Comparative Analysis of the Hemodynamic Effects of Remimazolam and Propofol During General Anesthesia: A Retrospective Study.

PURPOSE: Hypotension is common during anesthesia induction. However, minimal hemodynamic effects of remimazolam anesthesia have been reported. We hypothesized that remimazolam would have weaker hemodynamic effects than would propofol. To test this, we simultaneously evaluated the hemodynamics using the estimated continuous cardiac output (esCCO) system and heart rate variability (HRV) during anesthesia induction. METHODS: This was a single-center, observational, retrospective study of patients undergoing dental surgery under general anesthesia between 2020 and 2022. Seventy patients were divided into two groups: remimazolam (R group; n=34) and propofol (P group; n=36). The information obtained from the anesthesia records, patient information, esCCO system parameters, and HRV were integrated and analyzed. The percentages of various parameters were set to 100% for the pre-induction phase as the baseline. RESULTS: The %MAP (noninvasive mean arterial blood pressure) decreased over a narrower range in the R compared to the P group (-17.8% (-26.3%, -11.9%) vs. -22.6% (-32.9%, -17.0%); P=0.039). The %HR (heart rate) increased significantly in the R group and decreased in the P group (+10.7% (+6.5%, +18.6%) vs. -6.5% (-14.5%, +8.4%); P<0.01). The %SVesCCO (stroke volume calculated using the esCCO system) decreased significantly in both groups, but the R group showed a smaller difference compared to the P group (- 5.1% (-7.7%, -2.1%) vs. -10.0% (-13.8%, -5.6%); P<0.01). The rates of change in %LF nu (normalized unit of low frequency) and %HF nu (normalized unit of high frequency) were lower for the R than for the P group, although the difference was not significant (+6.8% (-14.5%, 32.4%) vs. +9.2% (-7.2%, +59.7%), P=0.30; +7.9% (-51.0%, +66.9%) vs. +22.8% (-26.1%, +61.6%), P=0.57). CONCLUSION: Remimazolam demonstrated a lower MAP reduction rate than propofol. A compensatory increase in HR occurred with a decrease in stroke volume. However, the HR increase was not attributable to the autonomic nervous system.

Analysis of Sedation Accident Records Available in the Japan Council for Quality Health Care Public Database.

OBJECTIVE: Medical accidents occur frequently. However, only a few studies have been conducted on sedation-related medical accidents. This study aimed to classify sedation accidents and analyze their causes using the (Patient-management Software Hardware Environment Livewear (P-mSHELL) model. METHODS: The Japan Council for Quality Health Care database on medical accidents was used. Sedation accidents that occurred during procedures between January 2010 and June 2022 were included. After examining the accident details for several variables, the accident factors were classified by factors in the P-mSHELL model, and statistical analyses, including multivariate analysis of each factor and outcome (presence or absence of residual disability), were conducted. RESULTS: Regarding the influence of the P-mSHELL factors on outcome, P factor (odds ratio = 6.347, 95% confidence interval = 2.000, 20.144) was a factor for having disability. There was a significant association between outcome and accident timing (that is, preoperative, intraoperative, or postoperative; p =0.01). No significant association was found between the outcomes and types of drugs used (p =1, 0.722, 0.594); however, there was a significant association between the incidence of respiratory depression and multiple drug use (p <0.001). CONCLUSIONS: To prevent sedation accidents, it is important to monitor patients throughout the perioperative period. However, it is especially important to know the patient's condition in advance, and strict postoperative management is essential, especially for high-risk patients, to prevent serious accidents.

Anti-inflammatory potential of remimazolam: A laboratory and clinical investigation.

BACKGROUND: Anesthetic agents, particularly intravenous anesthetics, may affect immune function and tumorigenic factors. We herein investigated whether the anti-inflammatory effects of anesthetic agents are attributed to their antioxidant properties. The antioxidant and anti-inflammatory effects of remimazolam, a new anesthetic, remain unclear. We hypothesized that remimazolam exerts anti-inflammatory effects due to its antioxidant properties, which may affect the postoperative inflammatory response. This retrospective clinical study examined this hypothesis using laboratory and clinical approaches. METHODS: The antioxidant effects of remimazolam and dexmedetomidine were assessed by electron spin resonance (ESR) spectroscopy, and postoperative inflammatory responses were compared in 143 patients who underwent transcatheter aortic valve replacement at Kindai University Hospital between April 2021 and December 2022. The primary endpoint was the presence or absence of the antioxidant effects of the anesthetics themselves using ESR. RESULTS: Remimazolam at clinical concentrations exerted antioxidant effects, whereas dexmedetomidine did not. Increases in C-reactive protein (CRP) levels on POD3 from preoperative values were significantly smaller in the remimazolam group than in the dexmedetomidine group (1.33 ± 1.29 vs. 2.17 ± 1.84, p = .014). CONCLUSIONS: Remimazolam exerted stronger anti-inflammatory effects than dexmedetomidine, and these effects were enhanced by its antioxidant properties, which may have affected postoperative CRP production.

