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Background: Prophylactic antibiotics and neuromuscular blocking agents (NMBA) are two of the major causative agents of anaphylaxis after induction of anesthesia., Case Presentation: One female and one male patients (aged 29 and 69 years, respectively) had Ring and Messmer scale grade III anaphylaxis after administration of prophylactic antibiotics following induction of anesthesia. They showed typical hemodynamic and respiratory features of life-threatening anaphylaxis. Postoperative skin tests in these two patients were positive for antibiotics and concurrently positive for rocuronium., Conclusions: Our present report suggests the possibility that both prophylactic antibiotics and NMBA concurrently and synergistically enhance anaphylactic reaction and the necessity to differentiate an immune mechanism from non-immune mechanisms when anesthesiologists encounter concurrent positive skin tests for both antibiotics and NMBA.

Malignant hyperthermia (MH) is a severe hypermetabolic disorder associated with dysregulation of calcium homeostasis and is triggered by inhalational anesthetics (isoflurane, sevoflurane, desflurane) and a depolarizing muscle relaxant (succinylcholine). We report the case of a 16-day-old infant undergoing laparoscopic surgery. The patient developed hyperthermia and hypercarbia with muscle rigidity. After the diagnosis of MH, dantrolene was administered with sufficient hydration. The patient was transferred to the pediatric intensive care unit for monitoring and treatment of acute renal injury due to myoglobinuria. Subsequently, two variants of the ryanodine receptor 1 (RYR1) gene were identified in the patient as the mutation point at c.1589G > A p.Arg530His and c.1841G > T p.Arg614Leu, which are known to be associated with MH. This was a rare case of MH in a 16-day-old infant that might be related to two RYR1 mutations inherited from the parents.

Background: We compared the pharmacokinetics of levobupivacaine when administered intraperitoneally, subcutaneously, and intravenously in an anesthetized rat model, to estimate the toxicity risk of a local anesthetic when absorbed from the peritoneum., Methods: Thirty-two rats were anesthetized with sevoflurane. In Experiment 1, we administered 5.0 mg/kg of levobupivacaine intraperitoneally (IP) (n = 7), subcutaneously (SC) (n = 6), or intravenously (IV) (n = 6). In Experiment 2, we administered 2.5 mg/kg of levobupivacaine IP (n = 7) or SC (n = 6). Data are shown as median [range] of Experiment 1., Results: In either of experiments, the time to reach maximum plasma concentration of levobupivacaine was shorter in the IP group than in the SC group (IP: 2 [2-5] min; SC: 5 [2-10] min; P = 0.04), and the maximum concentration of levobupivacaine did not differ between the IP and SC groups (IP: 0.45 [0.05-0.67] µg/mL; SC: 0.47 [0.21-0.62] µg/mL; P = 0.90). The area under the curve from time 0 to 120 min after levobupivacaine administration was significantly higher in the SC group than in the IP group in both experiments (IP: 0.29 [0.10-0.54] mg h/L; SC: 0.78 [0.39-0.98] mg h/L; P = 0.04)., Conclusion: Levobupivacaine is rapidly absorbed following IP administration, but its maximum plasma concentration within 2 h following IP administration is no statistical difference as that following SC administration. On the other hand, when levobupivacaine is given subcutaneously, T max can exceed 1 h, so we need to be aware of local anesthetic toxicity during this period.

The objective of this study was to examine the impact of around-the-clock (ATC) administration of intravenous (IV) acetaminophen following robot-assisted radical prostatectomy (RARP). Intravenous infusion of acetaminophen was started on the day of the operation at 1000 mg/dose every 6 h, and the infusion was continued on a fixed schedule until postoperative day 2 a.m. In a retrospective observational study, we compared 127 patients who were administered IV acetaminophen on a fixed schedule (ATC group) with 485 patients who were administered analgesic drugs only as needed (PRN group). We investigated postoperative pain intensity and additional analgesic consumption on postoperative day 0, 1, 2, 3, and 5 between the two groups. Postoperative pain scores were significantly lower in the ATC group than in the PRN group at 1 and 2 days, and this period matched the duration of ATC administration of IV acetaminophen. Postoperative frequency of rescue analgesia was significantly lower in the ATC group than in the PRN group at postoperative 0, 1, and 2 days. ATC administration of IV acetaminophen has the potential to be a very versatile and valuable additional dose to achieve appropriate postoperative analgesia in patients with RARP.

Introduction: For successful pulmonary segmentectomy, the identification of boundaries between segments is important. Previous measures include tracing the intersegmental vessels by staining with a dye via the affected pulmonary artery or bronchus and inflating with oxygen via a high frequency ventilator. However, problems with these methods have been reported., Aim: We developed a novel method using a manual jet ventilator (MJV) and investigated its efficacy in identification of the pulmonary intersegmental plane., Material and Methods: Patients underwent MJV for pulmonary segmentectomy in the period from January 2013 to December 2017 at our institution. The patients' characteristics, resected segments, availability of clear resection planes, and complications associated with MJV from medical records were investigated. A questionnaire survey was conducted with the surgeons on the effectiveness of lung segment identification using MJV., Results: Of 199 cases of planned pulmonary segmentectomy, 171 cases with descriptions of identified intersegmental planes were analyzed. Of these, 152 (89%) cases showed a clear boundary. There were 19 cases where the exact boundaries were not clearly identified, but segmentectomy was still performed. Furthermore, we found that identification of the right upper lobes was difficult (p = 0.0028). A subjective questionnaire was answered by the 12 surgeons who performed the procedures. All 12 responded that MJV was very effective or effective regarding clarity, safety, shorter identification time, and shorter resection time., Conclusions: MJV enabled surgeons to more easily and safely identify the pulmonary intersegmental plane, thereby suggesting that MJV has clinical significance during pulmonary segmentectomy., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2020 Fundacja Videochirurgii.)

Background: We investigated the potential safety of remimazolam and propofol in malignant hyperthermia- (HM-) susceptible patients using ryanodine receptor 1- (RYR1-) expressing human embryonic kidney- (HEK-) 293 cells., Methods: We compared the enhanced responsiveness of HEK-293 cells expressing wild-type RYR1 with that of mutant RYR1 to caffeine following perfusion with remimazolam or propofol. Furthermore, we investigated whether RYR1 enhanced the responsiveness of cells to remimazolam or propofol and compared the median effective concentration (EC 50 ; i.e., the concentration required to reach half-maximal activation) using an unpaired two-tailed t -test while a P < 0.05 was considered significant., Results: Remimazolam and propofol did not promote the caffeine-induced increase in intracellular Ca 2+ levels in HEK-293 cells expressing mutant RYR1 even with exposure to approximately 100-fold the clinically used concentration. In wild-type RYR1, EC 50 values of remimazolam following refusion vs. nonperfusion were 2.86 mM vs. 2.75 mM ( P = 0.76) while for propofol perfusion vs. nonperfusion, they were 2.76 mM vs. 2.75 mM, respectively ( P = 0.83). In mutant RYR1, EC 50 values of remimazolam refusion vs. nonperfusion were 1.58 mM vs. 1.71 mM, respectively ( P = 0.63) while for propofol perfusion vs. nonperfusion, they were 1.65 mM vs. 1.71 mM, respectively ( P = 0.73). Remimazolam and propofol increased intracellular Ca 2+ levels in a concentration-dependent manner, but the effect was not enhanced by RYR1. EC 50 values of remimazolam with non-RYR1 vs. wild-type RYR1 were 1.00 mM vs. 0.92 mM, respectively ( P = 0.91) while those of propofol were 1.09 mM vs. 1.05 mM, respectively ( P = 0.84)., Conclusions: The increase in intracellular Ca 2+ concentration caused by remimazolam or propofol was not considered an RYR1-mediated reaction. We conclude that remimazolam and propofol can be safely used as an anesthetic in MH-susceptible patients with RYR1 -mutation without causing MH and may be safely substituted for an MH-triggering anesthetic when RYR1-mediated MH occurs., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2021 Tomoyuki Watanabe et al.)

