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BACKGROUND: Few studies (in other countries than the US) have reported on the efficacy and safety of dexmedetomidine for sedation of patients undergoing surgical or medical procedures under local anesthesia without intubation outside the intensive care unit. We performed a randomized, double-blind study in Japan. METHODS: Adult patients were randomly allocated to receive placebo, dexmedetomidine 0.5 μg/kg (DEX 0.5 group), or dexmedetomidine 1.0 μg/kg (DEX 1.0 group) over 10 min. Then, both dexmedetomidine groups received dexmedetomidine 0.2–0.7 μg/kg/h for maintaining an Observer’s Assessment of Alertness/Sedation Scale (OAA/S) score of ≤ 4; however, propofol was administered to rescue patients whose score exceeded this value. The primary endpoint was the percentage of patients who did not require rescue propofol to achieve and maintain an OAA/S score of ≤ 4. RESULTS: In total, 162 patients were included in the placebo (n = 53), DEX 0.5 (n = 53), and DEX 1.0 (n = 56) groups. Propofol was not required in significantly more patients in the dexmedetomidine 0.5 and 1.0 μg/kg groups (52.8% and 57.1%, respectively) compared with the placebo group (1.9%) (P < 0.001 for both). Common adverse events were protocol-defined hypotension, respiratory depression and bradycardia. The incidence of bradycardia was significantly higher in the DEX 0.5 (26.4%) and DEX 1.0 (30.4%) groups than in the placebo group (9.4%) (P = 0.041 and P = 0.008, respectively). CONCLUSION: We concluded that a loading dose of 0.5 or 1.0 μg/kg dexmedetomidine followed by infusion at a rate of 0.2–0.7 μg/kg/h provided effective and well-tolerated sedation in patients undergoing surgical or medical procedures under local anesthesia without intubation. Clinical trials.gov identifier: NCT01438931

Some patients experience severe chronic pain after intramedullary spinal cord tumor (IMSCT) resection, but the underlying mechanisms have yet to be fully elucidated. We aimed to investigate perioperative factors associated with chronic pain after IMSCT resection.We analyzed data from a postal survey and the medical records of patients who had undergone IMSCT resection in our institution between 2000 and 2008. Chronic pain was assessed using the Neuropathic Pain Symptom Inventory score, and its associations with factors related to tumor pathology, patient demographics, neurological findings, surgery, anesthesia, and perioperative management were determined.Seventy-eight consecutive patients (55 men and 23 women; age 17 to 79 y) were included in the statistical analysis of the present study. In univariate analyses, sex, body mass index, preoperative tumor-related pain, preoperative nonsteroidal anti-inflammatory drugs, intraoperative hypotension, postoperative corticosteroids, and decrease in Japanese Orthopaedic Association (JOA) scores were found to be associated with postsurgical chronic central pain. Logistic regression analysis identified 3 significant factors: a decline in JOA scores compared with preoperative values (odds ratio [OR], 3.33; 95% confidence interval [CI], 1.18-9.42; P=0.023), intraoperative hypotension (OR, 3.01; 95% CI, 1.02-8.97; P=0.047), and postoperative corticosteroids (OR, 3.21; 95% CI, 1.02-10.09; P=0.046).Decline in JOA score, intraoperative hypotension, and postoperative corticosteroids are independently associated with postsurgical chronic central pain. Intraoperative hypotension and the use of postoperative corticosteroids can be avoided or modified during perioperative management. As results from animal studies have indicated that the administration of corticosteroids may intensify chronic pain, further studies in larger cohorts are required to definitively determine the effect of corticosteroids on postsurgical central pain.

This trial was conducted to confirm the non-inferiority of remimazolam versus propofol in the induction and maintenance of general anesthesia in surgical patients. Surgical patients (n = 375) were randomized to remimazolam started at 6 or 12 mg/kg/h by continuous intravenous (IV) infusion until the loss of consciousness (LoC), followed by 1 mg/kg/h to be adjusted as appropriate until the end of surgery or IV propofol administered as a slow bolus of 2.0–2.5 mg/kg until LoC followed by 4–10 mg/kg/h until the end of surgery. Efficacy was measured via the combined primary endpoint of no intraoperative awakening/recall, no need for rescue sedatives, and no body movements. Adverse events and adverse drug reactions (ADRs) were monitored for safety. Efficacy rates were 100% in all treatment groups, and the non-inferiority of remimazolam was demonstrated [95% confidence interval (− 0.0487; 0.0250)]. The time to LoC was longer in the remimazolam 6 (p

The Hermansky-Pudlak syndrome (HPS) is a rare set of disorders characterized by oculocutaneous albinism, bleeding diathesis, and pulmonary fibrosis, with the latter 2 conditions presenting major challenges in anesthetic management. We report a 53-year-old woman with pulmonary fibrosis secondary to HPS who underwent video-assisted bullectomy to treat recurrent pneumothorax. Preoperative bleeding time and platelet count were within normal limits, but the surgeons had difficulty with continuous oozing from the incision site; the surgical blood loss was 270 mL, which was a relatively large amount for this surgery. Because of her restrictive lung disease, the patient's tidal volume was only 250 mL under pressure-controlled ventilation, with a peak inspiratory pressure of 30 cm H2O and a positive end-expiratory pressure of 5 cm H2O. She also had postoperative respiratory insufficiency, with a partial pressure of arterial CO2 of 112 mm Hg and a pH of 7.08 on arterial blood gas analysis. Then, the patient needed mechanical ventilation for 4 days. In conclusion, patients with HPS require strict respiratory management to support their restrictive pulmonary dysfunction, and, also, we should consider preventive management for hemostasis and adequate analgesia to reduce the patient's work of breathing.

