Remimazolam is approved in Japan for induction and maintenance of general anesthesia and is under regulatory assessment in the USA and the European Union for procedure sedation [1, 2]. Remimazolam is safe for use in patients with malignant hyperthermia at the basic research level, and there are reports of its successful clinical use [5, 6]. In the present case, no muscle biopsy was performed, but the patient’s older sister had developed malignant hyperthermia, and considering that the patient was at risk, we needed to use intravenous anesthetics to avoid inhalation agents. Both intraoperatively and postoperatively, there was no elevation of body temperature or end-expiratory carbon dioxide concentration, or masseter muscle or generalized muscular rigidity, suggestive of malignant hyperthermia during the use of remimazolam.

Compared to midazolam, remimazolam is characterized by a shorter duration of action and better adjustability [7]. Another advantage is that remimazolam can be antagonized by flumazenil. The use of remimazolam tends to achieve hemodynamic stability more easily than propofol. Therefore, remimazolam is useful for patients with potentially unstable hemodynamics [3]. Patients who undergo liver transplantation usually have end-stage liver disease and cirrhosis. In patients with cirrhosis, the metabolism of vasodilator substances is decreased, causing peripheral blood vessels to dilate and decrease vascular resistance. To compensate for this, the heart rate increases with activation of sympathetic nervous system and the renin-angiotensin system, resulting in a hyperdynamic state [4]. The response to heart rate changes in intravascular volume, such as bleeding, is small, and blood pressure can easily decrease. In addition, portal hypertension causes splenic hypertension, which leads to anemia and low platelet counts. In combination with decreased production of coagulation factors, bleeding during transplant may be massive. Moreover, severe hypotension and arrhythmias may arise after liver graft reperfusion. In addition, liver transplantation procedures involve repeated clamping and unclamping of the portal vein, collateral blood vessels, and the inferior vena cava. These factors cause circulatory instability during the anesthetic management of liver transplantation [4]. In this case, the decrease in blood pressures were extremely mild, and the required use of vasoconstrictors was minimal. The patient’s young age and normal cardiac function may have contributed to this. However, remimazolam may have contributed to hemodynamic stability.

Remimazolam is metabolized by tissue carboxylesterase, and its clearance is decreased in patients with severe hepatic impairment. Therefore, careful administration is required [8]. In patients with severe hepatic impairment, clearance was 38.1% lower than in healthy volunteers in the three-compartment recirculation model, and thus, recovery was slightly delayed (healthy: 8.0 min, moderate: 12.1 min, severely hepatic impairment: 16.7 min) [8]. Furthermore, the volume of distribution of remimazolam in patients with severe liver failure (Child–Pugh class C) is 1.01 L/kg [1]. The protein binding rate is approximately 92% [1]. In this study, the patient had a significant hepatic damage, and a long anhepatic period between the removal of the liver and the reperfusion of the transplanted liver. This might have caused the prolonged metabolism of remimazolam. In addition, rapid bleeding could increase blood levels of remimazolam. We adjusted the dose of remimazolam from 0.9 to 1.1 mg/kg/h depending on the vital signs, the bispectral index, and electroencephalogram findings. After reperfusion and stabilization of vital signs, we discontinued remimazolam and started propofol approximately 3 h before the end of the surgery. We extubated her the next day without the use of flumazenil, suggesting that there was no apparent prolongation of the effects of remimazolam. The electroencephalogram changes during remimazolam infusion include an initial increase in beta frequency band and a late increase in delta frequency band [9]. The bispectral index increased suddenly several times during the operation. However, although the patient was not evaluated in detail using the modified Brice questionnaire, no intraoperative awareness was noted in the interview the day after surgery.

In summary, we maintained stable hemodynamics using remimazolam for anesthetic management of a patient undergoing a liver transplantation, which was characterized by a hyperdynamic state and circulatory instability.

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