In recent years the still relatively new short-acting benzodiazepine remimazolam has been approved and clinically implemented in several countries and regions. Remimazolam is also now approved in the EU and the market launch in Germany is expected in the not too distant future. This is therefore a good point in time to summarize the current evidence for various areas of application, including general anesthesia, sedation and intensive care medicine as well as different dosing schemes.
UNASSIGNED: In den letzten Jahren wurde das noch relativ neue, kurzwirksame Benzodiazepin Remimazolam in diversen Ländern und Regionen zugelassen und klinisch implementiert. Auch in der EU ist Remimazolam inzwischen zugelassen, und die Markteinführung in Deutschland wird in nicht allzu ferner Zukunft erwartet. Dies ist also ein guter Zeitpunkt, die bisherigen Erkenntnisse zu Remimazolam und die aktuelle Evidenz zu verschiedenen Einsatzbereichen, insbesondere bezüglich der Anästhesie, Sedierung und Intensivmedizin sowie der verschiedenen Dosierungsschemata zu beleuchten.

BACKGROUND: Benzodiazepines are used in pediatric patients with congenital heart disease (CHD) because of their mild hemodynamic depressant effects. A novel short-acting benzodiazepine, remimazolam, is expected to be suitable for these patients. We examined the characteristics of remimazolam anesthesia in pediatric patients with CHD undergoing cardiac catheterization.
METHODS: This single-center retrospective study included pediatric patients undergoing cardiac catheterization for CHD. The primary outcome was the remimazolam dose for loss of consciousness. Secondary outcomes included the mean maintenance remimazolam dose, recovery time from anesthesia, predicted remimazolam concentration at emergence, decrease in blood pressure and heart rate, vasopressor administration during anesthesia, electroencephalogram index (bispectral index: BIS or patient state index: PSI), and life-threatening adverse events.
RESULTS: Thirty-nine patients, aged 2 months to 16 years, were included. Thirty-three patients received a median [interquartile] midazolam dose of 0.10 [0.10-0.10] mg.kg-1 in the pre-anesthesia room. The remimazolam dose for loss of consciousness was 0.34 [0.26-0.45] mg.kg-1. The mean maintenance dose was 1.0 [0.8-1.4] mg.kg-1.h-1. The recovery time was 15 [12-17] min. The predicted remimazolam concentration at emergence was 0.4-1.2 µg.ml-1 in 3-6-year-old patients. Blood pressure and heart rate decreased by 30% in 15 and 6 patients, respectively. Vasopressors were administered as a bolus in 8 patients. The BIS or PSI did not fall ≤ 60 or ≤ 50, respectively, in 51% of patients before tracheal intubation. No life-threatening adverse events were reported.
CONCLUSIONS: Remimazolam is a good alternative anesthetic agent for pediatric patients undergoing cardiac catheterization for CHD.

The transcarotid approach was introduced in Japan in April 2024 as an alternative approach for transcatheter aortic valve replacement (TAVR). Because carotid artery blood flow is reduced on one side during the procedure, there is a risk of intraoperative brain stroke. Therefore, it is crucial to check for cerebral complications immediately after the procedure. We report a case involving an 87-year-old female who underwent transcarotid TAVR under general anesthesia with remimazolam and remifentanil. The operation was completed in a short period. There was no evidence of hypotension during the induction of anesthesia, and intraoperative blood pressure control was easy. However, there was a decrease in local oxygen saturation for approximately nine minutes intraoperatively. Following the administration of flumazenil, the patient was quickly awakened, and neurological findings were confirmed to be normal. The patient was discharged without complications. Our findings suggest that remimazolam, an ultra-short-acting benzodiazepine, is feasible for the transcarotid TAVR procedure due to its minimal circulatory impact and ability to facilitate rapid and reliable arousal.

Remimazolam is a novel ultra-short-acting benzodiazepine with a unique pharmacokinetic profile that makes it an attractive option for use in general anesthesia. This review paper provides an in-depth analysis of remimazolam\'s applications in the field of general anesthesia, focusing on its pharmacological properties, clinical efficacy, safety profile, and potential advantages compared to other anesthetic agents. Remimazolam acts on GABAa receptors, offering rapid onset and recovery times due to its unique metabolic pathway involving tissue esterases. Clinical trials have demonstrated its efficacy in procedural sedation and general anesthesia, showing a favorable safety profile with minimal cardiovascular and respiratory depression. Compared to traditional anesthetics such as propofol, remimazolam presents distinct advantages, including predictable pharmacokinetics, reduced risk of prolonged sedation, and a reliable safety margin. These attributes position remimazolam as a promising agent in various clinical settings. The purpose of this review is to synthesize current evidence on remimazolam and discuss its potential to improve clinical outcomes in anesthesia practice.