Background : Although an increase in sympathetic nerve activity is generally associated with a decrease in the photoplethysmography (PPG) amplitude, the present case study demonstrates that nociceptive stimuli, such as tracheal intubation, paradoxically induce an increase in PPG amplitude. To the best of our knowledge, this is the first study to capture an increase in the PPG amplitude in response to sympathetic nerve activation. Case presentation : A 73-year-old woman underwent open surgery. Following anesthesia induction, tracheal intubation was performed, which resulted in increased heart rate and raised blood pressure. While nociception usually decreases the PPG amplitude, the opposite was found. Conversely, the vascular stiffness K value, our research group's unique monitoring method to quantify the strength of sympathetic activity, increased reflecting increased peripheral vascular resistance. Conclusions : We report a paradoxical case of increased PPG amplitude following tracheal intubation. It is important to note that the PPG amplitude does not always decrease with nociceptive stimuli. J. Med. Invest. 68 : 383-385, August, 2021.

Background: Remimazolam is a novel short-acting benzodiazepine characterized by metabolism independent from organ function. We report intraoperative MEP responses of two patients who underwent spine surgery under general anesthesia using remimazolam., Case Presentation: In case 1, MEP monitoring was successfully performed with the use of a fixed dose of remimazolam at 0.5 mg/kg/h and remifentanil at 0.2 μg/kg/min. In case 2, an increasing dose of remimazolam from 0.5 to 1.5 mg/kg/h during the operation did not affect MEP signals. In both cases, remimazolam was titrated to maintain the values of entropy electroencephalogram (EEG) monitoring at 40-60., Conclusions: General anesthesia using remimazolam and remifentanil can be a valuable alternative for spine surgery with MEP monitoring by EEG to assess the optimal dose.

Objectives: To investigate the outcomes of patients with in-hospital cardiac arrest (IHCA) who underwent cardiopulmonary resuscitation (CPR) using an automated external defibrillator (AED) in non-monitored areas. Additionally, to detect correlated factors associated with rate of return of spontaneous circulation (ROSC) and survival rate, among collected data., Methods: This study included 109 patients. After investigating patient characteristics and resuscitation-related factors, the correlated factors associated with ROSC rates and survival rate were analyzed using univariate and multivariate analyses., Results: The rate of survival to hospital discharge was 21.1%. CPR with AED performed since 2013 was associated with a higher ROSC rate (adjusted odds ratio [AOR] 3.24, 95% confidence interval [CI]: 1.21 to 9.52, p < 0.05), but not with the survival rate after ROSC. Tracheal intubation was significantly associated with a higher ROSC rate (AOR 3.62, 95% CI: 1.27 to 11.7, p < 0.05) and a lower survival rate after ROSC (hazard ratio 6.6, 95% CI: 1.2 to 43.3, p < 0.05). Dysrhythmia as the cause of cardiac arrest and intensive care unit (ICU) admission after ROSC were associated with higher survival rates (hazard ratio 0.056, 95% CI: 0.004 to 0.759, p < 0.05, and hazard ratio 0.072, 95% CI: 0.017 to 0.264, p < 0.0001, respectively)., Conclusions: The factors associated with ROSC rate and those associated with the survival rate after ROSC were different. Although initial shockable rhythms on AED were not associated with the survival rate, dysrhythmia as the etiology of cardiac arrest, and ICU admission were significantly associated with higher survival rates after ROSC., Competing Interests: Declaration of competing interest None., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

We developed a new face mask concept for oxygen administration using non-woven textiles. The aim of this study was to evaluate whether the new mask improves acceptability without compromising O 2 delivery and CO 2 elimination. 10 healthy adult volunteers were randomized to either the conventional plastic face mask-first group or the new face mask-first group. Participants were asked to wear the assigned mask with O 2 at 3 L/min for 10 min while seated. End tidal O 2 concentration (et-O 2 ) and end tidal CO 2 concentration (et-CO 2 ) were measured via a sampling tube located at the mouth. After a 10-min rest period, the other mask was tested in the same manner. Mask discomfort was evaluated using a 100 mm visual analog scale (VAS) where 0, comfortable and 100, uncomfortable. The results showed that use of the new mask caused less discomfort than the conventional mask (new, 11; conventional, 33) (P = 0.002). Median et-O 2 with the new mask was 33%, compared with 30% with the conventional mask (P = 0.008). There were no significant differences in et-CO 2 by mask type (new, 32 mmHg; conventional, 30 mmHg). In conclusion, the new mask was more comfortable and provided higher et-O 2 than the conventional mask.

Restless legs syndrome (RLS) is a neurological sensory disorder associated with sensory and motor symptoms that most commonly occur at night and during periods of rest. It is characterized by altered or abnormal sensations primarily in the legs and the urge to move the associated limbs. Perioperative procedures, including general anesthesia, can cause exacerbations of RLS. This is a case report of a suspected RLS exacerbation in a 22-year-old woman who had no formal diagnosis of RLS despite reporting symptoms that met all essential diagnostic criteria by the International RLS Study Group. Despite her previous diagnoses of dehydration induced-muscle pain or nocturnal cramps, we suspected her to have RLS. The patient underwent general anesthesia for a bilateral sagittal split ramus osteotomy using a combined inhalational and intravenous anesthetic technique with sevoflurane, propofol, remifentanil, and dexmedetomidine. After successful completion of the surgery and returning to the ward, she began moving her lower extremities and complaining of unpleasant sensations in both ankles. Bed rest exacerbated the suspected RLS symptoms despite a continuous infusion of dexmedetomidine. The RLS symptoms continued to worsen and spread to her upper extremities. After increasing the dexmedetomidine infusion from 0.2 to 0.4 μg/kg/h, almost all symptoms improved, and she slept for 3 hours. Upon awakening, the unpleasant sensations were completely relieved by walking and stretching. The patient was formally diagnosed with RLS by a neurologist after discharge. In this case, an infusion of dexmedetomidine was helpful in successfully managing a suspected exacerbation of RLS., (© 2020 by the American Dental Society of Anesthesiology.)

