Safety and efficacy of oral rehydration therapy until 2 h before surgery: a multicenter randomized controlled trial.

PURPOSE: In many countries, patients are generally allowed to have clear fluids until 2-3 h before surgery. In Japan, long preoperative fasting is still common practice. To shorten the preoperative fasting period in Japan, we tested the safety and efficacy of oral rehydration therapy until 2 h before surgery. METHODS: Three hundred low-risk patients scheduled for morning surgery in six university-affiliated hospitals were randomly assigned to an oral rehydration solution (ORS) group or to a fasting group. Patients in the ORS group consumed up to 1,000 ml of ORS containing balanced glucose and electrolytes: 500 ml between 2100 the night before surgery and the time they woke up the next morning and 500 ml during the morning of surgery until 2 h before surgery. Patients in the fasting group started fasting at 2100 the night before surgery. Primary endpoints were gastric fluid volume and pH immediately after anesthesia induction. Several physiological measures of hydration and electrolytes including the fractional excretion of sodium (FENa) and the fractional excretion of urea nitrogen (FEUN) were also evaluated. RESULTS: Mean (SD) gastric fluid volume immediately after anesthesia induction was 15.1 (14.0) ml in the ORS group and 17.5 (23.2) ml in the fasting group (P = 0.30). The mean difference between the ORS group and fasting group was -2.5 ml. The 95% confidence interval ranged from -7.1 to +2.2 ml and did not include the noninferior limit of +8 ml. Mean (SD) gastric fluid pH was 2.1 (1.9) in the ORS group and 2.2 (2.0) in the fasting group (P = 0.59). In the ORS group, mean FENa and FEUN immediately after anesthesia induction were both significantly greater than those in the fasting group (P < 0.001 for both variables). The ORS group reported they had been less thirsty and hungry before surgery (P < 0.001, 0.01). CONCLUSIONS: Oral rehydration therapy until 2 h before surgery is safe and feasible in the low-risk Japanese surgical population. Physicians are encouraged to use this practice to maintain the amount of water in the body and electrolytes and to improve the patient's comfort.

[Nasotracheal intubation using a fiberscope with a 32Fr blue line endobroncheal tube in a patient with micrognathism].

A 61-year-old woman with pulmonary lymphangioleiomyomatosis was scheduled for video-assisted thoracoscopic surgery for partial resection of the lung. The patient had micrognathism and a recent history of difficult airway management [difficult mask ventilation and intubation (Cormak grade III)]. On induction, mask ventilation was accomplished with the use of nasal airway. We initially inserted Airtraq laryngoscope and gained a view of Cormak grade III. Therefore, a 32 Fr left-sided Blue Line endobroncheal tube was nasotracheally intubated using a fiberscope (3.1-mm diameter). Nasotracheal intubation with a 32F Blue Line endobroncheal tube can be a choice for patients with difficult airway when one lung ventilation is required.

[A phase II clinical study of once-a-day fentanyl citrate patch in patients with cancer pain--switching from once-every-three-days fentanyl patch to once-a-day fentanyl citrate patch].

We examined the efficacy and safety of a new transdermal fentanyl citrate patch (HFT-290), which was applied once daily in patients with cancer pain who were receiving a stable dose of once-every-three-day application transdermal fentanyl patch [TDF (72 hr)]. After TDF (72 hr) was applied for three days at the same dose used before starting the study, treatment was switched to HFT-290 (once daily) for 9 days. The analgesic effect was judged with a 5-point scale based on each patient's assessment of pain on a 100-mm visual analog scale (VAS). Seventy-eight patients were enrolled. The efficacy rate (95% confidence interval) of the analgesic effect at the time of final removal of HFT-290 (the primary efficacy end-point) was high at 83.9% (71.7-92.4%; 47/56 patients). Furthermore, based on the shift of the VAS, good pain control was achieved after switching. All adverse drug reactions were either mild or moderate, and the main reactions were those commonly observed with opioid analgesics. No respiratory depression was observed. HFT-290 demonstrated good tolerability after switching from TDF (72 hr) and provided stable pain control.

Impact of fresh-frozen plasma from male-only donors versus mixed-sex donors on postoperative respiratory function in surgical patients: a prospective case-controlled study.

