[Efficacy and safety of sugammadex (Org 25969) in reversing deep neuromuscular block induced by rocuronium or vecuronium in Japanese patients].

BACKGROUND: Efficacy and safety of sugammadex in reversing neuromuscular block induced by rocuronium or vecuronium were investgated in Japanese patients. METHODS: We studied 99 Japanese patients undergoing surgery requiring general anesthesia. Patients were allocated randomly to receive intubation dose of rocuronium or vecuronium. During surgery, patients received additional dose of rocuronium or vecuronium for maintenance of deep block. At 1-2 PTC, 0.5-8.0 mg . kg-1 of sugammadex was administered. The neuromuscular block was monitored with acceleromyography using TOF stimuli. Sevoflurane was administered to all treatment groups after intubation. RESULTS: For the rocuronium-induced neuromuscular block, the mean recovery time of the T4/T1 ratio to 0.9 decreased from 66.9 min in the sugammadex 0.5 mg kg-1 group to 1.3 min in the sugammadex 8.0 mg kg-1 group. For the vecuronium-induced neuromuscular block it decreased from 79.5 min in the sugammadex 0.5 mg . kg-1 group to 2.9 min in the sugammadex 8.0 mg . kg-1 group. No clinical evidence of recurarization or residual curarization was observed. CONCLUSIONS: The efficacy and safety of sugammadex were confirmed in Japanese surgical patients for reversal from deep block.

Anesthesia for pancreatoduodenectomy in a patient with history of coronary artery bypass graft surgery: determination of optimal surgical management by the graft clamping test.

We report a case of a 72-year-old man undergoing pancreatoduodenectomy, who had a history of coronary artery bypass graft surgery using the right gastroepiploic artery. We intraoperatively used the graft clamping test, which was assessed via electrocardiography and transesophageal echocardiography, to verify patency of the right gastroepiploic artery graft. Because the graft clamping test was positive, first, we interposed the saphenous vein graft between the splenic artery and right coronary artery. The abdominal surgery was then successfully performed without any cardiac complications. In such a complicated case, anesthesiologists who are responsible for assessment of the graft clamping test play a crucial role in determining the optimal surgical procedure.

[Nationwide questionnaire survey on anesthesiology in undergraduate medical education in Japan].

BACKGROUND: Since the establishment of Model Core-Curriculum for Medical Education in 2001, undergraduate medical education has been progressively renovated in Japan. We conducted a questionnaire survey to investigate how this curriculum changed undergraduate anesthesiology education and how it affected our work load as the teaching staff of medical schools. METHODS: The questionnaire sent to 80 medical universities in Japan, consisted of 4 parts; (1) activity of institution and human resources, (2) lectures, (3) clerkship, and (4) future direction of the lectures and clerkship. RESULTS: The response rate was 59%. The number of staff engaged in undergraduate education was variable; ranging from 4 to 28. The number of lectures was 0 to more than 25 units per year and 6 institutions discontinued conventional didactic lectures. Although clinical clerkship program was being offered to students in most institutions, informed consent for clinical procedures by the students was obtained only in 11 of 47 institutions. CONCLUSIONS: The result shows that there is still room for improvement in educational environment, including manpower or curriculum. A written informed consent should be completed to provide patients' safety and to fulfill the clinical practice by medical students.

Effects of sivelestat, a new elastase inhibitor, on IL-8 and MCP-1 production from stimulated human alveolar epithelial type II cells.

PURPOSE: The alveolar epithelial cell type II (AEC-II) is itself able to amplify lung inflammation by producing inflammatory cytokines and chemokines, leading to the activation and recruitment of phagocytes. Sivelestat, a new neutrophil elastase inhibitor, has been shown to attenuate acute lung injury in animal experiments. In the current study, we assessed the effects of sivelestat on the production of chemokines from cultured A549 cells, a human AEC-II-like cell line. METHODS: A549 cells were stimulated with endotoxin or tumor necrosis factor-alpha in the presence of sivelestat (1-100 microg x ml(-1)). Culture supernatant levels of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) were determined by enzyme-linked immunosorbent assay. The expression of IL-8 and MCP-1 mRNAs in stimulated A549 cells in the presence of sivelestat (100 microg x ml(-1)) was quantified by real-time polymerase chain reaction. RESULTS: Sivelestat, at 100 microg x ml(-1) reduced the accumulation of IL-8 and MCP-1 in the culture medium. The high dose of sivelestat significantly inhibited the expression of IL-8 mRNA in A549 cells. The drug also decreased MCP-1 mRNA expression, although not significantly. CONCLUSION: These data suggest that a high dose of sivelestat regulates the production of IL-8 and MCP-1 in AEC-II.

