases referred to anesthetic methods and total numbers of cases were 727,723. The incidences of cardiac arrest per 10,000 cases due to all etiology are estimated to be 6.77 cases in average, 5.33 cases in inhalation anesthesia, 34.26 cases in total intravenous anesthesia (TIVA), 5.26 cases in inhalation anesthesia plus epidural or spinal or conduction block, 5.29 cases in TIVA plus epidural or spinal or conduction block, 0.73 cases in spinal with continuous epidural block (CSEA), 2.85 cases in epidural anesthesia, 1.63 cases in spinal anesthesia, 2.53 cases in conduction block and 46.51 cases in other methods. However, the incidences of cardiac arrest per 10,000 cases totally attributable to anesthesia are estimated to be 0.78 case in average, 0.51 case in inhalation anesthesia, 1.35 cases in TIVA, 0.97 case in inhalation anesthesia plus epidural or spinal or conduction block, 1.51 cases in TIVA plus epidural or spinal or conduction block, 0.73 case in CSEA, 1.71 cases in epidural anesthesia, 0.54 case in spinal anesthesia, 2.52 cases in conduction block and 1.08 cases in other methods. The incidences of severe hypotension per 10,000 cases due to all etiology are estimated to be 16.64 cases in average, 13.61 cases in inhalation anesthesia, 100.36 cases in TIVA, 13.32 cases in inhalation anesthesia plus epidural or spinal or conduction block, 9.07 cases in TIVA plus epidural or spinal or conduction block, 3.65 cases in CSEA, 6.26 cases in epidural anesthesia, 7.31 cases in spinal anesthesia, 2.52 cases in conduction block and 28.12 cases in other methods. On the other hand, the incidences of cardiac arrest per 10,000 cases totally attributable to anesthesia are estimated to be 2.40 cases in average, 1.65 cases in inhalation anesthesia, 0.81 cases in TIVA, 3.92 cases in inhalation anesthesia plus epidural or spinal or conduction block, 2.77 cases in TIVA plus epidural or spinal or conduction block, 2.56 cases in CSEA, 3.42 cases in epidural anesthesia, 2.71 cases in spinal anesthesia, zero case in conduction block and zero case in other methods. The incidences of severe hypoxia per 10,000 cases due to all etiology are estimated to be 5.32 cases in average, 6.7 cases in inhalation anesthesia, 9.17 cases in TIVA, 5.16 cases in inhalation anesthesia plus epidural or spinal or conduction block, 4.53 cases in TIVA plus epidural or spinal or conduction block, 2.56 cases in CSEA, zero case in epidural anesthesia, 1.08 cases in spinal anesthesia, zero case in conduction block and 1.08 cases in other methods. On the other hand, the incidences of severe hypoxia per 10,000 cases totally attributable to anesthesia are estimated to be 2.39 cases in average, 3.22 cases in inhalation anesthesia, 2.43 cases in TIVA, 2.26 cases in inhalation anesthesia plus epidural or spinal or conduction block, 2.77 cases in TIVA plus epidural or spinal or conduction block, zero case in CSEA, zero case in epidural anesthesia, 0.54 cases in spinal anesthesia, zero case in conduction block and 1.08 cases in other methods. The mortality rates of cardiac arrest per 10,000 cases due to all etiology are estimated to be 3.56 cases in average, 2.82 cases in inhalation anesthesia, 24.55 cases in TIVA, 1.4 cases in inhalation anesthesia plus epidural or spinal or conduction block, 1.51 cases in TIVA plus epidural or spinal or conduction block, zero cases in CSEA, 0.57 cases in epidural anesthesia, 0.27 cases in spinal anesthesia, zero case in conduction block and 42.18 cases in other methods. On the other hand, the mortality rates of cardiac arrest per 10,000 cases totally attributable to anesthesia are estimated to be 0.08 case in average, 0.09 case in inhalation anesthesia, 0.27 case in TIVA, 0.05 case in inhalation anesthesia plus epidural or spinal or conduction block, zero case in TIVA plus epidural or spinal or conduction block, zero case in CSEA, 0.57 case in epidural anesthesia, zero case in spinal anesthesia, conduction block and other methods. The outcomes of cardiac arrest totally attributable to anesthesia are 70.2% of full recovery without any sequelae, 10.5% of death within 7 days, 1.8% of vegetative state and 17.5% of unknown results while the outcome of critical events including severe hypotension and severe hypoxia totally attributable to anesthesia is 94.9% of full recovery without any sequelae, 0.4% of death within 7 days, 0.2% of vegetative state and 4.5% of unknown results. These results indicate that there are no differences in mortality and morbidity totally attributable to anesthesia among anesthetic methods in 1999 at Certificated Training Hospitals of Japan Society of Anesthesiologists.

