Effect of remimazolam on intraoperative neurophysiology monitoring of visual-evoked potential: a case series.

There are very few reports on the effects of benzodiazepines such as midazolam and diazepam on intraoperative visual-evoked potential (VEP), and there is no report on the effect of remimazolam at all. Five patients underwent neurosurgery using VEP monitoring for avoiding surgical injury to the optic nerve. In all cases, drug administration was based on actual body weight. General anesthesia was induced with propofol and remifentanil, and then maintained with propofol at target concentrations of 2.7-3.5 µg/ml for maintaining bispectral index (BIS) between 40 and 60. After resection of the tumor under stable VEP, we discontinued propofol immediately followed by infusion of remimazolam at 12 mg/kg/h for a few seconds, then reduced to 1 mg/kg/h. After a time, when blood levels of remimazolam appeared to be stable, VEP was monitored again and compared to controls. In all cases, we were able to confirm that there was reproducibility. Remimazolam may provide a comparable quality of anesthesia to that of existing drugs for VEP in neurosurgery.

The intraoperative motor-evoked potential when propofol was changed to remimazolam during general anesthesia: a case series.

Remimazolam is a short-acting benzodiazepine that was approved for clinical use in 2020. We report three patients who underwent surgery for cerebral and spinal cord tumors, in whom transcranial electrical stimulation-motor-evoked potential (TES-MEP) was successfully monitored under general anesthesia with remimazolam. During total intravenous anesthesia with propofol at a target concentration of 2.7 - 3.5 µg/mL and 0.1 - 0.35 µg/kg/min of remifentanil, delayed awakening, bradycardia, and hypotension during propofol anesthesia were expected in all three cases. With patient safety as the top priority, we considered changing the anesthetic agent. Propofol was replaced with remimazolam at a loading dose of 12 mg/kg/h for a few seconds (case 3), followed by 1 mg/kg/h for maintenance (cases 1-3). TES-MEP was recorded during propofol and remimazolam administration in all three patients. Amplitudes of TES-MEP during anesthesia with propofol and remimazolam were 461.5 ± 150 µV and 590.5 ± 100.9 µV, 1542 ± 127 µV and 1698 ± 211 µV, and 581.5 ± 91.3 µV and 634 ± 82.7 µV sequentially from Case 1. Our findings suggest that intraoperative TES-MEP could be measured when anesthesia was managed with remimazolam at 1 mg/kg/h.

Differential effects of the formin inhibitor SMIFH2 on contractility and Ca2+ handling in frog and mouse cardiomyocytes.

Genetic mutations in actin regulators have been emerging as a cause of cardiomyopathy, although the functional link between actin dynamics and cardiac contraction remains largely unknown. To obtain insight into this issue, we examined the effects of pharmacological inhibition of formins, a major class of actin-assembling proteins. The formin inhibitor SMIFH2 significantly enhanced the cardiac contractility of isolated frog hearts, thereby augmenting cardiac performance. SMIFH2 treatment had no significant effects on the Ca2+ sensitivity of frog muscle fibers. Instead, it unexpectedly increased Ca2+ concentrations of isolated frog cardiomyocytes, suggesting that the inotropic effect is due to enhanced Ca2+ transients. In contrast to frog hearts, the contractility of mouse cardiomyocytes was attenuated by SMIFH2 treatment with decreasing Ca2+ transients. Thus, SMIFH2 has opposing effects on the Ca2+ transient and contractility between frog and mouse cardiomyocytes. We further found that SMIFH2 suppressed Ca2+ -release via type 2 ryanodine receptor (RyR2); this inhibitory effect may explain the species differences, since RyR2 is critical for Ca2+ transients in mouse myocardium but absent in frog myocardium. Although the mechanisms underlying the enhancement of Ca2+ transients in frog cardiomyocytes remain unclear, SMIFH2 differentially affects the cardiac contraction of amphibian and mammalian by differentially modulating their Ca2+ handling.

Effect of remimazolam on intraoperative neuromonitoring during thyroid surgery: a case series.

Intraoperative neuromonitoring is widely used to prevent accidental injury during thyroid surgery. Anesthesia should be performed without muscle relaxant or agents with high muscle-relaxant potency. Remimazolam, a novel intravenous anesthetic, became available for clinical use in 2020. Remimazolam is an ultra-short-acting benzodiazepine with a very high clearance rate. However, there are very few data regarding its effect on currently used intraoperative neurological monitoring. Five patients underwent thyroid surgery using intraoperative recurrent laryngeal neuromonitoring. In all cases, intubation was performed after the administration of rocuronium. Anesthesia was maintained by continuous administration of remimazolam at the recommended dose and remifentanil, and no additional rocuronium or sugammadex was administered. Recurrent laryngeal nerve activity could be detected at the first stimulus after surgery was started, and monitoring continued thereafter. Intraoperative monitoring was performed without problems and all surgeries were completed without any complications. Anesthesia with remimazolam at the normal dose did not prolong the time to first positive electromyogram in patients undergoing thyroid surgery, and enables intraoperative recurrent laryngeal nerve monitoring to be performed without any serious perioperative adverse events. Remimazolam may provide a comparable quality of anesthesia to that of existing drugs for neuromonitoring during thyroid surgery.

Effect of sex and polymorphisms of CYP2B6 and UGT1A9 on the difference between the target-controlled infusion predicted and measured plasma propofol concentration.