Inflammation occurs along with infection during sepsis. 15-Epi-lipoxin A4 has protective and resolving effects in experimental models of infection. In this study, we examined the effects of 15-epi-lipoxin A4 combined with antibiotics on Escherichia coli-induced peritonitis.Prospective experimental study.University research laboratory.Male C57BL/6 mice.Mice were injected with E. coli to induce peritonitis and were given either 15-epi-lipoxin A4 (1 μg/mouse) or placebo (saline) with antibiotics (ceftazidime). The effects of 15-epi-lipoxin A4 on peritoneal cell populations, bacterial burden, and cytokine production were assessed. Survival rates were observed for up to 7 days. In addition, we examined the effects of 15-epi-lipoxin A4 on peritoneal macrophages stimulated with lipopolysaccharide, CpG DNA, or live E. coli.Treatment with 15-epi-lipoxin A4 significantly reduced the number of neutrophils in the peritoneum, inhibited production of cytokines and chemokines, and decreased bacterial load in the serum. Combined treatment of 15-epi-lipoxin A4 with antibiotics significantly improved survival in E. coli-infected mice. 15-Epi-lipoxin A4 also attenuated the production of interleukin-6 and tumor necrosis factor-α by lipopolysaccharide- or CpG DNA-stimulated peritoneal macrophages. Furthermore, 15-epi-lipoxin A4 combined with antibiotics synergistically reduced the production of interleukin-6 and tumor necrosis factor-α by peritoneal macrophages stimulated with live E. coli.15-Epi-lipoxin A4 combined with antibiotics attenuated systemic inflammation, inhibited bacteria dissemination, and improved survival in E. coli-infected mice. The reduced production of interleukin-6 and tumor necrosis factor-α by peritoneal macrophages suggested that 15-epi-lipoxin A4 blocked the initial proinflammatory response. Taken together, these data suggested that 15-epi-lipoxin A4 combined with antibiotics was beneficial in regulating the proinflammatory response in sepsis without exacerbating infection.

Doxapram is the only dedicated respiratory stimulant used to aid recovery of breathing after major surgery. Doxapram acts on peripheral chemoreceptors and although the central action of doxapram has been suggested, its detailed neuronal mechanism is unknown. We assessed doxapram-induced changes in spontaneous cervical nerve (C4) inspiratory activity and the firing of action potentials in pre-inspiratory and inspiratory neurones in the medulla. Experiments were performed in neonatal rat brainstem-spinal cord preparations, which can produce respiratory rhythm for several hours under in vitro conditions. Doxapram application (for 15 min) increased the frequency and amplitude of C4 activity dose-dependently. Doxapram induced changes in the electrophysiological properties of pre-inspiratory and inspiratory neurones. Our results suggest that respiratory activity enhancement was likely to be induced via effects on the potassium channels of pre-inspiratory and inspiratory neurones and indicate the central actions of doxapram.

AQP4 (aquaporin-4), a water channel protein that is predominantly expressed in astrocyte end-feet, plays an important role in the brain oedema formation, and is thereby considered to be a potential therapeutic target. Using a stopped-flow analysis, we showed that propofol (2,6-diisopropylphenol), a general anaesthetic drug, profoundly inhibited the osmotic water permeability of AQP4 proteoliposomes in the presence of Zn2+. This propofol inhibition was not observed in AQP1, suggesting the specificity for AQP4. In addition, the inhibitory effects of propofol could be reversed by the removal of Zn2+. Other lipid membrane fluidizers also similarly inhibited AQP4, suggesting that the modulation of protein–lipid interactions plays an essential role in the propofol-induced inhibition of AQP4. Accordingly, we used Blue native PAGE and showed that the profound inhibition caused by propofol in the presence of Zn2+ is coupled with the reversible clustering of AQP4 tetramers. Site-directed mutagenesis identified that Cys253, located at the membrane interface connecting to the C-terminal tail, is responsible for Zn2+-mediated propofol inhibition. Overall, we discovered that propofol specifically and reversibly inhibits AQP4 through the interaction between Zn2+ and Cys253. The findings provide new insight into the functional regulation of AQP4 and may facilitate the identification of novel AQP4-specific inhibitors.

Purpose We evaluated the safety and efficacy of long-term administration of dexmedetomidine in patients in the intensive care unit (ICU). Primary endpoint was the incidence of hypotension, hypertension, and bradycardia. Secondary endpoints were withdrawal symptoms, rebound effects, the duration of sedation with Richmond Agitation-Sedation Scale (RASS) ≤ 0 relative to the total infusion time of dexmedetomidine, and the dose of additional sedatives or analgesics. Methods Dexmedetomidine 0.2–0.7 μg/kg/h was continuously infused for maintaining RASS ≤ 0 in patients requiring sedation in the ICU. Safety and efficacy of short-term (≤24 h) and long-term (>24 h) dexmedetomidine administration were compared. Results Seventy-five surgical and medical ICU patients were administered dexmedetomidine. The incidence of hypotension, hypertension, and bradycardia that occurred after 24 h (long-term) was not significantly different from that occurring within 24 h (short-term) (P = 0.546, 0.513, and 0.486, respectively). Regarding withdrawal symptoms, one event each of hypertension and headache occurred after the end of infusion, but both were mild in severity. Increases of mean arterial blood pressure and heart rate after terminating the infusion of dexmedetomidine were not associated with the increasing duration of its infusion. The ratio of duration with RASS ≤ 0 was ≥ 85 % until day 20, except day 9 (70 %) and day 10 (75 %). There was no increase in the dose of additional sedatives or analgesics after the first 24-h treatment period. Conclusions Long-term safety of dexmedetomidine compared to its use for 24 h was confirmed. Dexmedetomidine was useful to maintain an adequate sedation level (RASS ≤ 0) during long-term infusion.

BACKGROUND:In Japan, routine clinical care does not normally involve the use of a monitoring device to guide the administration of neuromuscular blocking drugs or their antagonists. Although most previous reports demonstrate that sugammadex offers more rapid and reliable antagonism from rocuronium-i

Objective:Physical and psychological symptoms in cancer patients are frequently overlooked by medical staff. However, little is known regarding the potential impacts of concurrent physical and psychological symptoms on the overlooking of other symptoms. The aim of this study was to examine the impact of concurrent symptoms on the overlooking of other symptoms in cancer inpatients.Method:A total of 255 cancer inpatients in the general wards of one university hospital, who were referred to the palliative care team, were included. On the day of referral, nurses and patients were independently assessed for the presence of the following eight symptoms: pain, fatigue, nausea and vomiting, shortness of breath, lack of appetite, dry mouth, sleep problems, and distressed feelings. The presence of delirium was also separately assessed by nurses and psychiatrists on the team. A total of nine symptoms detected by nurses and those reported by patients or psychiatrists were compared, and logistic regression analysis was performed to identify the variables associated with the overlooking of these symptoms.Results:The most frequently reported symptom was pain (76.5%), followed by distressed feelings (49.8%), sleep problems (34.1%), and delirium (25.1%). The proportion of those overlooked was more than one quarter (25.0–63.6%) for all symptoms except pain (12.8%). Significant associations were found between the overlooking of shortness of breath and concurrent delirium (odds ratio [OR] = 110.9); the overlooking of sleep problems and concurrent lack of appetite (OR = 9.1); and the overlooking of distressed feelings and concurrent dry mouth (OR = 27.7). No patient demographic characteristic was associated with the overlooking of any other symptoms.Significance of results:The presence of some specific concurrent symptoms is likely to lead to the overlooking of other symptoms in cancer inpatients by nurses. Comprehensive assessments of physical and psychological symptoms in daily clinical practice are needed.