[Perioperative mortality and morbidity in 1999 with a special reference to age in 466 certified training hospitals of Japanese Society of Anesthesiologists--report of Committee on Operating Room Safety of Japanese Society of Anesthesiologists].

Perioperative mortality and morbidity in Japan from Jan. 1 to Dec. 31, were studied retrospectively. Committee on Operating Room Safety of Japanese Society of Anesthesiologists (JSA) sent confidential questionnaires to 774 Certified Training Hospitals of JSA and received answers from 60.2% of the hospitals. We analyzed their answers with a special reference to the age group. The total number of anesthetics available for this analysis was 732,788. All cases were divided in to 7 groups; group A(< 1 months), group B(< 12 months), group C(< 5 years), group D(< 18 years), group E (< 65 years), group F(< 85 years), and group G(> 85 years). The incidences of all critical events including cardiac arrest, severe hypotension, and severe hypoxemia were 168.14, 47.86, 24.63, 14.65, 28.43, 50.4, and 43.68 per 10,000 in patients with group A, B, C, D, E, F, and G, respectively. The overall mortality rate (death during anesthesia and within 7th postoperative day) were 74.10, 6.63, 3.30, 3.07, 4.82, 13.74, and 11.84 per 10,000 anesthetics in patients with group A, B, C, D, E, F, and G, respectively. The incidences of cardiac arrest were 54.15, 8.84, 5.08, 2.56, 4.84, 11.02, and 6.66 per 10,000 in patients with group A, B, C, D, E, F, and G, respectively. The mortality rates after cardiac arrest were 42.75, 2.95, 2.54, 1.70, 2.00, 6.56, and 5.18 in patients with group A, B, C, D, E, F, and G, respectively. The incidences of all critical events, the incidence of cardiac arrest, and the overall mortality rate were much higher in group A than other groups and lower in group D. Mortality and morbidity due to all kinds of causes including anesthetic management, intraoperative events, co-existing diseases, and operation were as follows. The incidence of all critical events attributable to co-existing disease were the highest in these four groups, and 94.04, 15.46, 7.87, 6.13, 7.26, 17.38, and 16.29 per 10,000 in patients with group A, B, C, D, E, F, and G, respectively. The incidences of all critical events attributable to anesthetic management were 31.35, 16.94, 4.60, 6.09, 10.77, and 14.07 per 10,000 in patients with group A, B, C, D, E, F, and G, respectively. The incidence of cardiac arrest in group A was much more attributable to co-existing disease and operation than other causes. The incidences of cardiac arrest attributable to anesthetic management were 0.00, 1.47, 0.25, 0.34, 0.83, 0.92, and 0.22 per 10,000 in patients with group A, B, C, D, E, F, and G, respectively. The mortality rates in these groups were 0.00, 0.00, 0.00, 0.17, 0.07, 0.05, and 1.48, and no death was found in cases under 5 years of age. The two cases of death in G group were due to too high anesthesia levels in spinal anesthesia. Other causes including overdose of anesthetics, toxic effect of local anesthetic, improper management of airway, and incompatible blood transfusion were preventable with the anesthesiologists' effort in protocol development and skilled assistance.

[Perioperative mortality and morbidity for the year of 1999 in 466 Japanese Certified Anesthesia-training Hospitals: with special reference to ASA-physical status--report of Committee on Operating Room Safety of Japan Society of Anesthesiologists].