INTRODUCTION: To examine whether sex and polymorphisms of cytochrome P450 (CYP) 2B6 and UDP-glucuronosyltransferase (UGT) 1A9 affect the difference between predicted and measured plasma propofol concentration during continuous infusion by target-controlled infusion. RESULTS: Blood samples of 69 patients (48 men and 21 women) were obtained at 4 h after initial propofol infusion. Percentage performance error (PE) was calculated to assess the difference between measured and predicted propofol concentration. Regression coefficients (ß) and 95% confidence intervals (CI) of sex and the polymorphisms of CYP2B6 and UGT1A9 for PE were, separately and mutually, estimated with linear regression. Covariates included age and body mass index in the minimal adjusted model, and additionally included clinical factors (mean blood pressure, heart rate, volume of intravenous fluid, surgical site, surgical position, and pneumoperitoneum) in the full adjusted model. PE was higher in men than in women (28.7% versus 10.5%, p = 0.015). Female sex was inversely associated with PE: the minimal adjusted ß = - 8.84 (95% CI, - 16.26 to - 1.43); however, the fully adjusted ß with clinical factors became not significant. The average of PE did not differ between polymorphisms of CYP2B6 and UGT1A9, and ß of CYP2B6 516G>T polymorphisms mutually adjusted with female sex was not significant. Mean blood pressure, heart rate, and volume of intravenous fluid were independently associated with PE in the full adjusted model. CONCLUSIONS: Under 4 h anesthesia with propofol target-controlled infusion in our population, sex differences appeared to exist in the propofol concentration, which might be largely mediated by clinical factors, such as hemodynamic status. TRIAL REGISTRATION: UMIN-CTR UMIN000009015 , Registered 1 October 2012.

Cardiotonic actions of quercetin and its metabolite tamarixetin through a digitalis-like enhancement of Ca2+ transients.

The plant-derived flavonoid, quercetin (QCT), has many biological actions, including cardioprotective actions, resulting from its antioxidant and anti-inflammatory effects. In this study, effects of QCT and its metabolites on the contraction and Ca2+ transients (CaT) of mouse single cardiomyocytes were simultaneously measured and compared with those of isoproterenol and digoxin. Furthermore, cardiac function and plasma concentrations were analyzed after bolus intravenous administration of QCT in mice. QCT and its metabolite, tamarixetin, as well as isoproterenol and digoxin, enhanced the contraction and CaT of cardiomyocytes. The inotropic action of isoproterenol was accompanied by an increase in the velocities of sarcomere shortening and relengthening and CaT decay through activation of cAMP-dependent protein kinase; however, no such lusitropic effects accompanied the inotropic action of QCT, tamarixetin or digoxin. Intravenous administration of QCT to mice resulted in a sustained increase in cardiac systolic function; QCT was rapidly metabolized to tamarixetin and its plasma concentration was maintained at high levels over a similar time frame as the enhancement of cardiac systolic function. These results suggest that QCT exerts a cardiotonic action in vivo at least, in part, through digitalis-like enhancement of CaT by itself and its metabolite tamarixetin.

Hematoma After Transversus Abdominis Plane Block in a Patient With HELLP Syndrome: A Case Report.

We herein present a case of intramuscular hematoma that developed after transversus abdominis plane block in a patient undergoing cesarean delivery. The patient had HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count) preoperatively. Ultrasonography-guided transversus abdominis plane block was performed at the end of surgery. Postoperatively, the platelet count and antithrombin III level decreased, and computed tomography revealed intramuscular hematomas that possibly were related to vascular injury and potential disseminated intravascular coagulation. We should be mindful of the possibility of intramuscular hematoma formation in patients with HELLP syndrome, even when using ultrasound guidance.

Case of a Cardiopulmonary Arrest Due to Postoperative Subglottic Stenosis Developed on the Second Day after Lung Surgery.

We experienced a case of the cardiopulmonary arrest due to subglottic stenosis developed on the second day after lung cancer surgery. Case : A 73-year-old female who was diagnosed with primary lung cancer was referred to our department for surgery. The second day after left lung segmentectomy, she showed respiratory discomfort symptoms and exhibited hoarseness and stridor, which were revealed as the subglottic stenosis by bronchoscopy. During the emergency airway management, she went into cardiopulmonary arrest. We performed cardiopulmonary resuscitation and simultaneous urgent tracheotomy.

[Anesthetic management of a patient with Klippel-Trenaunay syndrome undergoing caesarean section].

Klippel-Trenaunay syndrome (KTS) is characterized by capillary and venous malformation and hypertrophy of bone and soft tissues. A 29-year-old primigravida, who had been diagnosed of KTS by her hemangiomas and varicosities in the right leg, pubic area, rectum, vagina and lower abdominal area, was scheduled to receive caesarean section at 37 weeks gestation because vaginal delivery might cause hemorrhagic complications and extension of the venous lesions. Regional anesthesia was avoided because of the possible injuries of unknown venous malformations or varicose veins in the epidural or spinal space. The cesarean section was performed under general anesthesia uneventfully and an infant was delivered normally. There were no complications such as massive hemorrhage, disseminated intravascular coagulation and deep venous thrombosis in the perioperative period. Careful anesthetic considerations for the prevention of hemorrhagic and thrombotic complications are necessary for cesarean section in a patient with KTS.