Many technologies have been developed for minimally invasive monitoring of cardiac output. Estimated continuous cardiac output (esCCO) measurement using pulse wave transit time is one noninvasive method. Because it does not require any additional sensors other than those for conducting 3 basic forms of monitoring (electrocardiogram, pulse oximeter wave, and noninvasive (or invasive) arterial blood pressure measurement), esCCO measurement is potentially useful in routine clinical circulatory monitoring for any patient including low-risk patients. We evaluated the efficacy of noninvasive esCCO using pulse wave transit time in this multicenter study.We compared esCCO and intermittent bolus thermodilution cardiac output (TDCO) in 213 patients, 139 intensive care units (ICUs), and 74 operating rooms (ORs), at 7 participating institutions. We performed electrocardiogram, pulse oximetry, TDCO, and arterial blood pressure measurements in patients in ICUs and ORs; a single calibration was performed to measure esCCO continuously. TDCO measurement was performed once daily for ICU patients and every hour for OR patients, and just before the removal of the pulmonary arterial catheter from patients in both the ICU and OR. We evaluated esCCO against TDCO with correlation analysis and Bland and Altman analysis and also assessed the change of bias over time. Furthermore, we inspected the impact of change in systemic vascular resistance (SVR) on change in bias because abnormal SVR was assumed to be a factor contributing to the change of the bias.From among 588 esCCO and TDCO datasets (excluding calibration points), 587 datasets were analyzed for 213 patients. The analysis results show a correlation coefficient of 0.79 (P0.0001, 95% confidence limits of 0.756-0.819), a bias (mean difference between esCCO and TDCO) of 0.13 L/min (95% confidence interval of bias 0.04-0.22 L/min), and a precision (1 SD) of 1.15 L/min (95% prediction interval was -2.13 to 2.39 L/min). There were no significant differences among 3 defined time intervals over 48 hours after calibration (repeated-measures analysis of variance P = 0.781) in the ICU. The influence of SVR on esCCO analysis showed a correlation coefficient between SVR and an error of 0.37 (P0.0001, 95% confidence interval 0.298-0.438).The efficacy of noninvasive esCCO technology was compared with TDCO in 213 cases. Five hundred eighty-seven datasets comparing esCCO and TDCO showed close correlation and small bias and precision, which were comparable to current arterial waveform analysis technologies.

Because the safety of intravenous fentanyl patient-controlled analgesia (iv-PCA) administered during labor remains unclear, we retrospectively examined the labor records from January 2005 to December 2007 in our institution, with a focus on both maternal and neonatal outcomes, as compared to no analgesia. Parturients over 35 weeks of gestational age who received fentanyl iv-PCA (iv-PCA group) or no analgesia (control group) during labor were enrolled. The former group received iv-PCA through a pump programmed to give a loading dose of 0.05 mg fentanyl, followed by bolus injection of 0.02 mg fentanyl, with a lock-out interval of 5 min. This analgesia was initiated at the parturient’s request and was discontinued before the second stage of labor, to ensure neonatal safety. During labor, both maternal and fetal heart rates, maternal pulse oximeter oxygen saturation (SpO2), respiratory rate, and sedation and nausea scores were continuously monitored, and the neonatal outcomes including umbilical arterial pH, Apgar scores, and other parameters were recorded. The data of 129 of the 143 parturients who received fentanyl iv-PCA were analyzed, while 697 parturients delivered without any analgesia during the 3-year study period. While iv-PCA prolonged the duration of labor and increased oxytocin use, no obvious maternal or neonatal complications of fentanyl use were recorded. Except for the significantly lower rate of emergency cesarean section in the iv-PCA group, both the maternal and neonatal outcomes were comparable between the groups. As compared to no analgesia, fentanyl iv-PCA appears to be safe and clinically acceptable as analgesia during labor, particularly in nulliparous women.

Summary 1. Propofol (2,6-diisopropylphenol) is an intravenous anaesthetic used for the induction and maintenance of general anaesthesia; it also potently and dose-dependently depresses respiration. The aim of the present study was to analyse propofol-induced changes in spatiotemporal patterns of inspiratory-related neural activity and to investigate the involvement of the GABAA receptor by using an optical imaging technique. 2. The brain stems and spinal cords of 0–1-day-old Wistar rats were isolated and stained using a fluorescent voltage-sensitive dye. Neuronal activity in the preparation was detected using an optical recording apparatus containing a charge-coupled device (CCD)-based camera. 3. Bath-applied propofol (7.5 μmol/L) decreased the C4 burst rate to 45.9% of baseline. Although optical signals corresponding to membrane depolarization during the pre-inspiratory phase in the parafacial region of the ventral medulla decreased to 28.7% of baseline following propofol application, those during the inspiratory phase in the caudal part of the rostral ventrolateral medulla did not. 4. The inhibitory effect of bath-applied propofol was reversed by 2 μmol/L bicuculline. 5. Changes in optical signals corresponding to the population activity of pre-inspiratory neurons were parallel to changes in the C4 burst rate. 6. The results suggest that propofol decreases the inspiratory burst rate by reducing the activity of pre-inspiratory neurons and that GABAA receptor activation plays a role in propofol-induced central respiratory depression. These results are consistent with those of previous electrophysiological studies.

