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Sevoflurane and droperidol prolong the QT interval, and advancing age is not only associated with a prolongation of the QT interval but is also a risk factor for drug-induced QT interval prolongation. In this study, we compared the effect of sevoflurane and droperidol on the corrected QT (QTc) interval and the dispersion of ventricular repolarization (time interval from the peak to the end of the T wave [Tp-e]) in elderly patients with those in younger patients.Under sevoflurane anesthesia (1.5%-2.5%) with an antiemetic dose of droperidol (1.25 mg), the QT interval and the Tp-e interval, which indicates transmural dispersion of repolarization across the myocardial wall, were measured in 30 elderly patients (70 years and older) and in 30 younger patients (20-69 years) for 2 hours. The QT interval was normalized for heart rate (QTc) using 3 different formulas: Bazett, Matsunaga, and Van de Water. Data are presented as mean +/- sd.The elderly group was 24.4 years older (P0.05) than the younger group. The QTc intervals in the 2 groups before anesthesia were not significantly different. Using all 3 formulas, the QTc interval in the elderly patient group was significantly prolonged by sevoflurane (the QTc intervals at preanesthesia and 60, 75, 90, and 120 minutes after sevoflurane exposure were 0.434 +/- 0.028 seconds, 0.450 +/- 0.037 seconds, 0.463 +/- 0.037 seconds, 0.461 +/- 0.037 seconds, and 0.461 +/- 0.038 seconds, respectively, with the Bazett formula). The sevoflurane-induced QTc interval prolongation in the elderly patient group was significantly greater than that in the younger patient group (0.450 +/- 0.037 seconds vs 0.432 +/- 0.034 seconds, 60 minutes after sevoflurane exposure; 0.463 +/- 0.037 seconds vs 0.441 +/- 0.037 seconds, 75 minutes after sevoflurane exposure; and 0.461 +/- 0.038 seconds vs 0.436 +/- 0.030 seconds, 120 minutes after sevoflurane exposure with the Bazett formula), but the sevoflurane-induced QTc interval prolongation was neither further enhanced with time nor by droperidol. The Tp-e interval was not affected in either group.Sevoflurane causes greater QTc interval prolongation in elderly patients than in younger patients. Although sevoflurane does not affect the transmural dispersion of repolarization and sevoflurane-induced QTc prolongation does not advance with time and by droperidol administration, QT interval prolongation and its associated arrhythmias should be carefully monitored during sevoflurane anesthesia in elderly patients.

Recent studies have shown that similar to cerebral gray matter (mainly composed of neuronal perikarya), white matter (composed of axons and glias) is vulnerable to ischemia. Edaravone, a free radical scavenger, has neuroprotective effects against focal cerebral ischemia even in humans. In this study, we investigated the time course and the severity of both gray and white matter damage following global cerebral ischemia by cardiac arrest, and examined whether edaravone protected the gray and the white matter. Male Sprague-Dawley rats were used. Global cerebral ischemia was induced by 5 minutes of cardiac arrest and resuscitation (CAR). Edaravone, 3 mg/kg, was administered intravenously either immediately or 60 minutes after CAR. The morphological damage was assessed by cresyl violet staining. The microtubule-associated protein 2 (a maker of neuronal perikarya and dendrites), the β amyloid precursor protein (the accumulation of which is a maker of axonal damage), and the ionized calcium binding adaptor molecule 1 (a marker of microglia) were stained for immunohistochemical analysis. Significant neuronal perikaryal damage and marked microglial activation were observed in the hippocampal CA1 region with little axonal damage one week after CAR. Two weeks after CAR, the perikaryal damage and microglial activation were unchanged, but obvious axonal damage occurred. Administration of edaravone 60 minutes after CAR significantly mitigated the perikaryal damage, the axonal damage, and the microglial activation. Our results show that axonal damage develops slower than perikaryal damage and that edaravone can protect both gray and white matter after CAR in rats.

