Search

The aims of the present study were to establish a population pharmacokinetic (PPK) model of cefazolin for adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) and to assess the probability of target attainment (PTA) for the prophylaxis of surgical site infection (SSI) using cefazolin. Adult patients who underwent cardiac surgery with CPB were enrolled in the prospective study. Blood samples for plasma cefazolin assay were collected, and total and unbound drug concentrations were measured and analysed using the nonlinear mixed-effects modelling (NONMEM) software considering saturable plasma protein binding. Using the PPK model, plasma unbound cefazolin concentration-time courses with current prophylaxis protocols were simulated, and the PTA for common SSI pathogens was estimated. A total of 199 blood samples were obtained from 27 patients. A one-compartment model with first-order elimination plus an on/off CPB compartment best described the data. The population mean for systemic drug clearance (CL) was reduced and that for the volume of distribution (V) was increased during CPB compared with the pre-CPB values. CPB-induced hypoalbuminemia was associated with reduced maximum protein binding (Bmax). The simulation studies suggested that the current dosing protocols are insufficient for attaining PTA > 0.9 throughout surgery against pathogens with minimum inhibitory concentrations (MICs) >8 mg/L. A new dosing protocol that achieves a PTA > 0.9 for pathogens with a MIC of 16 mg/L was proposed. PPK modelling with simulation may be valuable for devising a cefazolin prophylaxis protocol for patients undergoing cardiac surgery with CPB.

McCune-Albright syndrome (MAS) is a rare disorder. MAS is classically defined by the occurrence of fibrous dysplasia, café-au-lait skin macules, and precocious puberty. In addition to precocious puberty, other hyperfunctioning endocrinopathies may occur. We evaluated hypothalamic-pituitary-adrenal function in two cases of typical MAS associated with fibrous dysplasia and growth hormone excess. Pituitary adenoma or hyperplasia was not detected by magnetic resonance imaging. Hormonal data showed normal or low cortisol levels, despite high ACTH levels in the blood. A high ratio of circulating ACTH to cortisol was found in the two cases. Insulin tolerance and CRH tests showed hyper-responses of ACTH and an insufficient increase in cortisol levels. No involvement of 11β-HSD1 by GH excess was suggested because basal levels of ACTH and cortisol showed no changes, even after therapy for acromegaly by somatostatin analogues. Patients with Cushing's disease cases of pituitary macroadenoma can have high circulating ACTH precursor levels, and elevated ACTH precursors have been observed in ectopic ACTH syndrome. Autonomous cortisol excess was excluded by the level of midnight cortisol and the level of cortisol after a low-dose dexamethasone suppression test in the two cases. Finally, the gel filtration profiles of immunoreactive ACTH contents showed the presence of aberrant ACTH precursors. To the best of our knowledge, there have been no reports of MAS associated with aberrant ACTH precursors. Our findings in these cases emphasize that attention should be to secretion of inactive ACTH precursors in MAS.

To investigate the effects of alveolar recruitment maneuver (ARM) during one-lung ventilation (OLV) on end-expiratory lung volume (EELV) of the dependent lung. Patients who were planned to undergo lung resection surgery for lung tumors and needed OLV for at least 1 h were included in the study. After turning the patients into the lateral position under total intravenous anesthesia, OLV was commenced using a double-lumen endobronchial tube. EELV was measured using the nitrogen washout technique at 20 min after OLV started (baseline) and 15, 30, 45, 60 min after ARM was performed on the dependent lung. Among 42 patients who completed the study, EELV increased at 15 min after ARM by 20% or greater compared with baseline in 21 patients (responders). Responders were significantly shorter in height (158 vs. 165 cm, p = 0.01) and had smaller preoperative functional residual capacity (2.99L vs. 3.65L, p = 0.02) than non-responders. Before ARM, responders had significantly higher driving pressure (14.2 vs. 12.4 cmH2O, p = 0.01) and lower respiratory system compliance (23.6 vs. 31.4 ml/cmH2O, p = 0.0002) than non-responders. Driving pressure temporarily dropped after ARM in responders, while no significant change was observed in non-responders. Fourteen out of 21 responders kept EELV 20% or more increased EELV than baseline at 60 min after ARM. EELV of the dependent lung was increased by 20% or greater in half of the patients responding to ARM. The increased volume of the dependent lung caused by ARM was maintained for 60 min in two-thirds of the responders.

Pembrolizumab, or anti-programmed death receptor 1 antibody, is an immune checkpoint inhibitor that can cause immune-related adverse events. We herein report for the first time the progression of hypopituitarism and hypothyroidism after treatment with pembrolizumab in a patient with adrenal metastasis of non-small-cell lung cancer. Severe primary hypothyroidism occurred three weeks after the first administration of pembrolizumab. Four months after the discontinuation of pembrolizumab, isolated adrenocorticotropic hormone (ACTH) deficiency was noted. Corticotropin-releasing hormone and rapid ACTH tests performed repeatedly showed that the patient's pituitary and adrenal function had been gradually deteriorating. It is important to diagnose adrenal insufficiency without delay in order to prevent adrenal crisis.