The rapid diagnosis of pathogens and prompt initiation of appropriate antibiotic therapy are critical factors to reduce the morbidity and mortality associated with sepsis. In this study, we evaluated a multiplex polymerase chain reaction (PCR-M) test that detects bacteria and fungi in whole-blood specimens, comparing its features to those of a blood culture (BC). Following evaluation of the performance for sensitivity and specificity of PCR-M, 78 blood samples from 54 patients with suspected bacterial infections were evaluated. Whole-blood samples for PCR-M were collected at the same time as BC, and PCR-M results were compared with BC results. As a result, minimum sensitivity of the kit was 1-100 cfu/ml. The PCR-M test correctly identified specificity for 13 out of 14 strains blinded to the assay analyst. Of 78 blood samples examined, 56 (72%) were negative by both methods, and 22 (28%) were positive by at least one of the two methods. PCR-M detected organisms in 21 cases (27%) compared with 12 cases (15%) in BC. The correlation of positives between PCR-M and BC was 92% (11/12), and both methods identified the same organisms in these 11 cases. With higher positive rate compared with BC, PCR-M could detect and identify potentially significant microorganisms within a few hours by using a small volume of a single whole-blood sample. Early detection of microorganisms has the potential to facilitate early determination of appropriate treatment and antimicrobial selection.

The accumulation of autophagosomes within axons is often observed in axonopathies associated with various neurological disorders, including those following excitotoxic insults. Nevertheless, the life cycle of autophagosomes in axons is not well understood. In the present study, we used microexplant cultures of cerebellar granule cells from GFP-LC3 transgenic mice to perform time-lapse imaging of LC3-positive dots in identified axons. Since these GFP-LC3 dots were never observed in granule cells on an Atg5-null background, they were considered to represent autophagosomes. Under physiological conditions, the autophagosomes showed bidirectional and saltatory movement with a bias towards one direction. Such vectorial movement was largely blocked by the dynein motor inhibitor EH NA (erythro-9-[3-(2-hydroxynonyl)] adenine), suggesting that the autophagosomes moved towards the soma, where most lysosomes are located. Interestingly, the application of the glutamate analog N-methyl-D-aspartic acid (NMDA) as an excitotoxin increased the number of autophagosomes in axons, while it did not significantly change its movement characteristics. These results suggest that autophagosomes play important roles in axons and are dynamically regulated under physiological and pathological conditions.

本邦ではロクロニウムが諸外国から約10年遅れて2007年に発売され，発売後急速に使用量が増加している．しかし，世界ではベクロニウムもスキサメトニウムもまだ多くの国で使用されており，それなりの理由があると考えられる．ロクロニウムは速い作用発現，蓄積作用がなく持続投与が可能，水溶性であるなどの特徴があるが，作用持続時間はベクロニウムと変わりはなく，アナフィラキシー反応の発生頻度，集中治療患者への長期投与での蓄積の可能性，小児での使用に対する懸念が残されている．また，迅速導入時や帝王切開術の麻酔での筋弛緩薬として，さらに緊急事態発生時の使用には，スキサメトニウムが優れていると考えられ，ベクロニウムとスキサメトニウムはまだまだ捨てがたい筋弛緩薬といえる．

BACKGROUND: We hypothesized that mixed venous hemoglobin oxygen saturation (SvO 2 ) can be estimated by calculation from CO 2 production, cardiac output, and arterial oxygen saturation measured using a noninvasive cardiac output (NICO) monitor (Novametrix-Respironics, Wallingford, CT). METHODS: Twenty-three patients undergoing aortic aneurysm repair underwent SvO 2 monitoring using a pulmonary artery catheter and cardiac output monitoring using a NICO monitor. The estimated SvO 2 value calculated from NICO monitor-derived values was compared with the SvO 2 value measured using a pulmonary artery catheter. The accuracy of this estimation was analyzed with Bland-Altman method. The ability of this estimation to track the change of SvO 2 was also evaluated using correlation analysis to compare the changes of estimated SvO 2 and measured SvO 2 . RESULTS: The bias ± limits of agreement of the estimated SvO 2 against measured SvO 2 was -2.1% ± 11.2%. The change of estimated SvO 2 was modestly correlated with the change of measured SvO 2 . CONCLUSIONS: SvO 2 derived from the values measured by the NICO monitor cannot be used interchangeably with the values measured spectrophotometrically using the pulmonary artery catheter. More refinement is required to obtain more reliable estimate of SvO 2 less invasively. However, large changes of SvO 2 may be detected with this method and can be used as a precautionary sign when the balance between oxygen supply and demand is compromised without inserting a central venous catheter.

Recent endoscopic technology has revealed that small intestinal injury is a serious threat to patients receiving nonsteroidal anti-inflammatory drugs (NSAIDs). We previously showed that Japanese herbal medicine, Orengedokuto (OGT; Huang-Lian-Jie-Du-Tang in Chinese), protects mice from lethal indomethacin (IND)-induced enteropathy. To elucidate the mechanism of the protective effect of OGT, we performed microarray analyses and high power statistical analyses of microarray data using new bioinformatics tools. Female BALB/c mice were subcutaneously injected with IND (20 mg/kg) once a day for 2 days. OGT-treated mice received a diet containing OGT from the first IND injection until the end of the experiment. Gene expression signals of small intestine were obtained with GeneChip®. Analyses for overrepresentation of Gene Ontology categories were conducted using MetaGene Profiler (MGP) and the changes were visualized by Cell Illustrator Online (CIO). Furthermore, active ingredients of OGT were investigated. MGP and CIO suggested a critical role for the adenosine system, especially adenosine deaminase (ADA), a key enzyme of adenosine catabolism. Quantitative real time RT-PCR and in situ hybridization showed that OGT decreased the expression of ADA, which possibly resulted in the elevation of the anti-inflammatory nucleoside adenosine. Blockade of the adenosine A2a receptor abrogated the protective effect of OGT. Berberine, a major ingredient of OGT, suppressed ADA expression and reduced the incidence of lethality. OGT may prevent IND-induced enteropathy by decreasing ADA which results in the elevation of adenosine. Modulation of the adenosine system may be an efficient therapeutic strategy for NSAID-induced enteropathy.

This study investigated the accuracy of the NICO monitor equipped with the newer software. Additionally, the effects of the increased dead space produced by the NICO monitor on ventilatory settings were investigated.Forty-two patients undergoing elective aortic reconstruction participated in this prospective, observational study at a university hospital. Cardiac output was continuously monitored using both the NICO monitor and continuous cardiac output (CCO) measured by a pulmonary artery catheter. A NICO monitor equipped with ver. 4.2 software was used for the first 21 patients while a NICO monitor equipped with ver. 5.0 software was used for the rest of the patients. Cardiac output measured by bolus thermodilution (BCO) at 30 min intervals was used as a reference.The bias +/- precision of the NICO monitor was 0.18 +/- 0.88 l/min with ver. 4.2 software (n = 182) and 0.18 +/- 0.83 l/min with 5.0 software (n = 194). The accuracy of the NICO monitor is comparable to CCO, whose bias +/- precision against BCO is 0.19 +/- 0.81 l/min (n = 376). At the same level of CO(2) production and minute ventilation, PaCO(2) was lower in the patients monitored by NICO with ver. 5.0 software than patients with ver. 4.2 software.This study demonstrated the improved performance of the NICO monitor with updated software. The performance of the NICO monitor with ver. 4.2 or later software is similar to CCO. However, the cardiac output measurement did not fulfill the criteria of interchangeability to the cardiac output measurement by bolus thermodilution. Updates to ver. 5.0 attenuated the effects of rebreathing introduced by the NICO monitor without compromising the accuracy of the cardiac output measurement.