Propofol, most frequently used as a general anesthetic due to its versatility and short-acting characteristics, is thought to exert its anesthetic actions via GABA A receptors; however, the precise mechanisms of its adverse action including angialgia remain unclear. We examined the propofol-induced elevation of intracellular calcium and morphological changes in intracellular organelles using SHSY-5Y neuroblastoma cells, COS-7 cells, HEK293 cells, and HUVECs loaded with fluorescent dyes for live imaging. Although propofol (>50 μM) increased intracellular calcium in a dose-dependent manner in these cells, it was not influenced by the elimination of extracellular calcium. The calcium elevation was abolished when intracellular or intraendoplasmic reticulum (ER) calcium was depleted by BAPTA-AM or thapsigargin, respectively, suggesting that calcium was mobilized from the ER. Studies using U-73122, xestospongin C, and dantrolene revealed that propofol-induced calcium elevation was not mediated by G-protein coupled receptors, IP3 receptors, or ryanodine receptors. We performed live imaging of the ER, mitochondria and Golgi apparatus during propofol stimulation using fluorescent dyes. Concomitant with the calcium elevation, the structure of the ER and mitochondria was fragmented and aggregated, and these changes were not reversed during the observation period, suggesting that propofol-induced calcium elevation occurs due to calcium leakage from these organelles. Although the concentration of propofol used in this experiment was greater than that used clinically (30 μM), it is possible that the concentration exceeds 30 μM at the site where propofol is injected, leading the idea that these phenomena might relate to the various propofol-induced adverse effects including angialgia., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: This study aimed to evaluate whether the three ryanodine receptor type 1 (RYR1) variants (p.Ser2345Thr, p.Ser2345Arg, and p.Lys3367Arg) which we identified in Japanese malignant hyperthermia (MH) patients with a clinical grading scale rank of 6 were causative for MH., Methods: We prepared human embryonic kidney (HEK)-293 cells transfected with wild-type RYR1 or one of the RYR1 variants, along with myotubes cultured from muscle pieces. Calcium kinetics were examined by calculating the 340/380-nm ratio under various caffeine and 4-chloro-m-cresol (4CmC) concentrations with the ratiometric dye Fura-2 AM. Half-maximal effective concentration (EC 50 ) values were calculated from dose-response curves. Statistical analysis was based on one-way analysis of variance with a Dunnett's multiple comparison test, using a P value < 0.05 as evidence of statistical significance., Results: In functional analysis using HEK-293 cells, we found significant reductions in the EC 50 of p.Ser2345Thr and p.Ser2345Arg in comparison with wild-type RYR1 (P < 0.001), while the EC 50 of p.Lys3367Arg was not significantly different (P = 0.062 for caffeine and P > 0.999 for 4CmC). On the other hand, functional analysis using myotubes showed significant differences in the EC 50 values for all variants (P < 0.001 for all comparisons)., Conclusions: p.Ser2345Thr and p.Ser2345Arg appear capable of causing a calcium metabolism disorder that leads to the onset of MH, and p.Ser2345Arg can be considered as a diagnostic mutation, because it meets the European Malignant Hyperthermia Group criteria. However, patients with p.Lys3367Arg might have mutations in genes other than RYR1 that are capable of causing MH.

Background: Postoperative Nausea and Vomiting (PONV) is a common complication of general anesthesia. Several kinds of antiemetics, including 5-Hydroxytryptamine3 (5-HT3) receptor antagonists and Neurokinin-1 (NK-1) receptor antagonists, have been used to treat PONV., Objectives: To compare the antiemetic effect of NK-1 receptor antagonists, including fosaprepitant., Data Sources: Online databases (PubMed, MEDLINE, Scopus, The Cochrane Library databases) were used., Study Eligibility Criteria, Participants, and Interventions: Randomized Controlled Trials (RCTs) performed in patients over 18 years with ASA-PS of I-III, aimed to assess the efficacy of antiemetics including NK-1 receptor antagonists and 5-HT3 receptor antagonists, and compared the incidence of PONV were included., Study Appraisal and Synthesis Methods: All statistical assessments were conducted by a random effect approach and odds ratios and 95% Confidence Intervals were calculated., Results: Aprepitant 40mg and 80mg significantly reduced the incidence of vomiting 0-24hours postoperatively (Odds Ratio [OR = 0.40]; 95% Confidence Interval [95% CI 0.30-0.54]; p < 0.001, and OR = 0.32; 95% CI 0.19-0.56; p < 0.001). Fosaprepitant could also reduce the incidence of vomiting significantly both 0-24h and 0-48hours postoperatively (OR = 0.07; 95% CI 0.02-0.24; p < 0.001 and OR = 0.07; 95% CI 0.02-0.23; p < 0.001)., Limitations: Risk factors for PONV are not considered, RCTs using multiple antiemetics are included, RCTs for fosaprepitant is small, and some bias may be present., Conclusions and Implications of Key Findings: Aprepitant and fosaprepitant can be effective prophylactic antiemetics for postoperative vomiting. However, more studies are required for higher-quality meta-analyses., Systematic Review Registration Number: CRD42019120188., (Copyright © 2020 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.)

Background: Previous studies showed that remifentanil-induced anesthesia can inhibit surgical stress response in non-diabetic adult patients and that low-dose glucose loading during anesthesia may attenuate fat catabolism. However, little is known about the influence of glucose loading on metabolism in elderly patients, whose condition may be influenced by decreased basal metabolism and increased insulin resistance. We hypothesized that, in elderly patients, intraoperative low glucose infusion may attenuate the catabolism of fat without causing harmful hyperglycemia during remifentanil-induced anesthesia., Methods: Elderly, non-diabetic patients scheduled to undergo elective surgery were enrolled and randomized to receive no glucose (0G group) or low-dose glucose infusion (0.1 g/kg/hr. for 1 h followed by 0.05 g/kg/hr. for 1 h; LG group) during surgery. Glucose, adrenocorticotropic hormone (ACTH), 3-methylhistidine (3-MH), insulin, cortisol, free fatty acid (FFA), creatinine (Cr), and ketone body levels were measured pre-anesthesia, 1 h post-glucose infusion, at the end of surgery, and on the following morning., Results: A total of 31 patients (aged 75-85) were included (0G, n = 16; LG, n = 15). ACTH levels during anesthesia decreased significantly in both groups. In the LG group, glucose levels increased significantly after glucose loading but hyperglycemia was not observed. During surgery, ketone bodies and FFA were significantly lower in the LG group than the 0G group. There were no significant differences in insulin, Cr, 3-MH, and 3-MH/Cr between the two groups., Conclusion: Remifentanil-induced anesthesia inhibited surgical stress response in elderly patients. Intraoperative low-dose glucose infusion attenuated catabolism of fat without inducing hyperglycemia., Trial Registration: This study has been registered with the University hospital Medical Information Network Center (http://www.umin.ac.jp/english/)., Trial Registration Number: UMIN000016189. The initial registration date: January 12th 2015.

Aims: Amino acids, especially branched chain amino acids (BCAAs), have important regulatory roles in protein synthesis. Recently studies revealed that BCAAs protect against ischemia/reperfusion (I/R) injury. We studied the signaling pathway and mitochondrial function affecting a cardiac preconditioning of BCAAs., Main Methods: An in vivo model of I/R injury was tested in control, mTOR +/+ , and mTOR +/ - . Mice were randomly assigned to receive BCAAs, rapamycin, or BCAAs + rapamycin. Furthermore, isolated cardiomyocytes were subjected to simulated ischemia and cell death was quantified. Biochemical and mitochondrial swelling assays were also performed., Key Findings: Mice treated with BCAAs had a significant reduction in infarct size as a percentage of the area at risk compared to controls (34.1 ± 3.9% vs. 44.7 ± 2.6%, P = 0.001), whereas mice treated with the mTOR inhibitor rapamycin were not protected by BCAA administration (42.2 ± 6.5%, vs. control, P = 0.015). This protection was not detected in our hetero knockout mice of mTOR. Western blot analysis revealed no change in AKT signaling whereas activation of mTOR was identified. Furthermore, BCAAs prevented swelling which was reversed by the addition of rapamycin. In myocytes undergoing simulated I/R, BCAA treatment significantly preserved cell viability (71.7 ± 2.7% vs. 34.5 ± 1.6%, respectively, p < 0.0001), whereas rapamycin prevented this BCAA-induced cardioprotective effect (43.5 ± 3.4% vs. BCAA, p < 0.0001)., Significance: BCAA treatment exhibits a protective effect in myocardial I/R injury and that mTOR plays an important role in this preconditioning effect., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Two types of amniotic fluid embolism (AFE) have been described : cardiopulmonary collapse type and disseminated intravascular coagulation (DIC) type, with the latter proposed as uterine type. This report describes a healthy 28-year-old woman who developed AFE during a cesarean section. Because of a previous cesarean section, the patient underwent an elective cesarean section, under combined spinal-epidural anesthesia, at 38 weeks of pregnancy. She began coughing 5 minutes after delivery of the fetus, subsequently becoming unconscious and developing glossoptosis and bradycardia. Her blood pressure decreased to 76/43 mmHg, and AFE was suspected. Her uterus was atonic, and she experienced persistent noncoagulant bleeding, with a final blood loss of 6300 ml. Considerable blood transfusion was required. The patient survived, and she and her baby were discharged without any sequelae on the eighth postoperative day. This patient met the Japanese criteria for clinical AFE, with an obstetrical DIC score of 21 meeting the criteria for obstetrical DIC. Early diagnosis and treatment likely resulted in patient survival. J. Med. Invest. 67 : 207-210, February, 2020.