OBJECTIVE: There is scarce evidence on the hemodynamic stability of remimazolam during anesthetic induction in patients with significant coronary artery disease. This study aims to compare the effects of remimazolam and propofol on post-induction hypotension in patients undergoing coronary artery bypass grafting (CABG).
METHODS: Randomized controlled trial.
METHODS: Tertiary teaching hospital.
METHODS: Adult patients undergoing isolated CABG.
METHODS: Patients were randomly allocated to received either remimazolam (n = 50) or propofol (n = 50) for anesthetic induction. The remimazolam group received an initial infusion at 6 mg/kg/h, which was later adjusted to 1-2 mg/kg/h to maintain a bispectral index of 40-60 after loss of consciousness. In the propofol group, a 1.5 mg/kg bolus of propofol was administered, followed by 1-1.5% sevoflurane inhalation as needed to achieve the target bispectral index.
METHODS: The primary outcome was the area under the curve (AUC) below the baseline mean arterial pressure (MAP) during the first 10 min after anesthetic induction. Secondary outcomes included the AUC for MAP <65 mmHg and the requirement for vasopressors.
RESULTS: The remimazolam group demonstrated a significantly lower AUC under the baseline MAP compared to the propofol group (mean [SD], 169.8 [101.0] mmHg·min vs. 220.6 [102.4] mmHg·min; mean difference [95% confidence interval], 50.8 [10.4-91.2] mmHg·min; P = 0.014). Additionally, the remimazolam group had a reduced AUC for MAP <65 mmHg (7.3 [10.3] mmHg·min vs. 13.9 [14.9] mmHg·min; P = 0.007) and a lower frequency of vasopressor use compared to the propofol group (60% vs. 88%, P = 0.001).
CONCLUSIONS: Remimazolam may offer improved hemodynamic stability during anesthetic induction in patients undergoing CABG, suggesting its potential advantage over propofol for patients with significant coronary artery disease in terms of hemodynamic stability.

Remimazolam was derived from its parent compound by adding an ester linkage into its structure so that the drug becomes a substrate for ester metabolism. As a result, it undergoes organ-independent ester hydrolysis, although the clinical benefits in terms of shorter recovery are not uniformly observed in clinical practice. Remimazolam is mainly tested in procedural sedation. In comparison to propofol, the current gold standard for procedural sedation, its proposed attractiveness is shorter wake-up times and a clear-headed recovery. Its clear advantages over propofol are better hemodynamic stability, lack of pain on injection and availability of a reversal agent in the form of flumazenil. Data on patient and proceduralist satisfaction are lacking. Remimazolam is also used for induction and maintenance of general anesthesia in Japan (where it is approved for this purpose). In this scenario, it is not clear if it can achieve the same degree of lack of recall as propofol. The use of remimazolam in obstetrics, pediatrics and high-risk populations is an emerging area.

(1) Background: Remimazolam is a newly developed sedative agent. The results of previous meta-analyses highlight the strengths of remimazolam for use during colonoscopy procedures. The primary aim of the present study was to investigate whether, in patients undergoing colonoscopy procedures (P), the use of remimazolam (I) compared with other sedative agents (C) could lead to a greater incidence of hypotension, bradycardia, and hypoxia (O). (2) Methods: In the following study, we conducted an extensive literature search using two electronic databases. We included all randomized control trials, which involved a comparison of the hemodynamic changes in remimazolam versus a placebo and other sedative agents during colonoscopy procedures. Data extraction, data synthesis, and the assessment of risk of bias were performed by the authors. (3) Results: A total of seven articles met our inclusion criteria. The combined analysis of the selected studies revealed no statistically significant difference in hypotension, bradycardia, or hypoxia incidence when comparing remimazolam and the control group. However, in comparison with the group administered propofol, the pooled data of the selected studies revealed statistically significant differences in the incidence of both hypotension and bradycardia but not hypoxia. (4) Conclusions: Our findings indicate that there is no significant difference in hypotension, bradycardia, and hypoxia incidence when comparing remimazolam and other agents. Nevertheless, when comparing the remimazolam and propofol groups, the results demonstrated statistically significant differences in the incidence of both hypotension and bradycardia but not hypoxia.

