Comparison of remimazolam and midazolam for sedation during colonoscopy in Japanese patients: A propensity score matching analysis.

Objectives: To compare the efficacy and safety of sedation with midazolam and remimazolam for colorectal endoscopy. Methods: This single-center, two-arm, post-hoc analysis of the REM-IICTJP01 study investigated the efficacy and safety of remimazolam for gastrointestinal endoscopic sedation. We enrolled 40 and 208 patients who underwent colonoscopy under remimazolam and midazolam sedation, respectively, during the same period. The primary outcome was the time from the end of the colonoscopy until discharge. The secondary outcomes included the time from the end of the colonoscopy until awakening, dosage, and adverse events. Propensity score matching was employed to eliminate the effect of confounding factors. Results: Thirty-seven patients in each group were matched. After propensity matching, the time to awakening after colonoscopy was 28.0 (13.0-37.0) min in the midazolam group and 0 (0-0) min in the remimazolam group; moreover, the time till discharge was 40.0 (35.0-46.5) min in the midazolam group and 0 (0-5.0) min in the remimazolam group, both of which were significantly shorter in the remimazolam group (p < 0.01). The number of additional doses was 0 (0-0) and 2 (1-3) in the midazolam and remimazolam groups, respectively. The total dose was 2.0 (2.0-3.5) and 6.0 (5.0-7.0) mg in the midazolam and remimazolam groups, respectively. Conclusions: Remimazolam yielded significantly faster times to awakening and discharge safely compared to midazolam.

Remimazolam in General Anesthesia: A Comprehensive Review of Its Applications and Clinical Efficacy.

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.

Effect of remimazolam versus propofol on hypotension after anesthetic induction in patients undergoing coronary artery bypass grafting: A randomized controlled trial.

STUDY 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). DESIGN: Randomized controlled trial. SETTING: Tertiary teaching hospital. PATIENTS: Adult patients undergoing isolated CABG. INTERVENTIONS: 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. MEASUREMENTS: 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. MAIN 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.

The Effect of Lidocaine-Prilocaine Cream Combined with or Without Remimazolam on VAS and APAIS Anxiety Score in Patient Undergoing Spinal Anesthesia.

Purpose: This study aimed to investigate patients' expectative pain of spinal anesthesia puncture and anxiety pre-anesthesia, and to examine the effect of lidocaine-prilocaine cream and remimazolam prior to spinal anesthesia puncture on pain relief and anxiety release. Methods: Patients undergoing spinal anesthesia were divided into control, lidocaine-prilocaine cream, and lidocaine-prilocaine cream with remimazolam groups. A questionnaire consisting of The Amsterdam Preoperative Anxiety and Information Scale (APAIS) and patient's concerns and Visual Analog Scale (VAS) was used to evaluate patient's anxiety and pain. The primary outcomes were differences in VAS and anxiety scores. Patient's spinal anesthesia-related concerns, advent events and hemodynamic index were also recorded. Results: The expected spinal anesthesia puncture pain was 5.34±0.27 and anxiety scores before spinal anesthesia was 10.88 ± 0.64. A statistically significant positive correlation of 31.3% was detected between VAS and APAIS scores (r = 0.313; P=0.003). The VAS score at the time of puncture decreased by 29.7% (3.78±0.40, P=0.001) in lidocaine-prilocaine cream group and 29.2% (3.75±0.39, P=0.001) in lidocaine-prilocaine cream with remimazolam group compared with the expected VAS score. Lidocaine-prilocaine cream combined with or without remimazolam reduced the percentage of moderate pain (21.4% and 31.3% vs 50.0%, P=0.0001) and increased mild pain (60.7% vs 59.4% vs 22.7%, P=0.03). Anxiety score in lidocaine-prilocaine cream group was reduced by 2.84 (8.04±0.76 vs 10.88 ± 0.46, P=0.05) when compared with pre-anesthesia. Concerns about postoperative pain (P=0.03) and fear of the needle or intervention (P=0.000) both decreased post-anesthesia among groups. Conclusion: Approximately half of the patients scheduled for spinal anesthesia experienced a moderate level of preoperative anxiety. The patient's pain expectation from the spinal anesthesia puncture was moderate, which was higher than the actual pain. Lidocaine-prilocaine cream with or without remimazolam sedative before spinal anesthesia puncture reduced the patient's pain and anxiety scores after surgery.