Background and aims : Severe aortic stenosis (AS) has been normally treated with surgical aortic valve replacement (AVR) whereas recently, transcatheter aortic valve implantation (TAVI) has been introduced as a minimally invasive operation for patients with high surgical risk and frailty. In this study, we have evaluated postoperative physical function and nutrition intake in the patients following AVR and TAVI. Methods : This prospective observational study involved 9 patients with surgical aortic valve replacement (AVR) and 7 patients with transcatheter aortic valve implantation (TAVI). Body composition was measured one day prior surgery, postoperative day (POD) 1, POD 3, POD 5 and POD 7. Hand grip strength, calf circumference and gait speed were measured one day before surgery and on the day of discharge. Results : Skeletal muscle was significantly decreased in AVR patients at postoperative day 3 and 7, while there was no change in TAVI patients. Patients with TAVI showed higher dietary intake after surgery compared to patients with AVR, and they maintained hand grip strength and calf circumference at discharge. Conclusions : In elderly patients with AS, TAVI can improve post-operative recovery maintaining nutritional status and physical function even. J. Med. Invest. 67 : 139-144, February, 2020.

Dravet syndrome (DS) is a rare and severe form of epilepsy that begins in infancy. This is particularly burdensome because repeated epileptic seizures lead to cognitive decline. We describe the case of a 12-year-old girl who was diagnosed with DS and was scheduled to have gingival reduction around her mandibular molars. Despite the patient being intellectually disabled, she was able to cooperate somewhat during medical procedures, including intravenous cannulation. Under the assumption that the major problem with anesthesia for DS would be the regulation of body temperature-induced seizures, we used body temperature management equipment to maintain the patient's body temperature during the procedure. We opted for intravenous sedation and administered a total dose of 4.5 mg midazolam throughout the procedure. Anesthesia was completed within 1 hour and 20 minutes without any adverse events. To the best of our knowledge, no previous studies have documented the anesthetic management of DS. In this case, no adverse events occurred perioperatively. However, the patient's temperature rose to that which indicated a slight fever despite the use of a standard cooling technique.

Study Objective : the incidence of postoperative nausea and vomiting (PONV) following single-injection intraarticular anesthesia was compared to that following continuous epidural anesthesia. Design : Prospective, double-blind, randomized study. Setting : University-affiliated teaching hospital. Patients : Forty-eight patients finally participated in this study, and each group contained twenty-four patients. Interventions : Patients scheduled to undergo lower limb surgery under general anesthesia were randomly allocated into two groups, to receive either single-injection intraarticular or continuous epidural anesthesia for postoperative analgesia. Measurements : The incidence and severity of PONV, complete response rates (i.e., no vomiting or rescue antiemetic use), and pain scores were recorded 2, 24, and 48 h postoperatively. Main results : No significant differences between groups were observed in the incidence and severity of PONV, rescue antiemetic use, or complete response rate at any of the time points, but only the use of rescue analgesics was significantly less in continuous epidural anesthesia group during the 2-24h postoperative period (P=0.04). Conclusion : While the use of single-injection intraarticular anesthesia following lower limb surgery did not prevent PONV more than continuous epidural anesthesia in this study, the intraarticular technique still provides greater simplicity, safety, and cost-effectiveness. J. Med. Invest. 66 : 303-307, August, 2019.

Background: Methylmalonic acidemia (MMA) is a metabolic disorder of organic acids and is characterized by the accumulation of methylmalonic acids., Case Presentation: The patient was a 19-year-old female diagnosed with severe MMA at 3 days of age, who was scheduled for renal replacement therapy. Preoperatively, there was no evidence of metabolic acidosis or electrolyte abnormalities. Glucose was administered preoperatively following a 6-h fast. Anesthesia was administered using thiamylal, remifentanil, rocuronium, and sevoflurane. After tracheal intubation, the patient underwent an ultrasound-guided bilateral rectus sheath block with ropivacaine. A drop in blood sugar level was treated with 5% glucose. Extubation was performed after intravenous administration of sugammadex., Conclusions: We report the anesthetic management of a patient with MMA using a combination of general anesthesia and rectus sheath block.

Background: It is well known that the programmed intermittent epidural bolus (PIEB) technique effectively provides epidural anesthesia in labor. This randomized double-blind trial compared the postoperative analgesic efficacy of PIEB with that of continuous epidural infusion (CEI) in patients undergoing gynecological surgery under combined general-epidural anesthesia., Methods: Patients undergoing open gynecological surgery under combined general-epidural anesthesia were randomized at a 1 : 1 ratio to receive PIEB or CEI. In the PIEB group, the pump delivered 4 mL ropivacaine 0.2% plus fentanyl 2  μ g/mL every hour. In the CEI group, the pump delivered the same solution at a rate of 4 mL/h. In both groups, additional 4 mL boluses of ropivacaine 0.2% plus fentanyl 2  μ g/mL were provided, when necessary, by patient-controlled epidural analgesia after surgery. The primary outcome was the total ropivacaine dose 40 hours after surgery. The secondary outcomes were the number of PCEA boluses and postoperative pain (evaluated on an 11-point numerical rating scale) 3, 24, and 48 hours after surgery., Results: In total, 57 patients were randomized ( n = 28 and 29 in the PIEB and CEI groups, resp.). The two groups differ significantly in terms of the total ropivacaine dose 40 hours after surgery (mean (standard deviation): 155.38 (4.55) versus 159.73 (7.87) mL, P = 0.016). Compared to the CEI group, the PIEB group had significantly lower numerical rating scale scores 3 hours (median [lower-upper quartiles]: 0 [0-0.5] versus 3 [0-5.5], P = 0.002), 24 hours (1 [0-2] versus 3 [1-4], P = 0.003), and 48 hours (1 [0-2] versus 2 [2-3.5], P = 0.002) after surgery., Conclusion: PIEB was better than CEI in terms of providing postoperative analgesia after open gynecological surgery under combined general-epidural anesthesia.

Waldenström's macroglobulinemia (WM) manifests as hyperviscosity syndrome. Cryoglobulinemia, which may increase blood viscosity or induce thrombosis in association with decreased body temperature, can occur in combination with WM. We describe the management of an 82-year-old woman with WM, hyperviscosity syndrome, and cryoglobulinemia who required open aortic valve replacement. Decreased body temperature in this patient was prevented during cardiopulmonary bypass by using a forced air warming system and normothermic cardioplegia with continuous warm blood cardioplegia perfusion.