Oral clonidine premedication reduces minimum alveolar concentration of sevoflurane for laryngeal mask airway insertion in children.

BACKGROUND: Sevoflurane is widely employed for inhalational induction in children. Clonidine deepens volatile anesthetics and reduces several types of MAC of sevoflurane. Laryngeal mask airway is a useful device for pediatric anesthesia. The aim of the current study was to determine whether oral clonidine premedication can reduce MAC of sevoflurane for an LMA insertion in children. METHODS: Fifty-six ASA physical status I patients (3-11 years) scheduled for general anesthesia were randomly divided into two groups of 28 patients each. One group (clonidine group) received clonidine 4 microg x kg(-1) approximately 100 min before anesthesia, and the other (control) group did not. Anesthesia was induced with sevoflurane. Each concentration of sevoflurane, at which an LMA insertion was attempted, was predetermined according to the modification of Dixon's up-and-down method with 0.25% as a step size and held constant for at least 20 min before the trial. All responses ('movement' or 'no movement') to an LMA insertion were assessed. RESULTS: Minimum alveolar concentration values of sevoflurane for an LMA insertion were lower in the clonidine group (1.31% +/- 0.18% [mean +/- sd]) than in the control group (2.00% +/- 0.16%). Logistic regression analysis revealed that sevoflurane EC95 values were 1.79% and 2.49% in the clonidine and control groups, respectively. CONCLUSIONS: Oral clonidine premedication reduced the MAC (EC50) and EC95 values of sevoflurane for LMA insertion by 38% and 28%, respectively.

[Critical events in the operating room among 1,440,776 patients with ASA PS 1 for elective surgery].

BACKGROUND: The Japanese Society of Anesthesiologists (JSA) survey of critical incidents in the operating room has shown that preoperative complications are the leading causes of critical incidents, and affect the occurrence, severity and outcome of critical incidents which are due to causes other than preoperative complications. Causes of critical events in the operating room were examind in patients for elective surgery with American Society of Anesthesiologists physical status (ASA PS) 1. METHODS: JSA has conducted annual surveys of critical incidents in the operating room by sending and collecting confidential questionnaires to all JSA Certified Training Hospitals. From 1999 to 2002, 3,855,384 anesthesia patients were registered. Among these, 1,440,776 patients with ASA PS 1 for elective surgery were analyzed. The causes of critical incidents were classified as follows: totally attributable to anesthetic management (AM), mainly to intraoperative pathological events (IP), to preoperative complications (PC), and to surgical management (SM). IP consists of coronary ischemia mainly due to coronary vasospasm, arrhythmias, pulmonary embolism, and other conditions. RESULTS: The incidences of cardiac arrest, critical incidents other than cardiac arrest and subsequent death were 9.86, 59.41 and 3.12 per 100,000 anesthesia cases, respectively. IP and SM were responsible for 36.6% and 34.5% of cardiac arrest, respectively. AM and SM were responsible for 46.7% and 26.8% of critical incidents other than cardiac arrest, respectively. SM, IP and AM were responsible for 66.7%, 22.2% and 4.4% of subsequent deaths (within 7 postoperative days), respectively. Coronary ischemia and pulmonary embolism were the main causes of death due to IP. The incidences of cardiac arrest and death totally attributable to AM were 1.87 and 0.14 per 100,000 anesthesia cases, respectively. Medication problems were responsible for 48.1% of arrests, while airway/ventilation problems were for 57.2% of critical incidents other than arrest. Human factors (SM combined with AM) were responsible for 53.5%, 73.5%, and 71.1% of cardiac arrest, critical incidents other than arrest and death, respectively. CONCLUSIONS: Even in elective patients with good physical status, non-lethal incidents were not rare, and lethal incidents were also reported. We should pay significant attention to the following findings, and take some measures to overcome these problems especially related to human factors. Firstly, SM badly harmed some operative patients. Secondly, coronary vasospasm and pulmonary embolism were the main causes of death due to IP. Thirdly, drug administration and airway/ventilation management were the major causes of critical incidents totally attributable to AM. Human factors were responsible for 70.6% of critical incidents and 71.1% of deaths.

[Anesthetic management for Cesarean section in a patient with left ventricular noncompaction].

Left ventricular noncompaction (LVNC) is a rare disease characterized by heart failure, arrhythmia, and embolic events. We report anesthetic management of a pregnant woman with LVNC. At 24 weeks gestation of the first pregnancy, the patient was scheduled for Cesarean section. Preoperatively the patient had symptomatic heart failure, and was anesthetized with propofol and fentanyl aiming at stable intraoperative hemodynamics. About 2 years later, the patient also underwent cesarean section under spinal anesthesia at 34 weeks gestation of the second pregnancy, because her cardiac function was almost normal and she was not receiving anticoagulant therapy. Both perioperative courses were uneventful. Careful preoperative assessment and close anesthetic planning are necessary.

