ANAESTHESIOLOGY - GENERAL ANAESTHESIA / REVIEW ARTICLE
Remimazolam: a comprehensive review
1
Department of Anesthesiology and Intensive Therapy, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland
Submission date: 2025-07-22
Final revision date: 2025-08-31
Acceptance date: 2025-09-11
Publication date: 2025-10-01
Corresponding author
Aleksander Aszkiełowicz
Department of Anesthesiology and Intensive Therapy, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland
Department of Anesthesiology and Intensive Therapy, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland
Anaesthesiol Intensive Ther 2025;57(1):257-266
KEYWORDS
pharmacokineticselderly patientsprocedural sedationremimazolampediatric anesthesiaintravenous anesthesiaICU sedation
TOPICS
ABSTRACT
Remimazolam is a novel, ultra-short-acting benzodiazepine that has emerged as a promising agent in modern anesthetic and intensive care practice. This review presents a detailed analysis of its pharmacokinetic and pharmacodynamic properties, clinical efficacy, and safety profile across various patient populations and procedural contexts. The drug’s rapid metabolism by plasma esterases, minimal reliance on hepatic or renal function, and availability of a reversal agent (flumazenil) distinguish it from traditional sedatives such as propofol and midazolam. Clinical data support its utility in procedural sedation, general anesthesia, and ICU sedation, particularly in elderly and hemodynamically unstable patients. Pediatric applications are discussed, highlighting the early evidence and dosing considerations. The review also compares remimazolam with other agents such as propofol and dexmedetomidine, underlining its advantages in cardiovascular stability and recovery profiles. While current results are encouraging, the article emphasizes the need for further research to establish standardized protocols and explore its long-term safety, especially in vulnerable populations.
REFERENCES (72)
1.
Goudra BG, Singh PM. Remimazolam: the future of its sedative potential. Saudi J Anaesth 2014; 8: 388-391. DOI: https://doi.org/10.4103/1658-3....
2.
Kilpatrick GJ, McIntyre MS, Cox RF, Stafford JA, Pacofsky GJ, Lovell GG, et al. CNS 7056: a novel ultra-short-acting benzodiazepine. Anesthesiology 2007; 107: 60-66. DOI: https://doi.org/10.1097/01.ane....
3.
Freyer N, Knöspel F, Damm G, Greuel S, Schneider C, Seehofer D, et al. Metabolism of remimazolam in primary human hepatocytes during continuous long-term infusion in a 3-D bioreactor system. Drug Des Devel Ther 2019; 13: 1033-1047. DOI: https://doi.org/10.2147/DDDT.S....
4.
Antonik LJ, Goldwater DR, Kilpatrick GJ, Tilbrook GS, Borkett KM. A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): part I. Safety, efficacy, and basic pharmacokinetics. Anesth Analg 2012; 115: 274-283. DOI: https://doi.org/10.1213/ANE.0b....
5.
Sheng XY, Liang Y, Yang XY, Li LE, Ye X, Zhao X, et al. Safety, pharmacokinetic and pharmacodynamic properties of single ascending dose and continuous infusion of remimazolam besylate in healthy Chinese volunteers. Eur J Clin Pharmacol 2020; 76: 383-391. DOI: https://doi.org/10.1007/s00228....
6.
Schüttler J, Eisenried A, Lerch M, Fechner J, Jeleazcov C, Ihmsen H. Pharmacokinetics and pharmacodynamics of remimazolam (CNS 7056) after continuous infusion in healthy male volunteers: part I. Pharmacokinetics and Clinical Pharmacodynamics. Anesthesiology 2020; 132: 636-651. DOI: https://doi.org/10.1097/ALN.00....
7.
Zhou Y, Hu P, Jiang J. Metabolite characterization of a novel sedative drug, remimazolam in human plasma and urine using ultra high-performance liquid chromatography coupled with synapt high-definition mass spectrometry. J Pharm Biomed Anal 2017; 137: 78-83. DOI: https://doi.org/10.1016/j.jpba....
