An amendment to this paper has been published and can be accessed via the original article.

A preliminary study has shown effective cancer pain relief by intrathecal betamethasone (ITB). However, further evidence is needed to support this new approach. Cancer patients with opioid-resistant pain received lumbar intrathecal administration of betamethasone 2 or 3 mg once a week for 28 days. Immediate and short-term analgesia (using a percentage pain reduction scale and a numerical rating scale, NRS) and long-term analgesia (using NRS) were assessed. Patients were classified into two groups according to the most painful site of metastasis: vertebral column and/or surrounding nerve plexus metastases (group A) and other metastases distal from the vertebral column (group B). A total of 104 patients received ITB. Pain relief was observed not only in the lower half but also in the upper half of the body. The proportion of group A patients who experienced immediate analgesia was 81% (47/58), which was significantly greater than that of group B ( P  < 0.001). A decrease in NRS scores 1 day after ITB administration was observed in significantly more patients in group A than in group B ( P  < 0.001). Long-term analgesia was also recorded in a greater proportion of patients in group A than in group B in the 7-day (59%, 38/64 vs 6%, 2/33) and 28-day periods (71%, 40/56 vs 31%, 8/26) ( P  < 0.001). No adverse effects related to neurotoxicity were recorded. Intrathecal injection of betamethasone produced analgesia for opioid-resistant cancer pain, and may be a potent therapeutic option for intolerable pain from vertebral column and/or surrounding nerve plexus metastases.

60歳代，女性．統合失調症による緊張病性昏迷状態に対し電気けいれん療法（ECT）を施行した．チオペンタールによるECTでは施行回数に伴いけいれん誘発が困難となった．レミフェンタニルを併用しチオペンタールを減量することでけいれんを誘発したが，さらに回数を重ねたところ，けいれんが生じなくなった．静脈麻酔薬をチオペンタールからケタミンに変更した．ケタミン単独投与によるECTでは，けいれんは誘発できたが精神状態が悪化した．レミフェンタニルを併用しケタミンを減量したところ，けいれんは生じ精神状態も良好となった．

A 37-year-old female patient with myotonic dystrophy was scheduled for laparoscopic cholecystectomy for gall stone under general anesthesia with continuous propofol infusion. Rocuronium was administered with careful monitoring using TOF- Watch®, measuring train-of-four count (Tc), TOF ratio (Tr), and posttetanic count The total amount of rocuronium was 70 mg ; 0.6 mg .kg⁻1 for anesthetic induction and 0.3 mg .kg⁻1 when Tc exceeded 1. When the operation was completed, Tc was 4, Tr was uncountable and she showed reaction to calling her name. Then sugammadex 2 mg .kg⁻1, rapidly antagonized the neuromuscular block, such that the Tr recovered to 100% but tidal volume was 250 ml in 3 minutes. Additional dorsage of sugammadex, 2 mg .kg⁻1, was required for tidal volume to recover to 530 ml. After 20 minutes of first administration of sugammadex, we extubated the tracheal tube without respiratory depression. To avoid respiratory depression, we did not use postoperative opioids. Intraoperative transversus abdominis plane block and postoperative thoracic epidural block with ropivacaine were successful for postoperative pain relief.

Study Objectives: To evaluate the accuracy of target-controlled infusion (TCI) of propofol based on total body weight (TBW) in severely obese patients using the Marsh pharmacokinetic model. Design: Prospective study. Setting: A large tertiary care teaching hospital. Patients: Severely obese (body mass index ≥35) adult patients who underwent scheduled surgery between April 1, 2014 and March 31, 2015. Interventions: None.

Dexmedetomidine, an α2-adrenergic/imidazoline receptor agonist, is a widely used intravenous anesthetic. Its primary current usage is for sedation of patients in the intensive care unit. The mouse air pouch model is versatile in studying the anti-inflammatory effect of a drug on a local inflammation, which is induced by a variety of substances. In the present study, using the carrageenan-induced air pouch inflammation model, we tested whether dexmedetomidine mitigates inflammation occurring locally in the mouse air pouch. We found that dexmedetomidine dose-dependently inhibited the production of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in the pouch and decreased the number of white blood cells (WBC) recruited into the pouch. Dexmedetomidine also dose-dependently inhibited the production of neutrophil chemokines, cxcl1 and cxcl2. Furthermore, the dexmedetomidine-induced decreased recruitment of WBC into the pouch was successfully reversed with intra-pouch administration of cxcl1/cxcl2, but not TNF-α or IL-6. Lastly, the inhibition of the production of the cytokines and chemokines with dexmedetomidine was reversed by the treatment of yohimbine, suggesting that dexmedetomidine's anti-inflammatory effect is primarily via the stimulation of the α2-adrenergic receptor. We conclude that dexmedetomidine has an anti-inflammatory property in the carrageenan-induced mouse air pouch inflammation model, and that the dexmedetomidine-induced inhibition of production of the neutrophil chemokines, cxcl1 and cxcl2, may be related, at least in part, to the inhibition of WBC intra-pouch recruitment.

