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Introduction Clinical trials of direct-acting antivirals for patients with decompensated cirrhosis have been conducted, but there is limited information on the medicinal applications in clinical settings. We aimed to evaluate the safety and efficacy of sofosbuvir/velpatasvir for decompensated cirrhotic patients with genotypes 1 and 2 in real-world clinical practice. Methods A prospective, multicenter study of 12-week sofosbuvir/velpatasvir was conducted for patients with decompensated cirrhosis at 33 institutions. Results The cohort included 71 patients (52 genotype 1, 19 genotype 2): 7 with Child–Pugh class A, 47 with class B, and 17 with class C (median score 8; range 5–13). The albumin–bilirubin (ALBI) score ranged from − 3.01 to − 0.45 (median − 1.58). Sixty-nine patients (97.2%) completed treatment as scheduled. The overall rate of sustained virologic response at 12 weeks post-treatment (SVR12) was 94.4% (67/71). SVR12 rates in the patients with Child–Pugh classes A, B, and C were 85.7%, 97.9%, and 88.2%, respectively. Among 22 patients with a history of hepatocellular carcinoma treatment, 20 (90.9%) achieved SVR12. The Child–Pugh score and ALBI grade significantly improved after achieving SVR12 (p = 7.19 × 10−4 and 2.42 × 10−4, respectively). Notably, the use of diuretics and branched-chain amino acid preparations significantly reduced after achieving SVR12. Adverse events were observed in 19.7% of the patients, leading to treatment discontinuation in two patients with cholecystitis and esophageal varices rupture, respectively. Conclusion Twelve weeks of sofosbuvir/velpatasvir in real-world clinical practice yielded high SVR rates and acceptable safety profiles in decompensated cirrhotic patients with genotypes 1 and 2. Achievement of SVR not only restored the liver functional reserve but also reduced or spared the administration of drugs for related complications. Trial Registration UMIN registration no, 000038587. Electronic supplementary material The online version of this article (10.1007/s40121-020-00329-y) contains supplementary material, which is available to authorized users.

AIM Direct-acting antivirals (DAAs) are currently available even for patients with decompensated cirrhosis. Reportedly, hepatic functional reserve improved in the short term after achievement of sustained virologic response (SVR). We aimed to clarify the outcomes after achievement of SVR in patients with decompensated cirrhosis who were treated by DAAs in real-world clinical practice. METHODS A prospective, multicenter study of 12-week sofosbuvir/velpatasvir was conducted in 86 patients with decompensated cirrhosis, who were evaluated for 48 weeks post-treatment. RESULTS The cohort included 8 patients with Child-Pugh class A, 56 with B, and 22 with C. The proportion of Child-Pugh class A patients increased from 9.1% at baseline to 44.1% at 48 weeks post-treatment, while that of class B and C patients decreased from 66.2% to 35.1% and from 24.7% to 14.3%, respectively. Among the patients with Child-Pugh class B and C, univariate analysis identified low total bilirubin, Child-Pugh score, Child-Pugh class B, ALBI score, and high serum albumin as factors associated with improvement to Child-Pugh class A. The optimal cut-off value of the factors for predicting improvement to Child-Pugh class A were 1.4 mg/dL for total bilirubin, 2.9 g/dL for serum albumin, 8 points for Child-Pugh score, and -1.88 for ALBI score. CONCLUSION Achievement of SVR with sofosbuvir/velpatasvir improved the liver functional reserve at 12 weeks post-treatment and maintained the stable effects until 48 weeks post-treatment in patients with decompensated cirrhosis. Specifically, the patients with less advanced conditions had the likelihood of improving to Child-Pugh class A at 48 weeks post-treatment. This article is protected by copyright. All rights reserved.

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

AIM: Cooling the pharynx and upper oesophagus would be more advantageous for rapid induction of therapeutic hypothermia since the carotid arteries run in their vicinity. The aim of this study was to determine the effects of pharyngeal cooling on brain temperature and the safety and feasibility for patients under resuscitation. METHODS: Witnessed non-traumatic cardiac arrest patients (n=108) were randomized to receive standard care with (n=53) or without pharyngeal cooling (n=55). In the emergency room, pharyngeal cooling was initiated before or shortly after return of spontaneous circulation by perfusing physiological saline (5 °C) into a pharyngeal cuff for 120 min. RESULTS: There was a significant decrease in tympanic temperature at 40 min after arrival (P=0.02) with a maximum difference between the groups at 120 min (32.9 ± 1.2°C, pharyngeal cooling group vs. 34.1 ± 1.3°C, control group; P

Neuroprotective effects of esmolol in laboratory and clinical settings have been reported. The present study was designed to quantitatively evaluate the neuroprotective effects of esmolol using logistic regression curves and extracellular potentials.In 42 gerbils, bilateral occlusion of common carotid arteries was performed for 3, 5, or 7 minutes (n=7 in each group). In treated animals, esmolol (200 µg/kg/min) was administered for 90 minutes, 30 minutes before the onset of ischemia. Direct current potentials were measured in the bilateral CA1 regions, in which histologic evaluation was performed 5 days later. Relations of neuronal damage with ischemic duration and duration of ischemic depolarization were determined using logistic regression curves.There was no significant difference in onset time between the 2 groups (the control group vs. the esmolol group: 1.65±0.46 vs. 1.68±0.45 min, P=0.76), and significant differences in durations of ischemic depolarization were not observed with any ischemic duration. However, logistic regression curves indicated that esmolol has a neuroprotective effect from 2.95 to 7.66 minutes of ischemic depolarization (P0.05), and esmolol prolonged the duration of ischemic depolarization causing 50% neuronal damage from 4.97 to 6.34 minutes (P0.05). Logistic regression curves also indicated that esmolol has a neuroprotective effect from 3.77 to 7.74 minutes of ischemic duration (P0.05), and esmolol prolonged the ischemic duration causing 50% neuronal damage from 4.26 to 4.91 minutes (P0.05).Esmolol has neuroprotective effects in the acute phase of ischemia by a mechanism other than shortening the duration of ischemic depolarization.

Purpose: Delirium is a common complication in postoperative critically ill patients. Although abnormal melatonin metabolism is thought to be one of the mechanisms of delirium, there have been few studies in which the association between alteration of perioperative plasma melatonin concentration and postoperative delirium was assessed. Materials: We conducted a prospective observational study to assess the association of perioperative alteration of plasma melatonin concentration with delirium in 40 postoperative patients who required intensive care for more than 48 hours. We diagnosed postoperative delirium using Confusion Assessment Method for the intensive care unit and measured melatonin concentration 4 times (before the operation as the preoperative value, 1 hour after the operation, postoperative day 1, and postoperative day 2). Results: Postoperative delirium occurred in 13 (33%) of the patients. Although there was no significant difference in preoperative melatonin concentration, Delta melatonin concentration at 1 hour after the operation was significantly lower in patients with delirium than in those without delirium (-1.1 vs 0 pg/mL, P = .036). After adjustment of relevant confounders, Delta melatonin concentration was independently associated with risk of delirium (odds ratio, 0.50; P = .047). Conclusions: Delta melatonin concentration at 1 hour after the operation has a significant independent association with risk of postoperative delirium. (c) 2013 Elsevier Inc. All rights reserved.