[Critical incidents during regional anesthesia in Japanese Society of Anesthesiologists-Certified Training Hospitals: an analysis of responses to the annual survey conducted between 1999 and 2002 by the Japanese Society of Anesthesiologists].

BACKGROUND: Recently, a national survey in France including 35,439 patients who had received spinal anesthesia showed that the incidences of cardiac arrest and mortality associated with spinal anesthesia were 2.5 and 0.8 per 10,000 anesthetics, respectively. In this study, we investigated these values using data obtained from annual surveys conducted by the Japanese Society of Anesthesiologist (JSA). METHODS: Since 1994, JSA has conducted annual surveys concerning critical incidents in the operating theater by sending confidential questionnaires to JSA-certified training hospitals, then collecting and analyzing the responses. We investigated critical incidents associated with regional anesthesia using data from annual surveys between 1999 and 2002. The questionnaire was identical in each survey conducted during these years. The total number of anesthetics available for this analysis was 3,855,384, of which spinal anesthesia, combined spinal-epidural anesthesia and epidural anesthesia were performed in 409,338, 146,282, and 69,001 patients, respectively. In patients receiving regional anesthesia, 628 critical incidents including 108 cardiac arrests, and 45 subsequent deaths were reported. The causes of critical incidents were classified as follows: totally attributable to anesthetic management, due mainly to intraoperative pathological events, preoperative complications, and surgical management. IP consists of coronary ischemia including coronary vasospasm not suspected preoperatively, arrhythmias including severe bradycardia, pulmonary thromboembolism, and other conditions. Mortality was determined by postoperative day 7. Statistical analysis was performed by chi-square test and Mann-Whitney test. A p value less than 0.05 was considered significant. RESULTS: The incidences of cardiac arrest and mortality due to all etiologies were 1.69 and 0.76 with spinal anesthesia, 1.78 and 0.68 with combined spinal-epidural anesthesia, and 1.88 and 0.58/10,000 anesthetics with epidural anesthesia, respectively. The incidences of cardiac arrest and mortality due to anesthetic management were 0.54 and 0.02 with spinal anesthesia, 0.55 and 0.00 with combined spinal-epidural anesthesia, and 0.72 and 0.14/10,000 anesthetics with epidural anesthesia, respectively. These values did not significantly differ among regional anesthesia. Death attributable to anesthetic management was reported in 2 patients: both patients were classified as ASA-PS 3 E, and developed cardiac arrest; one due to inadvertent high spinal anesthesia with spinal anesthesia, and the other due to local anesthetic intoxication with epidural anesthesia. Anesthetic management and intraoperative pathological events comprised 33 and 43% of cardiac arrests, respectively. The distribution of causes of death was as follows: anesthetic management, 5%; intraoperative pathological events, 34%; preoperative complications, 35%; surgical management, 26%. Among the causes of anesthetic management-induced critical incidents, inadvertent high spinal anesthesia was the leading cause of cardiac arrest in spinal and combined spinalepidural anesthesia: 90% of arrests occurred in patients with ASA-PS 1+2; 88% in patients below 65 years of age; 45 and 25% in patients undergoing hip or lower extremities surgery, and cesarean section, respectively. Among the causes of intraoperative pathological event-induced critical incidents, pulmonary thromboembolism was the leading cause of cardiac arrest in spinal and combined spinal-epidural anesthesia: 59% of arrests occurred in patients with ASA-PS 1+2; 81% in patients above 66 years of age; 91% in patients undergoing hip or lower extremity surgery. CONCLUSIONS: The incidence of cardiac arrest and mortality associated with spinal anesthesia in Japan was shown to be in the same order as in France by analyzing a larger population. In patients with good ASA-PS, critical incidents occurred more often under regional anesthesia than under general anesthesia. Inadvertent high spinal anesthesia should be carefully avoided. We should also pay much attention to subclinical deep vein thrombosis in patients who were scheduled for hip or lower extremity surgery, and tourniquet- or bone cement-associated pulmonary embolism in these patients.

The efficacy of fluorocarbon, surfactant, and their combination for improving acute lung injury induced by intratracheal acidified infant formula.