Background Sufficient analgesia for cancer pain is sometimes difficult to achieve with conventional treatments. We aimed at investigating the analgesic efficacy and safety of intrathecal betamethasone in patients with uncontrollable cancer pain. Methods Betamethasone 1 mg mixed with saline was injected into the lumbar intrathecal space once a week in 10 patients with persistent cancer pain in the lower half of the body. During the 4-week study period, the analgesic efficacy and adverse effects related to intrathecal betamethasone were observed. Results Long-lasting analgesia (mean numerical pain score ≤5) for 7 days, after immediate analgesia within 10 min, was obtained without the need to increase the morphine dose in 5 of 10 patients. In almost all of the patients, not only pain, but also uncomfortable symptoms were improved. Adverse effects related to neurotoxicity of intrathecal betamethasone, such as sensory and motor dysfunctions, were not observed in any patients. Conclusion When conventional cancer pain treatments are not successful, intrathecal betamethasone may be useful, as it probably induces long-lasting analgesia without adverse effects and improves activities of daily living, especially in patients with vertebral bone metastases.

Background: Previous studies reported a higher mortality risk and a greater need for renal replacement therapy in patients administered hydroxyethyl starch (HES) rather than other fluid resuscitation preparations. In this study, we investigated the association between 6% HES 70/0.5 use and postoperative acute kidney injury (AKI) in gastroenterological surgery patients. Methods: We conducted retrospective full-cohort and propensity-score-based analyses of patients who underwent gastroenterological surgery between June 2011 and August 2013 in a Japanese university hospital. The study sample comprised 66 AKI and 2,152 non-AKI patients in the full-cohort analysis and 35 AKI and 1,269 non-AKI patients in the propensity-score-based analysis. Propensity scores were calculated using an ordered logistic regression model in which the dependent variable comprised three groups based on HES infusion volumes (0, 1–999, and ≥ 1,000 ml). The association between HES groups and postoperative AKI incidence was analyzed using multiple logistic regression models. Other candidate independent variables included patient characteristics and intraoperative measures. Results: In the full-cohort analysis, 40 (60.6%) AKI patients were diagnosed as “risk,” 15 (22.7%) as “injury,” and 11 (16.7%) as “failure.” In the propensity-score-based analysis, the corresponding values were 22 (62.9%), 8 (22.9%), and 5 (14.3%). There was no significant association between total infused HES and postoperative AKI incidence in either the full-cohort or the propensity-score-based analysis (P = 0.168 and P = 0.42, respectively). Conclusions: AKI incidence was not associated with clinical 6% HES 70/0.5 administration in gastroenterological surgery patients treated at a single center.

Dopamine release in the nucleus accumbens (NAC) plays a crucial role in the action of various psychotropic and addictive drugs, such as antagonists of the N-methyl-D-aspartate subtype of the glutamate. Although both nitrous oxide and xenon are N-methyl-D-aspartate receptor antagonists, they differ in their potential for producing neuropsychological toxicity; therefore, we decided to examine their effects on both spontaneous and ketamine-induced extracellular dopamine levels in the NAC. A microdialysis probe was implanted into the NAC in each of 35 rats, which were randomly assigned to one of six groups: exposure to 40% O 2 , exposure to 60% nitrous oxide (0.27 MAC), exposure to 43% xenon (0.27 MAC) for 60 min, and three groups exposed to either 40% O 2 , 60% nitrous oxide, or 43% xenon for 70 min and 80 mg/kg ketamine was given i.p. 10 min after the initiation of gas exposure. Perfusate samples were collected every 20 min, and the dopamine levels were measured using a high-performance liquid chromatography system. Nitrous oxide, but not xenon, significantly increased the dopamine level. Ketamine significantly increased the dopamine level, and this was significantly inhibited by xenon, but not by nitrous oxide. These data suggest that the difference in neuropsychological activity between nitrous oxide and xenon is partly due to their differential effects on the mesolimbic dopamine system.

白質病変は慢性脳低灌流が原因と考えられ,高齢者や脳血管病変患者には高頻度に認められる。また,認知機脳障害など臨床徴候に関連している。急性脳虚血においても白質病変の重要性が認識されつつあり,神経細胞体傷害が主体である灰白質病変とは,その傷害のメカニズムや薬物への感受性が異なる。すなわち,白質病変増悪の病因や治療法を調べることは,急性脳虚血の治療という観点からも重要である。われわれは,脳白質病変を主体とするラット脳慢性低灌流モデルを用いて,過換気による低二酸化炭素血症により線条体の白質病変が特異的に増悪すること,この白質病変の急性増悪がN-methyl-D-aspartate受容体拮抗薬ケタミンにより軽減されることを明らかにした。術後せん妄の病因の一つとして低二酸化炭素血症があり,線条体は認知機能やワーキングメモリーに関与している部位であることから,白質病変の増悪がこの術後せん妄など脳機能障害の一因である可能性がある。

