Anesthetic management with remimazolam for a patient with hereditary angioedema:a case report.

BACKGROUND: Hereditary angioedema (HAE), a genetic disorder caused by C1-inhibitor deficiency or dysfunction, may cause mucosal edema in the upper airway during tracheal intubation and extubation. CASE REPORT: A 57-year-old man with HAE and a history of laryngeal edema, scheduled to undergo cervical laminoplasty under general anesthesia. General anesthesia was induced by continuous injection of remimazolam and remifentanil, during which manual mask ventilation and intubation were performed without difficulty. The patient was extubated under deep anesthesia. After emergence from general anesthesia, he had no significant upper airway edema and was treated with a C1-inhibitor seven hours post-surgery because of slight tongue swelling. No additional airway edema was observed, and the patient was discharged from the intensive care unit the following day. CONCLUSIONS: Deep anesthesia tracheal extubation with remimazolam may be effective in preventing upper airway edema during anesthetic management in patients with HAE. J. Med. Invest. 71 : 184-186, February, 2024.

The Serotonin-Mediated Anti-Allodynic Effect of Yokukansan on Paclitaxel-Induced Neuropathic Pain.

Refractory peripheral neuropathy can occur as a side effect in 60-70% of patients receiving Paclitaxel (PTX). Yokukansan (YKS) is a Japanese herbal medicine reported to have analgesic properties for entrapment nerve injuries. Therefore, we investigated the anti-allodynic effect of Yokukansan on Paclitaxel-induced neuropathic pain. All experiments used 6-week-old male Sprague Dawley rats. Mechanical allodynia was evaluated using a dynamic plantar aesthesiometer. A mobile touch-stimulator unit applied progressively increasing force to the mid-plantar region of the hind paw in a vertical direction until the animal withdrew its paw. This was carried out before the Paclitaxel administration and during the first, second, third, and fourth weeks. Using a rat model of PTX-induced neuropathic pain (PTX rat), we injected PTX (intraperitoneally, 2 mg/kg) five times every 2 days. Using the dynamic plantar test, we evaluated the anti-allodynic effect of YKS (orally administered, 1 g/kg). YKS administration on a daily basis significantly enhanced the withdrawal threshold in PTX rats and reduced the expression level of activated microglia immunostaining with Iba1, a specific marker for microglia. The intrathecal administration of WAY-100635 (5-hydroxytryptamine [5-HT]1A receptor antagonist) and Ketanserin (5-HT2A/2C receptor antagonist) inhibited the protective effects of YKS. YKS exhibited an anti-allodynic effect in a rodent model of PTX-induced neuropathic pain by reducing the sensitivity to pain stimuli. These results suggest that Yokukansan may activate 5-HT receptors in the spinal cord, mediating Paclitaxel-induced neuropathic pain.

Elastic Banding Compression as a Novel Treatment to Maintain Hemodynamics in a Patient With Klippel-Trenaunay Syndrome.

Klippel-Trenaunay syndrome (KTS) is also associated with venous thrombosis originating from varicose veins in the lower extremities, pulmonary embolism, and pulmonary hypertension. This study describes the anesthetic management of laparoscopic cholecystectomy in a 54-year-old male KTS patient with orthostatic hypotension due to massive varicose veins in the lower extremities and pulmonary thromboembolism. Compressing the varicosities with an elastic bandage can maintain stable circulatory dynamics even under general anesthesia management to prevent position and insufflation-induced changes that can occur spontaneously.

Effects of Remimazolam on Intracellular Calcium Dynamics in Myotubes Derived from Patients with Malignant Hyperthermia and Functional Analysis of Type 1 Ryanodine Receptor Gene Variants.