Survey on the Awareness of the Use of Oropharyngeal Throat Packs in Dental Anesthesia: An International Online Survey.

INTRODUCTION: Oropharyngeal throat packs (OPTPs) are frequently used to administer general anesthesia during oral surgery and dental procedures. However, the use of OPTPs has remained controversial, with concerns about their effectiveness, the potential for falling short of expectations, and the inherent risk of serious oversight in removing them. This study aimed to assess the awareness of dental anesthesiologists in the United States of America (USA) and Japan regarding the use of OPTPs. METHODS: An online questionnaire was distributed to 41 dental anesthesia education facilities in May 2023 and responses were obtained from 32 facilities. RESULTS: The responses to the questionnaire indicated that dental anesthesiologists in both the USA and Japan believe that using OPTPs during general anesthesia with airway securement is of significant importance, albeit with varying primary purposes for their application. In contrast, notable disparities were observed between the USA and Japan regarding the perceived importance and routine use of OPTPs during open-airway general anesthesia. In both countries, there is a common understanding that the residual risks of OPTPs are severe and that multiple preventive procedures are required. CONCLUSIONS:  The present study showed that dental anesthesiologists in the USA and Japan believed that the use of OPTPs was generally necessary for dental anesthesia. However, there was a difference in awareness between Japan and the USA regarding the importance of OPTPs for open-airway general anesthesia. Therefore, there should be a consensus among dental anesthesiologists in Japan and the USA on using OPTPs during open-airway general anesthesia in the near future.

Remimazolam-Based Anesthesia in Patients with Heart Failure Due to Mitral Regurgitation and Low Left Ventricular Function: A Case Series.

Background and Objectives: Remimazolam is a new ultrashort-acting benzodiazepine anesthetic. Remimazolam appears to be useful in patients with severe valvular disease because of its minimal cardiovascular impact. In this retrospective case series study, we assessed the efficacy and safety of remimazolam for maintaining hemodynamic stability during anesthetic induction and maintenance. Cases: MitraClip was performed on 18 cases with severe mitral regurgitation with low left ventricular function who presented with heart failure, and remimazolam was administered for general anesthesia with induction (12 mg/kg/h) and maintenance (1 mg/kg/h). The impact of remimazolam on the hemodynamics at anesthetic induction and during anesthetic maintenance was investigated retrospectively using electronic medical records. Blood pressure decreased significantly during anesthetic induction with remimazolam (78.5 [72, 81.25] and 66.1 [62.2, 74.2], median [IQR], p = 0.0001), but only mildly, by about 10 mmHg. There was no significant change in the cardiac index (2.0 [1.8, 2.4] vs. 1.9 [1.8, 2.3], p = 0.57642) or pulse rate (73.5 ± 8.85 vs. 74.7 ± 11.7, mean ± SD, p = 0.0876) during anesthetic induction with remimazolam. All patients underwent MitraClip without major hemodynamic concerns, with no or small increases in inotropes. Conclusions: Remimazolam may be used safely in patients with severe mitral regurgitation and low left ventricular function presenting with heart failure.

Carbamazepine-Induced Systemic Lupus Erythematosus in a Patient With Idiopathic Trigeminal Neuralgia: A Case Report.

A 50-year-old woman presented with a mandibular second molar and facial pain and was diagnosed with idiopathic trigeminal neuralgia. Carbamazepine (CBZ) was initiated at 300 mg/day, successfully relieving the pain. However, on the 8th day of CBZ treatment, the patient developed symptoms resembling those of systemic lupus erythematosus with malaise, nausea, and facial erythema. CBZ was immediately discontinued. Subsequently, she experienced numbness in both lower limbs and mild fever, which resolved within a few days. Laboratory tests revealed leukopenia (2.8 × 103/µL), elevated C-reactive protein levels (0.46 mg/dL), and the presence of antinuclear antibodies (ANA) and anti-Sjögren's syndrome-related antigen A antibodies. The clinical course suggested CBZ-induced drug-induced lupus erythematosus (DILE). This case highlights the possibility of DILE onset even after short-term CBZ treatment, the importance of prompt discontinuation of the causative drug in patients suspected of DILE, and the conduct of ANA testing in diagnosing DILE.