BACKGROUND: To reduce the risk of transfusion-related acute lung injury (TRALI), plasma products are mainly made from male donors in some countries because of the lower possibility of alloimmunization; other countries are considering this policy. The advantage of male-only fresh-frozen plasma (FFP) should be examined in a prospective case-control study. STUDY DESIGN AND METHODS: This study compared pulmonary function after the transfusion of FFP derived from either male donors only (FFP-male) or mixed donors (FFP-mixed) in informed surgical patients treated at a tertiary university hospital in Japan. The factors contributing to pulmonary distress (PD) after transfusion were then statistically examined. RESULTS: Eighty-two patients participated in this study (FFP-male, n = 55; FFP-mixed, n = 27). Nineteen patients developed PD (PaO(2)/FiO(2) ratio [P/F] < 300) within 6 hours after transfusion: seven had congestive pulmonary edema (transfusion-associated circulatory overload), five had permeability pulmonary edema (possible TRALI), and seven had no apparent pulmonary edema. A multivariate logistic regression analysis revealed that the use of cardiopulmonary bypass and preoperative liver dysfunction were significantly associated with a P/F of less than 300 (odds ratios [ORs], 8.95 [p = 0.004] and 6.54 [p = 0.005], respectively), while the use of FFP-male was significantly associated with the absence of PD (OR, 0.219; p = 0.022). All the patients with possible TRALI had received either white blood cell or granulocyte antibody-positive FFP. The lysophosphatidylcholine level was not correlated with PD. CONCLUSIONS: Our data suggests that the use of FFP derived from male donors may be advantageous for posttransfusion pulmonary function, although PD is also determined by background characteristics.

[Case of thyroid crisis with persistent tachycardia diagnosed postoperatively].

A 35-year-old man with multiple bone fractures underwent an emergency operation. On arriving at the operating room, his heart rate was 160 beats x min(-1), and blood pressure was 100/50 mmHg. We anesthetized him with oxygen, sevoflurane, fentanyl and remifentanil. We suspected hypovolemia, and treated him with crystalloid and transfused red cells and fresh frozen plasma so that heart rate and blood pressure could be stabilized. Tachycardia of 140 beats x min(-1) persisted, and landiolol was continuously administered at a rate of 5-10 mg x hr(-1) after a 2.5 mg bolus injection. Heart rate became controlled around 120 beats x min(-1) without hypotension during anesthesia. Finally, we noticed thyroid crisis in this case, and diagnosed it with laboratory data after operation. We should be aware that atypical tachycardia is caused by thyroid crisis.

Ca(2+) buffering capacity of mitochondria after oxygen-glucose deprivation in hippocampal neurons.

In an earlier study, we showed that mitochondria hyperpolarized after short periods of oxygen-glucose deprivation (OGD), and this response appeared to be associated with subsequent apoptosis or survival. Here, we demonstrated that hyperpolarization following short periods of OGD (30 min; 30OGD group) increased the cytosolic Ca(2+) ([Ca(2+)](c)) buffering capacity in mitochondria. After graded OGD (0 min (control), 30 min, 120 min), rat cultured hippocampal neurons were exposed to glutamate, evoking Ca(2+)influx. The [Ca(2+)](c) level increased sharply, followed by a rapid increase in mitochondrial Ca(2+) [Ca(2+)](m). The increase in the [Ca(2+)](m) level accompanied a reduction in the [Ca(2+)](c) level. After reaching a peak, the [Ca(2+)](c) level decreased more rapidly in the 30OGD group than in the control group. This buffering reaction was pronounced in the 30OGD group, but not in the 120OGD group. The enhanced buffering capacity of the mitochondria may be linked to preconditioning after short-term ischemic episodes.

Calcium loading capacity and morphological changes in mitochondria in an ischemic preconditioned model.

The concept of the mitochondrial permeability transition (mPT) has been used to explain cell death induced by calcium deregulation, which is in turn induced by a disruption in the mitochondrial loading capacity of cytosolic calcium (CLC). Whether mitochondria have specific morphologies representing the CLC and the mPT remains controversial. We examined ultrastructural changes in the mitochondria of cultured hippocampal neurons preconditioned with oxygen-glucose deprivation (OGD) for 30 min (30OGD) or 120 min (120OGD). The CLC was then evaluated using simultaneous imaging of the mitochondrial and plasma Ca++ concentrations after the induction of Ca++ influx by the application of glutamate. In the 30OGD group, the CLC increased as the mitochondria rapidly reacted to the increase in plasma Ca++, which was soon cleared. In the 120OGD group, however, the CLC was disturbed because the mitochondrial uptake of Ca was blunted, and the plasma Ca++ was not cleared after glutamate application. We classified the specific morphological changes in the mitochondria according to a previously reported classification. Rounded mitochondria with scarce interior content were observed in the 120OGD group, a model of prolonged lethal OGD, and disruptions in the mitochondrial outer membrane were frequently confirmed, suggesting mPT. The 30OGD group, a model of enhanced CLC in preconditioned neurons, was characterized by round mitochondria with condensed matrices. After glutamate application, the mitochondria became even more rounded with expanded matrices, and outer membrane disruptions were occasionally seen. Our observations suggest that subpopulations of mitochondria with specific morphologies are linked to the CLC and mPT.