Remimazolam is a novel general anesthetic and its safety in patients with malignant hyperthermia (MH) is unknown. We used myotubes derived from the skeletal muscle of patients with MH to examine the response to ryanodine receptor 1 (RYR1) agonist and remimazolam in MH-susceptible patients. Patients underwent muscle biopsy for the Ca2+-induced Ca2+ release (CICR) rate test, a diagnostic tool for MH in Japan. Ten patients had myotubes obtained from skeletal muscle cultures, and the genes associated with malignant hyperthermia in these patients were analyzed. The EC50 of caffeine, cresol, and remimazolam to induce intracellular calcium concentration change were compared between myotubes from CICR-negative genetic test patients and myotubes from other patients. Eight of the ten were CICR-positive, five of whom had RYR1 causative gene mutations or variants. Two patients had CICR-negative genetic tests, and as expected had the highest EC50 (the concentration of a drug that gives a half-maximal response) in response to caffeine, 4CmC and remimazolam. Three patients had a positive CICR but no known variants in RYR1 or CACNA1S (voltage-gated calcium channel subunit alpha1S). Myotubes in these patients had significantly lower EC50s for all agents than myotubes in CICR-negative patients. When myotubes from a patient who was CICR-negative and had no gene variant were used as a control, myotubes from CICR-positive patients were more hyper-responsive than controls to all stimulants used. The EC50 for remimazolam was lowest for myotubes from CICR-positive, RYR1-mutant patients, at 206 µM (corresponding to 123 µg/mL). The concentration was more than 80-times higher than the clinical concentration. RYR1 gene variants in R4645Q and W5020G were shown to be causative gene mutations for MH. Intracellular calcium in myotubes from MH patients are elevated at high concentrations of remimazolam but not at clinically used concentrations of remimazolam. Remimazolam appears to be safe to use in patients with MH.

Remimazolam-based anesthesia with flumazenil allows faster emergence than propofol-based anesthesia in older patients undergoing spinal surgery: A randomized controlled trial.

BACKGROUND: Remimazolam is a novel, ultrashort-acting benzodiazepine that can be antagonized by flumazenil. This study aimed to determine whether remimazolam-based anesthesia with flumazenil provides a more rapid emergence than propofol-based anesthesia in older patients undergoing spinal surgery. METHODS: This was a prospective, single-blind, randomized controlled trial. Forty-four patients > 75 years old who had undergone spinal surgery were enrolled in this study. They were randomly assigned to the remimazolam or propofol group (1:1) using a computer randomization system stratified by age and body weight. For anesthesia induction and maintenance, remifentanil was administered at a defined dose in both groups, and remimazolam or propofol was adjusted to maintain the bispectral index or state entropy monitoring within 40-60. All anesthetics were discontinued simultaneously after the postoperative X-ray and 0.5 mg flumazenil was administered to the remimazolam group. The primary outcome was extubation time after discontinuing anesthesia, and the secondary outcomes were time to eye opening, obeying commands, and achieving a white fast-track score (WFTS) of 12. RESULTS: Thirty-nine patients were finally analyzed: remimazolam group (n = 20), propofol group (n = 19). There were no significant differences in intraoperative variables, such as operative time, anesthesia time, and patient background, between the 2 groups. Extubation times were significantly shorter in the remimazolam group than in the propofol group (4 vs 8 minutes, P < .001). The time to eye opening, obeying commands, and achieving a WFTS of 12 were significantly shorter in the remimazolam group (P < .001, for all comparisons). CONCLUSION: Remimazolam-based anesthesia with flumazenil resulted in a faster emergence than propofol-based anesthesia in older patients undergoing spinal surgery.

Prediction of blood pressure changes during surgical incision using the minimum evoked current of vascular stiffness value under sevoflurane anesthesia.

Necessary and sufficient opioids should be administered for safe and stable anesthesia. However, opioid sensitivity varies among individuals. We previously reported that sympathetic responses to nociceptive stimuli under propofol anesthesia could be predicted by measuring the minimum evoked current of the vascular stiffness value (MECK). However, this result has only been proven under propofol anesthesia. We propose that MECK could be used under anesthesia with a volatile anesthetic. Thirty patients undergoing laparotomy with sevoflurane anesthesia received 0.7 minimum alveolar concentration (MAC) sevoflurane and intravenous remifentanil at a constant concentration of 2 ng/mL, followed by tetanic stimulation, to measure MECK. After tetanic stimulation, the same anesthetic conditions were maintained, and the rate of change in systolic blood pressure (ROCBP) during the skin incision was measured. The correlation coefficient between the MECK and ROCBP during skin incision under sevoflurane anesthesia was R = - 0.735 (P < 0.01), similar to that in a previous study with propofol (R = - 0.723). Thus, a high correlation was observed. The slope of the linear regression equation was - 0.27, similar to that obtained in the study on propofol (- 0.28). These results suggest that, as with propofol anesthesia, MECK can be used as a predictive index for ROCBP under 0.7 MAC sevoflurane anesthesia.Clinical trial registration: Registry, University hospital Medical Information Network; registration number, UMIN000047425; principal investigator's name, Noboru Saeki; date of registration, April 8, 2022.