Perioperative mortality and morbidity in Japan for the year 1999 were studied retrospectively. Committee on Operating Room Safety of the Japan Society of Anesthesiologists (JSA) sent confidential questionnaires to 774 Certified Training Hospitals of JSA and received answers from 60.2% of the hospitals. We analyzed their answers with special reference to ASA physical status (ASA-PS). The total number of anesthetics analyzed was 655, 644. Mortality and morbidity due to all kinds of causes including anesthetic management, intraoperative events, co-existing diseases, and operation were as follows. The incidence of cardiac arrest (per 10,000 anesthetics) was 0.68, 3.76, 14.37, 67.03, 0.36, 4.68, 27.96, 206.30 in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. The incidences of critical events including cardiac arrest, severe hypotension, and severe hypoxemia were 8.93, 26.99, 71.30, 188.52, 8.68, 31.27, 136.16, and 790.92 in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. The mortality rates (death during anesthesia and within 7th postoperative day) after cardiac arrest were 0.16, 0.94, 5.71, 33.51, 0.00, 1.46, 16.41 and 167.76 per 10,000 anesthetics in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. The overall mortality rates were 0.24, 1.66, 12.16, 67.03, 0.00, 3.51, 34.65 and 417.14 in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. Overall mortality and morbidity were higher in emergency anesthetics than in elective anesthetics. ASA-PS correlated well with overall mortality and with morbidity, regardless of etiology. The incidences of cardiac arrest totally attributable to anesthesia were 0.24, 0.45, 1.47, 8.38, 0.36, 1.75, 2.43 and 11.34 in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. The incidences of all critical events totally attributable to anesthesia were 4.92, 8.81, 14.74, 20.95, 4.34, 11.40, 15.80 and 22.67 in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. The mortality rates after cardiac arrest totally attributable to anesthesia were 0.00, 0.00, 0.61 and 4.53 in patients with ASA-PS of I-IV, I E-II E, III E, and IV E, respectively. The overall mortality rates totally attributable to anesthesia were 0.00, 0.04, 0.18, 0.00, 0.00, 0.61 and 4.53 in patients classified to ASA-PS of I, II, III, IV, I E-II E, III E, and IV E, respectively. Only one death, due to overdose of anesthetics, was reported among patients with good physical status (ASA-PS of I, II, II E and II E). Anesthetic management was mainly responsible for critical events in patients with good physical status, while co-existing diseases were in those with poor physical status. The major co-existing diseases or conditions leading to critical events were heart diseases in elective anesthetics, and hemorrhagic shock in emergency anesthetics. We reconfirmed that ASA-PS is beneficial to predict perioperative mortality and morbidity. It also seems likely that we should make much more efforts to reduce anesthetic morbidity in patients with good physical status, and to improve preanesthetic assessment and preparation of cardiovascular conditions in those with poor physical status.

[Perioperative mortality and morbidity for the year 1999 in 466 Japanese certified anesthesia-training hospitals: with special reference to operative regions--report of Committee on Operating Room Safety of Japanese Society of Anesthesiologists].

Perioperative mortality and morbidity in Japan for the year 1999 were analyzed retrospectively with special reference to operative regions. The total number of analyzed cases was 701,940. The percentages for each operative region were as follows, craniotomy 4.5%, thoracotomy 3.3%, heart and great-vessels 3.9%, thoracotomy with laparotomy 0.8%, laparotomy except caeserian-section 31.7%, ceserian-section 3.2%, head-neck and otolarynx 14.5%, chest-abdomen-perineum 11.1%, spine 3.5%, extremity including peripheral-vessel 16.5%, and others 6.9%. The incidence of serious events, including cardiac arrest and severe hypotension and hypoxemia suggesting impending cardiac arrest was 34.58 per 10,000 cases in all operative regions. The events were observed more frequently in heart and great-vessels 247.26, thoracotomy with laparotomy 128.91 and thoracotomy 61.55, and less frequently in chest-abdomen-perineum 13.52 and extremity including peripheral-vessel 16.99. Regarding the prognosis of events, the cases with no sequela were 69.9% in all operative regions. While there were fewer cases with no sequela in craniotomy 50.4%, thoracotomy with laparotomy 54.3% and heart and great-vessels 58.6%, there were more cases in head-neck and oto-larynx 95.2% and chest-abdomen-perineum 90.5%. The incidence of serious events totally attributable to anesthetic management was 7.79 per 10,000 cases in all operative regions. The events were observed more frequently in thoracotomy 12.82, heart and great-vessels 12.29 and spine 11.06, and less frequently in extremity including peripheral-vessel 5.17 and chest-abdomen-perineum 6.05. Regarding the prognosis of events, the cases with no sequela were 93.1% in all operative regions. There were fewer cases with no sequela in thoracotomy with laparotomy 80.0% and craniotomy 81.8%. The main cause of events in thoracotomy and spine was the inadequate airway management, and in heart and great-vessels was the overdose or miss-selection of drugs. Although the incidence of serious events totally attributable to anesthetic management was one fourth of all events, most of them resulted from human factors. Thus, the more efforts are necessary to improve the outcomes. While the total deaths from 701,940 cases, including death on the operation day or within 7 days after it, were 528 cases (7.52 per 10,000 cases), the deaths totally attributable to anesthesia were 7 cases (0.10 per 10,000 cases).