Background Sevoflurane-induced respiratory depression has been reported to be due to the action on medullary respiratory and phrenic motor neurons. These results were obtained from extracellular recordings of the neurons. Here, the authors made intracellular recordings of respiratory neurons and analyzed their membrane properties during sevoflurane application. Furthermore, they clarified the role of gamma-aminobutyric acid type A receptors in sevoflurane-induced respiratory depression. Methods In the isolated brainstem-spinal cord of newborn rat, the authors recorded the C4 nerve burst as an index of inspiratory activity. The preparation was superfused with a solution containing sevoflurane alone or sevoflurane plus the gamma-aminobutyric acid type A receptor antagonist picrotoxin or bicuculline. Neuronal activities were also recorded using patch clamp techniques. Results Sevoflurane decreased C4 burst rate and amplitude. Separate perfusion of sevoflurane to the medulla and to the spinal cord decreased C4 burst rate and amplitude, respectively. Both picrotoxin and bicuculline attenuated the reduction of C4 burst rate. Sevoflurane reduced both intraburst firing frequency and membrane resistance of respiratory neurons except for inspiratory neurons. Conclusion Under the influence of sevoflurane, the region containing inspiratory neurons, i.e., the pre-Bötzinger complex, may determine the inspiratory rhythm, because reduced C4 bursts were still synchronized with the bursts of inspiratory neurons within the pre-Bötzinger complex. In contrast, the sevoflurane-induced decrease in C4 burst amplitude is mediated through the inhibition of phrenic motor neurons. gamma-Aminobutyric acid type A receptors may be involved in the sevoflurane-induced respiratory depression within the medulla, but not within the spinal cord.

Background and objective: Vascular endothelial growth factor (VEGF) is known to contribute to the development of pulmonary oedema, and has been suggested to have a protective role against lung injury. To determine the role of VEGF in acute lung injury (ALI) and ARDS, VEGF levels were measured in lung epithelial lining fluid (ELF) collected from patients with ALI/ARDS. Methods: Forty patients with ALI/ARDS underwent bronchoscopic microsampling to collect ELF on days 0 (onset of ALI/ARDS), 1, 3, 5, 7 and 10, unless the patient was extubated or had died. Twelve patients, who underwent bronchoscopy for examination of small, peripheral pulmonary nodules, served as controls. Results: The initial (day 0) levels of VEGF in ELF of the ALI/ARDS patients who survived and those who did not were 5.5 ng/mL (IQR: 2.3–19.7) and 1.7 ng/mL (IQR: 0.0–6.4), respectively. On days 0, 5, 7 and 10, the VEGF levels in ELF were significantly greater in survivors than in non-survivors (P

医療者主導で行われていた医療体制が患者主導に変わりつつあるなか, 麻酔においても, 患者が納得したうえで施行されることが以前にも増して求められるようになってきた. 患者が麻酔に期待することは ｢痛みがないこと, 安全であること｣ である. 当院では1999年より, APS (acute pain service) を導入し, 多職種のチームによる術後痛の緩和を行っている. 術後痛緩和は主に電動式のPCA (patient-controlled analgesia) ポンプを使用しており, これまで4,000例以上の管理を行ってきた. 多くのポンプを稼動させ安全に管理するためにはシステム作りが重要であり, コメディカルの協力が不可欠である.

Efficacy and safety of sugammadex in reversing neuromuscular block induced by rocuronium or vecuronium were investgated in Japanese patients.We studied 98 Japanese patients undergoing surgery requiring general anesthesia. Patients were allocated randomly to receive intubation dose of rocuronium or vecuronium. During surgery, patients received additional doses of rocuronium or vecuronium for maintenance of moderate block. At T2 reappearance sugammadex 0-4.0 mg . kg-1 was administered. The neuromuscular block was monitored with acceleromyography using TOF stimuli. Sevoflurane was administered to all treatment groups after intubation.For the rocuronium-induced neuromuscular block, the mean recovery time of the T4/T1 ratio to 0.9 decreased from 82.1 min in the placebo group to 1.8 min in the 4.0 mg . kg-1 sugammadex group. For the vecuronium-induced neuromuscular block, it decreased from 83.2 min in the placebo group to 2.1 min in the sugammadex 4.0 mg . kg-1 group. Plasma concentrations of sugammadex were approximately dose proportional over the dose range of 0.5 to 4.0 mg . kg-1 and independent of the neuromuscular blocking agents used. No clinical evidence of recurarization or residual curarization was observed.The efficacy and safety of sugammadex were confirmed in Japanese surgical patients.

Efficacy and safety of sugammadex in reversing neuromuscular block induced by rocuronium or vecuronium were investgated in Japanese patients.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.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.The efficacy and safety of sugammadex were confirmed in Japanese surgical patients for reversal from deep block.

Propofol reduces the cerebral metabolic rate for oxygen (CMRO2), regional CMRO2 (rCMRO2), cerebral blood flow (CBF), and regional CBF (rCBF), but maintains the coupling of cerebral metabolism and blood flow. Under mild to moderate hypothermia, the coupling is maintained, while rCBF is reduced, but no direct measurement of rCMRO2 has yet been reported. This study aimed to evaluate the effects of propofol under normothermic and mild hypothermic temperatures upon rCMRO2, rCBF, and their regional coupling, through direct measurement by positron emission tomography.Rhesus monkeys were anesthetized with 65% nitrous oxide and propofol. Then rCBF and rCMRO2 were measured under four sets of conditions: infusion of a low-propofol dose (12 mg.kg(-1) x h(-1)) at normothermic temperatures (38 degrees C), a high dose (25 mg x kg(-1) x h(-1)) at normothermic temperatures, a low dose under mild hypothermia (35 degrees C), and a high dose under mild hypothermia. The ratio of rCBF/rCMRO(2) was calculated from these data.Reductions in CMRO2 and rCMRO2 in most regions were associated with two factors: the higher propofol dose and the induction of hypothermia, but there was no interaction between these factors. Concerning blood flow, no significant reduction was observed, except for CBF by the induction of hypothermia. The ratio of rCBF/rCMRO2 was constant in this study setting.During propofol anesthesia, it is possible to reduce cerebral metabolism throughout the entire brain as well as in any brain region by increasing the propofol dose or inducing hypothermia. The concurrent use of these two interventions has an additive effect on metabolism, and can be considered as safe, as their combination does not impair the coupling of cerebral metabolism and blood flow.