We conducted the current study to compare the efficacy of partial liquid ventilation (PLV), pulmonary surfactant (PSF), and their combination in ameliorating the acidified infant-formula-induced acute lung injury (ALI). In the Part I study, 42 rabbits receiving volume-controlled ventilation with positive end-expiratory pressure 10 cm H(2)O were randomly divided into 6 groups (groups noninjuryI, gas ventilation [GVi], PLVi, PSFi, PLVi-->PSFi, and PSFi-->PLVi). ALI was induced by intratracheal acidified infant formula (2 mL/kg, pH 1.8). Group GVi received neither PLV nor PSF therapy. Groups PLV and PSF received intratracheal fluorocarbon 15 mL/kg or surfactant 100 mg/kg, respectively, 30 min after acidified infant formula. Groups PLVi-->PSFi and PSFi-->PLVi received both treatments at 30-min intervals. In Part II, 42 rabbits (in 6 groups) undergoing pressure-controlled ventilation received the same drug therapies as in Part I. The lungs were excised to assess biochemical and histological damage 150 min after induction of ALI. In Parts I and II, PSF, fluorocarbon, and their combination attenuated lung leukosequestration and edema and superoxide production of neutrophils, consequently improving oxygenation, lung mechanics, and pathological changes. Independent of ventilation mode, PSF followed by fluorocarbon provided the most beneficial effects and fluorocarbon followed by PSF produced the least efficacy.

[Supplemental survey in 2003 concerning life-threatening hemorrhagic events in the operating room].

BACKGROUND: We previously showed that pre-operative hemorrhagic shock and surgical hemorrhage were the major causes of life-threatening events in the operating room and subsequent fatality. We investigated the background of these events. METHODS: The Subcommittee on Surveillance of Anesthesia-Related Critical Incidents, Japanese Society of Anesthesiologist (JSA) sent confidential questionnaires to all JSA-certified training hospitals (n=862). The questionnaires were composed of two parts: one for examining all life-threatening events in the operating room and the other for examining the background of massive hemorrhage in the operating room. The number of patients registered between January 1, 2003 and December 31, 2003 was 1,367,790 from 782 hospitals. Life-threatening hemorrhagic events were reported in 1,011 patients, of whom 876 patients were available for further analysis of the background of the events. Fatality within 7 postoperative days following these events was 45.4%. RESULTS: In patients who developed life-threatening events due to hemorrhage, 35.2% had blood loss of more than 12 l x 60 kg(-1) of body weight, 44.9% had a maximal hemorrhagic speed of more than 240 ml x min(-1) x 60 kg(-1) of body weight, and 39.1% had a minimal hemoglobin concentration of less than 5 g x dl(-1). The main sources of hemorrhage were as follows: the abdominal aorta, 15.4%; the thoracic aorta, 14.0%; the liver, 12.6%; intra-cranium, 8.2%; the pelvic organs, 8.0%; celiac or mesenteric artery, 7.8%; the lung, 7.1%. Of patients who developed life-threatening events due to preoperative hemorrhagic shock, 18.3% underwent cardiac massage preoperatively, 50.0% lost consciousness, 58.5% were intubated, and 16.4% were retrospectively judged to have had no operative indications. Human factors also affected the life-threatening events due to preoperative hemorrhagic shock: delayed decision making concerning indications for surgical treatment, 15.6%; delayed admission to the operating room, 16.6%; delayed supply of blood products, 25.5%; problems in surgical management, 16.3%; problems in anesthetic management, 28.1%. These problems in anesthetic management included shortage of supportive anesthesiologists. This was partly explained by the time of their admission to the operating room: 67.0% of the patients admitted during the week end or at night. Of the patients who developed life-threatening events due to surgical hemorrhage, 58.0% were predicted preoperatively to develop massive hemorrhage by anesthesiologists, and 66.7% were informed of the risks of massive hemorrhage and associated complications. The main causes of surgical hemorrhage were as follows: adhesion or invasion, 44.7%; and problems in surgical judgments or techniques, 43.7%. Anesthetic management affected the development of life-threatening events in these patients: lack of infusion prior to hemorrhage, shortage of supportive anesthesiologists, delay in ordering additional blood products, delayed judgment to start blood transfusion, and shortage of rapid infusion/transfusion apparatus. Delay for hospitals in obtaining blood supply from blood banks was reported in 13.0% of cases, and delayed supply from inhospital blood transfusion service to the operating room in 16.0%. Despite massive hemorrhage, ABO cross-matching was omitted only in 13.4% of patients, and transfusion of ABO-compatible, instead of ABO-identical red blood cells, was performed only in 1.3%. CONCLUSIONS: To reduce life-threatening hemorrhagic events in the operating theater, reorganization of emergency medical service and blood supply, improvement of surgical techniques, improved triage of patients with hemorrhagic shock, flexible application of compatible blood products in emergency situations, and improvement of the quality and number of anesthesiologists should be considered.

Attenuation of acute lung injury with propofol in endotoxemia.