[Questionnaire survey of anesthesiologists' opinion regarding the Japanese guidelines for transfusion].

BACKGROUND: Anesthesiologists' opinions regarding the Japanese guidelines for transfusion were surveyed. METHODS: From December 28, 2004 to January 28, 2005 a questionnaire survey was performed in 958 hospitals registered with the Japanese Society for Anesthesiologists. Queries regarding the guidelines for packed red cells, fresh frozen plasma, platelet concentrates, autologous blood transfusions, and other miscellaneous subjects were sent to these hospitals. RESULTS: A total of 537 hospitals (56.1%) responded to the survey. The guidelines for packed red cells were complied with and widely accepted. The trigger value of hemoglobin concentration was 7-9 g x dl(-1). Although 54.4% of the anesthesiologists used the coagulation disorder as the triggering factor for transfusion of fresh frozen plasma, only 19.6% of the hospitals monitored coagulopathy. In most hospitals, the trigger value of hemorrhage for use of fresh frozen plasma was the bleeding amount of less than 3000 ml, which is less than 70% of the recommended triggering value (bleeding exceeding 100% of circulating blood volume). The guideline for platelet concentrate transfusions for elective surgery was somewhat accepted (77.1%), but the triggering value; 3 x 10(4) x l(-1) for cardiopulmonary bypass surgery was considered too strict (41.4%). CONCLUSIONS: These guidelines for transfusions appear to be widely accepted. The most dominant complaint was the inadequacy of the guidelines for rapid massive bleeding.

[Randomized, multicenter study of interaction between Org 9426 (rocuronium bromide) and anesthetic agents in Japanese population].

BACKGROUND: The purpose of this randomized, multi-center phase III trial was to investigate the influence of sevoflurane and propofol on the neuromuscular blocking effects and pharmacokinetic parameters of Org 9426 (rocuronium bromide) in Japanese population. METHODS: Thirty-nine adult Japanese patients participated in this randomized, multi-center study. Neuromuscular function was monitored continuously with TOF-Watch SX (Organon NV, Netherlands) after anesthetic induction with propofol. These subjects randomly received either 0.6 mg x kg(-1) or 0.9 mg x kg(-1) of rocuronium for endotracheal intubation. These two groups were further divided to two anesthetic regiments : sevoflurane group and propofol group. The difference in onset and recovery of rocuronium-induced neuromuscular block was statistically analyzed with two-way ANOVA. RESULTS: Mean duration for maximal block was 76 seconds and 66 seconds, respectively. The duration between Org 9426 administration and 25% recovery of first twitch response was significantly prolonged in patients given 0.9 mg x kg(-1) of Org 9426. Sevoflurane also significantly increased this duration. However, the serum concentration of Org 9426 was not statistically different between the four study groups. CONCLUSIONS: The duration of Org 9426-induced neuromuscular blockade was significantly increased under sevoflurane anesthesia compared to propofol anesthesia. This difference may be attributed to pharmacodynamic change.

Perioperative circulating blood volume analysis in management of a 13-year-old female patient with an extraadrenal pheochromocytoma and refractory ventricular tachycardia: a case report.

This report describes the use of discrete real-time monitoring of blood volume (BV) and cardiac index (CI) by a dye densitography analyzer before, during, and after removal of a pheochromocytoma. The BV expanded by about 1.1 L and CI increased by about 2.2-fold after the tumor was removed. In lieu of a rapid catecholamine determination, the hemodynamic data were used to choose a supplemental catecholamine to stabilize the patient during and after the protracted surgery. This case demonstrates the importance of hemodynamic monitoring (BV and CI) to predict or detect cardiac and other complications, particularly in young patients with catecholamine-secreting tumors.

Neuroprotective effect of propofol on necrosis and apoptosis following oxygen-glucose deprivation--relationship between mitochondrial membrane potential and mode of death.