Impaired oxygen utilization during rapid cooling on cardiopulmonary bypass.

UNLABELLED: Little attention has been paid to oxygen demand/supply balance during the cooling phase of cardiopulmonary bypass (CPB). We examined the changes in systemic oxygen utilization caused by the initiation of deep hypothermic CPB. METHODS: We calculated the changes in systemic oxygen consumption (VO2) and its related parameters in 5 patients who underwent reconstruction of the aortic arch using deep hypothermic CPB. Rectal temperature was decreased to 18 centigrade on average. RESULTS: VO2 decreased immediately after the initiation of hypothermic CPB. VO2 decreased by an average of 50% and 64%, while rectal temperatures decreased from 35 to 34 and 32 centigrade, respectively. Hemoglobin-bound oxygen accounted for 68% of VO2 just before CPB and 28% after the rectal temperature decreased to 32 centigrade. This decrease in VO2 correlated with the maximum temperature gradient between the venous and the arterial blood during the cooling phase. The abrupt decrease in VO2 by initiating CPB was associated with an increase in mixed venous oxygen saturation and a decrease in oxygen extraction ratio. VO2 values during the cooling phase were much lower than those during the rewarming phase at any given rectal temperatures. VO2 values at rectal temperatures of 34 and 32 centigrade during the cooling phase of CPB were 40% and 29% of those during the rewarming phase of CPB, respectively. This difference was caused by the changes in VO2 derived from hemoglobin-bound oxygen, and VO2 derived from dissolved oxygen did not show any significant changes during the cooling and the rewarming phase. Hysteresis of VO2 was also observed as a function of the nasopharyngeal temperature. The arterial lactate concentration showed an insignificant but gradual increase during the cooling phase. CONCLUSION: These observations suggested that an immediate decrease in VO2 and the following low values of VO2 caused by the initiation of deep hypothermic CPB could not be simply due to a decrease in the metabolic rate for oxygen but rather due to disturbances in oxygen utilization, one of which seemed to be caused by the impaired oxygen release from hemoglobin. It was also suggested that an increase in mixed venous oxygen saturation by initiating hypothermic CPB did not necessarily indicate an adequate oxygen/demand supply balance.

[Safe levels of hemoglobin concentration in autologous blood transfusion].

It has been generally accepted that an adequate oxygen-carrying capacity can be achieved with a hemoglobin concentration of 7 g/dl, as far as the patient's intravascular volume is sufficient to allow tissue perfusion. To guarantee patient's safety in the operating theater, patient's oxygenation, ventilation, circulation and temperature, which enable oxygen utilization in tissues, should be monitored vigilantly and ensured strictly. This is also true when taking care of anemic patients outside the operating theater, because failure of these functions in anemic patients leads directly to tissue hypoxia. Besides the standard monitoring, measuring oxygen carrying capacity/consumption parameters and gastric/sigmoidal intramucosal pH have been shown to be helpful to estimate tissue oxygenation. Therefore, safe levels of hemoglobin concentration should be determined according to the ability of doctors and nursing staffs to evaluate and to maintain patient's systemic and tissue oxygenation as well as to the patient's pathophysiological conditions.