Endotoxin causes acute lung injury (ALI) through many mediators of inflammatory and immune responses. Propofol is an antiinflammatory and immunosuppressive drug. We conducted this study to evaluate whether propofol attenuates ALI associated with endotoxemia. Thirty-two anesthetized rabbits were randomly divided into four groups (n = 8 each). ALI was induced by IV endotoxin 5 mg/kg over 30 min in 3 groups. In 2 of the ALI groups, IV administration of propofol (2 or 5 mg/kg as a bolus followed by continuous infusion at 4 or 15 mg x kg(-1) x h(-1)) was started 15 min before endotoxin. The other ALI group received soybean-oil emulsion. The nonlung injury control group received infusion of both vehicles. The lungs were mechanically ventilated with 40% oxygen for 6 h after endotoxin. Hemodynamics did not differ among groups. The large dose of propofol attenuated lung leukosequestration, pulmonary edema (as assessed by lung wet/dry weight ratio), and pulmonary hyperpermeability (as assessed by albumin levels in bronchoalveolar lavage fluid) and resulted in better oxygenation, lung mechanics, and histological change. The small dose of propofol failed to do so. Our findings suggest that a large dose of propofol successfully mitigates physiological, biochemical, and histological deterioration in ALI in endotoxemia.

[Anesthetic management for a patient of myotonic dystrophy with pheochromocytoma].

We experienced an anesthetic management for a patient of myotonic dystrophy with pheochromocytoma. Much attention is required to manage myotonic dystrophy on surgical manipulation. This disease interacts with anesthetic drugs. It may cause prolongation of drug action used during anesthesia compared with the usual case. It also may cause dangerous interactions such as severe arrhythmia and malignant hyperthermia. That is why we were faced with serious limitation in choosing anesthetic and adjuvant drugs. At the same time, the case of pheochromocytoma must be handled with scrupulous care. Pheochromocytoma causes severe hypertension and sometimes tachycardia leading to intracranial hemorrhage or adrenaline-induced severe hypovolemia. Besides, laparoscopic operation was scheduled to resect the pheochromocytoma. This operation demanded the anesthetic management with artificial ventilation. It must be difficult to cope with these conditions by limited number of drugs. This time, we managed this case by epidural anesthesia with propofol and nitrous oxide without opioid and muscular relaxant. Though, this patient was not fully awake from anesthesia and could not take enough breaths on his own. We extended the period of spontaneous breathing with careful check whether the patient has resumed spontaneous breathing. It took us fourteen days till extubation.

Oral clonidine does not change ventilatory response to carbon dioxide in sevoflurane-anesthetized children.

BACKGROUND: Clonidine is a useful premedicant for pediatric anesthesia. The drug has potential for ventilatory depression. The aim of the current study was to determine the effects of clonidine premedication on the ventilatory response to hypercapnia during sevoflurane anesthesia using the carbon dioxide (CO(2)) steady state method. METHODS: Sixty children (3-13 yr) were assigned to receive clonidine 4 microg x kg(-1) or placebo. Anesthesia was maintained with spontaneous breathing and 2% sevoflurane. Minute ventilation (VE), respiratory rate (RR), endtidal CO(2) pressure (P(ECO(2)), and arterial hemoglobin oxygen saturation (SpO2) were measured with a facemask tightly fitted before and during 7% CO(2) inhalation. RESULTS: Compared with placebo, oral clonidine failed to reduce VE volume before CO(2) loading under general anesthesia with 2% sevoflurane. Inhalation of CO(2) increased VE. Oral clonidine did not attenuate the increase in VE induced by hypercapnic challenge under sevoflurane anesthesia. There were no differences in RR, P(ECO(2), or SpO2 between the placebo and clonidine groups before and during CO(2) loading. CONCLUSION: These data suggest that oral clonidine is a suitable premedication for sevoflurane anesthesia under spontaneous breathing conditions in children.

[Critical incidents due to drug administration error in the operating room: an analysis of 4,291,925 anesthetics over a 4 year period].