The aim of this work was to investigate the effect of oral carbohydrate with amino acid [oral nutritional supplement (ONS)] solution on oxidative stress in healthy persons. Fourteen healthy volunteers were segregated into control and ONS groups. Volunteers in the ONS group ingested 250 ml of Arginaid Water (Nestle Japan, Tokyo, Japan) in the evening before the experiment and at 7:00 am on the day of the experiment. Volunteers in the control group fasted after dinner and drank only water until 7:00 am on the day of the experiment. In both groups, blood was collected at 9:00 am. The serum total oxidant levels and antioxidant capacity were assessed by d-ROMs (derivatives of reactive oxygen metabolites) test and BAP (biological antioxidant potential) test, respectively. In the ONS group, the serum d-ROMs level was significantly lower than in the control group (297 ± 43 and 327 ± 41 U.CARR, respectively, p = 0.018), while the serum BAP level was significantly higher than the control group (2410 ± 432 and 1979 ± 397 µmol/l, respectively, p = 0.005). The OXY level of Arginaid Water was much higher than preOp drink (Nutricia, Ireland). In conclusion, our study showed that an ONS with arginine loading could decrease oxidative stress and increase antioxidant capacity in healthy volunteers.

Cetuximab is a drug targeting the epidermal growth factor receptor, which is indicated for the treatment of unresectable advanced or recurrent head and neck or colorectal cancer. Cetuximab also enhances the cytotoxic effects of radiation in squamous cell carcinoma. The severity of infusion reactions (IR) is categorized from grade 1 to 5; grades 3 and 4 are associated with life-threatening reactions (anaphylaxis), whereas grade 5 indicates death. The incidence of grade 3-4 IR with premedication is reported to be 1.1%. We herein describe a case of a 77-year-old man who developed IR during intravenous administration of cetuximab. The patient developed grade 3-4 anaphylaxis with pruritus, rash and urticaria, followed by hypotension and bradycardia. The timely diagnosis and treatment with intravenous infusion of a vasopressor drug and Ringer's acetate solution proved to be effective. The case presented herein demonstrated an unfeatured aspect of cetuximab-related IR as dermatological reactions over the entire body followed by circulatory collapse.

A 54-year-old woman diagnosed with multiple sclerosis (MS) at the age of 19 years was scheduled to undergo temporomandibular joint mobilization. She was currently in a remission phase from her MS but with persistent sequelae, including impaired eyesight and muscle weakness of the limbs. In addition, the blood vessels in her upper limbs were compromised by the formation of internal shunts secondary to vascular prosthesis replacements for plasma exchange therapy in MS. After a previous joint mobilization surgery, her temporomandibular joint developed adhesions with resultant trismus. One of the adverse effects of general anesthesia can be exacerbations of MS symptoms. Minimizing mental and physical stress caused by surgical and anesthetic procedures and maintenance of stable body temperature are important considerations. Awake intubation was performed under sedation with midazolam and fentanyl. After intubation, anesthesia was induced with propofol, remifentanil, and rocuronium. Maintenance of anesthesia was achieved with oxygen-N 2 O-sevoflurane, remifentanil, fentanyl, and rocuronium. In this case, no adverse events occurred intraoperatively. However, the patient experienced lingering weakness of the limbs in the postoperative period, and activities of daily living of the patient were affected.

The aim of the present study was to evaluate the usefulness of a closed-loop system (STG-55; Nikkiso, Tokyo, Japan), a type of artificial endocrine pancreas for the continuous monitoring and control of intraoperative blood glucose, for preventing postoperative acute kidney injury (AKI) in patients undergoing hepatectomy. Thirty-eight patients were enrolled in this study. Glucose concentrations were controlled with either a manual injection of insulin based on a commonly used sliding scale (manual insulin group, n = 19) or the programmed infusion of insulin determined by the control algorithm of the artificial endocrine pancreas (programmed insulin group, n = 19). After the induction of anesthesia, a 20-G intravenous catheter was inserted into the peripheral forearm vein of patients in the programmed insulin group and connected to an artificial endocrine pancreas (STG-55). The target range for glucose concentrations was set to 100-150 mg/dL. The mean serum creatinine concentrations of preoperative, postoperative 24 and 48 h were 0.72, 0.78, and 0.79 mg/dL in the programmed insulin group, and 0.81, 0.95, and 1.03 mg/dL in the manual insulin group, respectively. Elevations in serum creatinine concentrations postoperative 48 h were significantly suppressed in the programmed insulin group. The STG-55 closed-loop system was effective for maintaining strict blood glucose control during hepatectomy with minimal variability in blood glucose concentrations and for suppressing elevations in serum creatinine concentrations. Strict blood glucose control by an artificial endocrine pancreas during hepatectomy may prevent postoperative AKI.

Postoperative nausea and vomiting (PONV) occur in 30-50% of patients undergoing general anesthesia and in 70-80% of high PONV risk patients. In this study, we investigated the efficacy of fosaprepitant, a neurokinin-1 (NK1) receptor antagonist, compared to ondansetron, a selective 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, in moderate to high PONV risk patients from our previous randomized controlled trials. Patients (171 patients from 4 pooled studies) with the Apfel simplified score ≥ 2 and undergoing general anesthesia were randomly allocated to receive intravenous fosaprepitant 150 mg (NK1 group, n = 82) and intravenous ondansetron 4 mg (ONS group, n = 89) before induction of anesthesia. Incidence of vomiting was significantly lower in the NK1 group compared to the ONS group 0-2, 0-24, and 0-48 hours after surgery (2 versus 17%, 2 versus 28%, and 2 versus 29%, resp.). However, no significant differences in PONV, complete response, rescue antiemetic use, and nausea score were observed between groups 0-48 hours after surgery. In moderate to high PONV risk patients, fosaprepitant decreased the incidence of vomiting and was superior to ondansetron in preventing postoperative vomiting 0-48 hours after surgery.

We describe the case of a 37-year-old woman who had been diagnosed with Ehlers-Danlos syndrome (EDS) 4 years earlier and was scheduled to undergo removal of synovial chondromatosis in the temporomandibular joint. EDS is a heritable connective tissue disorder and has 6 types. In this case, the patient was classified into EDS hypermobility type. The major clinical feature of this type is joint hypermobility. The patient had sprain or subluxation of the elbows and ankles and dislocation of the knees. Anticipated problems during general anesthesia would be affected by the disease type. For this patient, extra attention was directed to positional injury-induced neuropathy and articular luxation, cutaneous injuries, injuries related to intubation and ventilation, and postoperative pain. Anesthesia was induced with propofol, remifentanil, and rocuronium and maintained with oxygen-air-desflurane, propofol, remifentanil, fentanyl, and rocuronium. In this case, the patient was safely managed without adverse events.

Objective: Enhanced recovery after surgery is increasingly desired nowadays, and preoperative nutrient intake may be beneficial for this purpose. In this study, we investigated whether the intake of preoperative carbohydrate with amino acid (ONS) solution can improve starvation status and lipid catabolism before the induction of anesthesia., Methods: This randomized, prospective clinical trial included 24 patients who were divided into two groups before surgery under general anesthesia: a control group, comprising patients who fasted after their last meal the day before surgery (permitted to drink only water), and an ONS group, comprising patients who consumed ONS solution 2 h before surgery. Biochemical markers, the respiratory quotient, and psychosomatic scores were assessed at the initiation of anesthesia., Results: Compared with the control group, the ONS group showed significantly lower serum free fatty acid levels [control group: 828 (729, 1004) µEq/L, ONS group: 479 (408, 610) µEq/L, P = 0.0002, median (25th, 75th percentile)] and total ketone bodies [control group: 119 (68, 440) µmol/L, ONS group: 40 [27, 64] µmol/L, P = 0.037]. In addition, analysis using the Visual Analog Scale showed higher preoperative scores for anxiety, hunger, and thirst for the control group, with no differences in any other measure of subjective well-being between groups., Conclusions: The results of this study suggest that preoperative ONS intake improves lipid catabolism and starvation status before the induction of anesthesia. Furthermore, it can provide better preoperative mental health compared with complete fasting.