Carboxylesterase 1-Based Drug-Drug Interaction Potential of Remimazolam: In-Vitro Studies and Literature Review.

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. CONCLUSION: 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.

Effects of Propofol, Low and High Doses of Remimazolam on Hemodynamic and Inflammatory Response in Laparoscopic Surgery.

Background: This study explored the effects of different doses of remimazolam tosilate (RT) and propofol combined with remifentanil anesthesia on hemodynamic and inflammatory responses in patients undergoing laparoscopic surgery. Subjects and Methods: Ninety patients with a BMI of less than 35 kg/m², classified as ASA II-III and scheduled for laparoscopic surgery, were enrolled in this study. Patients were divided into three groups: low-dose RT group (A), high-dose RT group (B), and propofol group (C). The changes in hemodynamic indices such as SBP, DBP, HR, MAP, and inflammatory response indices such as IL-6, SAA, CRP, and PCT, along with extubation time and doses of sufentanil, remifentanil, urapidil, and phenylephrine, were compared among the three groups. Results: There were no statistically significant differences in extubation time, doses of sufentanil and remifentanil, or the usage rates and average doses of urapidil and phenylephrine between the three groups. The average dose of phenylephrine in group A was lower than in group B and group C, with a statistically significant difference. There were no statistically significant differences among the groups in SBP, DBP, HR, and MAP from T0 to T2, nor in IL-6, SAA, CRP, or PCT levels. Conclusion: Using RT for induction and maintenance of anesthesia in laparoscopic surgery ensures stable hemodynamic and inflammatory responses in patients. Low-dose RT may reduce the usage rate and dose of vasopressors such as phenylephrine during surgery.

Effect of remimazolam and propofol anesthesia on autonomic nerve activities during Le Fort I osteotomy under general anesthesia: blinded randomized clinical trial.

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

A Comparison of Hypotension, Bradycardia, and Hypoxia Incidence between the Use of Remimazolam and Other Sedative Agents during Colonoscopy Procedures: A Systematic Review and Meta-Analysis.

(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.

Remimazolam and Its Place in the Current Landscape of Procedural Sedation and General Anesthesia.

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.

Anesthesia management for percutaneous mitral valve repair in a patient with mitochondrial cardiomyopathy and low cardiac function: a case report.

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. CASE PRESENTATION: 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. CONCLUSION: Anesthesia management with remimazolam appears to be a safe and effective for MitraClip™ implantation in patients with mitochondrial cardiomyopathy.

Advantages of remimazolam for sedation in impacted tooth extraction.

OBJECTIVES: This study aims to compare the sedative effects of remimazolam and midazolam during impacted tooth extraction to provide a comfortable sedation treatment for patients with dental anxiety. METHODS: A prospective randomized controlled trial was conducted, in which 60 patients undergoing intravenous sedation for mandibular impacted third molar extraction were evenly divided into either the remimazolam or midazolam group. Prior to receiving a nerve blocker, the patients were sedated with remimazolam or midazolam. Various parameters were recorded and analyzed, including onset time, awakening time, recovery time, modified dental anxiety scale (MDAS) scores before and after surgery, patient-doctor satisfaction levels, postoperative side effects within 24 hours, heart rate (HR), and mean arterial pressure (MAP) at different time points. RESULTS: Compared with the midazolam group, patients in the remimazolam group demonstrated significantly shorter onset, awakening, and recovery times as well as lower postoperative MDAS scores and higher levels of patient-doctor satisfaction. Fewer postoperative side effects were reported in the remimazolam group, although the differences were not statistically significant. CONCLUSIONS: The use of remimazolam demonstrates faster onset and recovery, superior efficacy in reducing dental anxiety, and enhanced satisfaction among patients and doctors, thereby presenting distinct advantages for sedation treatment for patients with dental anxiety.

Remimazolam for sedation in gastrointestinal endoscopy: A comprehensive review.