Partially Hydrolyzed Guar Gum Intake Supports the Gut Microbiota and Attenuates Inflammation during Influenza H1N1 Virus Infection in Mice.

Partially hydrolyzed guar gum (PHGG) is a soluble dietary fiber that is effective for defecation control. It influences the gut microbiota, by which it is metabolized to yield short-chain fatty acids (SCFAs), and it was also recently shown to protect against influenza infection in humans. We here investigated the effects of PHGG in a mouse model of influenza H1N1 virus infection. Eight-week-old C57BL/6 mice were fed normal chow with or without PHGG (500 mg/kg per day) for 4 weeks, infected with H1N1 at 10 weeks of age, and analyzed at 12 weeks of age. Administration of PHGG attenuated the decline in body weight induced by H1N1 infection without affecting food intake. It also ameliorated intestinal atrophy and increased the production of SCFAs including acetic acid, propionic acid, and butyric acid in the cecum, thereby preventing the inhibitory effect of H1N1 infection on SCFA production. The H1N1-induced increases in the serum concentrations of inflammatory cytokines including interferon-γ and interleukin-6 and anti-inflammatory cytokine such as interleukin-10 were all inhibited by PHGG intake. In addition, PHGG administration attenuated inflammatory gene expression in the lung and promoted both natural killer cell activity and regulatory T-cell differentiation in the spleen. Our findings suggest that the consumption of PHGG may improve the gut environment and thereby limit the inflammatory response to H1N1 infection. They may thus provide the basis for novel dietary intervention strategies to suppress the excessive inflammation associated with virus infection.

Remimazolam Requires Less Vasopressor Support during Induction and Maintenance of General Anesthesia in Patients with Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement: A Retrospective Analysis from a Single Center.

Introduction: We compared the hemodynamics during general anesthesia with remimazolam and conventional anesthetics in patients with severe aortic stenosis (AS). Methods: This was a retrospective single-center analysis. We reviewed the records of 42 patients who underwent transcatheter aortic valve implantation with a transfemoral artery approach under general anesthesia from January to December 2020. Patients were divided into three groups based on the general anesthetic used for (induction/maintenance) remimazolam/remimazolam (Group R/R), propofol/sevoflurane (Group P/S), and midazolam/propofol (Group M/P). Vasopressor use (ephedrine, phenylephrine, and noradrenaline) was compared among the groups. Results: The number of patients in each group was 15 (Group R/R), 13 (Group P/S), and 14 (Group M/P), with no significant difference in background characteristics and intraoperative vital signs. For anesthesia induction, doses of ephedrine and phenylephrine used were significantly lower in Group R/R (ephedrine [mg]: Group R/R 2 [0-4] vs. Group P/S 8 [8-12], P < 0.001, Group R/R vs. Group M/P 5 [0-15], P = 0.39; phenylephrine (mg): Group R/R 0 [0-0.08] vs. Group P/S 0.15 [0.10-0.20], P = 0.03, Group M/P 0.21 [0.04-0.40], P = 0.08). For anesthesia maintenance, the noradrenaline dose used was low in the Group R/R (noradrenaline [µg/kg/min]: Group R/R 0.019 [0.015-0.039], Group P/S 0.042 [0.035-0.045], P = 0.02, Group M/P 0.048 [0.040-0.059], P < 0.01). Conclusion: In patients with severe AS, induction and maintenance of anesthesia with remimazolam resulted in less overall vasopressor use than conventional general anesthetics.

Detection of secondary upper gastrointestinal tract cancer during follow-up esophagogastroduodenoscopy after gastrectomy for gastric cancer.

Aim: Esophagogastroduodenoscopy (EGD) may contribute to early detection of secondary cancer in the upper gastrointestinal tract although the clinical relevance of follow-up after gastrectomy remains unclear. This study aimed to elucidate the effectiveness of follow-up EGD by investigating the incidence of secondary cancer in any part of the upper gastrointestinal tract. Methods: Data from 1438 patients who underwent curative partial gastrectomy for primary gastric cancer between 2008 and 2014 and follow-up EGD at least once during a 5-year follow-up period were retrospectively reviewed. Incidence rates of remnant gastric cancer, laryngeal cancer, and esophageal cancer detected after follow-up EGD were determined, and risk factors for secondary cancers were examined. The characteristics of clinicopathological diagnoses of secondary cancers were reviewed and compared according to the frequency of follow-up EGD. Results: The average annual frequency of EGD was 0.7, while the 5-year cumulative incidence rates of remnant gastric cancer and secondary laryngeal and esophageal cancers were 2.9% and 1.3%, respectively. Risk factors for remnant gastric cancer included heavy smoking, proximal gastrectomy, and tumor size ≥ 30 mm. All secondary cancers were resectable upon diagnosis, with endoscopically resectable cancer accounting for 81.0% of cases. Our results found a significantly higher proportion of endoscopically resectable cancers during regular follow-up than during infrequent follow-up. Conclusions: Follow-up EGD can be a useful modality for detecting secondary upper gastrointestinal tract cancer, likely leading to curative treatment for secondary cancer. Focusing on patients presenting with risk factors may increase the value of follow-up EGD after gastrectomy.