Charcot-Marie-Tooth disease (CMTD) is a hereditary peripheral neuropathy and is characterized by progressive muscle atrophy and motor-sensory disorders in all 4 limbs. Most reports have indicated that major challenges with general anesthetic administration in CMTD patients are the appropriate use of nondepolarizing muscle relaxants and preparation for malignant hyperthermia in neuromuscular disease. Moderate sedation may be associated with the same complications as those of general anesthesia, as well as dysfunction of the autonomic nervous system, reduced perioperative respiratory function, difficulty in positioning, and sensitivity to intravenous anesthetic agents. We decided to use intravenous sedation in a CMTD patient and administered midazolam initially and propofol continuously, with total doses of 1.5 mg and 300 mg, respectively. Anesthesia was completed in 3 hours and 30 minutes without adverse events. We suggest that dental anesthetic treatment with propofol and midazolam may be effective for patients with CMTD.

It is important for the anesthesiologists to understand pathophysiology of perioperative stress hyperglycemia, because it offers strategies for treatment of stress hyperglycemia. The effect of glucose tolerance is different in the choice of the anesthetic agent used in daily clinical setting. Specifically, the volatile anesthetics inhibit insulin secretion after glucose load and affects glucose tolerance. During minor surgery by the remifentanil anesthesia, the stress reaction is hard to be induced, suggesting that we should consider low-dose glucose load. Finally it is necessary to perform the glycemic control of the patients who fell into stress hyperglycemia depending on the individual patient. However, there are a lot of questions to be answered in the future. The prognosis of the perioperative patients is more likely to be greatly improved if we can control stress hyperglycemia.

Background: We investigated the effects of a novel method of anesthesia combining propofol and volatile anesthesia on the incidence of postoperative nausea and vomiting in patients undergoing laparoscopic gynecological surgery., Methods: Patients were randomly divided into three groups: those maintained with sevoflurane (Group S, n=42), propofol (Group P, n=42), or combined propofol and sevoflurane (Group PS, n=42). We assessed complete response (no postoperative nausea and vomiting and no rescue antiemetic use), incidence of nausea and vomiting, nausea severity score, vomiting frequency, rescue antiemetic use, and postoperative pain at 2 and 24h after surgery., Results: The number of patients who exhibited a complete response was greater in Groups P and PS than in Group S at 0-2h (74%, 76% and 43%, respectively, p=0.001) and 0-24h (71%, 76% and 38%, respectively, p<0.0005). The incidence of nausea at 0-2h (Group S=57%, Group P=26% and Group PS=21%, p=0.001) and 0-24h (Group S=62%, Group P=29% and Group PS=21%, p<0.0005) was also significantly different among groups. However, there were no significant differences among groups in the incidence or frequency of vomiting or rescue antiemetic use at 0-24h., Conclusion: Combined propofol and volatile anesthesia during laparoscopic gynecological surgery effectively decreases the incidence of postoperative nausea. We term this novel method of anesthesia "combined intravenous-volatile anesthesia (CIVA)"., (Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.)

Purpose: Activation of the mitochondrial calcium-activated potassium (mKCa) channel reportedly confers resistance to myocardial ischemic stress. However, the role of the mKCa channel in postconditioning induced by volatile anesthetic remains unclear., Methods: Male Japanese white rabbits underwent coronary artery occlusion for 30 min followed by reperfusion for 3 h. Volatile anesthetic, isoflurane, was administered at 3 min prior to reperfusion for 5 min. Rabbits were injected with the mKCa channel blocker, iberiotoxin, or the mKCa channel opener, NS1619, at 8 min prior to reperfusion. Myocardial infarct size and the area at risk (AAR) were measured at the end of the experiment., Results: Isoflurane significantly reduced infarct size (23.0 ± 9.8% of the AAR, P<0.05) compared with the control (44.0 ± 9.1%). Iberiotoxin abolished the cardioprotective impact of isoflurane (43.0 ± 11.6%), while iberiotoxin alone exerted no effect on infarct size (45.0 ± 9.5%). NS1619 and isoflurane/NS1619 both significantly reduced infarct size (21.0 ± 10.3% and 19.0 ± 8.8%, respectively, P<0.05 vs control group), but isoflurane/NS1619 showed no additional benefits compared with isoflurane alone., Conclusion: These results indicate that activation of the mKCa channel contribute isoflurane-induced postconditioning.

Background: This study investigated plasma concentrations of substance P (SP) in patients undergoing general anesthesia (GA) and postoperative nausea and vomiting (PONV). This prospective, observational, cohort study included 23 patients who underwent scheduled surgery under general anesthesia. Blood was collected from the radial artery at predetermined time points (15-30 mins prior anesthesia, 15-30 mins after surgery/GA, and 24 h after surgery). PONV, SP concentrations, risk factors, and analgesics used were measured., Findings: Nine of 23 patients experienced PONV. In patients without PONV, SP concentrations significantly decreased ( P  < 0.0001) at the end of surgery/GA, compared to baseline, and recovered at 24 h after surgery/GA (452.9 ± 146.2 vs. 666.9 ± 176.5 vs. 580.7 ± 168.6 pg/mL, respectively), whereas SP levels were unchanged during surgery/GA and increased at 24 hours after surgery ( P  = 0.020) in patients with PONV (726.1 ± 167.8 vs. 655.8 ± 168.0 vs. 779.7 ± 220.7 pg/mL, respectively)., Conclusions: These finding suggest that SP levels may be utilized as an objective marker for PONV.

Background: Barber-Say syndrome (BSS) is a very rare congenital disorder characterized by macrostomia, cutis laxa, and other features. We report our experience of performing general anesthesia on a Japanese child with BSS., Case Presentation: A bilateral repair of the corners of the mouth under general anesthesia was planned for an 18-month-old male with macrostomia; the child was 75 cm in height and weighed 9.9 kg. As insertion of the peripheral intravenous catheter was difficult, it was inserted before the surgery by a pediatrician. The patient wore a mask and was ventilated manually after loss of consciousness with intravenous anesthesia. A mask for adults provided a superior fit and was effective in preventing air leakage from the corners of the mouth. After rocuronium was administered, the larynx was spread with a Macintosh laryngoscope. There was no laryngeal anatomical abnormality, and tracheal intubation was readily possible. The operation was completed without incident. Stiffening of both arms occurred for several seconds one hour after the operation ended, but the patient did not develop other complications., Conclusions: Mask ventilation and the insertion of an intravenous catheter may be difficult in the general anesthesia of patients with BSS, and anesthetic management requires caution.

Purpose: Postoperative nausea and vomiting (PONV) is the most common complication after surgery, and opioid administration increases its incidence. We compared the preventive effects of fosaprepitant, a neurokinin-1 (NK1) receptor antagonist, with those of ondansetron on PONV in patients who underwent lower limb surgery with postoperative epidural opioid administration., Methods: This prospective, double-blind, randomized study included 38 patients who underwent lower limb surgery. They were randomly allocated to receive intravenous fosaprepitant 150 mg (n = 19; NK1 group) or ondansetron 4 mg (n = 19; ONS group) before general anesthesia. All patients received postoperative epidural fentanyl for pain control. The incidence of nausea and vomiting, complete response rate (no vomiting and no rescue antiemetic use), rescue antiemetic use, nausea score (0-3), and visual analog scale (VAS 0-10) score for pain were recorded at 2, 24, and 48 h after surgery., Results: No patient in the NK1 group experienced vomiting (0%) during the first 24 and 48 h after surgery, while 5 of 19 (26%) patients in the ONS group experienced this complication, indicating a significant difference between groups. There were no significant differences in the incidence of PONV, complete response rate, rescue antiemetic use, nausea score, and VAS score for pain between the NK1 and ONS groups during the study period., Conclusions: Fosaprepitant was more effective than ondansetron in decreasing the incidence of vomiting after lower limb surgery with postoperative opioid administration. Meanwhile, fosaprepitant was not inferior to ondansetron in decreasing the incidence and severity of PONV.