Worldwide, a majority of routine endoscopic procedures are performed under some form of sedation to maximize patient comfort. Propofol, benzodiazepines and opioids continue to be widely used. However, in recent years, Remimazolam is gaining immense popularity for procedural sedation in gastrointestinal (GI) endoscopy. It is an ultra-short-acting benzodiazepine sedative which was approved by the Food and Drug Administration in July 2020 for use in procedural sedation. Remimazolam has shown a favorable pharmacokinetic and pharmacodynamic profile in terms of its non-specific metabolism by tissue esterase, volume of distribution, total body clearance, and negligible drug-drug interactions. It also has satisfactory efficacy and has achieved high rates of successful sedation in GI endoscopy. Furthermore, studies have demonstrated that the efficacy of Remimazolam is non-inferior to Propofol, which is currently a gold standard for procedural sedation in most parts of the world. However, the use of Propofol is associated with hemodynamic instability and respiratory depression. In contrast, Remimazolam has lower incidence of these adverse effects intra-procedurally and hence, may provide a safer alternative to Propofol in procedural sedation. In this comprehensive narrative review, highlight the pharmacologic characteristics, efficacy, and safety of Remimazolam for procedural sedation. We also discuss the potential of Remimazolam as a suitable alternative and how it can shape the future of procedural sedation in gastroenterology.

The effects of remimazolam combined with sufentanil on respiration, circulation and sedation level in patients undergoing colonoscopy.

BACKGROUND: The main sedative which is propofol in painless gastroenteroscopy, has a high risk of reducing blood pressure and respiratory depression. Remimazolam (a short-acting benzodiazepine) is expected to be widely used in painless gastroenteroscopy due to its rapid onset, rapid metabolism and light respiratory and circulation inhibition. METHODS: A randomized, single-blind, parallel, controlled study, 123 outpatients who were undergoing painless colonoscopy and ramdomly divided into group A, B and C, in Hangzhou First People's Hospital, July-December 2021. All patients were intravenously injected with 5 µg sufentanil for analgesic preconditioning. The group A was induced by 0.2 mg/kg remimazolam besylate. The group B was induced by 0.25 mg/kg remimazolam besylate. And the group C was inducted by 2.0 mg /kg propofol. If the patients had limb movement or MOAA/S score > 3 and so on, remimazolam besylate was added at 2.5 mg/ time in group A and B, and propofol emulsion injection was added at 0.5 mg/kg/ time in group C. During the operation, according to the actual situation, remimazolam was per added 2.5 mg in the experimental group, and propofol was 0.5 mg/kg in the control group. Heart rate (HR), non-invasive blood pressure (BP), respiratory rate (RR), pulse oxygen saturation (SpO2), and improved vigilance/sedation score (MOAA/S) of patients was recorded from entering endoscopy room to get out of the anesthesia recovery room, also including perioperative adverse events, other medications or treatments, the time of patients waking up and leaving the hospital. RESULTS: The successful rate of induction in three groups was 100%. There was no significant difference in the sedation completion rate among the three groups (Group A:90.2%, Group B: 92.7%, Group C: 92.7%, P = 1.000). The rate of adverse events after administration: group A(27.0%) and B(36.8%) both lower than group C(71.0%),P < 0.001;There was no significant difference between group A and group B, P > 0.744;The average time from the last drug administration to meet the discharge criteria of the subjects in three groups was as follows: The average time of group A(16.2 min) and Group B(16.5 min) both shorter than group C(19.6 min), P = 0.001; There was no significant difference between group A and group B, P = 0.742. CONCLUSIONS: This study revealed that remimazolam is a safe and effective medication for colonoscopy sedation, the security of remimazolam is better than propofol, and the sedative effect with the initial dose of 0.25 mg/kg of remimazolam is optimal. TRIAL REGISTRATION: China Clinical Trial Center with registration number: 2100052615,02/11/2021.

Remimazolam protects the liver from ischemia-reperfusion injury by inhibiting the MAPK/ERK pathway.