Background: McCune-Albright syndrome (MAS) is a rare disorder. MAS is caused by an activating postzygotic somatic mutation in the GNAS, and, is classically defined by the occurrence of fibrous dysplasia (FD), café-au-lait skin macules, and precocious puberty. Autonomous GH and/or PRL production in MAS has been reported. However, there have been no reports of ACTH excess in MAS. Method: Plasma ACTH and serum cortisol (F) levels were assessed using electrochemiluminescence immunoassays (Eclusys ACTHTM and Eclusys Cortisol IITM, respectively; Roche Diagnostics K.K., Tokyo, Japan).Clinical Cases: Case1; 42-year-old man showed craniofacial deformities and suffered from multiple bone fractures. He was diagnosed with FD at the age of 23 years. Café-au-lait macules were found on his back. He had slightly acromegaloid features. He showed no cushingoid features. Pituitary adenoma or hyperplasia was not detected by MRI. The diagnosis of GH excess was confirmed by no suppression of serum GH levels by a 75-g oral glucose tolerance test (nadir GH: 2.34 ng/mL) and an elevated serum IGF-I level (307 ng/mL; normal range: 92-257 ng/mL). The patient was treated with monthly subcutaneous lanreotide injection and then GH excess was well controlled. Basal ACTH and F levels in blood were 40.6-63.4 pg/mL and 8.0-10.5 μg/dL, respectively. The urinary free cortisol (UFC) level was 53 μg/day. Autonomous F excess was excluded by the level of midnight F (1.2 μg/dL) and the level of F (0.2 μg/dL) after a low-dose (1 mg) dexamethasone suppression test (DST). Case2; A 32-year-old man was diagnosed with MAS and gigantism at the Pediatrics Department at the age of 5 years. Treatment of GH excess was well controlled by monthly octreotide depot. He had no acromegaloid features and no cushingoid features. Café-au-lait macules were observed from the left flank to the back. Pituitary adenoma or hyperplasia was not detected by MRI. Basal ACTH and F levels in blood were 35.5-73.1 pg/mL and 7.0-11.7 μg/dL, respectively. The UFC level was 61 μg/day. Autonomous F excess was excluded by the level of F (

STUDY DESIGN A cross-sectional study. OBJECTIVE The aim of this study was to evaluate activity of the nucleus accumbens (NAc) in response to lumbar mechanical stimulation in patients with chronic low back pain (cLBP) using functional magnetic resonance imaging (fMRI). SUMMARY OF BACKGROUND DATA Although a modified activity of the NAc was characterized in cLBP patients, its pathological significance has yet to be determined. We hypothesized that NAc activation in response to pain might differ depending on the extent of psychiatric problems, which might be associated with the affective/motivational background of chronic pain. METHODS Twenty-one patients with cLBP (four men, 17 women) were recruited. Subjects were divided into two groups on the basis of scores on the patient version of the Brief Scale for Psychiatric problems in Orthopaedic Patients (BS-POP) scores: ≥17 (High Score, HiS group) and

Background Respiratory management in patients with esophagobronchial fistulae is challenging since positive pressure ventilation (PPV) may not be feasible due to air leaks and possible risks for regurgitation and aspiration of gastric contents. We and others have previously reported that spontaneous respiration may be one of the good options of respiratory management during general anesthesia in those patients. However, adverse events associated with this respiratory strategy have not been reported previously. We experienced a 77-year-old male patient who suffered unexpected impairment of oxygenation due to intraoperative pneumothorax, which was assumed to have been exacerbated by spontaneous respiration during esophageal bypass surgery. Case presentation The patient was planned to undergo esophageal bypass surgery for esophagobronchial fistulae associated with malignant esophageal cancer. Both of two esophagobronchial fistulae were located in the proximal part of the left main bronchus. For the risks of air leaks and aspiration associated with PPV and further damage to the tissue around the fistulae, we decided to maintain spontaneous respiration under general anesthesia and obtain abdominal muscle relaxation with epidural anesthesia. After catheterization of epidural anesthesia, the patient was sedated with 35 mg of intravenous pethidine and was nasotracheally intubated under bronchoscopic guidance. We confirmed that the tip of the tracheal tube was located above the carina. Then anesthesia was induced and maintained with sevoflurane so that his spontaneous respiration could be maintained thereafter. His spontaneous respiration was assisted with 3 cmH2O of pressure support. Approximately 60 min into the surgery, percutaneous arterial oxygen saturation (SpO2) suddenly dropped from 99 to 89% with an inspiratory fraction of oxygen of 0.4. We assumed that lung atelectasis associated with airway secretion or pulmonary soiling was the most likely reason for impaired oxygenation; however, arterial oxygenation only partially regained even after they were suctioned. After the completion of the surgery, chest X-ray revealed right pneumothorax. After a chest drainage tube was inserted, right pneumothorax was ameliorated and SpO2 returned to the baseline level. Conclusions Although spontaneous respiration may be useful in a patient with esophagobronchial fistulae, oxygenation can be impaired more seriously than PPV in case intraoperative pneumothorax occurs.

Background Neonatal exposure to anesthetics induces neuronal apoptosis and long-term cognitive dysfunction in rodents. We showed that the nicotinamide adenine dinucleotide phosphate-oxidase inhibitor apocynin not only reduces neurotoxicity by decreasing superoxide levels and preventing mitochondrial dysfunction but also improves long-term memory impairment in neonatal mice exposed to sevoflurane. We also found that after the contextual fear conditioning test, glutamatergic neurons expressed c-Fos (neural activation) regardless of previous exposure to sevoflurane. Moreover, there were fewer c-Fos-expressing glutamatergic neurons in the basolateral amygdala (BLA) after exposure to sevoflurane than after exposure to carrier gas. In this study, we investigated whether the administration of apocynin prior to sevoflurane exposure would preserve glutamatergic neurons in the BLA. Methods Apocynin (50 mg/kg) was injected intraperitoneally into six-day-old male mice 30 min before 6 h of exposure to 3% sevoflurane or carrier gas only. The mice were allowed to mature and then were subjected to the contextual fear conditioning test. The neural activation and neuron population in the BLA were investigated 2 h later. Results Administration of apocynin prior to neonatal sevoflurane exposure not only prevented learning deficits but also preserved c-Fos-expressing glutamatergic neurons in the BLA. Conclusions Apocynin mitigates the cognitive impairment induced by neonatal sevoflurane exposure and preserves c-Fos-expressing glutamatergic neurons in the basolateral amygdala.