8.
Kilpatrick GJ. Remimazolam: non-clinical and clinical profile of a new sedative/anesthetic agent. Front Pharmacol 2021; 12: 690875. DOI: https://doi.org/10.3389/fphar.....
9.
Masui K. Remimazolam besilate, a benzodiazepine, has been approved for general anesthesia! J Anesth 2020; 34: 479-482. DOI: https://doi.org/10.1007/s00540....
10.
Wesolowski AM, Zaccagnino MP, Malapero RJ, Kaye AD, Urman RD. Remimazolam: pharmacologic considerations and clinical role in anesthesiology. Pharmacotherapy 2016; 36: 1021-1027. DOI: https://doi.org/10.1002/phar.1....
11.
Wiltshire HR, Kilpatrick GJ, Tilbrook GS, Borkett KM. A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): part II. Population pharmacokinetic and pharmacodynamic modeling and simulation. Anesth Analg 2012; 115: 284-296. DOI: https://doi.org/10.1213/ANE.0b....
12.
Chernik DA, Gillings D, Laine H, Hendler J, Silver JM, Davidson AB, et al. Validity and reliability of the Observer’s Assessment of Alertness/Sedation Scale: study with intravenous midazolam. J Clin Psychopharmacol 1990; 10: 244-251.
13.
Eisenried A, Schüttler J, Lerch M, Ihmsen H, Jeleazcov C. Pharmacokinetics and pharmacodynamics of remimazolam (CNS 7056) after continuous infusion in healthy male volunteers: part II. Pharmacodynamics of electroencephalogram effects. Anesthesiology 2020; 132: 652-666. DOI: https://doi.org/10.1097/ALN.00....
14.
European Medicines Agency. Byfavo: EPAR – Product Information 2024. Available at: https://www.ema.europa.eu/en/m....
15.
Doi M, Morita K, Takeda J, Sakamoto A, Yamakage M, Suzuki T. Efficacy and safety of remimazolam versus propofol for general anesthesia: a multicenter, single-blind, randomized, parallel-group, phase IIb/III trial. J Anesth 2020; 34: 543-553. DOI: https://doi.org/10.1007/s00540....
16.
Wu Q, Xu F, Wang J, Jiang M. Comparison of remimazolam-flumazenil versus propofol for recovery from general anesthesia: a systematic review and meta-analysis. J Clin Med 2023; 12: 7316. DOI: https://doi.org/10.3390/jcm122....
17.
Zhao TYM, Chen D, Xu ZX, Wang HL, Sun H. Comparison of bispectral index and patient state index as measures of sedation depth during surgeries using remimazolam tosilate. BMC Anesthesiol 2023; 23: 208. DOI: https://doi.org/10.1186/s12871....
18.
Wu X, Wang C, Gao H, Bai X, Zhang Z, Chen R, et al. Comparison of remimazolam and propofol about safety outcome indicators during general anesthesia in surgical patients: a systematic review and meta-analysis. Minerva Anestesiol 2023; 89. DOI: https://doi.org/10.23736/S0375....
19.
Chang Y, Huang YT, Chi KY, Huang YT. Remimazolam versus propofol for procedural sedation: a meta-analysis of randomized controlled trials. PeerJ 2023; 11: e15495. DOI: https://doi.org/10.7717/peerj.....
20.
Zhao M, Hu H, Li X, Li X, Wang D, Kuang M. The safety and efficacy between remimazolam and propofol in intravenous anaesthesia of endoscopy operation: a systematic review and meta-analysis. Int J Surg 2023; 109: 3566-3577. DOI: https://doi.org/10.1097/JS9.00....
21.
Ko CC, Hung KC, Illias AM, Chiu CC, Yu CH, Lin CM, et al. The use of remimazolam versus propofol for induction and maintenance of general anesthesia: a systematic review and meta-analysis. Front Pharmacol 2023; 14: 1101728. DOI: https://doi.org/10.3389/fphar.....