BACKGROUND: Wrong drugs, overdose of drugs, and incorrect administration route remain unsolved problems in anesthetic practice. We determined the incidence and outcome of drug administration error in the operating room of Japanese Society of Anesthesiologists Certified Training Hospitals. METHODS: Data were obtained from annual surveys conducted by Japanese Society of Anesthesiologists between 1999 and 2002. There were 4,291,925 cases of anesthetic delivery for this analysis. RESULTS: Incidence of critical incidents due to drug administration error was 18.27/100,000 anesthetics. Cardiac arrest occurred in 2.21 patients per 100,000 anesthetics. Causes of these critical incidents were as follows: overdose or selection error involving non-anesthetic drugs, 42.1%; overdose of anesthetics, 28.7%; inadvertent high spinal anesthesia, 17.9%; local anesthetic intoxication, 6.4%; ampule or syringe swap, 4.3%; blood mismatch, 0.6%. Incidence of death following these incidents was 0.44/100,000. Causes of death were as follows: overdose or selection error involving non-anesthetic drugs, 47.4%; overdose of anesthetics, 26.3%; inadvertent high spinal anesthesia, 15.8%; local anesthetic intoxication, 5.3%. Ampule or syringe swap did not lead to any fatalities. Death following inadvertent high spinal anesthesia and local anesthetic intoxication was reported only in patients who had developed cardiac arrest. It should be noted that 88 percent of ampule or syringe swap occurred in patients with American Society of Anesthesiologists-Physical Status 1 or 2, who did not seem to require complex anesthetic management. CONCLUSIONS: We should increase awareness that drug administration is generally performed with limited objective monitoring, although "To error is human". Increased vigilance is required to avoid drug administration error in the operating room. Additional anesthesia resident education, adequate supervision, and improved organization are necessary. Bar-coding technology might be useful in preventing drug administration error.

[Annual mortality and morbidity in operating rooms during 2002 and summary of morbidity and mortality between 1999 and 2002 in Japan: a brief review].

The Japanese Society of Anesthesiologists (JSA) conducts an annual survey of life-threatening events in operating rooms (OR) in JSA Certified Training Hospitals (JSACTH) by sending and collecting confidential questionnaires. Etiologies of the incidents were divided into four categories: those totally attributable to anesthetic management (AM), those resulting from preoperative complications (PC), those resulting from intraoperative pathological events (IP) and those related to surgical procedures (SP). IP resulted from coronary ischemia not suspected preoperatively, arrhythmias, pulmonary embolism, and other conditions. Outcomes were judged on the 7th post-operative day. In the year 2002, questionnaires were sent to 844 JSACTHs, and a total of 1,461,020 cases of anesthesia were documented from 773 JSACTHs. Of these, 1,277,045 cases of anesthesia from 712 JSACTHs were available for analysis. Seven hundred thirty nine cardiac arrests (5.79 per 10,000 anesthetics) and 806 deaths (6.31 per 10,000 anesthetics) due to life-threatening events in the OR were reported. The incidence of cardiac arrest and mortality totally attributable to AM was 0.38 and 0.11 per 10,000 anesthetics. These values tended to decrease after 1994, except the mortality totally attributable to AM, which were almost at constant level during recent years. The summary of the study between 1999 and 2002 was as follows. Among 3,855,384 anesthetics, 2,443 cardiac arrests (6.34 per 10,000 anesthetics) and 2,638 deaths (6.85 per 10,000 anesthetics) due to life-threatening events in the OR were reported. PC, SP, IP and AM were responsible for 64.7, 23.9, 9.4, and 1.5% of deaths, respectively. The major cause of PC related deaths was preoperative hemorrhagic shock, followed by cardiovascular diseases such as myocardial ischemia and congestive heart failure. Excessive surgical bleeding comprised 70.2% of SP-related deaths. The major causes of IP-related death were myocardial ischemia, pulmonary embolism, and severe arrhythmias. The incidence of cardiac arrest and death totally attributable to AM was 0.47 and 0.10/10,000 anesthetics, respectively. Among patients with ASA-PS 1(E) and 2(E), AM-related deaths occurred at a rate of 0.04/10,000 anesthetics. Half of AM-induced deaths were caused by airway or ventilatory problems. Other causes of AM-related death were medication accidents and infusion/transfusion accidents. Considerable effort is required to reduce intraoperative life-threatening events caused by human error, hemorrhage, and cardiovascular diseases.

Intratracheal application of recombinant surfactant protein-C surfactant to rabbits attenuates acute lung injury induced by intratracheal acidified infant formula.

UNLABELLED: Our aim in the current study was to determine whether recombinant surfactant protein-C (rSP-C) surfactant improves acute lung injury (ALI) induced by intratracheal acidified milk products. Twenty-eight rabbits were randomly divided into four groups. ALI was induced with intratracheal acidified infant formula (0.8 mL/kg, pH 1.8) in 3 groups. The control group received intratracheal acidified saline. Therapy groups received 1 of 2 doses of intratracheal rSP-C surfactant (0.5 or 2 SP-C mg/kg) 30 min after the acidified infant formula. The lungs were ventilated with 100% oxygen for 4 h after induction of ALI. Acidified infant formula dramatically reduced oxygenation and lung compliance, and increased resistance. Both doses of rSP-C improved the variables [mean PaO(2) (mm Hg) and compliance (mL/cm H(2)O) at 4 h: 61 and 0.4 for infant formula, 162 and 1.0 for small-dose rSP-C, and 152 and 1.2 for large-dose rSP-C, respectively; P < 0.05]. Pulmonary leukosequestration and edema, and severe morphological changes were attenuated by rSP-C treatment (ALI score: 14, 7, 7 in infant formula, small-dose rSP-C, and large-dose rSP-C; P < 0.05). The efficacy was similar for the two doses of rSP-C. These findings suggest that intratracheal administration of rSP-C ameliorates ALI induced by aspiration of acidified milk products. IMPLICATIONS: Small or large doses of recombinant surfactant protein-C surfactant given 30 min after intratracheal acidified infant formula attenuated physiological, biochemical, and morphological lung damage.