Mitochondrial membrane potential (MMP) appears to play an important role in apoptotic cascade and has been proposed as an index for apoptosis or necrosis. We examined the neuroprotective effect of propofol on mode of death, focusing on MMP. Hippocampal cell culture was divided into three groups: control, oxygen-glucose deprivation for 30 min (30OGD), 90 min (90OGD). Propofol was added to each culture group at a concentration of 0 microM (Vehicle), 0.1 microM (Pro0.1) or 1.0 microM (Pro1.0). MMP was expressed as normalized JC-1 fluorescence. ATP content was assayed using the luciferin-luciferase reaction. Neuronal viability and appearance of apoptosis were also assessed. ATP content was decreased after OGD (0.276 +/- 0.115 microM/microg (control), 0.172 +/- 0.125 microM/microg (30OGD) and 0.096 +/- 0.092 microM/microg (90OGD)). Propofol did not alter ATP content. MMP was hyperpolarized after 30OGD (1.26 +/- 0.23 (vehicle), 1.29 +/- 0.13 (Pro0.1) and 1.18 +/- 0.06 (Pro1.0)) but was depolarized after 90OGD (0.77 +/- 0.04 (vehicle), 0.89 +/- 0.04 (Pro0.1), but Pro1.0 prevented depolarization (1.03 +/- 0.15 (P < 0.05)). Viability of cells significantly decreased to 50.3 +/- 5.7% (vehicle), 46.1 +/- 7.5% (Pro0.1), but Pro1.0 significantly salvaged neurons 65.1 +/- 6.2% (higher than vehicle and Pro0.1 value, P < 0.05) after 90OGD. At 24 h after OGD, TUNEL-positive cells were increased to 34.5 +/- 6.2% (vehicle), 26.7 +/- 7.9% (Pro0.1) and 30.4 +/- 7.1% (Pro1.0) in the 30OGD group. No pharmacological effect of propofol on the incidence of apoptosis was found. Propofol inhibited acute neuronal death accompanied with the maintenance of MMP but did not prevent subsequent apoptosis. Propofol induces a moratorium on neuronal death, during which pharmacological intervention might be able to prevent cell death.

[Neuromuscular blocking effects, pharmacokinetics and safety of Org 9426 (rocuronium bromide) in Japanese patients].

BACKGROUND: The purpose of this study was to examine pharmacodynamics, pharmacokinetics and safety of Org 9426 (rocuronium bromide) in Japanese patients. METHODS: Seventy-eight patients anesthetized with thiopental, droperidol, fentanyl and nitrous oxide, were randomized to receive either a single dose of Org 9426 0.3 mg x kg(-1), 0.6 mg x kg(-1) or 0.9 mg x kg(-1). Contraction of the adductor pollicis to the ulnar nerve stimulation (0.1 Hz) was measured by acceleromyography. Blood was sampled over 6 hr and pharmacokinetic variables were calculated by plasma concentrations of Org 9426. RESULTS: Onset times for patients receiving 0.3 mg x kg(-1), 0.6 mg x kg(-1) or 0.9 mg x kg(-1) were 271.5 s, 140.0s and 125.4s, respectively. There was a dose-dependent increase in clinical durations until 25% recovery of twitch height (17.4 min in 0.3 mg x kg(-1) group, 37.2 min in 0.6 mg x kg(-1) and 60.4 min in 0.9 mg x kg(-1) group). Pharmacokinetic study revealed that elimination half life, steady state volume of distribution and plasma clearance of Org 9426 were 48-76 min, 146-181 ml x kg(-1), and 3.8-4.5 ml x min(-1) x kg(-1), respectively. No adverse effects were found except a case of local erythema on a forearm. CONCLUSIONS: The efficacy of neuromuscular block, stable pharmacokinetic behavior and excellent safety of Org 9426 were also confirmed in Japanese surgical patients.

[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.

[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.

[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.

Comparison of antagonizing potencies of dodecane analogues to isoflurane in goldfish.