BACKGROUND: Ischemia-reperfusion (I/R) injury is a major factor in liver damage following hepatic resection and liver transplantation, with anesthetics demonstrating the ability to shield organs from this type of injury. METHODS: Hypoxia-reoxygenation (H/R) was used to create in vitro I/R hepatocyte cell injury models. The CCK-8 assay, flow cytometer, LDH assay, and ELSIA were utilized to assess hepatocyte injury. The in vivo I/R injury rat model was then built. HE and TUNEL staining were used to assess liver tissue damage. Western-blot was applied to assess the activation of the MAPK/ERK pathway. RESULTS: Remimazolam (RMZL) remarkably improved cell viability and decreased apoptosis in H/R-induced hepatocyte injury. RMZL reduced the release of H/R-induced inflammatory mediators (TNF-α and IL-6) as well as LDH levels. We also discovered that RMZL inhibited p38 and ERK1/2 phosphorylation in vivo and in vitro. The stimulation of MAPK/ERK, on the other hand, abolished RMZL's anti-inflammation effects in H/R-induced hepatocyte injury. Furthermore, RMZL reduced liver tissue injury in I/R rats. CONCLUSION: RMZL prevented hepatic I/R damage by inhibiting MAPK/ERK signaling.

Successful use of remimazolam combined with remifentanil for painless gastroscopy in a patient with morbid obesity: a case report.

Backgroud: In recent years, as the number of people with obesity has surged, the number of morbidly obese patients has also grown. The pathophysiological changes in morbid obesity can lead to combined lung diseases, which may result in hypoventilation, hypoxemia, acute upper airway obstruction, acute respiratory distress syndrome, and sleep apnea syndrome, posing serious challenges to anesthesia management. Here, we describe a case of the administration of remimazolam combined with remifentanil in a patient with morbid obesity undergoing gastroscopy. This has rarely been reported in clinical practice, and we present our management experience here with the aim of providing a reference for clinical work. Case presentation: We report the case of a 32-year-old male hypertensive patient with a height of 180 cm, weight of 145 kg, and body mass index of 44.8 kg/m2. The patient's main complaint was intermittent hunger pain for more than 1 year, and duodenal polyps were found. Considering the patient's morbid obesity and the combination of sleep apnea syndrome and hypertension, we administered remimazolam along with remifentanil to ensure perioperative safety. Conclusion: The procedure lasted 30 min, and the anesthesia was satisfactory with no complications. Remimazolam combined with remifentanil intravenous anesthesia is safe for short gastroscopy in patients with morbidly obesity. The administration of a small dose of split-titration delivery facilitates the maintenance of stable vital signs.

Remimazolam for simultaneous percutaneous mitral valve clip and percutaneous left atrial appendage closure in an elderly patient with impaired cardiac function: A case report.

Remimazolam is a short-acting benzodiazepine sedative with a short half-life and little circulatory depression. The safe use of remimazolam in the anesthetic management of an elderly patient with impaired cardiac function is reported. The patient's hemodynamics remained stable, and the patient was managed without serious complications. Remimazolam may be an option for sedation in elderly patients with reduced cardiac function.

Clinical experience with remimazolam in pediatric anesthesiology: An educational focused review.

Remimazolam is a novel ultrashort-acting benzodiazepine, which like midazolam, results in sedation, anxiolysis, and amnesia through its agonistic effects on the gamma-amino butyric acid A receptor. As opposed to midazolam, its unique metabolism is via tissue esterases, which results in a rapid elimination with a limited context sensitive half-life and prompt dissipation of its effect when administration is discontinued. Remimazolam received FDA approval for use in adults in 2020. In preliminary and initial clinical trials, its efficacy and safety has been suggested in the adult population, both as a primary agent for procedural sedation or as an adjunct to general anesthesia. There are limited data regarding the use of remimazolam in infants and children and its use in this population remains off label as it does not hold FDA-approval in pediatric-aged patients. This narrative outlines the pharmacologic properties of this unique medication, reviews previous published reports of its role in pediatric-aged patients, and discusses dosing parameters and clinical use in this population.

Incompatibility of the short-acting benzodiazepine remimazolam with common perioperative medication.