A retrospective comparative study of anesthesia with remimazolam and remifentanil versus dexmedetomidine and remifentanil for transcatheter aortic valve replacement.

Remimazolam, an ultrashort-acting benzodiazepine, allows for rapid and reliable arousal. Rapid awakening using remimazolam may be beneficial in transcatheter aortic valve replacement (TAVR), as it allows rapid detection of neurologic deficits. The purpose of this study was to compare arousal time and outcomes between monitored anesthesia care (MAC) with remimazolam and remifentanil and conventional MAC with dexmedetomidine, propofol, and remifentanil. This study was a single center retrospective study. All TAVR cases performed under MAC (MAC-TAVR) at our institution between 2019 and 2021 were included. Patients were classified by anesthesia method into remimazolam and dexmedetomidine groups. Among 258 MAC-TAVR patients, 253 were enrolled. After propensity score matching, 76 patients were assigned to each group. The time from end of drug-administration to arousal [20.0 (16.0, 24.0) min vs. 38.5 (30.0, 56.3) min, p < 0.0001] and the time from attempted-arousal to arousal [1.0 (1.0, 1.0) min vs. 12.5 (3.0, 26.8) min, p < 0.0001] were significantly shorter in the remimazolam group. There was no significant difference in the length of ICU stay [2.0 (2.0, 2.0) days vs. 2.0 (2.0, 2.0) days, p = 0.157] and postoperative hospital stay [6.0 (4.0, 9.0) days vs. 5.0 (4.0, 8.0) days, p = 0.262].Trial registration: Clinical trial number: R03-123, Registry URL: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000051635 Registration number: UMIN000045195, Principal investigator's name: Atsuhiro Kitaura, Date of registration: 20 August 2021.

Successful Nafamostat Mesilate Administration for Andexanet Alfa-Induced Heparin Resistance.

Andexanet alfa is an analog of activated factor X and is used as an antagonist of anti-activated factor X agents. Andexanet alfa is useful for hemostasis in emergent bleeding during direct oral anticoagulant administration, which contributes to safety. In patients undergoing surgery with cardiopulmonary bypass because of heparin resistance, anesthesiologists are faced with a choice of anticoagulants. Herein, we experienced anesthesia for vascular prostheses with cardiopulmonary bypass for acute aortic dissection in a patient who had received andexanet alfa preoperatively. Heparin was initially used as the anticoagulant during cardiopulmonary bypass; however, despite the administration of large doses and antithrombin III preparations, anticoagulation was insufficient. Therefore, nafamostat mesilate was administered and sufficient anticoagulation was attained. The patient completed surgery under cardiopulmonary bypass, coagulation function was recovered shortly after withdrawal, and no obvious adverse effects were observed.

Two Cases of Inadequate Response to Remimazolam.

We report the inadequate efficacy of remimazolam in two patients undergoing long-term benzodiazepine analog therapy. Remimazolam is a recently developed ultrashort-acting benzodiazepine. It is primarily used as an anesthetic in surgical procedures, as it has minimal effect on cardiac function and antagonists are available. It is expected to become more widely used in the future. On the other hand, similar to other benzodiazepines, benzodiazepine tolerance can also pose a challenge with remimazolam. Herein, we report two cases who were taking long-term oral benzodiazepine analogs. One patient did not fall asleep despite a sufficient dose of remimazolam and required a change to propofol. The other patient required a high dose of remimazolam to fall asleep; however, multiple signs of arousal were noted intraoperatively. Our findings suggest that remimazolam may not be an ideal anesthetic in long-term benzodiazepine analog users. Comprehensive assessment of preoperative medications and careful monitoring of intraoperative sedation levels are necessary. Furthermore, it may be advisable to consider the use of alternative agents such as propofol.

Nine-Second Cardiac Arrest in a Patient With Anti-mitochondrial Antibody-Positive Myopathy Under General Anesthesia.