Objective: Acromegaly is associated with metabolic and neoplastic complications, but successful treatment of acromegaly can sometimes result in growth hormone deficiency (GHD). Nonalcoholic fatty liver disease may develop in GHD, although there are few reports of such cases after cured acromegaly.Methods: We report the case of a 41-year-old woman with nonalcoholic steatohepatitis associated with GHD after surgical cure of acromegaly.Results: Growth hormone (GH) replacement therapy improved serum triglyceride, hyaluronic acid, and type IV collagen levels as well as liver function and quality of life. Computed tomography (CT) showed reduced volumes of both visceral and subcutaneous fat and an increased liver/spleen CT attenuation value.Conclusion: Cured acromegalic patients should be carefully examined if GHD and associated metabolic disorders arise. Appropriate diagnosis of GHD and prompt treatment with GH replacement should ameliorate liver dysfunction and the metabolic changes associated with GHD.Abbreviations: ALT = alanine aminotransferase AST = aspartate aminotransferase BMI = body mass index CT = computed tomography GH = growth hormone GHD = growth hormone deficiency HbA1c = glycated hemoglobin IGF-1 = insulin-like growth factor 1 NAFLD = nonalcoholic fatty liver disease NASH = nonalcoholic steatohepatitis OGTT = oral glucose tolerance test rhGH = recombinant human GH

Key Clinical Message Juvenile nasopharyngeal angiofibroma (JNA) involves difficult anesthetic management because of the risk of massive bleeding, while airway management is rarely a problem in JNA. This report presents an unusual case of JNA causing airway obstruction.

The aim of the study was to evaluate the disposition of plasma unbound cefazolin in patients undergoing cardiothoracic surgery with cardiopulmonary bypass (CPB). Adult patients undergoing cardiothoracic surgery with CPB were enrolled in the study. Cefazolin sodium was given intravenously before skin incision (1 g) and at the beginning of CPB (2 g). Thereafter, an additional dose (1 g) was given every 4 hours. Seven to ten blood samples were collected before and during surgery. Plasma total and unbound (ultrafiltrated) cefazolin concentrations were analyzed using an HPLC‐UV method. Plasma protein binding was analyzed with the Langmuir model. Twenty‐seven patients (aged 70 ± 12 years, body weight 62 ± 12 kg, mean ± SD) with GFR >30 mL min−1 completed the study. There was a significant (P

BACKGROUND: Sevoflurane exposure during the early postnatal period causes neuroinflammation and neuronal apoptosis in rodents. Bone marrow stromal cells (BMSCs) have been shown to protect and repair the damaged central nervous system, for example in ischemic stroke models. In this study, we investigated whether intravenous administration of BMSCs ameliorated neurodegeneration, induced by sevoflurane exposure, in neonatal rats. METHODS: Sprague-Dawley rat pups (postnatal day 7) were exposed to 2% sevoflurane for 6 h (vehicle group, n = 7). BMSCs were administered 30 min after induction of sevoflurane anesthesia (BMSCs group, n = 7). The pups were exposed to carrier gas only, as a negative control (mock anesthesia group, n = 4). We assessed the therapeutic effects of BMSC treatment by measuring expression of the pro-inflammatory cytokine interleukin-6 (IL-6), and levels of cleaved caspase-3, in brain tissues immediately following sevoflurane anesthesia. RESULTS: Analysis of the cleaved caspase-3 bands revealed that levels of activated caspase-3 were elevated in the vehicle group compared with the mock anesthesia group, indicating that a single exposure to sevoflurane at subclinical concentrations can precipitate neuronal apoptosis. BMSC treatment did not suppress apoptosis induced by sevoflurane exposure (compared with the vehicle group). The vehicle group had higher proinflammatory cytokine IL-6 protein levels compared with the mock anesthesia group, indicating that sevoflurane exposure induces IL-6 expression. BMSC treatment suppressed sevoflurane-induced increases in IL-6 expression, indicating that these cells can inhibit the neuroinflammation induced by sevoflurane exposure (vehicle group vs. BMSC group). CONCLUSIONS: Intravenous administration of BMSCs reduces neuroinflammation, but does not attenuate apoptosis induced by sevoflurane exposure.

This study aimed to identify the incidence and risk factors for acute kidney injury (AKI) after liver resection surgery and to clarify the relationship between postoperative AKI and outcome. We conducted a historical cohort study of patients who underwent liver resection surgery with sevoflurane anesthesia from January 2004 to October 2011. Acute kidney injury was diagnosed based on the Acute Kidney Injury Network classification within 72 hr after the surgery. Patient data, surgical and anesthetic data, and laboratory data were extracted manually from the patients’ electronic charts. Multivariable logistic regression analysis was used to identify perioperative risk factors for postoperative AKI. Acute kidney injury was diagnosed in 78 of 642 patients (12.1%; 95% confidence interval [CI]: 9.7 to 14.9). Multivariable analysis showed an independent association between postoperative AKI and preoperative estimated glomerular filtration rate (adjusted odds ratio [aOR] 0.74; 95% CI: 0.64 to 0.85), preoperative hypertension (aOR 2.10; 95% CI: 1.11 to 3.97), and intraoperative red blood cell transfusion (aOR 1.04; 95% CI: 1.01 to 1.07). Development of AKI within 72 hr after liver resection surgery was associated with increased hospital mortality, prolonged length of stay, and increased rates of mechanical ventilation, reintubation, and renal replacement therapy. Perioperative risk factors for AKI after liver resection surgery are similar to those established for other surgical procedures. Further studies are needed to establish causality and to determine whether interventions on modifiable risk factors can reduce the incidence of postoperative AKI and improve patient outcome. This study was registered at the University Hospital Medical Information Network (UMIN) Center (UMIN 000008089).