Objective: The purpose of this study was to assess perioperative platelet function with 2 types of monitors (a whole-blood aggregometer [WBA analyzer; Mebanix, Tokyo, Japan]) and the Sonoclot monitor [Sienco, Wheat Ridge, CO]) in patients undergoing hypothermic cardiopulmonary bypass (CPB). Design: Prospective, observational study. Setting: Single-center study at a university hospital. Participants: Twenty-six patients who underwent coronary artery bypass grafting or valve replacement under hypothermic CPB without platelet transfusion or fresh frozen plasma administration. Interventions: Blood sampling was performed at the following time periods: after anesthetic induction, after CPB, and on the first postoperative day. These samples were assessed with the WBA analyzer and the Sonoclot. Measurements and Main Results: Significant attenuation of adenosine diphosphate–induced platelet aggregation was detected shortly after CPB by 2 WBA analyzer-derived parameters: a decrease in the filtration pressure rate and an increase in the platelet aggregatory threshold index. Platelet aggregation returned to the preoperative level on the next day. There was no correlation between the amount of postoperative mediastinal drainage and defects in platelet aggregation. On the other hand, time to peak obtained by the Sonoclot did not show any significant changes. Conclusions: Whole-blood aggregation measured with the WBA analyzer detected transient platelet dysfunction shortly after CPB, whereas the Sonoclot was less sensitive to this change.

Nicotine exposure is a risk factor in several breathing disorders Nicotinic acetylcholine receptors (nAChRs) exist in the ventrolateral medulla, an important site for respiratory control. We examined the effects of nicotinic acetylcholine neurotransmission on central respiratory control by addition of a nAChR agonist or one of various antagonists into superfusion medium in the isolated brainstem-spinal cord from neonatal rats. Ventral C4 neuronal activity was monitored as central respiratory output, and activities of respiratory neurons in the ventrolateral medulla were recorded in whole-cell configuration. RJR-2403 (0.1-10∝M), α4β2 nAChR agonist induced dose-dependent increases in respiratory frequency. Non-selective nAChR antagonist mecamylamine (0.1-100∝M), α4β2 antagonist dihydro-β-erythroidine (0.1-100∝M), α7 antagonist methyllycaconitine (0.1-100∝M), and α-bungarotoxin (0.01-10∝M) all induced dose-dependent reductions in C4 respiratory rate. We next examined effects of 20∝M dihydro-β-erythroidine and 20∝M methyllycaconitine on respiratory neurons. Dihydro-β-erythroidine induces hyperpolarization and decreases intraburst firing frequency of inspiratory and preinspiratory neurons. In contrast, methyllycaconitine has no effect on the membrane potential of inspiratory neurons, but does decrease their intraburst firing frequency while inducing hyperpolarization and decreasing intraburst firing frequency in preinspiratory neurons. These findings indicate that α4β2 nAChR is involved in both inspiratory and preinspiratory neurons, whereas α7 nAChR functions only in preinspiratory neurons to modulate C4 respiratory rate. Key terms: brainstem-spinal cord, neonatal rat, inspiratory neuron, preinspiratory neuron, nicotinic acetylcholine receptor.

In order to survey the current status of home care and support for patients with hematological diseases, questionnaires were sent to 3,591 hospitals and home care facilities in Tokyo and surrounding prefectures. The first survey showed that 81.7% of medical staff members at hospitals reported that they had experience with home care and support, but only 24.9% of home care facility staff members had such experience. The second questionnaire, surveying 1,202 personnel, identified four factors hampering successful establishment of home care and support networks for hematological diseases. These included insufficient familial support for patients, difficulty making end of life decisions by family members and patients, limited access to transfusion support, and financial problems.

Study Objective To determine whether morphine and its active metabolites such as morphine-3-glucuronide (M-3-G) and morphine-6-glucuronide (M-6-G) modulate immune function in patients with advanced cancer who required morphine for pain relief. Design Prospective observational clinical study. Setting Pain clinic of a university hospital. Patients Fifteen patients who visited our clinic for control of advanced cancer pain. Interventions During the initiation or changes of morphine therapy, venous blood samples were obtained at the enrollment of this study, 1 and 3 weeks after the change of morphine dose or route. Measurements Lymphocyte subpopulation CD4 + and CD8 + , activity of natural killer cell, phytohemagglutinin (PHA)-induced T-cell proliferation, and plasma immunoglobulin M and G concentrations were measured, as well as plasma concentrations of morphine, M-3-G, and M-6-G. Main Results At the entry of the study, 6 patients did not receive any type of morphine medication (group 1), whereas 9 patients were treated with morphine for 1 month (group 2). Cancer pain, rated as 4 at the entry period, was reduced to 2 of 10 (visual analogue scale) during the study periods. Although the plasma concentrations of M-3-G and M-6-G in Group 1 were significantly less than those in Group 2, plasma concentrations of immunologic markers were similar between the groups. In Group 1, Spearman linear regression analysis showed negative correlation between morphine-derived metabolites and immunoglobulins or PHA-induced T-cell proliferation, whereas poor correlation was found with all immunologic parameters in Group 2. Stepwise linear regression analyses showed that the metabolites, rather than morphine per se, modulated immune function, reflected by PHA-induced T-cell proliferation and immunoglobulin G concentration in Group 1. Conclusions The present study suggests that some of humoral and cellular immunity are modulated by morphine-derived metabolites at the early phase of morphine therapy in patients with advanced cancer.