Purpose: The primary aim of this study was to investigate volume effect and safety of up to 50 mL/kg BW 6% hydroxyethyl starch (HES) 130/0.4 in adult and pediatric patients undergoing major elective surgery. The need to infuse human albumin may be reduced or avoided in Japan if these large doses 6% HES 130/0.4 can be infused. Methods: The study was an uncontrolled, open-labeled, multi-center trial. Fifteen adult and 5 pediatric patients undergoing major elective surgery received 6% HES 130/0.4 (Voluven&#174) with a maximum dose of 50 mL/kg from the start of surgery until 2 hours after the end of surgery according to a treatment algorithm. The primary efficacy endpoint was the volume effect of 6% HES 130/0.4 determined by the volume of saved albumin during the investigational period and the time course of hemodynamic stability in adult and pediatric patients. Safety parameters were fluid balance, hemodynamic and laboratory parameters ECG, local and systemic tolerance and adverse events. Results: Adult patients received a mean of 32.0 mL/kg of 6% HES 130/0.4. For 12 out of 15 adult patients an average amount of 1033.8 mL (18.6 mL/kg) albumin could be saved. The other 3 adult patients did not receive more than 1000 mL of HES 130/0.4. All pediatric patients received approximately 50 mL/kg of HES 130/0.4; for these patients an average amount of 39.9 mL/kg body weight albumin could be saved. The majority of adult patients, and all pediatric patients were hemodynamically stable at all 3 time points. The observed changes of the assessed laboratory parameters including hematological and coagulation parameters or in any other safety parameter determined did not reveal any safety concern related to the administration of 6% HES 130/0.4 up to doses of 50 mL/kg body weight. Conclusion: The study results indicate that 6% HES 130/0.4 has a reliable volume effect, could contribute to significant human albumin savings and was safe and well tolerated up to a maximum dose of 50 mL/kg body weight in adult and pediatric patients undergoing major elective surgery.

Even after successful resuscitation, hemorrhagic shock frequently causes pulmonary inflammation that induces acute lung injury (ALI). We previously demonstrated that when CO is inhaled at a low concentration both prior to and following hemorrhagic shock and resuscitation (HSR) it ameliorates HSR-induced ALI in rats due to its anti-inflammatory effects. In the present study, we administered CO to the same model of ALI only after resuscitation and examined whether it exerted a therapeutic effect without adverse events on HSR-induced ALI, since treatment of animals with CO prior to HSR did not prevent lung injury. HSR were induced by bleeding animals to achieve a mean arterial pressure of 30 mmHg for 1 h followed by resuscitation with the removed blood. HSR resulted in the upregulation of inflammatory gene expression and increased the rate of apoptotic cell death in the lungs. This was determined from an observed increase in the number of cells positive for transferase-mediated dUTP-fluorescein isothiocyanate (FITC), nick-end labeling staining and activated caspase-3. HSR also resulted in prominent histopathological damage, including congestion, edema, cellular infiltration and hemorrhage. By contrast, CO inhalation for 3 h following resuscitation significantly ameliorated these inflammatory events, demonstrated by reduced histological damage, inflammatory mediators and apoptotic cell death. The protective effects of CO against lung injury were notably associated with an increase in the protein expression level of peroxisome proliferator-activated receptor (PPAR)-γ, an anti-inflammatory transcriptional regulator in the lung. Moreover, CO inhalation did not affect the hemodynamic status or tissue oxygenation during HSR. These findings suggest that inhalation of CO at a low concentration exerts a potent therapeutic effect against HSR-induced ALI and attenuates the inflammatory cascade by increasing PPAR-γ protein expression.

Purpose There is no recommendation on how increased body temperature should be treated in non-neurological critically ill patients. To understand the epidemiology of fever and its association with mortality, we conducted a systematic review of the literature to search for data related to the association between fever and mortality. Materials and Methods We searched MEDLINE and PUBMED related articles and reference lists from January 1978 to July 2011 to select observational studies for assessment of the association of fever with mortality in non-neurological critically ill patients. Results We reviewed 1464 articles and found 9 relevant articles. We found that (1) there is no uniform definition of fever, (2) fever (37.5°C to >39.0°C) was not significantly associated with mortality (odds ratio, 1.22; P = .52), and (3) high fever (39.3°C to 39.5°C) was significantly associated with mortality (odds ratio, 2.95; P = .03). We also found that there has been no multicenter prospective observational study including important confounding factors, such as the use of antipyretic treatments, steroids, and extracorporeal circuits. Conclusions The limited evidence available suggests that the recommended definition of fever (38.3°C) might be too low to predict increased mortality. Because fever is common in the intensive care unit, there is an urgent need for more studies in this field.

Background Pharyngeal cooling decreases brain temperature by cooling carotid arteries. This study was designed to evaluate the principle of pharyngeal cooling in monkeys and humans. Methods Monkeys (n = 10) were resuscitated following 12 min of cardiac arrest. Pharyngeal cooling (n = 5), in which cold saline (5°C) was perfused into the cuff at the rate of 500 ml/min, was initiated simultaneously with the onset of resuscitation for 30 min. Patients (n = 3) who were in an intensive care unit were subjected to 30 min of pharyngeal cooling under propofol anesthesia. Results In the animal study, core brain temperature was significantly decreased compared with that in the control group by 1.9°C (SD = 0.8, P < 0.001) and 3.1°C (SD = 1.0, P < 0.001) at 10 min and 30 min after the onset of cooling, respectively. The cooling effect was more evident in an animal with low postresuscitation blood pressure. Total dose of epinephrine, number of direct current shocks, and recovery of blood pressure were not different between the two groups. The pharyngeal epithelium was microscopically intact on day 5. In the clinical study, insertion of the cuff and start of perfusion did not affect heart rate or blood pressure. Tympanic temperature was decreased by 0.6 ± 0.1°C/30 min without affecting bladder temperature. The pharynx was macroscopically intact for 3 days. Conclusions Pharyngeal cooling rapidly and selectively decreased brain temperature in primates and tympanic temperature in humans and did not have adverse effects on return of spontaneous circulation, even when initiated during cardiac arrest in primates.