[Purpose] The aim of the study was to determine the effect of xenon irradiation of the stellate ganglion region on fibromyalgia. [Subjects] The study included 5 men and 22 women (age, 56.4 ± 16.3 years [range, 25–84 years]) who were diagnosed with fibromyalgia according to the modified 2010 criteria of the American College of Rheumatology between July and August 2013. [Methods] Bilateral xenon light irradiation (0.38–1.1 μm) around the stellate ganglion was performed in the supine position by physical therapists using a xenon phototherapy device. We evaluated pain before and after irradiation using the visual analogue scale. [Results] We did not observe a relationship between the change in the visual analogue scale score and duration of fibromyalgia. However, we observed a relationship between the change in the visual analogue scale score and the score for the Japanese version of the Fibromyalgia Impact Questionnaire using the Cochran-Armitage test for trend. [Conclusion] Xenon light irradiation of the stellate ganglion significantly decreased the visual analogue scale score in patients with fibromyalgia having a higher score in the Fibromyalgia Impact Questionnaire, suggesting that a stronger effect could be obtained in patients with more severe fibromyalgia.

Systemic inflammation induces brain neuronal inflammation, in turn causing acute cognitive disorders. Furthermore, neuronal inflammation is one cause of postoperative cognitive disorder (POCD) and delirium. However, no sufficiently established pharmacological treatment is available for neurocognitive inflammation. This study evaluated the possible neuroprotective effects of preconditioning with sevoflurane anesthesia on cognition and neuroinflammatory changes in an animal model of lipopolysaccharide (LPS)-induced systemic inflammation. Adult mice were randomly divided into (1) control, (2) 2% sevoflurane preconditioning for 1 h, (3) intraperitoneal 5 mg/kg LPS injection, and (4) 2% sevoflurane preconditioning for 1 h + LPS injection groups. At 24 h after 5 mg/kg LPS injection, microglial activation based on ionized calcium-binding adapter molecule 1 (Iba-1) expression in the hippocampus was determined using immunostaining and immunoblotting. IL-1β and IL-6 immunoblotting were used as inflammation markers, and β-site of amyloid precursor protein cleaving enzyme 1 (BACE1) immunoblotting was performed to evaluate amyloid β-protein (Aβ) accumulation. Long-term cognitive impairment was evaluated using fear conditioning tests. Intraperitoneal LPS increased levels of Iba-1 (150%), inflammation markers (160%), and Aβ accumulation (350%), and sevoflurane preconditioning suppressed these increases. Systemic LPS caused learning deficits. Sevoflurane also maintained long-term memory in mice receiving LPS injection. Sevoflurane preconditioning prevented long-term memory impairment in the mouse model administered systemic LPS by decreasing excessive microglial activation, inflammation, and Aβ accumulation. This study supports the hypothesis that sevoflurane preconditioning might also be beneficial for neuronal inflammation. Sevoflurane might be beneficial for reducing delirium and POCD.

Offset analgesia (OA) represents a disproportionately large decrease of pain perception after a brief, temporary increment of thermal pain stimulus and was reported attenuated in patients with neuropathic pain. We examined whether OA depends on the increment duration before offset, and whether individual features of OA distinguish patients with chronic pain and healthy controls. We used a Peltier-type thermal stimulator and OA paradigms including 5-, 10-, or 15-s duration of 1°C-increment (T2) over 45°C. We first examined OA response, on the left volar forearm, at 3 different T2's in 40 healthy volunteers, and OA and constant stimulus responses in 12 patients with chronic pain and 12 matched healthy controls. We measured magnitude of OA ([INCREMENT]OA) and maximum visual analogue scale (VAS) latency (time to peak VAS) during constant stimulus for each individual. Pain perception kinetics were compared with analysis of variance and sought for correlations with psychophysical parameters with a significance threshold at P < 0.05. In healthy controls, longer T2 at 10 or 15 seconds resulted in larger [INCREMENT]OA compared with T2 at 5 seconds (P = 0.04). In patients, [INCREMENT]OA was significantly smaller than controls at T2 = 5 or 10 seconds (P < 0.05) but grew comparable at T2 = 15 seconds with controls. Maximum VAS latency was longer in patients than in controls and negatively correlated with [INCREMENT]OA in patients. An OA index ([INCREMENT]OA/[maximum VAS latency]) proved diagnostic of chronic pain with an area under the receiver operating characteristic curve at 0.897. Patients with chronic pain showed impairment of OA and reduced temporal sharpening of pain perception, which might imply possible disturbance of the endogenous pain modulatory system.