There are two major subpopulations of peripheral helper T lymphocytes: T helper 1 (Th1) and T helper 2 (Th2) cells. Surgical stress increases the number of Th2 cells, and decreases that of Th1 cells, resulting in a decrease in the Th1/Th2 ratio, and, consequently, in suppressed cell-mediated immunity. Since anaesthesia can suppress the stress response to surgery, it may inhibit the decrease in the Th1/Th2 ratio. Using flow cytometry, we studied whether propofol anaesthesia (n = 9) or isoflurane anaesthesia (n = 9) had more effect on the decrease in the Th1/Th2 ratio after surgery in patients undergoing craniotomy. The Th1/Th2 ratio decreased significantly after isoflurane anaesthesia (p = 0.011), while it did not change after propofol anaesthesia. The ratio was significantly lower with isoflurane than propofol (p = 0.009). Propofol anaesthesia attenuated the surgical stress-induced adverse immune response better than isoflurane anaesthesia.

Four dicopper(II) oximato complexes of 2-[2-(α-pyridyl)methyl]imino-3-butanone oxime (pmiboH) and 2-[2-(α-pyridyl)ethyl]imino-3-butanone oxime (peiboH), [Cu2(pmibo)2](ClO4)2 (1), [Cu2(pmibo)2](NO3)2·CH3OH (2), [Cu2(peibo)2](ClO4)2·CH3OH (3) and [Cu2(peibo)2(H2O)2](ClO4)2 (4), were prepared and characterized structurally and magnetically. All the dicopper(II) oximato complexes have a common cationic structure in which the two Cu atoms are bridged through two NO bridges of the oximato ligand to afford a dinuclear structure. The cation moieties of 1 and 2 consist of one six-membered Cu2N2O2 chelate ring and four five-membered (CuN2C2 and CuNC2N) chelate rings, providing a planar configuration. The cation moieties of 3 and 4 are also composed of three six-membered (Cu2N2O2 and CuNC3N) chelate rings and two five-membered CuN2C2 chelate rings, giving a twisted-boat configuration. The −2J values (H=−2JS1S2) are 835, 825, 550 and 510 cm−1 for 1, 2, 3 and 4, respectively, indicative of a strong antiferromagnetic interaction in the solid state. All the dicopper(II) oximato complexes show seven 1H NMR signals at 23°C in the range of −0.5 to 30 ppm with the linewidths at half-height, Δν1/2 of 60–1500 Hz, which is characteristic of antiferromagnetic species and indicates that the dinuclear structure is kept in solution. The −2J values reflect the degree of distortion from the planarity of the Cu2 framework. The −2J values roughly correlate with the 1H NMR parameters; the larger the −2J values, the smaller the chemical shifts and linewidths. Complexes 1 and 2 were found to undergo an autoreduction reaction in dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF) and N,N-dimethylacetamide (DMA), and their behaviors were first monitored by UV–Vis and 1H NMR methods.

To investigate the association between steroid medication before hospital admission and barotrauma in mechanically ventilated patients with acute respiratory distress syndrome (ARDS).An observational single-center retrospective study was conducted using patients admitted to the general intensive care unit (ICU) of a university hospital in Japan. We analyzed 149 mechanically ventilated patients with ARDS hospitalized between March 2008 and March 2011. ARDS was identified according to criteria from the Berlin Definition. Barotrauma was defined as pneumothorax, subcutaneous emphysema, or mediastinal emphysema occurring during mechanical ventilation in the ICU. The influence of steroid medication before hospital admission on barotrauma was studied using multiple logistic regression analysis.There were no differences in baseline patient characteristics except for congestive heart failure, peak pressure during mechanical ventilation, and steroid pulse therapy between the barotrauma and non-barotrauma groups. Logistic regression analysis showed that peak pressure ≥35 cmH2O was associated with barotrauma in patients with ARDS [odds ratio (OR), 17.34; P 0.01], whereas steroid medication before hospital admission was not a significant factor for barotrauma (OR, 1.63; P = 0.51).Barotrauma in ARDS patients was associated with higher pressure during mechanical ventilation but not with steroid medication before hospital admission.