BACKGROUND: Remimazolam is a relatively new benzodiazepine with growing use in procedural sedation and general anaesthesia. Initiated by case reports, the physical incompatibility of remimazolam with ringer's acetated and ringer's lactated solution has been reported. More recently, remifentanil, fentanyl, rocuronium, vecuronium, dexmedetomidine, and midazolam, have been investigated and suggested safe for coadministration with remimazolam. Apart from case reports, incompatibility for other frequently used drugs remains unknown. METHODS: Sixty-five drugs and intravenous fluids were tested for possible precipitation with remimazolam in a simulated y-site administration. Equal volumes of the test drug were injected into the remimazolam solution, examined and photo documented at 1, 15, 30 and 60 min after mixture. Examination was taken by two independent investigators. pH was measured before, and 60 min after mixing the drugs. RESULTS: Seventeen (26.15%) drugs or fluids showed precipitation, 47 (72.31%) did not show any sign of interaction. Propofol could not be assessed, because of the turbidity of the substance itself. Precipitation occurred immediately and remained stable in all timestamps. The incompatible drug-remimazolam-mixtures had a median pH of 7.15 (6.67, 8.01), the non-precipitating mixtures a median pH of 4.75 (3.8, 5.6). The pH-values of both groups were significantly different (Mann-Whitney-U-test; p < .00001). There is an increasing risk for precipitation with more basic baseline pH-levels of the tested drug. No interaction was seen in baseline pH below 5. CONCLUSIONS: Remimazolam (Byfavo®) is incompatible with ampicillin/ sulbactam, calcium gluconate, clindamycin, dexamethasone, dimenhydrinate, an 148mval/l electrolyte - glucose 1% solution (E148G1®), furosemide, a 4% gelatine volume expander (gelafundin®), heparin sodium, insulin, meropenem, sodium bicarbonate 8.4%, prednisolone, the crystalloid infusions jonosteril® and sterofundin®, thiopental and tranexamic acid. The results strongly affirm remimazolam's safety requirements: A separate line for remimazolam and an approved compatible baseline infusion is mandatory and an alternative way to administer bolus medication is required.

Comparison of remimazolam tosilate and propofol during induction and maintenance of general anesthesia in patients undergoing laparoscopic cholecystectomy: a prospective, single center, randomized controlled trial.

BACKGROUND: Remimazolam tosilate (RT) is a new, ultrashort-acting benzodiazepine. Here, we investigated the efficacy and safety of RT for general anesthesia in patients undergoing Laparoscopic Cholecystectomy (LC). METHODS: In this study, 122 patients undergoing laparoscopic cholecystectomy were randomly allocated to receive either remimazolam tosilate (Group RT) or propofol group (Group P). RT was administered as a slow bolus of 0.3 mg kg- 1 for induction, followed by 1.0-2.0 mg kg- 1 h- 1 for maintenance of general anesthesia. Propofol was started at 2 mg kg- 1 and followed by 4-10 mg kg- 1 h- 1 until the end of surgery. The primary outcome was the time to bispectral index (BIS) ≤ 60. The secondary outcome included the time to loss of consciousness (LoC), and the time to extubation. Adverse events were also assessed. RESULTS: A total of 112 patients were recruited for study participation. Among them, the time to BIS ≤ 60 in Group RT was longer than that in Group P (Group RT: 89.3 ± 10.7 s; Group P: 85.9 ± 9.7 s, P > 0.05). While the time to LoC comparing remimazolam and propofol showed no statistical significance (Group RT: 74.4 ± 10.3 s; Group P: 74.7 ± 9.3 s, P > 0.05). The time to extubation in Group RT was significantly longer than that in Group P (Group RT: 16.0 ± 2.6 min; Group P: 8.8 ± 4.3 min, P < 0.001). Remimazolam tosilate had more stable hemodynamics and a lower incidence of hypotension during general anesthesia. CONCLUSIONS: Remimazolam tosilate can be safely and effectively used for general anesthesia in patients undergoing Laparoscopic Cholecystectomy. It maintains stable hemodynamics during induction and maintenance of general anesthesia compared with propofol. Further studies are needed to validate the findings. TRIAL REGISTRATION: Chictr.org.cn ChiCTR2300071256 (date of registration: 09/05/2023).