22.
Zhang J, Cairen Z, Shi L, Pang S, Shao Y, Wang Y, et al. Remimazolam versus propofol for procedural sedation and anesthesia: a systemic review and meta-analysis. Minerva Anestesiol 2022; 88: 1035-1042. DOI: https://doi.org/10.23736/S0375....
23.
Zhu X, Wang H, Yuan S, Li Y, Jia Y, Zhang Z, et al. Efficacy and safety of remimazolam in endoscopic sedation – a systematic review and meta-analysis. Front Med (Lausanne) 2021; 8: 655042. DOI: https://doi.org/10.3389/fmed.2....
24.
Ri HS, Jeon S, Yeo J, Jung H, Kang C, Choo H. Efficacy of remimazolam in preventing postoperative nausea and vomiting: a systematic review and meta-analysis. Sci Rep 2025; 15: 29236. DOI: https://doi.org/10.1038/s41598....
25.
Mao Y, Guo J, Yuan J, Zhao E, Yang J. Quality of recovery after general anesthesia with remimazolam in patients’ undergoing urologic surgery: a randomized controlled trial comparing remimazolam with propofol. Drug Des Devel Ther 2022; 16: 1199-1209. DOI: https://doi.org/10.2147/DDDT.S....
26.
Yang JJ, Lei L, Qiu D, Chen S, Xing LK, Zhao JW. Effect of remimazolam on postoperative delirium in older adult patients undergoing orthopedic surgery: a prospective randomized controlled clinical trial. Drug Des Devel Ther 2023; 17: 143-153. DOI: https://doi.org/10.2147/DDDT.S....
27.
Cai YH, Wang CY, Fang YB, Ma HY, Gao YQ, Wang Z. Preoperative anxiolytic and sedative effects of intranasal remimazolam and dexmedetomidine: a randomized controlled clinical study in children undergoing general surgeries. Drug Des Devel Ther 2024; 18: 1613-1625. DOI: https://doi.org/10.2147/DDDT.S....
28.
Kurup MT, Sarkar S, Verma R, Bhatia R, Khanna P, Maitra S. Comparative evaluation of intraoperative dexmedetomidine versus lidocaine for reducing postoperative cognitive decline in the elderly: a prospective randomized controlled trial. Anaesthesiol Intensive Ther 2023; 55: 349-357. DOI: https://doi.org/10.5114/ait.20....
29.
Lee S, Oh C, Jung J, Hong B, Jo Y, Lee S, et al. Retrospective comparison of the effects of remimazolam and dexmedetomidine on postoperative delirium in elderly patients undergoing orthopedic surgery of the lower extremities under spinal anesthesia. J Anesth 2024; 38: 771-779. DOI: https://doi.org/10.1007/s00540....
30.
Zhang H, Li H, Zhao S, Bao F. Remimazolam in general anesthesia: a comprehensive review of its applications and clinical efficacy. Drug Des Devel Ther 2024; 18: 3487-3498. DOI: https://doi.org/10.2147/DDDT.S....
31.
Rex DK, Bhandari R, Desta T, DeMicco MP, Schaeffer C, Etzkorn K, et al. A phase III study evaluating the efficacy and safety of remimazolam (CNS 7056) compared with placebo and midazolam in patients undergoing colonoscopy. Gastrointest Endosc 2018; 88: 427-437.e6. DOI: https://doi.org/10.1016/j.gie.....
32.
Brzózka VM, Piotrowski AJ. Prospective, randomised comparison of two intravenous sedation methods for magnetic resonance imaging in children. Anaesthesiol Intensive Ther 2023; 55: 81-86. DOI: https://doi.org/10.5114/ait.20....
33.
Abcejo AS, Teixeira MT. Remimazolam: patient safety considerations of a novel, practice-changing drug in perioperative medicine. APSF Newsletter 2023; 38: 80-83.