Purpose: Postoperative nausea and vomiting (PONV) is the most common postoperative complication. The postoperative use of opioids is known to increase the incidence. We compared fosaprepitant, a neurokinin-1 (NK1) receptor antagonist, and ondansetron for their preventive effects on PONV in patients who underwent gynecologic abdominal surgery with patient-controlled epidural analgesia., Methods: This prospective, double-blind, randomized study comprised 44 patients who underwent gynecologic abdominal surgery. They were randomly allocated to receive 150 mg intravenous fosaprepitant (n = 24; NKI group) or 4 mg ondansetron (n = 20; ONS group) before anesthesia, which was maintained with volatile anesthetics, remifentanil, fentanyl, and rocuronium. All patients received postoperative fentanyl by patient-controlled epidural anesthesia. The incidence of nausea and vomiting, complete response rate (i.e., no vomiting and no rescue antiemetic use), rescue antiemetic use, nausea score (0-3), and visual analog scale score (VAS 0-10) for pain were recorded at 2, 24, 48, and 72 h after surgery., Results: No (0 %) patient in the NKI group experienced vomiting after surgery; however, 4-6 (20-30 %) of 20 patients in the ONS group experienced vomiting. This difference was significant at 0-24, 0-48, and 0-72 h. During the study period, no significant differences existed between the NK1 and ONS groups in the incidence of PONV, complete response rate, rescue antiemetic use, nausea score, and VAS score for pain., Conclusion: Compared to ondansetron, fosaprepitant more effectively decreased the incidence of vomiting in patients who underwent gynecologic abdominal surgery with patient-controlled epidural analgesia.

Background: Sepsis and septic shock syndrome are among the leading causes of death in critically ill patients. Lipopolysaccharide (LPS) released by bacteria within the colon may translocate across a compromised epithelium, leading to oxidative stress, inflammation, sepsis, and eventually death., Methods: We examined the effects of a whey-based enteral formula high in cysteine (antioxidant precursor) and the addition of ω-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), against a mouse model of LPS-induced sepsis. Mice were fed either a whey-based diet with EPA-DHA (PAF), a whey-based diet without EPA-DHA (PSTD), or a casein-based control diet (CONT)., Results: Mice fed PAF or PSTD were protected against LPS-induced weight loss. Whey-based diets suppressed inflammatory cytokine release and oxidative stress damage. Furthermore, PAF and PSTD were able to inhibit autophagy, a mechanism in which the cell recycles damaged organelles. These anti-inflammatory and antioxidative effects of PSTD and PAF resulted in decreased liver inflammation and intestinal damage and promoted protective microbiota within the intestines., Conclusions: These data suggest a clinical role for whey peptide-based diets in promoting healing and recovery in critically ill patients., (© 2014 American Society for Parenteral and Enteral Nutrition.)

Objective: To investigate the cardioprotective effects of isoflurane and exendin-4 against myocardial ischemia/reperfusion injury and the signaling pathways through which these effects are mediated., Materials and Methods: For infarct size measurements, anesthetized mice were subjected to 30 min of coronary artery occlusion followed by 2 h of reperfusion. Wild-type or caveolin-3 knockout mice received isoflurane, exendin-4, or isoflurane with exendin-4 before ischemia index determination. Caveolin-3 expression in the heart was measured by immunoblotting., Results: Myocardial infarct size was smaller in the isoflurane- [1.0 minimum alveolar concentration (MAC)] or exendin-4- (30 ng/kg i.v.) treated groups than the controls. Infarct size was not affected by isoflurane at 0.5 MAC or 3 ng/kg i.v. exendin-4, but the combination of these treatments reduced infarct size. Pharmacological preconditioning (isoflurane at 1.0 MAC, 30 ng/kg i.v. exendin-4, or isoflurane at 0.5 MAC with 3 ng/kg i.v. exendin-4) increased caveolin-3 protein expression in the heart after infarct induction. The cardioprotective effects of isoflurane, exendin-4, and isoflurane with exendin-4 were abolished in caveolin-3 knockout mice., Conclusions: The combination of isoflurane and exendin-4 reduced infarct size, but it was not more effective than either agent alone, and the cardioprotective effects of these agents are mediated by caveolin-3 expression.

Purpose: Pharmacological preconditioning, including that with geranylgeranylacetone (GGA) and volatile anesthetics, has been shown to confer cardiac protection from ischemia/reperfusion injury although the mechanisms for this protection are poorly understood. Caveolins, integral membrane proteins that act as scaffolding proteins in caveolar membranes, localize molecules involved in cardiac protection. We have tested the hypothesis that caveolin-3 (Cav-3), the predominant isoform in cardiac myocytes, is essential for the synergistic effect observed between GGA and volatile anesthetics., Methods: Mice were randomly assigned to receive GGA, isoflurane [0.5 and 1.0 minimum alveolar concentration (MAC)], or GGA + isoflurane (0.5 MAC). An in vivo mouse model of ischemia/reperfusion injury was tested in wild-type and Cav-3 knockout mice, and the infarct size was determined. Biochemical assays were also performed in excised hearts., Results: Geranylgeranylacetone and therapeutic isoflurane (1.0 MAC) independently reduced infarct size (31.6 ± 6.1 and 28.0 ± 5.0% of the area at risk, respectively; n = 10) as compared to the controls (45.8 ± 9.4%; n = 10). The combination GGA + sub-therapeutic isoflurane (0.5 MAC) further decreased the infarct size to 19.3 ± 5.1% (n = 10). Preconditioning [GGA, isoflurane (1.0 MAC), and GGA + isoflurane] increased the amount of Cav-3 protein in the discontinuous sucrose-gradient buoyant fractions. Additionally, cardiac protection was not observed in Cav-3 knockout mice following the administration of GGA, isoflurane, and GGA + isoflurane., Conclusions: Combined administration of GGA + isoflurane had a synergistic effect, enhancing the protection against myocardial infarction to a greater extent than either drug alone. This beneficial effect is mediated by Cav-3 expression.

Background: Exendin-4, an exogenous glucagon-like peptide-1 receptor (GLP-1R) agonist, protects the heart from ischemia/reperfusion injury. However, the mechanisms for this protection are poorly understood. Caveolae, sarcolemmal invaginations, and caveolins, scaffolding proteins in caveolae, localize molecules involved in cardiac protection. We tested the hypothesis that caveolae and caveolins are essential for exendin-4 induced cardiac protection using in vitro and in vivo studies in control and caveolin-3 (Cav-3) knockout mice (Cav-3 KO)., Methods: Myocytes were treated with exendin-4 and then incubated with methyl-β-cyclodextrin (MβCD) to disrupt caveolae formation. This was then followed by simulated ischemia/reperfusion (SI/R). In addition, cardiac protection in vivo was assessed by measuring infarct size and cardiac troponin levels., Results: Exendin-4 protected cardiac myocytes (CM) from SI/R [35.6 ± 12.6% vs. 64.4 ± 18.0% cell death, P = 0.034] and apoptosis but this protection was abolished by MβCD (71.8 ± 10.8% cell death, P = 0.004). Furthermore, Cav-3/GLP-1R co-localization was observed and membrane fractionation by sucrose density gradient centrifugation of CM treated with MβCD + exendin-4 revealed that buoyant (caveolae enriched) fractions decreased Cav-3 compared to CM treated with exendin-4 exclusively. Furthermore, exendin-4 induced a reduction in infarct size and cardiac troponin relative to control (infarct size: 25.1 ± 8.2% vs. 41.4 ± 4.1%, P < 0.001; troponin: 36.9 ± 14.2 vs. 101.1 ± 22.3 ng/ml, P < 0.001). However, exendin-4 induced cardiac protection was abolished in Cav-3 KO mice (infarct size: 43.0 ± 6.4%, P < 0.001; troponin: 96.8 ± 26.6 ng/ml, P = 0.001)., Conclusions: We conclude that caveolae and caveolin-3 are critical for exendin-4 induced protection of the heart from ischemia/reperfusion injury.