BACKGROUND:The local anesthetic lidocaine can affect intra- and extra-cellular signaling pathways in both neuronal and non-neuronal cells, resulting in long-term modulation of biological functions, including cell growth and death. Indeed, lidocaine was shown to induce necrosis and apoptosis in vitro. While several studies have suggested that lidocaine-induced apoptosis is mitochondrial pathway-dependent, it remains unclear whether reactive oxygen species (ROS) are involved in this process and whether the observed cell death can be prevented by antioxidant treatment.METHODS:The effects of lidocaine and antioxidants on cell viability and death were evaluated using SH-SY5Y cells, HeLa cells, and HeLa cell derivatives. Cell viability was examined via MTS/PES ([3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt]/phenazine ethosulfate) assay. Meanwhile, cell apoptosis and necrosis were evaluated using a cell death detection assay with Annexin V-FITC and PI staining, as well as by assaying for caspase-3/7 and caspase-9 activity, and by measuring the release of lactate dehydrogenase, respectively. Mitochondrial transmembrane potential (ΔΨm) was assessed using the fluorescent probe tetramethylrhodamine ethyl ester.RESULTS:Lidocaine treatment resulted in suppression of the mitochondrial electron transport chain and subsequent attenuation of mitochondrial membrane potential, as well as enhanced ROS production, activation of caspase-3/7 and caspase-9, and induction of apoptosis and necrosis in SH-SY5Y cells in a dose- and time-dependent manner. Likewise, the anesthetics mepivacaine and bupivacaine also induced apoptosis in SH-SY5Y cells. Notably, the antioxidants N-acetyl cysteine (NAC) and Trolox successfully scavenged the mitochondria-derived ROS and suppressed local lidocaine-induced cell death.CONCLUSIONS:Our findings demonstrate that the local anesthetics lidocaine, mepivacaine, and bupivacaine inhibited the activity of mitochondria and induced apoptosis and necrosis in a dose-dependent manner. Furthermore, they demonstrate that treatment with the antioxidants NAC, Trolox, and GGA resulted in preservation of mitochondrial voltage and inhibition of apoptosis via suppression of caspase activation.

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.

Ultiva™ contains the potent short-acting μ-opioid receptor agonist remifentanil hydrochloride, and it is commonly administered intravenously during general anesthesia. It is not approved for epidural or intrathecal use in clinical practice because it contains glycine as an acidic buffer. However, at this moment, very limited information is available on epidural administration of Ultiva™.

The stiff-person syndrome (SPS) is a rare autoimmune neurologic disorder that affects the gamma-aminobutyric acid (GABA) mediated inhibitory network in the central nervous system with anti-glutamic acid decarboxylase (GAD) antibodies. SPS is characterized by muscle rigidity and painful episodic spasms in axial and lower limb muscles. This case report describes successful peri-operative management of a 61-year-old female (height, 158 cm; weight, 60 kg, ASA-PS 2) with her right upper arm fracture who was scheduled for open reduction and internal fixation. This patient had bulbar paralysis, dysphagia and muscle rigidity associated with a high titer of anti-GAD auto antibodies (2,800 U x ml(-1)). She was diagnosed as SPS and has been treated with predonisolone (30 mg x day(-1)) and diazepam (20 mg x day(-1)) for 1 year. Predonisolone (15 mg) and diazepam (30 mg) was given orally before induction of general anesthesia with propofol, remifentanil and rocuronium bromide. Posture change from supine to beach-chair position led to sudden drop in blood pressure to 38/25 mmHg, which recovered promptly by injecting intravenous ephedrine hydrochloride (28 mg) and hydrocortisone (100 mg). Postanesthetic course was uneventful without postoperative neurologic abnormalities.

Involuntary movement during and after neuraxial anesthesia, such as spinal and epidural anesthesia, is rarely observed. In this report, we describe a case of myoclonus-like involuntary movement of the upper extremities in a patient undergoing a planned repeat cesarean section under spinal anesthesia with bupivacaine that completely subsided after administration of 2 mg of midazolam. The myoclonus-like movement did not recur or cause any apparent neurological side effects.

Propofol is an intravenous drug widely used for anesthesia and sedation. Previously, propofol was shown to inhibit cyclo-oxygenase (COX) and 5-lipoxygenase (5-LOX) activities. Because these enzyme-inhibiting effects have only been demonstrated in vitro, this study sought to ascertain whether similar effects might also be observed in vivo. In the current studies, effects of propofol were tested in a murine model of arachidonic acid-induced ear inflammation. Specifically, propofol - as a pre-treatment -- was intraperitoneally and then topical application of arachidonic acid was performed. After 1 h, tissue biopsies were collected and tested for the presence of edema and for levels of inflammatory mediators. The results indicated that the administration of propofol significantly suppressed ear edema formation, tissue myeloperoxidase activity, and tissue production of both prostaglandin E2 and cysteinyl leukotrienes. From the data, it can be concluded that propofol could exert anti-COX and anti-5-LOX activities in an in vivo model and that these activities in turn could have, at least in part, suppressed arachidonic acid-induced edema formation in the ear.