Purpose Propofol infusion syndrome (PRIS) is a lethal condition caused by propofol overdose. Previous studies suggest that pathophysiological mechanisms underlying PRIS involve mitochondrial dysfunction; however, these mechanisms have not been fully elucidated. This study aimed to establish an experimental model of propofol-induced cytotoxicity using cultured human induced pluripotent stem cell (iPSC)-derived cardiomyocytes to determine the mechanisms behind propofol-induced mitochondrial dysfunction, and to evaluate the protective effects of coenzyme Q10 (CoQ10). Methods Human iPSC-derived cardiomyocytes were exposed to propofol (0, 2, 10, or 50 µg/ml) with or without 5 µM CoQ10. Mitochondrial function was assessed by measuring intracellular ATP, lactate concentrations in culture media, NAD+/NADH ratio, and the mitochondrial membrane potential. Propofol-induced cytotoxicity was evaluated by analysis of cell viability. Expression levels of genes associated with mitochondrial energy metabolism were determined by PCR. Intracellular morphological changes were analyzed by confocal microscopy. Results Treatment with 50 µg/ml propofol for 48 h reduced cell viability. High concentrations of propofol (≥ 10 µg/ml) induced mitochondrial dysfunction accompanied by downregulation of gene expression of PGC-1alpha and its downstream targets (NDUFS8 and SDHB, which are involved in the respiratory chain reaction; and CPT1B, which regulates beta-oxidation). Cardiomyocytes co-treated with 5 µM CoQ10 exhibited resistance to propofol-induced toxicity through recovery of gene expression. Conclusions Propofol-induced cytotoxicity in human iPSC-derived cardiomyocytes may be associated with mitochondrial dysfunction via downregulation of PGC-1alpha-regulated genes associated with mitochondrial energy metabolism. Co-treatment with CoQ10 protected cardiomyocytes from propofol-induced cytotoxicity.

Objective: Adrenal venous sampling (AVS) is the most reliable test to distinguish between unilateral and bilateral primary aldosteronism (PA). However, AVS is invasive, risky, and expensive, and alternative diagnostic methods are desirable. This study aimed to investigate the diagnostic power of saline infusion test (SIT) to distinguish between unilateral and bilateral PA. Design: Retrospective database analysis. Subjects and Methods: We selected 111 patients with PA diagnosed by confirmatory tests who underwent both SIT and successful AVS. Thirty-two patients had lateralized ratio (LR) over 4.0 and 79 patients had LR less than 4.0. Multiple regression analysis and receiver operating characteristic (ROC) analysis were used to examine whether the SIT had good diagnostic power to distinguish between patients with high LR and those with low LR. Results: The patients with high LR had significantly lower serum potassium levels (P

Study Objective To determine the relationship between preoperative catecholamine levels and intraoperative peak plasma lactate levels in patients who underwent adrenalectomy for pheochromocytoma. Design Retrospective observational study. Setting Operating room in one university hospital. Measurements The records of 27 ASA physical status 1 and 2 patients who underwent adrenalectomy for pheochromocytoma were studied. Preoperative catecholamine levels and intraoperative plasma lactate levels were recorded. Main Results Twenty cases had high lactate levels (>2 mmol/L). Preoperative urine epinephrine levels and urine metanephrine levels showed a moderate correlation with intraoperative peak plasma lactate levels ( r s = 0.475 and r s = 0.499, respectively; Spearman's rank correlation test). Receiver operating characteristic (ROC) curve analysis for preoperative urine epinephrine levels showed good performance for prediction of high lactate levels [>2 mmol/L, area under the curve (AUC) =0.800], whereas ROC for preoperative urine norepinephrine levels showed no predictive performance for high lactate levels. Conclusions Catecholamine release caused by surgical manipulation may be a possible cause of intraoperative transient lactic acidosis, and it should be considered as a differential diagnosis of intraoperative lactic acidosis. Intraoperative peak plasma lactate level was correlated with preoperative epinephrine-releasing activity.

Angiopoietin-1 and angiopoietin-2 are important factors in regulating endothelial vascular permeability. This study evaluated perioperative changes in serum levels of angiopoietin-1 and -2 in patients undergoing cardiac surgery.Measurement of serum levels of angiopoietin-1 and angiopoietin-2 in samples collected during a previously conducted prospective, multicenter, observational study.Three university hospitals.Eighty-four adult patients undergoing cardiac surgery.Serum levels of angiopoietins were measured at baseline, immediately after surgery, and the day after surgery (POD-1).Serum levels of angiopoietin-2 were elevated by POD-1 (median 3.3 ng/mL, interquartile range [IQR] 2.5-4.6 ng/mL) compared with baseline (median 1.6 ng/mL, IQR 1.3-2.1 ng/mL, p0.0001), and angiopoietin-1 levels were decreased immediately after surgery (baseline median 23.2 ng/mL, IQR 10.2-32.8 ng/mL; postoperative median 8.0 ng/mL, IQR 1.5-13.2 ng/mL, p0.0001). Angiopoietin-2 levels on POD-1 in patients undergoing off-pump coronary artery bypass grafting were significantly lower than those in patients undergoing aortic surgery (p = 0.0009) and valve surgery (p = 0.008). Angiopoietin-2 levels on POD-1 had a predictive performance of the area under the curve (AUC) of the receiver operating characteristic curve 0.74 for mechanical ventilation3 days. Angiopoietin-1 levels and the angiopoietin-2/angiopoietin-1 ratio showed lower predictive performance (AUC values 0.58 and 0.68, respectively).Angiopoietin-2 serum levels were elevated after cardiac surgery. Elevated angiopoietin-2 had a good predictive performance for respiratory failure after cardiac surgery, perhaps reflecting the severity of lung dysfunction related to postoperative increases in vascular permeability.