Little is known on the clinical effects of chloride on critically ill patients. We conducted this retrospective, observational study in 488 critically ill patients to investigate the incidence of chloride abnormalities, effects of hypochloremia in acid-base disorders, and association between chloride and clinical outcome. The study involved retrieval of arterial blood gas analyses, biochemical and demographical data from electrical records as well as quantitative acid-base analyses. For statistical analysis, the patients were stratified into three groups according to their chloride level (normal range: 98–106 mEq/L). The distribution of chloride levels was hyperchloremia 16.6%, normochloremia 74.6%, and hypochloremia 8.8%. The hypochloremic group was significantly alkalemic ( 𝑃 < 0 . 0 0 0 1 ) and has significantly higher apparent strong ion difference (SIDa) ( 𝑃 < 0 . 0 0 0 1 ) compared to the two other groups. The hypochloremic group had significantly longer stays in the ICU and hospital ( 𝑃 < 0 . 0 0 0 1 ) with higher mortality ( 𝑃 < 0 . 0 0 0 1 ). However, multiple regression analysis showed that chloride was not an independent factor of poorer outcome. In conclusion, the acid-base characteristics of the hypochloremic patients were alkalemia coexisting with higher SIDa. And although it was not an independent prognostic factor, hypochloremia was related to poorer outcome in critically ill settings.

Temporary brain ischemia occurring during surgery under general anesthesia may induce the death of neuronal cells and cause severe neurological deficits. On the other hand, it is not clear whether μ-opioid receptor agonists promote ischemic brain injury. It is known that duration of ischemic depolarization affects the degree of neuronal damage. However, the effects of fentanyl during brain ischemia on ischemic depolarization have not been investigated. Therefore, in the current study, the effects of fentanyl on ischemic neuronal damage and ischemic depolarization were quantitatively evaluated. Forty-two male gerbils were randomly assigned to a saline-administered group (control group, n = 21) and a fentanyl-administered group (fentanyl group, n = 21). Fentanyl at 50 μg/kg was first administered over a 10-min period and then 50 μg/kg/h was administered continuously for the fentanyl group. Forebrain ischemia was initiated by occlusion of bilateral common carotid arteries and sustained for 3, 5, or 7 min (n = 7 in each group). Direct-current potentials were measured in bilateral CA1 regions, in which histological evaluation was performed 5 days later. There were no significant differences in onset time, duration of ischemic depolarization, and percentage of neuronal damage between the two groups with any ischemic duration. In the relationships between ischemic time and neuronal damage and those between duration of ischemic depolarization and neuronal damage, there was no significant difference in the percentage of neuronal damage between the two groups. Fentanyl at a clinically relevant dose does not affect ischemic depolarization and ischemic neuronal damage.

The mechanism underlying neuropathic pain is still largely unclear. Recently, much attention has been focused on the role of brain-derived neurotrophic factor (BDNF) as a neuromodulator in the spinal cord. We previously reported that the expression of Bdnf exon I mRNA was remarkably up-regulated in the dorsal root ganglion (DRG) neurons with the rat L5 spinal nerve ligation (SNL) model. In the present study, we investigated whether neuropathic pain response would be reduced by the inhibition of the Bdnf exon I in the rat SNL model. We identified the promoter region of exon I and synthesized the decoy ODNs targeting the region. Reverse transcription-polymerase chain reaction analysis confirmed that the decoy ODN treatment reduced SNL-induced Bdnf exon I mRNA up-regulation in ipsilateral L4 and L5 DRGs. Furthermore, post-treatment with the decoy ODNs significantly attenuated SNL-induced tactile allodynia. This study suggested that decoy ODNs targeting the Bdnf exon I might provide a novel analgesic strategy for the treatment of neuropathic pain.

POPS研究会は，術後患者のQOLを高める術後疼痛管理サービス（Post Operative Pain Service：POPS）を標準化することを目的として活動している．その一環として，術後疼痛管理の全国アンケート調査を行ったので，一部を報告する．わが国における腹部手術の術後疼痛管理は，ディスポーザブルPCA注入器を用い，持続投与0.2%ロピバカイン4ml/h・PCA 3ml/回（充填時間30～60分）・フェンタニル0.3mg/日を2.5～3日間行う硬膜外PCAか，フェンタニル持続投与25μg/h・PCA 25μg/回（充填時間10分）を2～2.5日間行うIV-PCAが平均的であることがわかった．

Thrombotic microangiopathy (TMA) is a rare but potentially lethal complication encountered in solid organ and bone marrow transplant recipients that requires rapid recognition, diagnosis, and initiation of therapy. Several causes have been identified, including viral infections and various medications. We report a case of TMA after living-donor liver transplantation (LDLT). A 60-year-old man underwent LDLT for end-stage liver disease secondary to hepatitis C virus. After 6 months, he required re-transplantation because graft failure was caused by a small-for-size graft. The immunosuppressive regimen for the second transplantation consisted of tacrolimus and prednisolone; cyclosporine (CsA), mycophenolate mofetil, and prednisolone had been used for the first transplantation. Despite multiple transfusions of packed red blood cells and concentrated platelets, his hemoglobin and platelets decreased and lactate dehydrogenase increased following re-transplantation. Hematological evaluation revealed findings consistent with TMA. As soon as TMA was diagnosed, the calcineurin inhibitor (CNI) was changed from tacrolimus to CsA, and fresh frozen plasma (FFP) was given. The patient's platelets gradually increased after the CNI was changed, and no transfusions were needed. Therefore, tacrolimus was suspected as the cause of the patient's TMA. Early diagnosis, switching CNIs, and FFP supplementation allowed the TMA to resolve without the need for plasma exchange.

SummaryValidation of a scoring algorithm for non-overt disseminated intravascular coagulation (DIC) proposed by the International Society on Thrombosis and Haemostasis (ISTH) is still incomplete. It was the objective of this study to assess the impact of including AT to non-overt DIC scoring on the predictability for intensive care unit (ICU) death and the later development of overt-DIC defined by the Japanese Ministry of Health and Welfare (JMHW) or the ISTH. We performed a retrospective observational study conducted in 364 patients in critical care. Coagulation parameters obtained daily for DIC screening were utilised for scoring. There were 194 and 196 patients scored as positive non-overt DIC with and without AT, respectively; diagnostic agreement between the two was 78%. As compared with patients without non-overt DIC, these non-overt DIC patients had significantly higher mortality. In 37 ICU non-survivors, positive non-overt DIC scoring with AT preceded ICU death by a median of 6.8 days, which was significantly earlier as compared with a median of 5.4 days for non-overt DIC without AT (p=0.022). In patients who developed overt-DIC after admission, the time period from positive non-overt DIC to positive overt-DIC was significantly longer when AT was utilised (overt-DIC ISTH; 1.3 days vs. 0.1 days, p=0.004, overt-DIC JMHW; 2.5 days vs. 2.0 days, p=0.04, with AT vs. without AT, respectively). Non-overt DIC scoring predicted a high risk of death in critically ill patients. When information on AT levels was included, non-overt DIC scoring was found to predict development of overt-DIC significantly earlier than non-overt DIC scoring without AT.