Optimal Procedures for Double Tract Reconstruction After Proximal Gastrectomy Assessed by Postgastrectomy Syndrome Assessment Scale-45.

BACKGROUND: Although double tract reconstruction after proximal gastrectomy (PGDT) is commonly performed for proximal gastric or esophagogastric junction cancer, the impact of the procedure on postoperative quality of life (QOL) has not been clarified. We aimed to clarify the optimal PGDT procedure in terms of postoperative QOL. METHODS: Postoperative QOL was analyzed in 172 patients who underwent PGDT for proximal gastric cancer and were enrolled in the PGSAS-NEXT study, a multicenter cross-sectional study in Japan (UMIN000032221), in relation to the remnant stomach size, length of interposed jejunum between the esophagojejunostomy (E-J) and jejunogastrostomy (J-G), and size of the J-G. RESULTS: The remnant stomach size was approximately one-third in 13, half in 97, and two-thirds in 60 patients. Dissatisfaction scores for symptoms, diet, work, and daily life subscales were lower in patients with a larger stomach (p < 0.05). These patients also scored better in terms of weight loss (- 13.5%, - 14.0%, and - 11.2%, respectively) and amount of food ingested per meal (52%, 62%, and 66%). The length of the interposed jejunum was ≤ 10 cm in 62 and ≥ 11 cm in 97 patients. Weight loss (- 11.3% and - 13.8%) and dissatisfaction scores were better in the ≤ 10 cm group (p < 0.05). J-G size was ≤ 5 cm in 27 and ≥ 6 cm in 135 patients. The amount of food ingested (56%, 64%) and dissatisfaction scores were better in the > 6 cm group (p < 0.05). CONCLUSIONS: Larger remnant stomach, shorter length of interposed jejunum, and longer J-G might contribute to better postoperative QOL after PGDT.

Advantages of a robotic approach compared with laparoscopy gastrectomy for patients with high visceral fat area.

BACKGROUND: Gastric cancer surgery for obese patients is regarded as a technically challenging procedure. The morbidity after gastrectomy has been reported to be significantly higher in patients with high visceral fat area (VFA). Robotic gastrectomy (RG) is expected to be advantageous for complicated operations. However, whether RG is superior to conventional laparoscopic gastrectomy (LG) for patients with visceral fat obesity remains unclear. The present study aimed to clarify the impact of RG on the short- and long-term outcomes of patients with high VFAs. METHODS: This study included 1306 patients with clinical stage I/II gastric cancer who underwent minimally invasive gastrectomy between January 2012 and December 2020. The patients were subclassified according to VFA. The short- and long-term outcomes of RG were compared with those of LG in two VFA categories. RESULTS: This study included 394 (high-VFA, 151; low-VFA, 243) and 882 patients (high-VFA, 366; low-VFA, 516) in the RG and LG groups, respectively. RG was associated with a significantly longer operative time than LG (high-VFA, P < 0.001; low-VFA, P < 0.001). The incidence rates of overall and intra-abdominal infectious complications in the high-VFA patients were lower in the RG group than in the LG group (P = 0.019 and P = 0.048, respectively) but not significantly different from those in the low-VFA patients. In the multivariate analysis, LG was identified as the only independent risk factor of overall (odds ratio [OR] 3.281; P = 0.012) and intra-abdominal infectious complications (OR 3.462; P = 0.021) in the high-VFA patients. The overall survival of high-VFA patients was significantly better in the RG group than in the LG group (P = 0.045). CONCLUSIONS: For patients with visceral fat obesity, RG appears to be advantageous to LG in terms of reducing the risk of complications and better long-term survival.

Prognostic factors in patients who received paraaortic lymph node dissection for locally advanced gastric cancer with extensive lymph node metastasis.