Glucocorticoids and glucocorticoid receptors (GRs) suppress pituitary pro-opiomelanocortin (Pomc) gene expression. O-linked β-N-acetylglucosamine (O-GlcNAc) modification, mediated by O-GlcNAc transferase (OGT), plays an important role during gene transcription. However, whether OGT is involved in the GR-mediated transrepression that occurs in pituitary corticotroph cells is currently unknown. Here, we report that OGT regulates Pomc expression in the mouse corticotroph cell line AtT-20. The overexpression of OGT has an additive effect on the GR-mediated negative transcription pathway. Both the knockdown of OGT by RNA interference and the use of a chemical OGT inhibitor abolished the repressive effects of Pomc expression induced by GRs. OGT inhibition leads to both the decreased recruitment of GRs and the increased recruitment of RNA polymerase II to the Pomc locus. O-GlcNAc modification is involved in the negative regulation of Pomc transcription in corticotroph cells. OGT may be a promising therapeutic target for the treatment of Cushing's disease.

Neonatal mice exposed to sevoflurane show certain cognitive and behavioral impairments in adulthood. However, the mechanisms underlying long-term cognitive deficits induced by sevoflurane exposure remain unknown. The present study was performed to investigate whether there is differential neuronal activation between naive mice and sevoflurane-exposed neonates in fear-conditioning tests based on immediate early gene (c-Fos) expression. Male mice were exposed to 3% sevoflurane (SEVO group) or carrier gas alone (no anesthesia, NA group) for 6 hours on postnatal day 6. The mice were allowed to mature before performing the contextual fear-conditioning test. A reduced freezing response was confirmed in the SEVO group. Neural activation in the regions of the medial prefrontal cortex, hippocampus, and amygdala was investigated using c-Fos immunostaining 2 hours after the test. The types of neurons activated were also identified. The number of c-Fos-positive cells decreased by 27% in the basolateral amygdala in the SEVO group, while no significant changes were observed in other regions. Furthermore, glutamatergic, but not γ-aminobutyric acid (GABA)ergic, neurons expressed c-Fos after the contextual fear-conditioning test in both groups. The number of glutamatergic neurons in the basolateral amygdala in the SEVO group was reduced by 27%. Decreased neural activation in the basolateral amygdala may be associated with reduced freezing time in neonatal sevoflurane-exposed mice. Fewer glutamatergic neurons responding to fear stimuli in the basolateral amygdala may contribute to decreased neural activation and learning deficits in mice exposed to sevoflurane as neonates.

Background. This study aimed to determine the perioperative change in serum double-strand DNA (dsDNA) as a marker potentially reflecting neutrophil extracellular trap concentration in samples from patients undergoing cardiac surgery and to analyze a relationship between serum dsDNA concentrations and perioperative renal dysfunction. Methods. Serum dsDNA concentrations in samples that were collected during a previously conducted, prospective, multicenter, observational study were measured. Eighty patients undergoing elective cardiac surgery were studied. Serum samples were collected at baseline, immediately after surgery, and the day after surgery (POD-1). Results. Serum dsDNA concentration was significantly increased from baseline (median, 398 ng/mL [interquartile range, 372–475 ng/mL]) to immediately after surgery (median, 540 ng/mL [437–682 ng/mL], p<0.001), and they were reduced by POD-1 (median, 323 ng/mL [256–436 ng/mL]). The difference in serum creatinine concentration between baseline and POD-1 was correlated with dsDNA concentration on POD-1 (rs=0.61, p<0.001). Conclusions. In patients undergoing cardiac surgery, serum dsDNA concentration is elevated postoperatively. Prolonged elevation in dsDNA concentration is correlated with perioperative renal dysfunction. Further large-scale studies are needed to determine the relationship between serum concentration of circulating dsDNA and perioperative renal dysfunction.

The use of double-lumen endobronchial tubes (DLTs) is necessary for differential lung ventilation during pulmonary lobectomy. However, when used with conventional extubation procedures, coughing is more likely and is associated with an increased risk for parenchymal air leak along the staple line and possible subsequent lung injury. We examined the prevalence of coughing-associated air leaks at extubation and the efficacy of using supraglottic airways (SGAs) to prevent air leaks with post-lobectomy extubation.This study included 150 patients with pulmonary emphysema diagnosed using preoperative computed tomography, who underwent pulmonary lobectomy between April 2010 and March 2015. The patients were chronologically enrolled in two groups: the DLT group (60 patients) from April 2010 to August 2012, and the SGA group (90 patients) from September 2012 to March 2015. (Note: the DLT group only included cases without air leak present just prior to extubation). Data were collected on specific patient characteristics and operative and postoperative factors.Coughing at extubation occurred in 15 (25.0 %) of 60 DLT patients, and parenchymal air leaks developed in 10 (66.7 %) of these 15. Comparison of groups revealed the SGA group was significantly lower for the following: patients with coughing at extubation (P 0.001), coughing-associated air leaks at extubation (P 0.001), air leaks7 days (P = 0.006), reoperation due to air leaks (P = 0.013), and duration of chest tube drainage (P 0.001).The SGA is effective for preventing air leaks associated with coughing during conventional DLT extubation in post-lobectomy patients.