PURPOSE: We reported previously that long-chain fatty acids (carbon atoms > or =12) antagonize volatile anesthetics in goldfish. To examine the contribution of the carboxyl group to the antagonizing potency of fatty acids in vivo, we compared antagonizing potencies to isoflurane in goldfish among terminally substituted dodecane analogues. METHODS: Dodecane (carbon atoms = 12) analogues [fatty acid (DoAC), alcohol (DoAL), alkane (DoAK), sulfate (DoSF), trimethylammonium (DoTA)] were examined. We determined the EC50 (the anesthetic concentration producing a 50% effect) values of isoflurane in the absence or presence of these chemical compounds in goldfish by observing the escape reaction of goldfish from an electrical stimulus. RESULTS: DoAC at higher than 10 microM and DoAL at higher than 20 microM increased the EC50 values of isoflurane in a concentration-dependent manner compared with the control (P < 0.05). DoAC at 50 microM and DoAL at 100 microM increased the EC50 1.7- and 1.6 fold, respectively. DoAK, DoSF, and DoTA showed no significant differences from the control. In the comparison of DoAC and DoAL at the same concentration, DoAC was more effective than DoAL (P < 0.001). CONCLUSION: DoAC and DoAL showed antagonizing potencies to isoflurane, whereas DoAK, DoSF, and DoTA had no effect. DoAC was more effective than DoAL. The findings suggest that polarity of the chemical compounds may be necessary to exert antagonizing potency to isoflurane. Furthermore, a highly negative charge density of the carboxyl group may be responsible for the effective antagonization of DoAC to isoflurane.

[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.

Antagonizing potencies of saturated and unsaturated long-chain free fatty acids to isoflurane in goldfish.

PURPOSE: We have previously reported that myristate, a saturated free fatty acid (FFA) with 14 carbons (C14), antagonizes volatile anesthetics in goldfish. The hydrophobicity and molecular configuration of FFAs may play an important role in the antagonizing effect. To examine their contribution, we investigated the antagonizing potencies of saturated and unsaturated long-chain FFAs in goldfish. METHODS: Saturated and monounsaturated FFAs of C14-18 were tested. We determined the anesthetic concentration producing a 50% effect (EC50) of isoflurane in the absence or presence of FFA by observing the escape reaction of goldfish against an electrical stimulus. RESULTS: All FFAs increased the EC50 of isoflurane dose-dependently compared with reactions in the absence of FFA ( P < 0.05). For saturated FFAs, the relationship between chain lengths and antagonizing potencies was not linear. C18 was the most effective and C16 was the least effective antagonist ( P < 0.05). Among unsaturated FFAs, C14 was the most effective antagonist ( P < 0.05). In a comparison of saturated and unsaturated FFAs, saturated C14 and C18 were more effective antagonists than unsaturated FFAs of the same carbon numbers ( P <<0.05). CONCLUSION: The hydrophobicity of FFAs increases as the chain length increases. Therefore, our findings suggest that the antagonizing effect of long-chain FFAs in goldfish, in terms of their capacity to perturb the lipid membrane structure, may be determined not solely by their hydrophobicity but also by their molecular configuration.

[Incidence and characteristics of perioperative pulmonary thromboembolism in Japan].

BACKGROUND: Perioperative pulmonary thromboembolism (preoperative PTE) is widely recognized as one of the life-threatening perioperative complications in Japan. However, incidence of perioperative PTE is not well surveyed. The Japanese Society of Anesthesiologist (JSA) mailed the questionnaire about incidence of perioperative PTE and its characteristics to the institutions registered in JSA. METHODS: The questionnaire was mailed to 844 institutions. The items of the survey included age, sex, type of surgery and risk factors of the cases performed in 2002. Data were analyzed using chi-square test and Fisher's test, and P < 0.05 was taken as significant. RESULTS: Four-hundred sixty-seven out of 844 institutions responded (55.3%) effectively. There were 369 cases of perioperative PTE in 208 institutions (44.5% of the institutions responded). The incidence of perioperative PTE was 4.4 per ten thousand cases. Massive PTE or cardiac arrest at the onset occurred in 57 cases (15.4%). Out of these patients, 117 patients (31.7%) had obesity, and bed-ridden rest (> 4 days) patients and cancer patients were each 105 (28.5%). Sixty-six patients died from perioperative PTE, out of which 5 patients (7.5%) died during operation, 31 patients (47.0%) died within 7 days after the operation, and 30 patients (45.5%) died 8 days after the operation. The commonest type of surgery among mortality cases was abdominal surgery (20 cases: 30.3%), and the commonest risk factor was being bedridden (34.5 cases: 51.5%). The patients who had developed PTE during surgery counted 64, among whom the major type of operation was lower limb/pelvic surgery (36 cases: 56.3%). Major risk factors were being bed-ridden in 25 cases (39.1%) and lower limb/pelvic fracture in 25 cases (39.1%). Despite having dangerous risk factors, 128 patients (57.7%) received the measures not recommended or did not receive any preventive measure for PTE. CONCLUSIONS: This survey revealed that the incidence of perioperative PTE in Japan is considerable. On the ground that most PTE could be prevented, it is suggested that by employing preventive measures for PTE, the incidence of perioperative PTE will decrease.

[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.