Objective: This study aimed at evaluating two emergency medical service systems, one in which emergency life-saving technicians (ELSTs) are allowed to administer epinephrine (adrenaline) to patients with out-of-hospital cardiac arrest and one in which ELSTs are allowed to administer epinephrine, lidocaine, and atropine. Methods: A modified, prospective community health trial was conducted from April 1 to October 31, 2003. Areas served by physician-manned ambulances, where out-of-hospital cardiopulmonary resuscitation (CPR) was performed with resuscitative drugs (experimental areas), were compared to areas served by ELST-manned ambulances, where resuscitative drugs were not administered outside the hospital (reference areas). The sequence of emergency procedures performed in the experimental areas was divided into three phases. Phase I included administration of epinephrine, which simulated administration of epinephrine by ELSTs. Phase II started with the use of lidocaine or atropine. Phases I and II simulated administration of epinephrine, lidocaine, and atropine by ELSTs. Phase III began with administration of another drug. Outcomes, resuscitation rates and 1-month survival rates were determined, and differences between the two types of areas were analyzed. Results: For non-traumatic cardiac arrest, outcomes through phase II in the experimental areas were significantly better than those in the reference areas. Phase I—only outcomes in the experimental areas were better, but not significantly better, than those in the reference areas. Conclusion: Use of resuscitative drugs for non-traumatic prehospital CPR appears to be effective in terms of resuscitation rates and 1-month survival rates.

Neutrophils play an important role in ischemia-reperfusion injury. The neutrophil elastase not only causes tissue damage, but also mediates neutrophil priming. In the present study, we use a rabbit model of hepatoenteric ischemia-reperfusion to test the hypothesis that neutrophil elastase inhibition ameliorates an ischemia-reperfusion injury by attenuating neutrophil priming and suppressing enzymatic activity. Twenty-four Japanese white rabbits underwent 30 min of supraceliac aortic cross-clamping and 180 min of reperfusion under isoflurane anesthesia. The rabbits randomly received the neutrophil elastase inhibitor, sivelestat (n = 10), or saline (n = 14). Neutrophil priming was then assayed with luminol-dependent neutrophil chemiluminescence. Hepatic, intestinal, renal, and pulmonary damages were assessed with serum transaminase, lactate dehydrogenase concentrations, urinary N-acetyl glucosaminidase activity, and protein concentration in post mortem bronchoalveolar lavage fluid. We discovered that neutrophil elastase inhibition suppressed plasma neutrophil elastase, and that lipid peroxide concentrations increased after reperfusion. It improved ischemia-reperfusion injuries in the liver, intestine, kidney, and lung. Furthermore, inhibition of neutrophil elastase with sivelestat significantly attenuated post-reperfusion neutrophil priming. The results of this study demonstrate that neutrophil elastase inhibition could effectively attenuate an ischemia-reperfusion injury caused by supraceliac aortic cross-clamping, most likely from the attenuation of neutrophil priming.

The neural mechanisms of propofol-induced central respiratory depression remain poorly understood. In the present study, we studied these mechanisms and the involvement of gamma-aminobutyric acid (GABA)A receptors in propofol-induced central respiratory depression. The brainstem and the cervical spinal cord of 1- to 4-day-old rats were isolated, and preparations were maintained in vitro with oxygenated artificial cerebrospinal fluid. Rhythmic inspiratory burst activity was recorded from the C4 spinal ventral root. The activity of respiratory neurons in the ventrolateral medulla was recorded using a perforated patch-clamp technique. We found that bath-applied propofol decreased C4 inspiratory burst rate, which could be reversed by the administration of a GABAA antagonist, bicuculline. Propofol caused resting membrane potentials to hyperpolarize and suppressed the firing of action potentials in preinspiratory and expiratory neurons. In contrast, propofol had little effect on resting membrane potentials and action potential firing in inspiratory neurons. Our findings suggest that the depressive effects of propofol are, at least in part, mediated by the agonistic action of propofol on GABAA receptors. It is likely that the GABAA receptor-mediated hyperpolarization of preinspiratory neurons serves as the neuronal basis of propofol-induced respiratory depression in the newborn rat.

KL-6 is a pulmonary epithelial mucin more prominently expressed on the surface membrane of alveolar type II cells when these cells are proliferating, stimulated, and/or injured. We hypothesized that high levels of KL-6 in epithelial lining fluid and plasma would reflect the severity of lung injury in patients with acute lung injury (ALI). Epithelial lining fluid was obtained at onset ( day 0) and day 1 of acute respiratory distress syndrome (ARDS)/ALI by bronchoscopic microsampling procedure in 35 patients. On day 0, KL-6 and albumin concentrations in epithelial lining fluid were significantly higher than in normal controls ( P < 0.001), and the concentrations of KL-6 in epithelial lining fluid ( P < 0.002) and in plasma ( P < 0.0001) were higher in nonsurvivors than in survivors of ALI/ARDS. These observations were corroborated by the immunohistochemical localization of KL-6 protein expression in the lungs of nonsurvivors with ALI and KL-6 secretion from cultured human alveolar type II cells stimulated by proinflammatory cytokines. Because injury to distal lung epithelial cells, including alveolar type II cells, is important in the pathogenesis of ALI, the elevation of KL-6 concentrations in plasma and epithelial lining fluid could be valuable indicators for poor prognosis in clinical ALI.

Ventilation with a small tidal volume (Vt) is associated with better clinical outcomes than with a large Vt, particularly in critical settings, including acute lung injury. To determine whether Vtinfluences the lipopolysaccaharide (LPS) recognition pathway, we studied CD14 expression in rabbit lungs and the release of TNF-α by cultured alveolar macrophages after 240 min of ventilation with a large (20 ml/kg) vs. a small (5 ml/kg) Vt. We also applied small or large Vtto lungs instilled with 50 μg/kg of LPS. The alveolar macrophages collected after large Vtventilation revealed a 20-fold increase in LPS-induced TNF-α release compared with those collected after small Vtventilation, whereas TNF-α was undetectable without LPS stimulation. In animals ventilated with a large Vt, the expression of CD14 mRNA in whole lung homogenates and the expression of CD14 protein on alveolar macrophages, assessed by immunohistochemistry, were both significantly increased in the absence of LPS stimulation. A large Vtapplied to LPS-instilled lungs increased the pulmonary albumin permeability and TNF-α release into the plasma. These results suggest that mechanical stress caused by a large Vtsensitizes the lungs to endotoxin, a phenomenon that may occur partially via the upregulation of CD14.