Background Idiopathic pulmonary arterial hypertension (IPAH) is a progressive and fatal cardiovascular disease if left untreated. In patients with IPAH with psychiatric illness or other complications, careful attention is required when administering medical therapies that may affect their hemodynamics. Patients suffering from IPAH who undergo anesthesia and surgery have a high mortality and morbidity rate. We describe the treatment of intractable psychiatric symptoms with electroconvulsive therapy (ECT) in a patient with IPAH. Case presentation A 23-year-old woman with IPAH and type I diabetes mellitus (DM) presented with malignant catatonia. Her heart function was classified as New York Heart Association (NYHA) class III. She required a rapid cure and ECT due to various psychiatric symptoms resistant to conventional medications. Pulmonary hypertensive (PH) crisis is the most concerning complication that can be induced by the sympathetic stimulation of ECT. To avoid PH crisis, we administered oxygen using a laryngeal mask and administered remifentanil for anesthesia. We also prepared standby nitric oxide for possible PH crisis, although it was ultimately not needed. With 14 ECT sessions, her malignant catatonia was ameliorated without physical complications. Conclusion ECT is an acceptable option for the treatment of medication-refractory psychiatric disturbances in patients with IPAH, provided careful management is assured to prevent or address complications.

Tracheogastric tube fistulas are rare but fatal complications after esophagectomy. Anesthetic management for a patient with this complication is challenging because air leakage and mechanical ventilation may cause aspiration. We present a case report of the anesthetic management of a patient having 2-stage surgical repair combined with endoscopic mucosal resection for a giant carinal tracheogastric tube fistula. The first stage was separation of the gastric tube above the fistula with spontaneous breathing under local anesthesia and sedation. The second stage was complete separation and reconstruction of the digestive tract under epidural and general anesthesia with spontaneous breathing and pressure support before insertion of a decompression tube.

Although the receptor for advanced glycation end products (RAGE) has been used as a biological marker of alveolar epithelial cell injury in clinical studies, the mechanism for release of soluble RAGE from lung epithelial cells has not been well studied. Therefore, these studies were designed to determine the mechanism for release of soluble RAGE after lipopolysaccharide (LPS) challenge. For these purposes, alveolar epithelial cells from rat lungs were cultured on Transwell inserts, and LPS was added to the apical side (500 μg/ml) for 16 h on day 7. On day 7, RAGE was expressed predominantly in surfactant protein D-negative cells, and LPS challenge induced release of RAGE into the medium. This response was partially blocked by matrix metalloproteinase (MMP) inhibitors. Transcripts of MMP-3 and MMP-13 were upregulated by LPS, whereas RAGE transcripts did not change. Proteolysis by MMP-3 and MMP-13 resulted in soluble RAGE expression in the bronchoalveolar lavage fluid in the in situ rat lung, and this reaction was inhibited by MMP inhibitors. In human studies, both MMP-3 and -13 antigen levels were significantly correlated with the level of RAGE in pulmonary edema fluid samples. These results support the conclusion that release of RAGE is primarily mediated by proteolytic damage in alveolar epithelial cells in the lung, caused by proteases in acute inflammatory conditions in the distal air spaces.

Neurological deficits associated with methylergometrine have been reported primarily as a result of reversible cerebral vasoconstriction syndromes (RCVS). RCVS are characterized by reversible multifocal vasoconstrictions of the cerebral arteries heralded by acute severe headache with or without neurological deficits. Here, we present the first case of suspected RCVS with transient limb myoclonus following the intravenous administration of methylergometrine during cesarean section. A 31-year-old woman who received slowly infused intravenous methylergometrine during a cesarean section suddenly reported severe occipital headache after 40 min, followed by apnea and unconsciousness for 8 min. A second administration of methylergometrine to treat the weakness of her uterine contractions resulted in a repeated loss of consciousness within minutes and the development of limb myoclonus. No abnormalities were detected by brain computerized tomography, magnetic resonance imaging, and electroencephalogram. She fully recovered spontaneously within 12 h. We consider that the transient limb myoclonus in our patient appeared as a result of RCVS caused by the intravenous administration of methylergometrine.

We previously showed that compression of the nondependent lung during one-lung ventilation (OLV) in patients undergoing esophagectomy improves arterial oxygenation but impairs cardiac output (CO) and systemic oxygen delivery (DO(2)). The objective of this study was to test the hypothesis that the combination of nondependent lung compression and ephedrine improves arterial oxygenation without compromising DO(2).Twenty patients undergoing esophagectomy through a right thoracotomy were studied. Under general anesthesia, a left-sided double-lumen tube was placed, and the dependent lung was mechanically ventilated with a tidal volume of 8 ml/kg and a fraction of inspiratory oxygen of 0.8 during OLV. When nondependent lung was compressed by surgeons to improve surgical exposure, a randomly determined intravenous bolus of either ephedrine 4 mg (group E) or an identical volume of saline (group S) was administered. Arterial blood was sampled during two-lung ventilation (TLV), at 10 min of OLV (OLV1), and 5 min after nondependent lung compression (OLV2).The initiation of OLV resulted in a significant drop in PaO(2) at OLV1 (group E, 136 ± 69 mmHg; group S, 138 ± 83 mmHg; P 0.01) compared with TLV (group E, 404 ± 44 mmHg; group S; 367 ± 51 mmHg) and tended to improve at OLV2 (group E, 170 ± 63 mmHg; group S; 196 ± 121 mmHg). However, although CO and DO(2) significantly decreased in group S at OLV2 (4.0 ± 0.8 l/min, 621 ± 116 ml/min; P 0.01) compared with OLV1 (5.1 ± 0.7 l/min, 811 ± 140 ml/min), there was no significant difference in these parameters in group E for the two time points.Although arterial oxygenation was not significantly improved by the nondependent lung compression, the addition of intravenous ephedrine to nondependent lung compression prevented the decrease in systemic oxygen delivery without deterioration of arterial oxygenation during OLV in patients undergoing esophagectomy.