Impaired deformability might contribute to the accumulation of activated leukocytes within pulmonary microcapillaries, leading to acute lung injury. The purpose of our study was to investigate changes in leukocyte deformability during periods of inflammation after esophagectomy. The study group comprised 20 patients who underwent esophagectomy. Changes in leukocyte deformability were investigated by examining filtration through a silicon microchannel, which simulated human pulmonary microcapillaries. Changes in the neutrophil cytoskeleton were investigated by measuring neutrophil F-actin assembly. The severity of patient clinical outcome was evaluated by the lung injury score. Leukocyte filtration through the microchannel was significantly weaker in esophagectomy patients than in healthy subjects (p

Hemorrhagic shock causes oxidative stress that leads to tissue injuries in various organs including the lung, liver, kidney and intestine. Excess amounts of free heme released from destabilized hemoproteins under oxidative conditions might constitute a major threat because it can catalyze the formation of reactive oxygen species. Cells counteract this by rapidly inducing the rate-limiting enzyme in heme breakdown, heme oxygenase-1 (HO-1), which is a low-molecular-weight stress protein. The enzymatic HO-1 reaction removes heme. As such, endogenous HO-1 induction by hemorrhagic shock protects tissues from further degeneration by oxidant stimuli. In addition, prior pharmacological induction of HO-1 ameliorates oxidative tissue injuries induced by hemorrhagic shock. In contrast, the deletion of HO-1 expression, or the chemical inhibition of increased HO activity ablated the beneficial effect of HO-1 induction, and exacerbates tissue damage. Thus, HO-1 constitutes an essential cytoprotective component in hemorrhagic shock-induced oxidative tissue injures. This article reviews recent advances in understanding of the essential role of HO-1 in experimental models of hemorrhagic shock-induced oxidative tissue injuries with emphasis on the role of its induction in tissue defense.

腎機能は新生児で成人の約7分の1, 肝機能は半分程度しかない. しかし生後約1年を過ぎるとほぼ成人に近い機能を備えることになる. では, 精神の発達は何歳で成人と同じになるのだろうか？精神発達の未熟な子どもたちが手術を受けなければならないと知ったとき, その不安や恐怖は安易に想像できるものではないだろう. 大きな不安を抱えたまま手術に臨むと, 術後に異常行動を起こしたり, 果ては術後の回復を遅らせたりもする可能性がある. また, 記銘障害や学習障害を受けたりする子どもも少なくない. こうした望ましくない反応を防ぐための介入には, 前投薬, 両親との同伴麻酔導入などの麻酔導入方法の検討, 術後鎮痛, などがあげられる. 前投薬が最も効果的なのは2～5歳くらいの学童期以前の小児ではあるが, 年長児に使用した報告もある. 親同伴で麻酔を導入することが子どもの不安を軽減する, との報告もあるが, ミダゾラム前投薬の方が効果的である. ただし, 同伴することは親の不安を軽減するし, これは子どもの不安軽減にもつながる. マスクか静注導入かは意見が分かれる. PCAやPCEAは小児でも安全かつ有効に使用でき, ぜひとも慣れておきたい鎮痛方法である. 子どもたちがストレスなく周術期を過ごし, ひいてはその後の健やかな成長・発達に寄与できるようわれわれも関与すべきであろう.

Suppression of peri-infarct depolarizations (PIDs) is one of the major mechanisms of hypothermic protection against transient focal cerebral ischemia. Previous studies have shown the lack of hypothermic protection against permanent focal ischemia. We hypothesized the lack of hypothermic protection was due to the poor efficacy in suppression of PIDs. To examine the hypothesis, we elucidated the effects of hypothermia on the manner of propagation of PIDs with temporal and spatial resolutions using NADH (reduced nicotinamide adenine dinucleotide) fluorescence images by illuminating the parietal-temporal cortex with ultraviolet light. Spontaneously hypertensive rats (n=14) were subjected to permanent focal ischemia by occlusion of the middle cerebral and left common carotid arteries. 2-h hypothermia (30 degrees C) was initiated before ischemia. Although hypothermia delayed the appearance of PIDs, it did not suppress their appearance. Furthermore, 54% of the PIDs enlarged the high-intensity area of NADH fluorescence in the hypothermia group, similar to the normothermia group (53%). The high-intensity area of NADH fluorescence widened by each PID was larger in the hypothermia group than in the normothermia group. These findings suggest that PIDs even in hypothermia are one of the major factors causing growth of infarction, emphasizing the importance of therapy that targets suppression of PIDs even during hypothermia.

Brain-derived neurotrophic factor (BDNF) expression changes in the dorsal root ganglion (DRG) and spinal cord in some pain models. Recently, rat BDNF transcripts containing novel 5' untranslated exons were identified and characterized, and a new numbering system for rat BDNF exons was introduced. We examined the expression profiles of these novel BDNF transcripts in bilateral L4/5 DRGs in an L5-selective spinal nerve ligation (SSNL) model and bilateral L5 DRGs in a complete Freund's adjuvant (CFA) model of rats. L5SSNL increased significantly (P

BACKGROUND: Despite the absence of objective neurological deficits, patients with chronic whiplash-associated disorder (WAD) complain of symptoms such as headache, dizziness, and nausea. These symptoms are also often experienced by patients with cerebrospinal fluid (CSF) leak. It was recently reported that radioisotope (RI) cisternography is useful in the diagnosis of intracranial hypotension due to CSF leak. We investigated the relation between chronic WAD and CSF leak by RI cisternography and evaluated whether epidural blood patch (EBP) administration is effective in the treatment of chronic WAD. METHODS: We studied 66 patients with chronic WAD with symptoms lasting longer than 3 mo. All patients underwent RI cisternography to determine the presence of CSF leak. In patients in whom CSF leak was identified, EBP was administered. Symptoms were assessed before, 1 wk after, and 6 mo after EBP. Work status was also assessed and follow-up RI cisternography was performed. RESULTS: Of the 66 patients, 37 showed CSF leak, and 36 of these patients received EBP 2.2 ± 0.7 times. The mean duration of symptoms was 33 mo. One week after EBP, the percentage of patients with symptoms was decreased significantly compared with that before EBP; headache: 100% vs 17%, respectively, memory loss: 94% vs 28%, dizziness: 83% vs 47%, visual impairment: 81% vs 25%, nausea: 78% vs 42% (P < 0.01). These effects were also observed at the 6 month follow-up examination (P < 0.01). Work status was also significantly improved at follow-up. CONCLUSIONS: We conclude that CSF leak should be considered in some cases of chronic WAD and that EBP is an effective therapy for chronic WAD.