34.
Chen S, Wang J, Xu X, Huang Y, Xue S, Wu A, et al. The efficacy and safety of remimazolam tosylate versus propofol in patients undergoing colonoscopy: a multicentered, randomized, positive-controlled, phase III clinical trial. Am J Transl Res 2020; 12: 4594-4603.
35.
Chen SH, Yuan TM, Zhang J, Bai H, Tian M, Pan CX, et al. Remimazolam tosilate in upper gastrointestinal endoscopy: A multicenter, randomized, non-inferiority, phase III trial. J Gastroenterol Hepatol 2021; 36: 474-481. DOI: https://doi.org/10.1111/jgh.15....
36.
Zhang X, Li S, Liu J. Efficacy and safety of remimazolam besylate versus propofol during hysteroscopy: single-centre randomized controlled trial. BMC Anesthesiol 2021; 21: 156. DOI: https://doi.org/1186/s12871-02....
37.
Kim KM. Remimazolam: pharmacological characteristics and clinical applications in anesthesiology. Anesth Pain Med (Seoul) 2022; 17: 1-11. DOI: https://doi.org/10.17085/apm.2....
38.
Rex DK, Bhandari R, Lorch DG, Meyers M, Schippers F, Bernstein D. Safety and efficacy of remimazolam in high risk colonoscopy: a randomized trial. Dig Liver Dis 2021; 53: 94-101. DOI: https://doi.org/10.1016/j.dld.....
39.
Kim S-H, Cho JY, Kim M, Chung JM, Yang J, Seong C, et al. Safety and efficacy of remimazolam compared with midazolam during bronchoscopy: a single-center, randomized controlled study. Sci Rep 2023; 13: 20498. DOI: https://doi.org/10.1038/s41598....
40.
Huang H, Li H, Zhang X, Shi G, Xu M, Ru X, et al. Association of postoperative delirium with cognitive outcomes: a meta-analysis. J Clin Anesth 2021; 75: 110496. DOI: https://doi.org/10.1016/j.jcli....
41.
Mohanty S, Gillio A, Lindroth H, Ortiz D, Holler E, Azar J, et al. Major surgery and long term cognitive outcomes: the effect of postoperative delirium on dementia in the year following discharge. J Surg Res 2022; 270: 327-334. DOI: https://doi.org/10.1016/j.jss.....
42.
Meyer M, Götz J, Parik L, Renkawitz T, Grifka J, Maderbacher G, et al. Postoperative delirium is a risk factor for complications and poor outcome after total hip and knee arthroplasty. Acta Orthop 2021; 92: 695-700. DOI: https://doi.org/10.1080/174536....
43.
Kaneko S, Morimoto T, Ichinomiya T, Murata H, Yoshitomi O, Hara T. Effect of remimazolam on the incidence of delirium after transcatheter aortic valve implantation under general anesthesia: a retrospective exploratory study. J Anesth 2023; 37: 210-218. DOI: https://doi.org/10.1007/s00540....
44.
Girdler NM, Fairbrother KJ, Lyne JP, Neave N, Scholey A, Hargaden N, et al. A randomised crossover trial of post-operative cognitive and psychomotor recovery from benzodiazepine sedation: effects of reversal with flumazenil over a prolonged recovery period. Br Dent J 2002; 192: 335-339. DOI: https://doi.org/10.1038/sj.bdj....
45.
Kurup MT, Sarkar S, Verma R, Bhatia R, Khanna P, Maitra S, et al. Comparative evaluation of intraoperative dexmedetomidine versus lidocaine for reducing postoperative cognitive decline in the elderly: a prospective randomized controlled trial. Anaesthesiol Intensive Ther 2023; 55: 349-357. DOI: https://doi.org/10.5114/ait.20....
46.