We have previously found that compression of the non-dependent lung improves arterial oxygenation during one-lung ventilation (OLV) in patients undergoing esophagectomy. The purpose of this study was to investigate the effects of compression of the non-dependent lung on hemodynamic indices and oxygen delivery using a minimally invasive cardiac output (CO) monitor.Sixteen consecutive patients undergoing esophagectomy through a right thoracotomy were studied. Under general anesthesia, a left-sided double-lumen tube was placed for OLV, and the dependent lung was mechanically ventilated with a tidal volume of 8 ml kg(-1) body weight and a fraction of inspiratory oxygen of 0.8 during OLV. CO was monitored continuously using a FloTrac/Vigileo (Edwards Lifesciences) system. Surgeons compressed the non-dependent lung several times during surgery using a lung retractor to improve exposure of the surgical field. The oxygen delivery index was roughly estimated as the product of the cardiac index (CI) and arterial oxygen saturation as monitored by pulse oximetry (Spo2).Just before non-dependent lung compression, mean (+/- SD) CI and Spo2 were 2.6 +/- 0.6 L min(-1) m(-2) and 95.0 +/- 3.9%, respectively. At 1 min after non-dependent lung compression, Spo2 increased significantly to 97.8 +/- 2.2% (P0.05), but CI decreased significantly to 2.0 +/- 0.4 L min(-1) m(-2) (P0.05). The product of CI and Spo2 at 1 min was significantly lower (192.7 +/- 37.3) than baseline levels (250.5 +/- 66.3, P0.05).Although non-dependent lung compression may be a potentially effective measure to treat hypoxemia during OLV, it should be noted that CO and systemic oxygen delivery may be decreased by this maneuver.

Few studies have examined the frequency or severity of hemorrhagic complications following plexus or peripheral block in patients on anticoagulant therapy. We report successful anesthetic management by sciatic nerve block (SNB) of a patient with severe coronary artery disease who underwent lower-limb arterial thrombectomy and revascularization. A 72-year-old female with arteriosclerosis obliterans was diagnosed with acute arterial thrombosis and scheduled for emergency surgery. She had heart failure caused by three-vessel coronary artery disease and was taking anticoagulant therapy of warfarin and cilostazol. We performed SNB (popliteal approach) using a single injection of 20 ml 0.5% ropivacaine guided by ultrasound echography. There were no hemodynamic or respiratory disturbances during the operation. She had no local hematoma or neural disturbances during the clinical course, although heparin infusion was initiated perioperatively. Anesthetic management using SNB was successful. Ultrasound-guided SNB could be a useful technique in patients receiving anticoagulant therapy.

BACKGROUND: Phenylephrine is a selective alpha(1) adrenergic receptor agonist that increases arterial blood pressure by peripheral vasoconstriction. However, whether phenylephrine improves the outcome of cerebral ischemia in patients with internal carotid artery disease during hemorrhagic shock is unclear. METHODS: (Experiment 1) Twenty-one adult male Sprague-Dawley rats were anesthetized with isoflurane and their lungs mechanically ventilated. After the right common carotid artery was ligated, arterial blood was withdrawn until mean arterial blood pressure (MAP) reached 30 mm Hg to induce cerebral ischemia. After MAP was maintained at 30 mm Hg for 10 min, the animals were randomly allocated to three groups (n = 7 each). In the phenylephrine group, phenylephrine was administered IV to maintain a MAP of 70 +/- 3 mm Hg for 5 min. In the saline group, an identical volume of normal physiologic saline was continuously administered for 5 min. In the control group, neither phenylephrine nor saline was administered and MAP was maintained at 30 mm Hg. At 30 min of exsanguination, the withdrawn blood was reinfused IV at a rate of 0.25 mL/min. Diffusion-weighted magnetic resonance images were serially acquired and apparent diffusion coefficient maps were created to determine the volume of cytotoxic edema. (Experiment 2) To analyze the effect of phenylephrine on the regional cerebral blood flow (rCBF) in the right middle cerebral artery territory, rCBF was measured using laser Doppler flowmetry in 15 additional rats (n = 5 each). RESULTS: (Experiment 1) At 10 min of exsanguination, there were no significant differences in the volume of cytotoxic edema among the phenylephrine (357.5 +/- 93.5 mm(3)), saline (333.5 +/- 69.6 mm(3)), and control (303.1 +/- 85.8 mm(3)) groups. Low apparent diffusion coefficient regions significantly expanded with time in the control group, whereas they started to decrease just after phenylephrine infusion and almost all had disappeared within 30 min in the phenylephrine group. The final infarction volume in the phenylephrine group (3.9 +/- 2.6 mm(3), P < 0.01) was significantly lower than that in the saline group (341.5 +/- 213.7 mm(3)) and control group (509.1 +/- 197.0 mm(3)). (Experiment 2) Although rCBF decreased to 40%-50% of the baseline at 10 min of exsanguination, phenylephrine immediately increased rCBF over the baseline level. In the saline group, rCBF increased significantly, but there was some delay compared with the phenylephrine group. CONCLUSIONS: Phenylephrine ameliorated cytotoxic edema and decreased the infarction volume in a rat model of complete unilateral carotid artery occlusion with severe hypotension. These findings suggest that phenylephrine transiently increased CBF without increasing the tonus of cerebral vasculature during hemorrhagic shock.