To investigate the association between steroid medication before hospital admission and barotrauma in mechanically ventilated patients with acute respiratory distress syndrome (ARDS).

妊娠を契機にして発症した血栓性血小板減少性紫斑病(thrombotic thrombocytopenic purpura, TTP)の症例を経験した。妊娠23週の37歳の女性で意識障害,重度の貧血,血小板減少が見られ入院となった。A disintegrin and metalloproteinase with thrombospondin type 1 motif, member13(ADAMTS13)活性の低値,ADAMTS13インヒビター陽性を認めたため,血漿交換を6回施行した。ステロイドパルス療法,抗血小板薬の投与も行ったところ,速やかに血小板数増加とADAMTS13活性の改善を認め,インヒビターも陰性となった。その後定期的にADAMTS13活性を測定したが,低下は認められず,再発を疑わせる所見はなかった。ADAMTS13活性の定期測定がTTPの管理や血漿交換の適用の判断にも有用であった。

We report that the transversus abdominis plane block (TAP block) can be performed under ultrasound guidance using not a linear probe but a convex probe in a markedly obese patient undergoing laparoscopy-assisted distal gastrectomy. The TAP block is effective for providing perioperative analgesia. The common probe for the TAP block is a high-frequency linear probe, which can not depict the deeper tissues. We used a low-frequency convex probe for TAP block, which clearly showed the spread of local anesthetics in TAP block in a markedly obese patient. A convex probe is preferable for TAP block in markedly obese patients.

Dexmedetomidine is a highly-selective α2-adrenergic receptor agonist used for sedation of critically ill patients in an intensive care setting. Dendritic cells (DCs) in peripheral tissues sense certain foreign antigens and ingest and process them, while migrating to the regional lymph node. Then, DCs present the processed antigen on their surface to stimulate the clonal proliferation of cognitive lymphocytes, leading to the establishment of adaptive immunity. In murine bone marrow-derived DCs, dexmedetomidine significantly delayed the intracellular proteolytic degradation of ovalbumin, while it did not affect phagocytosis, decreased the expression of the surface molecules I-A(b) and CD86, and suppressed cognitive helper T-cell proliferation. Furthermore, dexmedetomidine significantly suppressed DC migration both in vitro, using a Matrigel migration assay, and in vivo, using a foot pad-popliteal lymph node migration assay, which may be ascribed to the inhibition of type IV collagenase/gelatinase activity. Finally, vaccination with dexmedetomidine-treated DCs significantly suppressed the contact hypersensitivity reaction in vivo. These results indicate that dexmedetomidine may suppress immunity by inhibiting DC antigen processing/presentation and migration.

Background: Although some studies conducted outside of Japan have addressed the effectiveness of intravenous immunoglobulins (IVIG) in treating infections, the dosing regimens and amounts used in Japan are very different from those reported. Here, we investigate the effectiveness of single-dose administration of IVIG in sepsis patients in Japan.Methods: We analyzed 79 patients admitted to the intensive care unit (ICU) of a tertiary care institution due to severe sepsis or septic shock. Patients were randomly divided into a group that was administered standard divided doses of IVIG (5 g/day for 3 days, designated the S group) or a group that was administered a standard single dose of IVIG (15 g/day for 1 day, H group); freeze-dried sulfonated human IVIG was used. The longitudinal assessment of procalcitonin (PCT) levels, C-reactive protein (CRP) levels, white blood cell count, blood lactate levels, IL-6 levels, Sequential Organ Failure Assessment (SOFA) score, and Systemic Inflammatory Response Syndrome (SIRS) was conducted. We also assessed mechanical ventilation duration (days), ICU stay (days), 28-day survival rate, and 90-day survival rate.Results: The study showed no significant differences in PCT levels, CRP levels, 28-day survival rate, and 90-day survival rate between the two groups. However, patients in the H group showed improvements in the various SIRS diagnostic criteria, IL-6 levels, and blood lactate levels in the early stages after IVIG administration. In light of the non-recommendation of IVIG therapy in the Surviving Sepsis Campaign Guidelines 2012, our findings of significant early post-administration improvements are noteworthy. IVIG's anti-inflammatory effects may account for the early reduction in IL-6 levels after treatment, and the accompanying improvements in microcirculation may improve blood lactate levels and reduce SOFA scores. However, the low dosages of IVIG in Japan may limit the anti-cytokine effects of this treatment. Further studies are needed to determine appropriate treatment regimens of single-dose IVIG.Conclusions: In this study, we investigated the effectiveness of single-dose IVIG treatment in patients with severe sepsis or septic shock. Although there were no significant effects on patient prognoses, patients who were administered single-dose IVIG showed significantly improved IL-6 levels, blood lactate levels, and disease severity scores.