A small percentage of cases of dermatomyositis are positive for anti-mitochondrial antibodies (AMA), a known marker for primary biliary cirrhosis. AMA-positive myositis is a rare disease that has been reported to be accompanied by myocarditis, resulting in low left ventricular function, supraventricular arrhythmias, and abnormalities of the conduction system. We present a case of AMA-positive myocarditis resulting in sinus arrest during general anesthesia. A 66-year-old female with AMA-positive myocarditis underwent artificial femoral head replacement for osteonecrosis of the femoral head under general anesthesia. During general anesthesia, a nine-second sinus arrest occurred without any inducement. The sinus arrest was thought to be influenced by not only over-suppression caused by severe supraventricular tachycardia derived from sick sinus syndrome but sympathetic depression caused by general anesthesia. Because of the potential for life-threatening cardiovascular events during anesthesia in patients with AMA-positive myositis, it was considered essential to provide adequate preoperative management and intraoperative monitoring during anesthesia for patients with this disease. Herein, we report our case with a literature review.

Safety of COVID-19 vaccine delivery by dentists: An observational cohort study.

Background/purpose: Although many coronavirus disease 2019 (COVID-19) vaccine injections have been administered worldwide, the safety of this practice remains unclear. This study aimed to compare the rates of complications associated with COVID-19 vaccines administered by dentists with those of vaccines administered by nurses. This study aimed to evaluate the safety of a vaccination program delivered by dentists. Materials and methods: This observational cohort study included 537 recipients of the second dose of the Pfizer COVID-19 vaccine, delivered as an intramuscular injection to the upper arm deltoid muscle by dentists or nurses at the study site. Vaccine recipients were divided into two groups according to the vaccination administrator (dentist vs. nurse groups). The rates of complications associated with intramuscular injection technique (numbness in the hand or arm at the time of the injection, vasovagal reflex at the time of the injection, vaccine-related shoulder injury, and prolonged numbness) were examined. Results: A total of 125 vaccine recipients were included (nurse group, n = 84; dentist group, n = 41). The overall incidence rate of complications was lower in the dentist group (2.4%; 1/41) than in the nurse group (8.3%; 7/84). However, this difference was not statistically significant (P = 0.3). Conclusion: This study suggests that the safety of COVID-19 vaccine administration is comparable between dentists and nurses.

The Impact of COVID-19 on Dental Anesthesiologists: An Online Survey of Board-Certified Dental Anesthesiology Specialists of the Japanese Dental Society of Anesthesiology.

OBJECTIVE: The impact of the COVID-19 pandemic on dental anesthesiologists has not been examined. This study aimed to determine how the COVID-19 pandemic affected Japanese dental anesthesiologists' professional lives. METHODS: An online questionnaire related to the effects of COVID-19 on dental anesthesiologists' professional lives was emailed to 351 board-certified dental anesthesiology specialists from the Japanese Dental Society of Anesthesiology. The endpoints of this study were changes in income and job satisfaction as a dental anesthesiologist from 2019 prior to the COVID-19 pandemic. RESULTS: A total of 141 dental anesthesiologists participated in the survey. Most respondents reported no change in income relative to 2019 for 2020 or 2021. Significantly more dental anesthesiologists reported income decreases relative to 2019 for 2020 (39%) vs 2021 (21.3%; P = .001). Very few dental anesthesiologists reported income increases relative to 2019 for 2020 (2.1%) vs 2021 (15.6%; P < .001). Job satisfaction as a dental anesthesiologist remained unchanged for all 3 years. CONCLUSION: Even though many Japanese dental anesthesiologist specialists lost income because of COVID-19, they maintained their job satisfaction.

Cardiac Arrest Following Torsades de Pointes Caused by Hypokalemia and Catecholamines in a Patient with Congenital Long QT Syndrome Type 1 After Surgical Aortic Valve Replacement: A Case Report.