UNASSIGNED: This study evaluated the effect of remimazolam and propofol on changes in autonomic nerve activity caused by surgical stimulation during orthognathic surgery, using power spectrum analysis of blood pressure variability (BPV) and heart rate variability (HRV), and their respective associations with cardiovascular fluctuations.
UNASSIGNED: A total of 34 patients undergoing Le Fort I osteotomy were randomized to the remimazolam (Group R, 17 cases) or propofol (Group P, 17 cases) groups. Observables included the low-frequency component of BPV (BPV LF; index of vasomotor sympathetic nerve activity), high-frequency component of HRV (HRV HF; index of parasympathetic nerve activity), balance index of the low- and high-frequency components of HRV (HRV LF/HF; index of sympathetic nerve activity), heart rate (HR), and systolic blood pressure (SBP). Four observations were made: (1) baseline, (2) immediately before down-fracture, (3) down-fracture, and (4) 5 min after down-fracture. Data from each observation period were compared using a two-way analysis of variance with a mixed model. A Bonferroni multiple comparison test was performed in the absence of any interaction. One-way analysis of variance followed by Tukey\'s multiple comparisons test was performed when a significant interaction was observed between time and group, with P < 0.05 indicating statistical significance.
UNASSIGNED: Evaluation of autonomic nerve activity in comparison with baseline during down-fracture showed a significant increase in BPV LF (P < 0.001), an increasing trend in HRV LF/HF in Group P, and an increasing trend in HRV HF in Group R. There were no significant differences in HR or SBP between the two groups.
UNASSIGNED: During down-fracture of Le Fort I osteotomy, sympathetic nerve activity was predominant with propofol anesthesia, and parasympathetic nerve activity was predominant with remimazolam anesthesia.

BACKGROUND: Mitochondrial cardiomyopathy occurs when impaired mitochondrial energy production leads to myocardial dysfunction. Anesthetic management in such cases is challenging due to risks of circulatory depression associated with anesthesia and mitochondrial dysfunction induced by anesthetics. Although there are reports of anesthetic management for patients with mitochondrial diseases, there are few reports specifically addressing cardiac anesthesia for patients with mitochondrial cardiomyopathy. We present a case where percutaneous mitral valve repair with MitraClip™ was successfully performed under remimazolam anesthesia in a patient with mitochondrial cardiomyopathy who developed functional mitral valve regurgitation due to low cardiac function and cardiomegaly.
METHODS: A 57-year-old woman was diagnosed with chronic cardiac failure, with a 10-year history of dilated cardiomyopathy. She was diagnosed with mitochondrial cardiomyopathy 8 years ago. Over the past 2 years, her cardiac failure worsened, and mitral valve regurgitation gradually developed. Surgical intervention was considered but deemed too risky due to her low cardiac function, with an ejection fraction of 26%. Therefore, percutaneous MitraClip™ implantation was selected. After securing radial artery and central venous catheterization under sedation with dexmedetomidine, anesthesia was induced with a low dose of remimazolam 4 mg/kg/h. Anesthesia was maintained with remimazolam 0.35-1.0 mg/kg/h and remifentanil 0.1 μg/kg/min. Noradrenaline and dobutamine were administered intraoperatively, and the procedure was completed successfully without circulatory collapse. The patient recovered smoothly from anesthesia and experienced no complications. She was discharged on the eighth day after surgery.
CONCLUSIONS: Anesthesia management with remimazolam appears to be a safe and effective for MitraClip™ implantation in patients with mitochondrial cardiomyopathy.

BACKGROUND: The ultra-short-acting benzodiazepine remimazolam, approved for procedural sedation and general anesthesia, is inactivated by carboxylesterase 1 (CES1).
OBJECTIVE: Remimazolam´s involvement in CES1-mediated drug-drug interactions (DDIs) was investigated.
METHODS: Possible interactions of remimazolam were studied in co-exposure experiments with eleven different drugs. Further, substrates and inhibitors of CES1, identified in the literature, were evaluated for possible in-vivo inhibition using pharmacokinetic and Ki or IC50 values. Compounds with only one published inhibitory concentration and CES1 substrates lacking inhibition data were assigned conservative Ki values.
RESULTS: In human liver homogenates and/or blood cells, remimazolam showed no significant inhibition of esmolol and landiolol metabolism, which, in turn, at up to 98 and 169 μM, respectively, did not inhibit remimazolam hydrolysis by human liver homogenates. In human liver S9 fractions, IC50 values ranged from 0.69 μM (simvastatin) and 57 μM (diltiazem) to > 100 μM (atorvastatin) and, for the remaining test items (bupropion, carvedilol, nelfinavir, nitrendipine, and telmisartan), they ranged from 126 to 658 μM. Remifentanil was ineffective even at 1250 μM. Guidance-conforming evaluation revealed no relevant drug-drug interactions with remimazolam via CES1. The algorithm-based predictions were consistent with human study data. Among CES1 inhibitors and substrates identified in the literature, only dapsone and rufinamide were found to be possible in-vivo inhibitors of remimazolam metabolism.
CONCLUSIONS: Data and analyses suggest a very low potential of remimazolam for pharmacokinetic DDIs mediated by CES1. The theoretical approach and compiled data are not specific to remimazolam and, hence, applicable in the evaluation of other CES1 substrates.