Although propofol and thiopental are commonly used as neuroprotective agents, it has not been determined which is more neuroprotective. This study was designed to quantitatively evaluate the neuroprotective effects of thiopental, propofol, and halothane on brain ischemia by determining P50, ischemic time necessary for causing 50% neuronal damage. Gerbils were anesthetized with thiopental, propofol, or halothane and underwent 2-vessel occlusion (0, 3, 5 or 10 min). Direct current potentials were measured in bilateral CA1 regions, in which histologic evaluation was performed 5 days later. In some animals, extracellular glutamate concentrations (microdialysis) were measured during 7.5 minutes of ischemia. P50 in the thiopental, propofol, and halothane groups were estimated to be 8.4, 6.5 (P

麻酔導入時の筋弛緩薬は現在ベクロニウムが用いられることが多い. スキサメトニウムはその副作用から敬遠される傾向にあるものの, 1分程度で挿管可能となるため急速導入時に依然として広く使用されている. ロクロニウムは欧米ではすでに10年以上前から臨床使用され, 挿管までの時間をスキサメトニウムと同程度に短縮することが可能な非脱分極性筋弛緩薬であるが, 投与量の増加により作用持続時間は延長する. スガマデクスは, 抗コリンエステラーゼ薬とはまったく別の薬理作用で, ロクロニウムまたはベクロニウムによる神経筋遮断を迅速に拮抗する. 深い筋弛緩状態からの回復が可能となり, 筋弛緩薬の使用法を大きく変化させる可能性がある.

Optimizing the performance and increasing the comfort of high-speed trains require the knowledge of aerodynamic effects of a train shape. One of the most critical problems is a compression wave caused by a train entering a tunnel. This noise mainly depends on the cross-sectional area distribution of a train nose. On the other hand, the aerodynamic drag, the stability for side wind, and the low-frequency vibration are attributed to tail shapes. In this study, we studied the effects of train tail shapes on the flow field experimentally. Two models having the same cross-sectional area distribution but with different tail shapes were tested in a low-speed wind tunnel. To analysis the flow field around the model, we used pressure sensitive paint and oil flow techniques. As a result, we could identify the effects of tail shapes for pressure drag and cross wind stability.

昨今の生命科学の進歩は薬理学の研究をより病態に応じた新薬の開発へと向かわせている．しかし，肝不全，腎不全，多臓器不全など，急性臓器不全は高い死亡率を示すにもかかわらず，その治療において決め手となる薬物は未だ開発されていない．これら急性臓器不全の組織障害の病態生理は完全に明らかでないが，好中球の活性化や虚血・再潅流にともなう酸化ストレスによる細胞傷害が大きな役割を果たしている．酸化ストレスはヘムタンパク質からヘムを遊離させる．遊離ヘムは脂溶性の鉄であることから，活性酸素生成を促進して細胞傷害を悪化させる．この侵襲に対抗するために，ヘム分解の律速酵素：Heme Oxygenase-1（HO-1）が細胞内に誘導される．HO-1によるヘム分解反応産物である一酸化炭素，胆汁色素には，抗炎症・抗酸化作用がある．したがって，遊離ヘム介在性酸化ストレスよって誘導されたHO-1は酸化促進剤である遊離ヘムを除去するのみならず，これらの代謝産物の作用を介して細胞保護的に機能する．一方，HO-1の発現抑制やHO活性の阻害は酸化ストレスによる組織障害を悪化させる．この，HO-1の細胞保護作用に着目して，HO-1誘導を酸化ストレスによる組織障害の治療に応用する試みがなされている．本稿では，急性臓器不全モデルにおいて障害臓器に誘導されたHO-1が，遊離ヘム介在性酸化ストレスから組織を保護するのに必須の役割を果たしていることを述べる．また，抗炎症性サイトカイン：インターロイキン11，塩化スズ，グルタミンがそれぞれ，肝臓，腎臓，下部腸管特異的にHO-1を誘導し，これら組織特異的に誘導されたHO-1が標的臓器の保護・回復に重要な役割を果たしていることを示す．HO-1誘導剤の開発は急性臓器不全の新しい治療薬となる可能性を秘めている．

手術による出血死は麻酔関連偶発症による死亡症例の17%を占めている. 手術に伴う大量出血が発生し, 危機的状況へと拡大していく過程には, 術前の患者状態や病巣の癒着・浸潤のほかに, 手術の手技と判断, 麻酔管理, 血液製剤の準備と追加供給状況, 緊急避難的輸血による対応の有無など, さまざまなヒューマンファクターが関与している. 手術出血死を回避するためには, 医療機関の組織的対応能力と血液センターとの連携を向上させる必要がある.

Peripheral arterial disease often causes ischemic ulcers due to impaired blood flow and consequentially induces intractable pain. For these patients, we have recently begun to administer morphine orally. In this study, we retrospectively examined the effects of oral morphine for the relief of pain caused by peripheral arterial disease.Oral morphine was administered to 17 cases of peripheral arterial disease between January, 2004 and February, 2006. The initial dosage was 5 mg or 10 mg, started on an as-needed basis. After the daily dosage of morphine became constant, we divided the dosage into four or six times a day and administered it regularly. With the exception of one case, a small amount of oral morphine, from 20 mg to 70 mg a day, could alleviate patient's pain. Eight cases had side effects such as nausea, constipation or drowsiness.Oral morphine is effective for pain relief of peripheral arterial disease patients. However, now in Japan, oral morphine, which we can prescribe for those patients with insurance, has a shorter duration of action, so we need to administer slow-release morphine. Oral morphine must be administered carefully because many peripheral arterial disease patients have cardiac disease or renal dysfunction as complications.