PURPOSE: While paraaortic lymph node (PAN) dissection (PAND) has been found to be efficacious for patients with extensive lymph node metastasis (ELM) of locally advanced gastric cancer (LGC), the optimal indications for PAND remain to be elucidated. Thus, the prognostic factors among these patients were evaluated. METHODS: A total of 35 patients with ELM of LGC who underwent gastrectomy with D2 and PAND between August 2008 and December 2019 were included and evaluated for long-term outcomes and prognostic factors. RESULTS: Preoperative chemotherapy was administered to 33 patients [neoadjuvant chemotherapy (NAC), n = 26; palliative chemotherapy followed by conversion surgery, n = 7], none of whom suffered surgical mortality. The pathological analysis identified PAN metastasis in 11 patients (31.4%). The 5-year overall and relapse-free survival (RFS) survival were 66.4% and 52.6%, respectively. Locoregional recurrence was found in one patient. The multivariate analysis revealed that NAC (P = 0.011) and < 3 metastatic PANs on preoperative imaging (P = 0.017) were independently associated with RFS. CONCLUSION: D2 and PAND after NAC can be a promising approach for patients with ELM of LGC. In particular, patients with a limited number of metastatic PANs can be considered good candidates for PAND.

Comparisons of surgical outcomes between robotic and laparoscopic total gastrectomy in patients with clinical stage I/IIA gastric cancer.

BACKGROUND: The robotic approach is especially promising for challenging surgeries, such as total gastrectomy. However, it remains unclear whether robotic total gastrectomy (RTG) is superior to conventional laparoscopic total gastrectomy (LTG). The present study aimed to clarify the impact of RTG on short- and long-term outcomes for patients with clinical stage I/IIA gastric cancer. METHODS: This study included 98 patients with clinical stage I/IIA gastric cancer who underwent minimally invasive total gastrectomy from October 2013 to December 2020 at the Shizuoka Cancer Center. The short- and long-term outcomes of RTG were compared with those of LTG. RESULTS: This study included 36 RTG and 58 LTG patients. RTG was associated with a significantly longer operative time than LTG (p = 0.023). All complications tended to be lower in the RTG group than in the LTG group (2.8% and 15.5%, respectively; p = 0.083). There were no patients with anastomotic leakage in the RTG group. The multivariate analysis identified LTG as the only independent risk factor for postoperative complications (odds ratio, 6.620; 95% confidence interval, 1.132-126.4; p = 0.034). The survival of the RTG and LTG groups was equivalent. CONCLUSIONS: RTG reduced the risk of complications compared to LTG. Patients treated using the two approaches showed equivalent survival.

Time interval after various types of gastrectomy until metachronous multiple gastric cancer: Analysis of data from a nationwide Japanese survey.

The factors influencing the time interval from the initial surgery for gastric cancer to the detection of metachronous multiple gastric cancer (MMGC) remain to be elucidated. The present study was performed to evaluate the association between the type of initial gastrectomy or reconstruction procedure and the time interval from initial gastrectomy to the detection of MMGC. A questionnaire survey on remnant stomach cancer was performed by the Japanese Society for Gastro-Surgical Pathophysiology in 2018. Participating facilities were requested to indicate the number of patients who underwent surgery for MMGC between 2003 and 2017, in association with the time interval from the initial gastrectomy until treatment for MMGC by type of initial gastrectomy or reconstruction procedure. Analyses were performed using data from 45 facilities. Gastrectomy for MMGC was performed on 1,234 patients during this period. Pylorus-preserving gastrectomy (PPG) accounted for only 3.6% (20/557) of the patients who underwent surgery for MMGC ≥10 years from initial gastrectomy, while PPG accounted for 10.1% (40/396) of patients who underwent surgery for MMGC within 5 years after initial gastrectomy. Billroth-II and Roux-en Y reconstruction accounted for 22.3% (103/462) and 1.3% (6/462), respectively, of patients who underwent surgery for MMGC ≥10 years from initial distal gastrectomy (DG), while such patients accounted for 8.0% (23/286) and 21.7% (65/286), respectively, of patients who underwent surgery for MMGC within 5 years after initial DG. Similarly, the proportion of each reconstruction procedure differed according to the time interval from initial proximal gastrectomy to treatment for MMGC. The types of gastrectomy or reconstruction procedure for initial gastrectomy differed significantly according to the time interval between the initial gastrectomy and treatment for MMGC, and the fact that PPG and R-Y reconstruction in DG is a relatively new method were assumed to be a major cause of these differences.