BACKGROUND We have reported previously the usefulness of intrathecal betamethasone for pain relief in cancer patients who suffer from intractable pain caused by vertebral metastasis. The mechanism by which betamethasone relieves pain may be related to alterations in cerebrospinal fluid (CSF) concentrations of pro-inflammatory cytokines and prostanoids. METHODS Thirteen cancer patients with intractable pain caused by vertebral metastasis received 2-3 mg betamethasone in the lumbar subarachnoid space. CSF concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, IL-8 and prostaglandin E(2) (PGE(2)) were measured with an enzyme-linked immunosorbent assay (ELISA) and a chemiluminescence enzyme immunoassay. Pain was measured using a numerical pain score (range, 0-10; 0, no pain; 10, worst pain imaginable). RESULTS Intrathecal betamethasone was associated with a significant decrease in the pain score in six patients. In these cases, the pain score decreased from 6.7 +/- 0.5 (mean +/- standard error of the mean) to 3.3 +/- 0.3 (P < 0.05), and the CSF concentrations of IL-8 and PGE(2) decreased significantly compared with pre-treatment levels (IL-8, 183.3 +/- 21.2 to 116.5 +/- 10.6 pg/ml; PGE(2), 43.8 +/- 10.3 to 14.7 +/- 3.0 pg/ml). There were no significant changes in the CSF concentrations of cytokines and PGE(2) in the remaining seven patients. CONCLUSION Pain relief with intrathecal betamethasone is related to decreases in the CSF concentration of IL-8 and PGE(2).

Background: The sigma-1 receptor is functionally linked with psychotomimetic effects of various drugs. A sigma-1 receptor agonist enhances bradykinin-induced intracellular Ca2+ concentration ([Ca2+]i) increase and induces c-Fos expression in a part of the brain. The aim of this study was to investigate the effects of several intravenous anaesthetics on the sigma-1 receptor. Methods: First, using Wistar rat brains, (+)[3H]SKF-10,047, a selective sigma-1 receptor agonist was displaced by propofol, dexmedetomidine, droperidol, and thiopental. Second, Fura-2 loaded NG-108 cells were incubated with (+)pentazocine, a selective sigma-1 receptor agonist, and propofol and then its fluorescence was observed after stimulation with bradykinin. Third, male ICR mice received Intrafat® or propofol intraperitoneally (i.p.), followed by pentazocine i.p. Brain slices were prepared and Fos-like immunoreactivity was detected using an immunohistochemical method. Results: Propofol, droperidol, and dexmedetomidine displaced (+)[3H]SKF-10,047 binding in a concentration-dependent manner with Ki50s of 10.2 ± 0.6, 0.17 ± 0.03, 5.73 ± 1.2 μM, respectively. Thiopental sodium was practically ineffective. Propofol produced a statistically significant reduction in the maximal binding capacity (Bmax) but did not affect the dissociation constant (Kd). (+)Pentazocine significantly enhanced bradykinin-induced [Ca2+]i increases, but propofol did not affect it. Pentazocine induced marked Fos-LI positive cells in the posterior cingulate and retrosplenial cortices (PC/RS), which was significantly reduced by propofol. Conclusions: These results suggest that propofol may be a sigma-1 receptor antagonist, and that various effects of propofol on the brain may be mediated, at least partly, by the sigma-1 receptor.

Spinal anesthesia combined with fentanyl is commonly used for cesarean section. We studied the appropriate dose of isobaric bupivacaine for spinal anesthesia when combined with a fixed dose of 20 microg fentanyl.Forty-seven women scheduled for cesarean section were allocated into four-groups according to the dose of 0.5% isobaric bupivacaine with 20 microg fentanyl; 1.0 ml (n=5), 1.5 ml (n=11), 2.0 ml (n=11), and 2.5 ml (n=20).The requirement of epidural anesthesia for pain relief or muscle relaxant was less in the 2.0 ml and 2.5 ml groups than the other groups. However, dyspnea due to high spinal anesthesia developed in 3 subjects out of 20 in the 2.5 ml group.Two ml of 0.5% isobaric bupivacaine was the most appropriate dose for cesarean section, when combined with 20 microg of fentanyl.