To study the impact of pre-morbid glycemic control on the association between acute hypoglycemia in intensive care unit (ICU) patients and subsequent hospital mortality in critically ill patients.We performed a multicenter, multinational, retrospective observational study of patients with available HbA1c levels within the 3-month period preceding ICU admission. We separated patients into three cohorts according to pre-admission HbA1c levels (6.5, 6.5-7.9, ≥8.0%, respectively). Based on published data, we defined a glucose concentration of 40-69 mg/dL (2.2-3.8 mmol/L) as moderate hypoglycemia and40 mg/dL (2.2 mmol/L) as severe hypoglycemia. We applied logistic regression analysis to study the impact of pre-morbid glycemic control on the relationship between acute hypoglycemia and mortality.A total of 3084 critically ill patients were enrolled in the study. Among these patients, with increasing HbA1c levels from6.5, to 6.5-7.9, and to ≥8.0%, the incidence of both moderate (3.8, 11.1, and 16.4%, respectively; p0.001) and severe (0.9, 2.5, and 4.3%, respectively; p0.001) hypoglycemia progressively and significantly increased. The relationship between the occurrence of hypoglycemic episodes in the ICU and in-hospital mortality was independently and significantly affected by pre-morbid glucose control, as assessed by adjusted odds ratio (OR) and 95 % confidence interval (CI) for hospital mortality: (1) moderate hypoglycemia: in patients with6.5, 6.5-7.9, and ≥8.0 % of HbA1c level-OR 0.54, 95% CI 0.25-1.16; OR 0.82, 95 % CI 0.33-2.05; OR 3.42, 95 % CI 1.29-9.06, respectively; (2) severe hypoglycemia: OR 1.50, 95% CI 0.42-5.33; OR 1.59, 95% CI 0.36-7.10; OR 23.46, 95% CI 5.13-107.28, respectively (interaction with pre-morbid glucose control, p = 0.009). We found that the higher the glucose level before admission to the ICU, the higher the mortality risk when patients experienced hypoglycemia.In critically ill patients, chronic pre-morbid hyperglycemia increases the risk of hypoglycemia and modifies the association between acute hypoglycemia and mortality.

Mortality and morbidity of acute kidney injury (AKI) after cardiac surgery still remain high. The authors undertook the present study to evaluate the utility of early postoperative urinary albumin (uAlb) as a diagnostic marker for predicting occurrence of AKI and its severity in pediatric patients undergoing cardiac surgery.A prospective observational study.A single-institution university hospital.All patients18 years of age who underwent repair of congenital heart disease with cardiopulmonary bypass between July 2010 and July 2012 were included in the study. Neonates age1 month were excluded from the study population.The association between uAlb and occurrence of AKI within 3 days after admission to the intensive care unit was investigated. Criteria from pediatric-modified Risk Injury Failure Loss and End-stage kidney disease (pRIFLE) were used to determine the occurrence of AKI. The value of uAlb was measured at intensive care unit admission immediately after cardiac surgery in all participants from whom a 5-mL urine sample was obtained.Of 376 patients, AKI assessed by pRIFLE was identified in 243 (64.6%): 172 for risk (R; 45.7%), 44 for injury (I; 11.7%), and 27 for failure (F; 7.2%). One hundred thirty-three patients (35.4%) were classified as being without AKI (normal [N]) by pRIFLE. The concentration of uAlb was significantly higher in AKI patients than in non-AKI patients (median [interquartile range]): uAlb (µg/mL): 13.5 (6.4-39.6) v 6.0 (3.4-16), p0.001; uAlb/Cr (mg/gCr): 325 (138-760) v 121 (53-269), p0.001.The utility of uAlb for prompt diagnosis of AKI was shown. Obtaining uAlb measurements early after pediatric cardiac surgery may be useful for predicting the occurrence and severity of AKI.

In patients with advanced oesophageal carcinoma with aortic invasion, any therapy potentially causes fatal haemorrhage. We describe here the successful application of intra-aortic stent graft to prevent haemorrhage before radical oesophagectomy for advanced oesophageal cancer. Four patients with advanced oesophageal cancer complicated by invasion of the aorta. Under general anaesthesia, aortic invasion is evaluated by an intravascular sonography. The stent graft is passed through the right femoral artery into the descending aorta. Subsequently, the stent graft is released to expand in the thoracic aorta during an artificial cardiac arrest. Aortography is performed to check for any stent migration or endoleakage. This procedure was successful in all four patients without any complications. All patients underwent radical oesophagectomy following aortic stent-grafting. One patient survived more than 2 years after stent grafting and operation. This procedure is safe and applicable for the patient with aortic invasion before radiochemotherapy or operation.

Oxidative stresses associated with ischemia/reperfusion, neutrophil activation, and anesthesia with certain volatile agents, etc., are thought to play an important role in the development of acute organ failure in critical illnesses, such as acute lung injury, acute coronary artery insufficiency, acute liver failure, acute renal failure, and multiple organ dysfunction syndrome. Such oxidative stressors provoke a set of cellular responses, particularly those that participate in the defense against tissue injuries. Free heme, which can be rapidly released from hemeproteins, may constitute a major threat in the oxidant stress because it catalyzes the formation of reactive oxygen species. To counteract such insults, cells respond by inducing the 33-kDa heat shock protein, heme oxygenase (HO)-1, the rate-limiting enzyme in heme degradation. Induced HO-1 as such removes free heme by an enzymatic process. In addition, HO-1 induction itself confers protection to tissues from further oxidative injuries. In contrast, the abrogation of HO-1 induction, or chemical ablation of HO activity abolishes the beneficial effect of HO-1, and results in the aggravation of tissue injuries. In this article, we review recent advances in the essential role of HO-1 in tissue protection in various models of experimental oxidative tissue injuries as well as in human disorders, which is related to critically ill conditions, with special emphasis on the role of its induction in tissue defense and its potential therapeutic implications. Drug Dev. Res. 67:130–153, 2006. © 2006 Wiley-Liss, Inc.

Institutional review board approval and patient informed consent were obtained. Radiofrequency ablation in a total of 10 sessions was performed for each mediastinal lymph node metastasis from esophageal cancer that had a mean largest diameter of 2.2 cm +/- 0.6 (standard deviation) in seven male patients (mean age, 59 years). During ablation, cooling and temperature of the tracheal mucosa were monitored in the proper position in eight of the 10 sessions; in the other two sessions, monitoring was not done because of tracheal stenosis (perforation resulted). Three of the four lymph nodes that were 2.0 cm or smaller in largest diameter showed no evidence of local progression for at least 1 year since ablation; all three of the nodes greater than 2.0 cm in largest diameter progressed within 6 months. The 1-year survival rate was 60%; the median survival time was 13 months. Radiofrequency ablation may be effective for local control of small metastatic mediastinal lymph nodes, and cooling and temperature monitoring of the tracheal mucosa in the proper position may prevent thermal tracheal damage.