Yang JJ, Lei L, Qiu D, Chen S, Xing LK, Zhao JW, et al. Effect of remimazolam on postoperative delirium in older adult patients undergoing orthopedic surgery: a prospective randomized controlled clinical trial. Drug Des Devel Ther 2023; 17: 143-153. DOI: https://doi.org/10.2147/DDDT.S....
47.
Pereira EM, Moraes VR, da Costa M, do Nascimento T, Slawka E, Galhardo Júnior C, et al. Remimazolam vs. propofol for general anaesthesia in elderly patients: a meta-analysis with trial sequential analysis. Eur J Anaesthesiol 2024; 41: 738-748. DOI: https://doi.org/10.1097/EJA.00....
48.
Chae D, Kim HC, Song Y, Choi YS, Han DW. Pharmacodynamic analysis of intravenous bolus remimazolam for loss of consciousness in patients undergoing general anaesthesia: a randomised, prospective, double-blind study. Br J Anaesth 2022; 129: 49-57. DOI: https://doi.org/10.1016/j.bja.....
49.
Kassai B, Rabilloud M, Dantony E, Grousson S, Revol O, Malik S, et al. Introduction of a paediatric anaesthesia comic information leaflet reduced preoperative anxiety in children. Br J Anaesth 2016; 117: 95-102. DOI: https://doi.org/10.1093/bja/ae....
50.
Verma RK, Paswan A, De A, Gupta S. Premedication with midazolam nasal spray: an alternative to oral midazolam in children. Anesth Pain Med 2012 Spring; 1: 248-251. DOI: https://doi.org/10.5812/aapm.4....
51.
Bd V, Goyal S, Sharma A, Kothari N, Kaloria N, Sethi P, et al. Comparison of intranasal dexmedetomidine-midazolam, dexmedetomidine-ketamine, and midazolam-ketamine for premedication in paediatric patients: a double-blinded randomized trial. Anaesthesiol Intensive Ther 2023; 55: 103-108. DOI: https://doi.org/10.5114/ait.20....
52.
Long X, Wen LX, Yang H, Zhu GH, Zhang QY, Jiang JJ, et al. ED95 of remimazolam in nasal administration for attenuating preoperative anxiety in children. Front Med (Lausanne) 2023; 10: 1253738. DOI: https://doi.org/10.3389/fmed.2....
53.
Ni MJ, Jin YT, Wu QL, Zhang N, Tian JH, Li J, et al. Effective dose of intranasal remimazolam for preoperative sedation in preschool children: a dose-finding study using Dixon’s up-and-down method. Front Pharmacol 2024; 15: 1372139. DOI: https://doi.org/10.3389/fphar.....
54.
Cai YH, Wang CY, Fang YB, Ma HY, Gao YQ, Wang Z, et al. Preoperative anxiolytic and sedative effects of intranasal remimazolam and dexmedetomidine: a randomized controlled clinical study in children undergoing general surgeries. Drug Des Devel Ther 2024; 18: 1613-1625. DOI: https://doi.org/10.2147/DDDT.S....
55.
Hirano T, Kimoto Y, Kuratani N, Cavanaugh D, Mason KP. Remimazolam for pediatric procedural sedation: results of an institutional pilot program. J Clin Med 2023; 12: 5937. DOI: https://doi.org/10.3390/jcm121....
56.
Kimoto Y, Hirano T, Kuratani N, Cavanaugh D, Mason KP. Remimazolam as an adjunct to general anesthesia in children: adverse events and outcomes in a large cohort of 418 cases. J Clin Med 2023; 12: 3930. DOI: https://doi.org/10.3390/jcm121....
57.
Yang X, Lin C, Chen S, Huang Y, Cheng Q, Yao Y. Remimazolam for the prevention of emergence delirium in children following tonsillectomy and adenoidectomy under sevoflurane anesthesia: a randomized controlled study. Drug Des Devel Ther 2022; 16: 3413-3420. DOI: https://doi.org/10.2147/DDDT.S....
58.