To protect the spinal cord during thoracoabdominal aortic aneurysm repair, motor evoked potentials (MEP) monitoring and cerebrospinal fluid drainage are often employed. Herein, we report a case, where intraoperative diminishment of motor evoked potentials was accompanied by multiple cerebral infarction. A 63-year-old man underwent elective surgery for both thoracoabdominal aortic aneurysm and abdominal aortic aneurysm. He had a past history of cerebral infarction, resulting in Wernicke aphasia but no paralysis. Preoperative magnetic resonance angiography and echocardiography revealed occlusion of the intercostal and lumbar arteries, mild aortic regurgitation, and atherosclerotic lesions at the aortic arch as well as descending aorta. Anesthesia and muscular relaxation were maintained with fentanyl, propofol, and continuous administration of vecuronium at 0.5 mg x kg(-1) x h(-1). The thoracoabdominal aortic aneurysm was repaired under distal aortic perfusion with femorofemoral bypass. After terminating the bypass, we found that the MEP at the lower limb had disappeared. Although we reconstructed intercostal arteries under mild hypothermia and partial bypass, the amplitude of MEP remained very low. Suspecting spinal cord ischemia, we performed cerebrospinal fluid drainage immediately after the operation. On the postoperative day 4, when we stopped the cerebrospinal fluid drainage and propofol administration, his level of consciousness was poor and brain CT revealed multiple cerebral infarction. On the postoperative day 30, he was discharged from an intensive care unit with complications of hemiplagia and paraplegia. Although cerebrospinal fluid drainage may be recommended to protect spinal cord during thoracoabdominal aortic aneurysm repair, we should consider performing brain CT to exclude a risk of brain herniation secondary to cerebrospinal fluid drainage if there is a possibility of cerebral incidents.

We previously demonstrated that the caudoputamen was exclusively further damaged by hypocapnia in a rat with chronic cerebral hypoperfusion which is characterized by white matter lesions (WML) and a well-established model for patients with cerebrovascular diseases and/or dementia, and suggest that this process may be the cause of long lasting postoperative delirium or brain dysfunction in such patients. In the present study, we investigated whether ketamine, a non-competitive N-methyl- d -aspartate receptor antagonist, could attenuate the neuronal damage in the caudoputamen. Ketamine, at doses of 10 and 20 mg/kg, which was given intraperitoneally before hypocapnia induction, attenuated the aggravation of WML score, neuronal damage, and astroglial proliferation in the rat caudoputamen. These results suggest that ketamine may be beneficial for preventing postoperative brain dysfunction, especially in patients with cerebrovascular diseases and/or dementia induced by hypocapnia, which is likely to occur in the mechanical ventilation used during surgery.

We report anesthetic management of a patient suspected of malignant hyperthermia with difficult tracheal intubation. A 64-year-old man was scheduled for a fixation of humerus bone fractures in prone position. He had a history of difficult tracheal intubation due to masseter spasm, and his niece was suspected to be malignant hyperthermia. Anesthesia was induced with propofol using a target controlled infusion. No muscle relaxant was given and spontaneous breathing was maintained. Trials for tracheal intubation failed whenever using a standard laryngoscope, a bronchofiberscope, a laryngeal mask airway or an intubating laryngeal mask airway. Resecting the epiglottic elevating bar of an intubating laryngeal mask airway enabled fiberoptic tracheal intubation. No symptom suggesting malignant hyperthermia developed.

A 42-year-old woman with an Arnold-Chiari abnormality was scheduled for cervical spine surgery. She had severe ankylosing spondylitis, and all her joints from ankles to occipitocervical joint were fixed except hip joints, which had been replaced with artificial joints 20 years before. She could bend her upper body only in a range from -20 to 70 degree from the sitting position. Her posture had been restricted to only sitting for over 20 years, and she complained vertigo when positioned in supine position. The trachea was intubated with an aid of bronchofiberscopy under sedation in sitting position, and then anesthesia was induced with propofol and fentanyl. When she was turned to prone position, nasal bleeding was noticed and the surgery was performed in a modified sitting position. The intra- and post-operative course was uneventful. The present case indicates that long-term restriction only to sitting position modulates circulatory control in response to changing postures, and that preoperative evaluation for appropriate posture for surgery is mandatory.

The cation of [Cu(L1)(OMe)(ClO4)Cu(bpy)] ClO4 (1) consists of two coppers triply bridged by an oximato, a methoxo, and a perchlorato ligand, where L1 is 3-[2-(2-pyridyl)ethyl]amino-2-butanone oxime. The geometry around each copper is distorted square-pyramidal. The cation of [Cu(L1)(OAc)2Cu(bpy)]ClO4 (2), consists of two coppers triply bridged by an oximato, an unidentate and a bidentate acetato ligand. The geometry around the coppers is intermediate between a square pyramid and a trigonal bipyramid.