Efficacy of partial liquid ventilation in improving acute lung injury induced by intratracheal acidified infant formula: determination of optimal dose and positive end-expiratory pressure level.

OBJECTIVES: Partial liquid ventilation with fluorocarbon was successfully used for acute lung injury induced by oleic acid or lung lavage. Positive end-expiratory pressure (PEEP) during partial liquid ventilation enhances the efficacy of fluorocarbon. The aim of the current study was to assess whether partial liquid ventilation can repair lung damage induced by intratracheal acidified infant formula and to determine the optimal fluorocarbon dose and PEEP level. DESIGN: Prospective, randomized animal study. SETTING: University research laboratory. SETTING AND SUBJECTS: Seventy-six male anesthetized rabbits. INTERVENTIONS: For study 1, acute lung injury was induced by intratracheal acidified infant formula in four groups. Next, three groups received 10, 15, or 20 mL/kg fluorocarbon, and the fourth group was conventionally gas ventilated. For study 2, acute lung injury was induced in five groups. One group was gas ventilated at a PEEP of 5 cm H2O, whereas the other four groups received fluorocarbon (15 mL/kg) and were assigned to one of four PEEP levels (5, 7.5, 10, or 12.5 cm H2O). The lungs were ventilated with 100% oxygen for 4 hrs after acute lung injury. MEASUREMENTS AND MAIN RESULTS: In study 1, fluorocarbon at doses of 15 and 20 mL/kg attenuated lung leukosequestration and edema and superoxide production of neutrophils, resulting in similar improvements in oxygenation, lung mechanics, and pathologic changes. The highest fluorocarbon dose caused mortality from pneumothorax. In study 2, the combination of PEEP with partial liquid ventilation improved gas exchange, lung compliance, pulmonary edema, and histologically observed damage. The beneficial effects of PEEP at 10 and 12.5 cm H2O were similar. Adverse side effects of 12.5 cm H2O PEEP included pneumothorax and hemodynamic instability. CONCLUSIONS: The combination of fluorocarbon and PEEP improved the physiologic, biochemical, and histologic lung injury induced by acidified infant formula. The beneficial effects of partial liquid ventilation are due, in part, to inhibition of pulmonary neutrophil accumulation and activation with fluorocarbon. The optimal fluorocarbon dose and PEEP level in our model were 15 mL/kg and 10 cm H2O, respectively.

Reductive surgery plus percutaneous isolated hepatic perfusion for multiple advanced hepatocellular carcinoma.

OBJECTIVE: To evaluate the efficacy of a novel 2-stage treatment with reductive surgery plus percutaneous isolated hepatic perfusion (PIHP) for multiple hepatocellular carcinoma (HCC), which was previously unresectable. SUMMARY BACKGROUND DATA: Surgical resection is the treatment of choice for HCC, but the majority of patients with advanced HCC are not suitable candidates. PIHP is a minimally invasive surgery that allows high-dose regional chemotherapy of the liver, and our phase II studies have shown its profound efficacy for the local control of advanced HCC. METHODS: Twenty-five patients with multiple advanced HCC were enrolled in this prospective study. In the first stage, all patients underwent reductive hepatectomy: major hepatectomy in 13 patients and segmentectomy or less in 12. In 2 patients with subsegmentectomy, the retropancreatic and periportal metastatic lymph nodes were synchronously resected. Regardless of the type of hepatectomy, all patients routinely underwent cholecystectomy, and ligations of the right gastric artery and arterial collaterals of the remnant liver to increase the safety and efficacy of PIHP. In the second stage, PIHP with doxorubicin 60-120 mg/m2/treatment was planned for a period of 1 to 3 months after surgery. RESULTS: Of 25 enrolled patients, 22 successfully underwent PIHP an average of 1.8 times for the local control of residual liver tumors. In the remaining 3 patients, PIHP was abandoned because 2 had rapid disease progression and 1 had liver failure after surgery. In 22 patients with the 2-stage treatment, 19 (86%) had objective local tumor control (10 complete remissions and 9 partial responses with a median response duration of 16 months). The actuarial survival rate of all 25 patients was 42% at 5 years. CONCLUSIONS: Reductive surgery plus PIHP produced a strong antitumoral effect on multiple advanced HCC, when liver function allows this concentrated treatment approach, and offers long-term survival in a subset of patients who were previously deemed to have unresectable disease.