Background: During perioperative fasting, lipid metabolism gradually increases, resulting in free fatty acids (FFA) and/or ketone bodies. Suppression of surgical stress by remifentanil may allow the safe administration of glucose infusions, avoiding both hyperglycemia and ketogenesis. The effects of glucose infusion on glucose and lipid metabolism were therefore investigated in patients undergoing minor surgery with remifentanil anesthesia., Methods: Thirty-four patients were randomized 1 : 1 to receive no glucose (0G group) or low-dose glucose (0.1 g/kg/h for 1 h followed by 0.05 g/kg/h for 1 h; LG group). The concentrations of glucose, adrenocorticotropic hormone (ACTH), 3-methylhistidine (3-MH), insulin, cortisol, FFA, creatinine (Cr), and ketone bodies were measured before anesthetic induction, 1 and 2 h after glucose infusion, at the end of surgery, and the next morning., Results: The concentrations of cortisol and ACTH decreased during surgery in both groups when compared with the concentrations before anesthesia and at the end of surgery (P < 0.05). Glucose and insulin concentrations were significantly higher in the LG than in the 0G group at 1 and 2 h after infusion. No patient experienced hyperglycemia. The concentrations of FFA and ketone bodies were lower in the LG than in the 0G group during surgery, but there were no significant between group differences in 3-MH/Cr., Conclusion: Infusion of low-dose glucose attenuated fat catabolism without causing hyperglycemia, indicating that infusion of low-dose glucose during remifentanil-induced anesthesia may be safe for patients., (© 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Aims: Geranylgeranylacetone (GGA) is commonly utilized to protect the gastric mucosa in peptic ulcer disease. Recently GGA has been shown to protect the myocardium from ischemia/reperfusion by activating heat shock proteins. However, the exact mechanism as to how GGA activates these protective proteins is unknown. Caveolae and caveolin-3 (Cav-3) have been implicated in ischemia, anesthetic, and opioid induced cardiac protection. Given the lipophilic nature of GGA it is our hypothesis that GGA induced cardiac protection requires caveolae and Cav-3., Main Methods: We used an in vivo mouse model of ischemia-reperfusion injury and performed biochemical assays in excised hearts., Key Findings: GGA treated control mice revealed increased caveolae formation and caveolin-3 in buoyant fractions, mediating heat shock protein 70 activation. Furthermore, control mice treated with GGA were protected against ischemia/reperfusion injury whereas Cav-3 knockout (Cav-3 KO) mice were not. Troponin levels confirmed myocardial damage. Finally, Cav-3 KO mice treated with GGA were not protected against mitochondrial swelling whereas control mice had significant protection., Significance: This study showed that caveolae and caveolin-3 are essential in facilitating GGA induced cardiac protection by optimizing spatial and temporal signaling to the mitochondria., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Patients with renal failure often experience decreased serum zinc that remains uncorrected after dialysis. A complication of this depletion is taste impairment, which can detrimentally influence diet and nutrition. However, because more than half of all serum zinc is bound to albumin, we hypothesized that normalizing serum zinc to albumin levels may be associated with taste impairment. A total of 65 patients undergoing dialysis but not receiving supplementary zinc and 120 control patients not undergoing dialysis (60 malnourished patients and 60 healthy controls) were tested for their receptiveness to saltiness using various salt concentrations. Patients' total protein and albumin levels were measured, and linear regressions were extrapolated between serum zinc levels and total protein or albumin. Patients undergoing dialysis had significantly lower levels of total serum zinc compared with control patients. However, uncorrected zinc levels were not correlated with taste impairment. Normalizing zinc levels against total protein or albumin resulted in extrapolated equations that revealed a significant correlation with taste impairment. Our data suggest a statistical correlation between zinc and albumin in both healthy subjects and patients undergoing maintenance hemodialysis, or protein-energy malnutrition without hemodialysis, allowing for a quantitative measure for taste impairment., (© 2013.)

Caveolae are flask-like invaginations of the cell surface that have been identified as signaling epicenters. Within these microdomains, caveolins are structural proteins of caveolae, which are able to interact with numerous signaling molecules affecting temporal and spatial dimensions required in cardiac protection. This complex moiety is essential to the mechanisms involved in volatile anesthetics. In this review we will outline a general overview of caveolae and caveolins and their role in protective signaling with a focus on the effects of volatile anesthetics. These recent developments have allowed us to better understand the mechanistic effect of volatile anesthetics and their potential in cardiac protection.

The incidence of postoperative nausea and vomiting (PONV) is 30-50% after surgery. PONV occurs frequently, especially after craniotomy. In this study, we investigated the preventive effects on PONV in a randomized study by comparing patients who had been administered fosaprepitant, a neurokinin-1 (NK1) receptor antagonist, or ondansetron intravenously. Sixty-four patients undergoing craniotomy were randomly allocated to receive fosaprepitant 150 mg i.v. (NK1 group, n = 32) or ondansetron 4 mg i.v. (ONS group, n = 32) before anesthesia. The incidence of vomiting was significantly less in the NK1 group, where 2 of 32 (6%) patients experienced vomiting compared to 16 of 32 (50%) patients in the ONS group during the first 24 and 48 hours following surgery. Additionally, the incidence of complete response (no vomiting and no rescue antiemetic use) was significantly higher in the NK1 group than in the ONS group, and was 66% versus 41%, respectively, during the first 24 hours, and 63% versus 38%, respectively, during the first 48 hours. In patients undergoing craniotomy, fosaprepitant is more effective than ondansetron in increasing the rate of complete response and decreasing the incidence of vomiting at 24 and 48 hours postoperatively.

Lubag disease is a genetic X-linked dystonia-parkinsonism syndrome afflicting Filipino men. This disease is characterized by dystonia dominating the first 10-15 years of the disorder, which is associated with or replaced by parkinsonian features in later years of life. A 49-year-old man with Lubag disease underwent general anesthesia for deep brain stimulation (DBS) surgery. Anesthesia was maintained mainly with propofol, remifentanil, rocuronium bromide, and sevoflurane. During magnetic resonance imaging, the patient was anesthetized with midazolam, fentanyl, and rocuronium bromide. The surgery was completed safely using these anesthetic agents. After DBS, some symptoms including involuntary movement improved within 10 days.

Anaphylaxis during anesthesia is a rare but life-threatening event. Sugammadex is a recently introduced drug that was specifically designed for the reversal of rocuroium and vecuronium-induced neuromuscular block. We describe the cases of a 74-year-old man and a 29-year-old man who developed an anaphylactoid reaction to sugammadex, presenting with cardiovascular collapse. Initial management consisted of fluid administration and intermittent i.v. ephedrine, epinephrine, and hydrocortisone. The patients made uncomplicated recovery and were discharged.