We investigated whether perioperative extensive epidural block (C3-L) affects postoperative immune response in patients undergoing radical esophagectomy. Patients undergoing radical esophagectomy were randomly assigned to either general anesthesia with continuous epidural infusion via 2 epidural catheters that was continued for postoperative analgesia (group E, n = 15) or intraoperative general anesthesia and postoperative IV morphine analgesia (group G, n = 15). Plasma levels of stress hormones, cytokines, C-reactive protein (CRP), leukocyte counts, and distribution of lymphocyte subsets were assessed before and after surgery and on postoperative days (PODs) 1 and 3. In comparison with group E, significant increases in plasma epinephrine level at the end of surgery (P0.05) and norepinephrine level at the end of surgery (P0.01) and on POD1 (P0.01) and POD3 (P0.01) and significant decrease in cluster of differentiation (CD4/CD8 ratio) at the end of surgery (P0.05) were observed in group G. However, there were no significant differences in other variables between groups. In both groups, plasma cortisol, adrenocorticotropic hormone, interleukin (IL)-1beta, IL-6, IL-10, and CRP levels were increased after surgery (each group P0.01) and IL-1beta, IL-6, IL-10, and CRP were still increased on POD1 and POD3 (each change, each group P0.01). Leukocyte counts were increased on POD1 (each group P0.05) and POD3 (each group P0.01). The proportion of lymphocytes decreased from the end of surgery to POD3 (each group P0.01). The proportion of B cells was increased on POD1 (each group P0.01); that of natural killer cells was decreased at POD1 and POD3 (each group P0.01). We conclude that tissue damage and inflammation apparently overcome the effects of extensive epidural block on stress response and immune function in radical esophagectomy.

There is currently no effective pharmacological treatment for amyotrophic lateral sclerosis (ALS). In a transgenic mouse model of ALS, intrathecal infusion of insulin-like growth factor (IGF)-1 showed a promising increase in survival. We performed a double-blind clinical trial to assess the effect of intrathecal administration of IGF-1 on disease progression in patients with ALS.Nine patients with ALS were randomly assigned to receive either a high dose (3 microg/kg of body weight) or low dose (0.5 microg/kg of body weight) of IGF-1 every 2 weeks for 40 weeks. The outcome measurements were the rate of decline of bulbar and limb functions (Norris scales) and forced vital capacity.The high-dose treatment slowed a decline of motor functions of the ALS patients in total Norris and limb Norris scales, but not in bulbar Norris or vital capacity. The intrathecal administration of IGF-1 had a modest but significant beneficial effect in ALS patients without any serious adverse effects.Intrathecal IGF-1 treatment could provide an effective choice for ALS although further studies in more patients are needed to confirm its efficacy and optimize dosages of IGF-1.

Objective:To evaluate the therapeutic effects of hypothermia for a short period (20 mins, 31°C) using a cardiac arrest model (5 mins) in rats.Design:Prospective animal study.Setting:Experimental laboratory in a university hospital.Subjects:Male Wistar rats (n = 42).Intervention:Direct current (DC) p

Hemorrhagic shock followed by resuscitation (HSR) induces oxidative stress, which leads to acute lung injury. Heme oxygenase (HO)-1 (EC 1.14.99.3), the rate-limiting enzyme in heme catabolism, is inducible by oxidative stress and is thought to play an important role in the protection from oxidative tissue injuries. In this study, we examined expression of HO-1 as well as tissue injuries in the lung, liver, and kidney after HSR in rats. We also pretreated animals with heme arginate (HA), a strong inducer of HO-1, and examined its effect on the HSR-induced lung injury. HO-1 expression significantly increased in the liver and kidney following HSR, while its expression in the lung was very low and unchanged after HSR. In contrast to HO-1 expression, tissue injury and tumor necrosis factor-alpha (TNF-alpha) gene expression was more prominent in the lung compared with those in the liver and kidney. HA pretreatment markedly induced HO-1 in pulmonary epithelial cells, and ameliorated the lung injury induced by HSR as judged by the improvement of histological changes, while it decreased TNF-alpha and inducible nitric oxide synthase gene expression, lung wet weight to dry weight ratio, and myeloperoxidase activity. In contrast, inhibition of HO-1 by tin-mesoporphyrin administration abolished the beneficial effect of HA pretreatment. These findings suggest that tissues with higher HO-1 may be better protected than those with lower HO-1 from oxidative tissue injury induced by HSR. Our findings also indicate that HA pretreatment can significantly suppress the HSR-induced lung injury by virtue of its ability to induce HO-1.

Objective The aim of the present study was to investigate whether glutamine pretreatment improves intestinal injury in rats with endotoxemia by its heme oxygenase-1 induction in the lower intestinal tract. Design Randomized, blinded, controlled animal study. Setting University-based animal research facility. Subjects Sprague-Dawley male rats, weighing 220-250 g (n = 201). Interventions Rats were treated with glutamine (0.75 g/kg) dissolved in lactated Ringer's solution via the tail vein. Endotoxemia was induced in rats by intraperitoneal injection of lipopolysaccharide (10 mg/kg or 20 mg/kg for survival study). Lipopolysaccharide-treated animals were pretreated with glutamine or lactated Ringer's solution 9 hrs before lipopolysaccharide treatment. Some of the glutamine-pretreated animals further received tin mesoporphyrin (1 micromol/kg), a specific inhibitor of heme oxygenase activity, 1 hr before lipopolysaccharide treatment. Measurements and main results Glutamine treatment markedly induced heme oxygenase-1 messenger RNA and protein in the mucosal epithelial cells as well as in the lamina propria cells in the ileum and the colon, whereas its expression in the duodenum and the jejunum was not influenced by the treatment. Glutamine treatment before lipopolysaccharide administration significantly ameliorated lipopolysaccharide-induced mucosal injury, inflammation, and apoptotic cell death in the ileum and the colon, as judged by significant decreases in tumor necrosis factor-alpha gene expression, histologic damage scores, and expression of activated caspase-3 and by an increase in gene expression of Bcl-2. In addition, glutamine treatment markedly decreased lipopolysaccharide-induced mortality. In contrast, treatment with tin mesoporphyrin abolished the beneficial effect of glutamine pretreatment. Conclusions Glutamine pretreatment significantly ameliorated intestinal tissue injury of rats following lipopolysaccharide treatment. The same treatment also improved the survival of animals from endotoxemia. The protective effect of glutamine is mediated by its lower intestine-specific induction of heme oxygenase-1, since its inhibition by tin mesoporphyrin completely abolished the beneficial effect of glutamine.