Study objectives To investigate, in mastectomy patients, the effectiveness of continuous cervical epidural block using a low-dose fentanyl infusion in combination with local anesthetics. Design Prospective, observational study. Setting 450-bed, university-affiliated hospital. Patients 21 ASA physical status I and II female patients undergoing modified radical mastectomy. Interventions An epidural catheter was inserted at the C 7 -Th 1 interspace before the induction of anesthesia. Anesthesia was maintained using a low concentration of sevoflurane with nitrous oxide-oxygen (N 2 O-O 2 ). A mixture of 100 μg fentanyl and 49 mL of 1% mepivacaine was prepared, and 7 mL of this solution was epidurally injected before the initial incision. This same solution was continuously infused at a rate of 7 mL/hr (fentanyl 17.5 μg/hr) throughout the anesthesia, and at 2 mL/hr (fentanyl 5 μg/hr) postoperatively. Measurements and main results Intraoperative mean arterial pressure (MAP) and heart rate (HR), postoperative pain and analgesic use, and the frequency of postoperative side effects of anesthesia, including nausea, dizziness, and respiratory depression, were recorded. The protocol described provided stable intraoperative hemodynamic control with no or low-dose nicardipine infusion. Sufficient postoperative analgesia was achieved in 18 of 21 patients. One patient reported postoperative nausea, and no other side effects were reported. Conclusions Continuous epidural infusion of the low-dose fentanyl mixture described above provides adequate intraoperative hemodynamic control and postoperative pain relief, with a low rate of side effects in mastectomy patients.

Although neuromuscular blocking agents (NMBAs) function as muscular nicotinic acetylcholine receptor (nAChR) antagonists, several studies have shown that they block neuronal nAChRs as well, which led us to hypothesize that these agents can affect neuronal nAChRs expressed in respiratory centers. To test this hypothesis, we studied the effects of two NMBAs on respiratory activity and respiratory neurons in brainstem-spinal cord preparations from neonatal rats. The application of either D-tubocurarine or vecuronium resulted in dose-dependent reductions in C4 respiratory rate. These reductions were concomitant with reductions in the depolarizing cycle rate of inspiratory (Insp) neurons; the depolarizing cycle rate of preinspiratory (Pre-I) neurons, however, was not affected. We also detected C4 burst activity during the depolarizing phase in Pre-I neurons, even during NMBA-induced respiratory depression. Both NMBAs inhibited drive potential amplitude and intraburst firing frequency in Insp and Pre-I neurons. These agents also induced a hyperpolarization and an increase in membrane resistance in Pre-I neurons, however they had no effect on these membrane properties in Insp neurons. Our findings indicate that these agents suppress central respiratory activity mainly through their inhibitory effects on Pre-I neurons and the Pre-I to Insp neuron synaptic drive, and that nAChRs are involved in central respiratory control.

Background In the partial CO(2) rebreathing method, monitored changes in CO(2) elimination and end-tidal CO(2) in response to a brief rebreathing period are used to estimate cardiac output. However, dynamic changes in CO(2) production during ischemia and reperfusion may affect the accuracy of these estimates. This study was designed to compare measurements of cardiac output as produced by the partial CO(2) rebreathing (NICO), bolus (BCO), and continuous thermodilution (CCO) methods of monitoring cardiac output. Methods Cardiac output was continuously monitored using both NICO and CCO in 28 patients undergoing aortic reconstruction. BCO measurements were taken at the following intervals when hemodynamic stability was achieved: (1) after anesthetic induction; (2) during aortic cross-clamp; (3) at reperfusion of the iliac artery; and, (4) during peritoneal closure. Results The bias and precision (1 SD) derived from all the measurements between NICO and BCO was -0.58 +/- 0.9 l/min, whereas for CCO and BCO it was 0.38 +/- 1.17 l/min. The bias between NICO and BCO was small after anesthetic induction and during cross-clamp, but increased following reperfusion. The bias between CCO and BCO was relatively small until reperfusion but increased significantly at peritoneal closure. Conclusions Results indicate that in aortic reconstruction surgery the performance of NICO monitoring is comparable with that of CCO; however, the direction of bias in these continuous measurement devices is the opposite.

Study Objective: To quantify the effects of sevoflurane on autonomic nerve function by analyzing changes in heart rate (HR) variability in sevoflurane anesthesia; and to investigate the effects of anesthetic depth and apnea on HR variability. Design: Prospective study. Setting: Operating room (OR) of a university medical center. Patients: 7 ASA physical status I and II patients scheduled for elective surgery. Interventions: Patients were premedicated with ranitidine 150 mg. Anesthesia was induced with thiopental sodium 4 mg/kg intravenously (IV) and succinylcholine 1 mg/kg IV, and maintained with nitrous oxide (N 2 O) 67% and sevoflurane in oxygen. Patients were ventilated mechanically at a rate of 15 breaths/min. Measurements: R-R interval of electrocardiography (ECG), electroencephalogram (EEG), noninvasive arterial blood pressure (BP), and end-tidal sevoflurane concentration were recorded. Measurements were performed 1) after patients arrived at the OR and were placed in the supine position, 2) a stable period after inhalation of 2% sevoflurane, and 3) following the appearance of an isoelectric EEG at a higher concentration of sevoflurane. At times 2) and 3), data were recorded during mechanical ventilation and during apnea. Main Results: There were decreases in both the low-frequency (LF; 0.04 to 0.15 Hz) and high-frequency (HF; 0.15 to 0.4 Hz) components of HR variability during anesthesia compared with the awake state. HF decreased during apnea at 2% sevoflurane, but LF did not change. Neither LF nor HF changed in response to the absence or presence of respiration during isoelectric EEG. Conclusions: Autonomic nerve activity was attenuated by sevoflurane. Parasympathetic input to the heart by respiration was markedly suppressed following the appearance of isoelectric EEG.

神経芽細胞腫を伴う7歳患児に対し,モルヒネの静脈内PCAによる在宅疼痛管理を行った.痙痛に対する患児の訴えが的確であり,PCAに対する両親の理解も良好であったため,在宅における痙痛の訴えに応じたボーラス投与や副作用監視が可能であった.病勢の進行とともにモルヒネ必要量が漸増し,最高時960mg・d-1まで及んだが,患児の日常生活に悪影響は認めなかった.またモルヒネ抵抗性の疼痛出現に対してはケタミンの持続静注併用が有効であった.本症例では高用量のモルヒネを必要としたが,注意深い疼痛評価や副作用監視,家族と疼痛緩和チームとの協力により,PCAによる良好な在宅疼痛管理を行い得た.