[Surgical volume and mortality due to intraoperative critical incidents at Japanese Society of Anesthesiologists certified training hospitals: an analysis of the annual survey in 2002].

BACKGROUND: We have previously showed that surgical volume affects mortality due to intraoperative critical incidents among patients undergoing cardiac surgery, the surgery with the highest risk, using data obtained by the annual survey in 2001 conducted by the Japanese Society of Anesthesiologists (JSA). In this study, we investigated whether surgical volume affects mortality due to intraoperative critical incidents independent of the surgical site. METHODS: We investigated this relationship using data obtained from the 2002 annual survey conducted by the Subcommittee on Surveillance of Anesthesia-related Critical Incidents, JSA. Between January 1, 2002 and December 31, 2002, 1,987,988 patients were registered from 704 training hospitals certified by the JSA. Intraoperative critical incidents occurred in 2,844 patients. Of these, 804 patients died within 7 postoperative days. The overall mortality was 4.61 per 10,000 anesthetics. Hospitals were divided into 5 groups according to their annual surgical cases: Group A, fewer than 1,000 (62 hospitals); Group B, 1,000-1,999 (204 hospitals); Group C, 2,000-3,999 (288 hospitals); Group D, 4,000-5,999 (110 hospitals); Group E, more than 6,000 (40 hospitals). Hospitals were also divided into 2 groups according to mortality: Group 1, under 20.00 per 10,000 anesthetics (672 hospitals); Group 2, equal to or higher than 20.00 per 10,000 anesthetics (32 hospitals). Total number of deaths in Group 2 was 158. Mortality was expressed as the mean (95% confidence interval). Statistical analysis was performed using chi-square test and Fisher test. A p value of <0.05 was considered significant. RESULTS: The mortality rates in Groups A-E were 14.89 (8.48-21.3), 3.86 (3.05-4.67), 3.88 (3.19-4.57), 4.04 (3.20-4.88), and 3.12 (2.19-4.05) per 10,000 anesthetics, respectively. Average surgical cases and mortality in Group 1 were 2,789 (2,775-3,002) and 3.24 (2.90-3.58), respectively, while those in Group 2 were 1,672 (1,243-2,101) and 22.18 (30.58-45.94), respectively. If all patients in Group 2 (n=53,509) had been treated in the hospitals of Group 1, 139-143 deaths might have been avoided. CONCLUSIONS: Surgical volume was shown to affect mortality independent of the surgical site. Hospitals with low surgical volume should pay significant attention to improving surgical outcomes. These results also suggest that centralization or regionalization should be discussed from the perspective of socio-economical problems as well as patient safety.

ONO-1714, a nitric oxide synthase inhibitor, attenuates endotoxin-induced acute lung injury in rabbits.

UNLABELLED: Overproduction of nitric oxide by inducible nitric oxide synthase (iNOS) expressed in the lung is thought to play a crucial role in the pathogenesis of endotoxin-induced acute lung injury (ALI). In this two-part study, we determined whether ONO-1714, a new selective iNOS inhibitor, attenuates endotoxin-induced ALI in rabbits. For Part I of the study, a control group received IV saline and ALI was induced by IV infusion of endotoxin 5 mg/kg over 30 min in 4 groups. Three groups received either 0.1, 0.03, or 0.01 mg/kg of ONO-1714 10 min before the start of endotoxin and the fourth group received saline. For Part II of the study, ALI was induced by endotoxin infusion in all 6 groups. One group was treated with saline. The other 5 groups received ONO-1714 0.1 mg/kg at various timings (10 min before or 1, 2, 3, or 4 h after ALI induction). The lungs were mechanically ventilated with 40% oxygen for 6 h after induction of ALI. In Part I, pretreatment with 0.1 mg/kg ONO-1714 mitigated endotoxin-induced ALI. In Part II, early posttreatment (within 2 h after the insult) with ONO-1714 was as effective as pretreatment in improving oxygenation, lung mechanics, lung leukosequestration, pulmonary edema, and histological change. However, lung damage was not improved in rabbits receiving the drug 3 or 4 h after endotoxin. These data suggest that the current study is a basis for future clinical trials to elucidate whether ONO-1714 can be a promising therapeutic approach in patients with acute respiratory distress syndrome induced by endotoxin/sepsis. IMPLICATIONS: An excess of nitric oxide is thought to play a crucial role in the pathogenesis of acute organ injury in endotoxemia. Early posttreatment with ONO-1714, a nitric oxide synthase inhibitor, attenuated physiological, biochemical, and pathological changes in endotoxin-induced acute lung injury in rabbits.