The Japanese Society of Anesthesiologists (JSA) Subcommittee on Surveillance of Anesthesiarelated Critical Incidents sent confidential questionnaires to all JSA Certified Training Hospitals (n=806 on average) every year from 1999 to 2002. Data collected in the identical forms each year were analyzed for incidence of cardiac arrest and other critical events during anesthesia and surgery, and for outcomes within 7 postoperative days. The principal cause of each critical incident selected from a list of 52 items provided on the questionnaires was also analyzed.With an average response rate of 75.0%, a total of 4, 297, 066 cases were documented over 4 years. A total of 2, 860 patients died within 7 postoperative days. The two principal causes of deaths were preoperative hemorrhagic shock and massive hemorrhage during surgery (Fig. 2), representing 32.8% [95% CI at p

Heme oxygenase-1 (HO-1) is induced by oxidative stress and is thought to confer protection against oxidative tissue injuries. HO-1 catalyzes the conversion of the heme moiety of hemeproteins, such as hemoglobin, myoglobin, and cytochrome P450, to biliverdin, liberating carbon monoxide (CO) in the process. CO reacts with hemoglobin to form carboxyhemoglobin. In this study, to examine the effect of anesthesia and/or surgery on endogenous CO production, we measured the amount of exhaled CO and the arterial carboxyhemoglobin concentration of patients who underwent surgery under general or spinal anesthesia. Both CO and carboxyhemoglobin concentrations were significantly larger on the day after surgery than during the preoperative period (P < 0.05) and in the recovery room (P < 0.05), regardless of anesthesia. However, neither index differed between general and spinal anesthesia. These results suggest that oxidative stress caused by anesthesia and/or surgery may induce HO-1, which catalyzes heme to produce CO, leading to increased exhaled CO concentration.

UNLABELLED We investigated the spatial and temporal patterns of c-Fos protein (Fos) expression in the dorsal horn of the spinal cord caused by plantar incision in the rat and the effects of pretreatment with local anesthetics. Bupivacaine (0.5%), lidocaine (2%), or saline for control was injected for nerve block and local infiltration before the plantar incision was made under anesthesia. Pain behavior and Fos expression in the L4-L5 segments of the spinal cord were assessed at 1, 3, 6, 24, 48, 72, and 120 h after the incision. The withdrawal threshold to mechanical stimulation decreased significantly at 1 h until 120 h (1-72 h, P < 0.01;120 h, P < 0.05), and pretreatment with local anesthetics increased the threshold significantly at 1 h (both groups: P < 0.01), 3 h (both groups: P < 0.01), and 6 h (bupivacaine, P < 0.01; lidocaine, P < 0.05) in comparison with that in the saline group. In the saline group, Fos expression was detected predominantly in laminae I-II and V-VI, and the total Fos expression was maximal at 1 h and then decreased gradually. Pretreatment with local anesthetics suppressed Fos expression significantly in all layers, and this suppression continued for several days. This study provides evidence of spatial and temporal changes in Fos expression induced by plantar incision. Our results indicate that although pretreatment with local anesthetics suppresses Fos expression for several days in the postoperative period, the analgesic effect is observed only for the expected duration of the local anesthetic used. IMPLICATIONS Prevention of early pain by pretreatment with local anesthetics provides little benefit for postoperative pain relief in the plantar incision model, although c-Fos expression is suppressed. The number of c-Fos-expressing neurons is not necessarily correlated with pain behavior.

術後の硬膜外ブロックは, 現在では質の高い術後疼痛管理法として広く用いられている. しかし, 副作用が出現すると鎮痛処置が制限されるため効果不十分となり, 患者満足度はますます低下する. またまれではあるが, さまざまな重篤な合併症が報告されている. 副作用や合併症の発生による入院期間の延長は, 結果としてコスト増加を引き起こす. 術後硬膜外ブロック中によくみられる副作用として, 悪心・嘔吐, 掻痒感, 下肢のしびれ感・運動麻痺, 低血圧, 呼吸抑制, 尿閉などがある. これらは, ある程度の頻度で必ず起こるが, 適切な対応により生命を脅かすような重篤な副作用となることは少ないため, 大きな注意が払われないことが多い. 術後痛研究会およびわれわれの調査結果でも, 悪心・嘔吐が最も多く30～50%, 下肢の運動麻痺・しびれが約30%で続き, 掻痒感も約20%の症例に認められた. 硬膜外ブロックの重篤な合併症としては, 硬膜外血腫, 膿瘍, 髄膜炎や脳炎, 全脊髄くも膜下麻酔, 局所麻酔薬中毒のように永続的な神経障害を残す, あるいはときとして致命的ともなる重篤な合併症が知られる. 最近, 硬膜外腔の貯留物が脊柱管を前方に圧迫することによって神経症状を呈するEpidural Compartment Syndromeという概念も報告されている. これらの重篤な合併症の発生はまれであるが, 硬膜外鎮痛法を用いるときは常に念頭におく必要がある. 合併症防止対策としては, 術後回診による一人ひとりの患者に応じた対応を確実に行うとともに, 病棟での管理であるということを念頭におき, 安全を最優先に考えたうえでの対処が必要である. 他科医師や看護師の教育とともに副作用に対する対応や器械の操作など基本的なことはマニュアルで示し, さらに講義など教育の場を設けて周知をはかる必要がある.

To determine the effectiveness of nasopharyngeal cooling for selective brain cooling and neuroprotection from ischemia.Prospective animal study.Experimental laboratory in a university hospital.Male Wistar rats (n = 28).In study 1, hippocampal temperature was decreased to 31 degrees C under spontaneous circulation. In the nasopharyngeal cooling group, physiologic saline (5 degrees C) was infused to the bilateral nasal cavities at the rate of 100 mL.min-1.kg weight-1. In the whole body cooling group, a fan and a water blanket (5 degrees C) were used. In study 2, ischemia and resuscitation were performed in normothermic and nasopharyngeal cooling (initiated with resuscitation after 5 mins of ischemia and continued for 20 mins) groups.The hippocampal temperature was decreased to 31 degrees C in 7 +/- 2 mins without any change in the rectal temperature in the nasopharyngeal cooling group, whereas a decrease in hippocampal temperature to 31 degrees C took 33 +/- 1 mins in the whole body cooling group. Although skull base region was cooled by nasopharyngeal cooling, the epidural temperature of the parietal region was lower than the hippocampal temperature, indicating that brain temperature was hematogenously lowered. There was no difference between changes in cerebral blood flow or between the ratios of oxygen extraction from arterial blood in the head region in the nasopharyngeal cooling and whole body cooling groups. In the second study, all animals were successfully resuscitated, and the times required for recovery of mean arterial blood pressure (60 mm Hg) after resuscitation in the nasopharyngeal cooling and normothermic groups were the same. The histologic damage was significantly attenuated in the nasopharyngeal cooling group (33 +/- 21% cell death in the hippocampus) compared with that in the normothermic group (73 +/- 11%).Nasopharyngeal cooling enables rapid and selective reductions in cortical and subcortical temperatures without disturbing the recovery of systemic circulation after resuscitation.