BACKGROUND Prevention of lethal arrhythmias in congenital long QT syndrome type 1 (LQT1) requires avoidance of sympathoexcitation, drugs that prolong QT, and electrolyte abnormalities. However, it is often difficult to avoid all these risks in the perioperative period of open heart surgery. Herein, we report hypokalemia-induced cardiac arrest in a postoperative cardiac patient with LQT1 on catecholamine. CASE REPORT A 79-year-old woman underwent surgical aortic valve replacement for severe aortic stenosis. Although the initial plan was not to use catecholamine, catecholamine was used in the Postoperative Intensive Care Unit with attention to QT interval and electrolytes due to heart failure caused by postoperative bleeding. Serum potassium levels were controlled above 4.5 mEq/L, and no arrhythmic events occurred. On postoperative day 4, the patient was started on insulin owing to hyperglycemia. Cardiac arrest occurred after the first insulin dose; the implantable cardioverter defibrillator was activated, and the patient's own heartbeat resumed. Subsequent examination revealed that a marked decrease in serum potassium level had occurred after insulin administration. The electrocardiogram showed obvious QT prolongation and ventricular fibrillation following R on T. Thereafter, under strict potassium management, there was no recurrence of cardiac arrest events. CONCLUSIONS A patient with LQT1 who underwent open heart surgery developed ventricular fibrillation after Torsades de Pointes, probably due to hypokalemia after insulin administration in addition to catecholamine. It is important to check serum potassium levels to avoid the onset of Torsades de Pointes in patients with long QT syndrome. In addition, the impact of insulin administration was reaffirmed.

Distinctive High Expression of Antiretroviral APOBEC3 Protein in Mouse Germinal Center B Cells.

Tissue and subcellular localization and its changes upon cell activation of virus-restricting APOBEC3 at protein levels are important to understanding physiological functions of this cytidine deaminase, but have not been thoroughly analyzed in vivo. To precisely follow the possible activation-induced changes in expression levels of APOBEC3 protein in different mouse tissues and cell populations, genome editing was utilized to establish knock-in mice that express APOBEC3 protein with an in-frame FLAG tag. Flow cytometry and immunohistochemical analyses were performed prior to and after an immunological stimulation. Cultured B cells expressed higher levels of APOBEC3 protein than T cells. All differentiation and activation stages of freshly prepared B cells expressed significant levels of APOBEC3 protein, but germinal center cells possessed the highest levels of APOBEC3 protein localized in their cytoplasm. Upon immunological stimulation with sheep red blood cells in vivo, germinal center cells with high levels of APOBEC3 protein expression increased in their number, but FLAG-specific fluorescence intensity in each cell did not change. T cells, even those in germinal centers, did not express significant levels of APOBEC3 protein. Thus, mouse APOBEC3 protein is expressed at distinctively high levels in germinal center B cells. Antigenic stimulation did not affect expression levels of cellular APOBEC3 protein despite increased numbers of germinal center cells.

DOCK8-expressing T follicular helper cells newly generated beyond self-organized criticality cause systemic lupus erythematosus.

Pathogens including autoantigens all failed to induce systemic lupus erythematosus (SLE). We, instead, studied the integrity of host's immune response that recognized pathogen. By stimulating TCR with an antigen repeatedly to levels that surpass host's steady-state response, self-organized criticality, SLE was induced in mice normally not prone to autoimmunity, wherein T follicular helper (Tfh) cells expressing the guanine nucleotide exchange factor DOCK8 on the cell surface were newly generated. DOCK8+Tfh cells passed through TCR re-revision and induced varieties of autoantibody and lupus lesions. They existed in splenic red pulp and peripheral blood of active lupus patients, which subsequently declined after therapy. Autoantibodies and disease were healed by anti-DOCK8 antibody in the mice including SLE-model (NZBxNZW) F1 mice. Thus, DOCK8+Tfh cells generated after repeated TCR stimulation by immunogenic form of pathogen, either exogenous or endogenous, in combination with HLA to levels that surpass system's self-organized criticality, cause SLE.

Anesthesia management in a patient with very long-chain acyl-Coenzyme A dehydrogenase deficiency.

BACKGROUND: In a patient with very long-chain acyl-Coenzyme A dehydrogenase (VLCAD) deficiency, metabolism of fatty acids is impaired and a supply of alternative energy is limited when glucose level is insufficient on starvation. CASE PRESENTATION: A 37-year-old woman with VLCAD deficiency was diagnosed with an ovarian cyst and was scheduled for laparoscopic ovarian cystectomy. Glucose was administered intravenously with the start of fasting. Anesthesia was induced with remifentanil, midazolam, and thiamylal, maintained with desflurane and remifentanil. Body temperature was maintained at 36.2-36.7 °C. During anesthesia, hypoglycemia did not occur, creatine kinase levels were in the normal range, and myoglobinuria was not detected. No shivering was observed after extubation. CONCLUSIONS: Glucose was administered to avoid perioperative hypoglycemia. Body temperature was controlled to avoid shivering, which would otherwise increase skeletal muscle energy needs. Blood creatine kinase did not increase, and myoglobinuria was not detected; thus, rhabdomyolysis was unlikely to develop.