Liu K, Liu C, Ulualp SO. Prevalence of emergence delirium in children undergoing tonsillectomy and adenoidectomy. Anesthesiol Res Pract 2022; 2022: 1465999. DOI: https://doi.org/10.1155/2022/1....
59.
Houben A, Ghamari S, Fischer A, Neumann C, Baehner T, Ellerkmann RK. Pediatric emergence delirium is linked to increased early postoperative negative behavior within two weeks after adenoidectomy: an observational study. Braz J Anesthesiol 2024; 74: 744114. DOI: https://doi.org/10.1016/j.bjan....
60.
Simonini A, Vittori A, Cascella M, Calevo MG, Marinangeli F. The impact of emergence delirium on hospital length of stay for children who underwent tonsillectomy/adenotonsillectomy: an observational retrospective study. Braz J Anesthesiol 2023; 73: 171-176. DOI: https://doi.org/10.1016/j.bjan....
61.
Shimizu J, Tabata T, Tsujita Y, Yamane T, Yamamoto Y, Tsukamoto T, et al. Propofol infusion syndrome complicated with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes: a case report. Acute Med Surg 2020; 7: e473. DOI: https://doi.org/10.1002/ams2.4....
62.
Finsterer J, Frank M. Propofol is mitochondrion-toxic and may unmask a mitochondrial disorder. J Child Neurol 2016; 31: 1489-1494. DOI: https://doi.org/10.1177/088307....
63.
Yamadori Y, Yamagami Y, Matsumoto Y, Koizumi M, Nakamura A, Mizuta D, et al. General anesthesia with remimazolam for a pediatric patient with MELAS and recurrent epilepsy: a case report. JA Clin Rep 2022; 8: 75. DOI: https://doi.org/10.1186/s40981....
64.
Horikoshi Y, Kuratani N, Tateno K, Hoshijima H, Nakamura T, Mieda T, et al. Anesthetic management with remimazolam for a pediatric patient with Duchenne muscular dystrophy. Medicine 2021; 100: e28209. DOI: https://doi.org/10.1097/MD.000....
65.
Koyama Y, Nishikawa H, Murase Y, Morita K, Tsuzaki K. General anesthesia using remimazolam and remifentanil in combination with local anesthetics without neuromuscular blocking agents in a patient with myotonic dystrophy. Korean J Anesthesiol 2023; 76: 391-393. DOI: https://doi.org/10.4097/kja.23....
66.
Morimoto Y, Yoshimatsu A, Yoshimura M. Anesthetic management for a patient with myotonic dystrophy with remimazolam. JA Clin Rep 2021; 7: 10. DOI: https://doi.org/10.1186/s40981....
67.
Zhou XH, Zhang CC, Wang L, Jin SL. Remimazolam induced cognitive dysfunction in mice via glutamate excitotoxicity. Transl Neurosci 2022; 13: 104-115. DOI: https://doi.org/10.1515/tnsci-....
68.
Chen X, Zhang J, Yuan S, Huang H. Remimazolam besylate for the sedation of postoperative patients undergoing invasive mechanical ventilation in the ICU: a prospective dose‒response study. Sci Rep 2022; 12: 19022. DOI: https://doi.org/10.1038/s41598....
69.
Tang Y, Yang X, Shu H, Yu Y, Xu J, Pan S, et al. Remimazolam besylate for sedation of postoperative patients in intensive care units: a phase I, open label, dose-finding study. Chin Med J (Engl) 2022; 135: 2134-2136. DOI: https://doi.org/10.1097/CM9.00....
70.
Tang Y, Gao X, Xu J, Ren L, Qi H, Li R, et al. Remimazolam besylate versus propofol for deep sedation in critically ill patients: a randomized pilot study. Crit Care 2023; 27: 474. DOI: https://doi.org/10.1186/s13054....
71.
Kempenaers S, Hansen TG, Van de Velde M. Remimazolam and serious adverse events. Eur J Anaesthesiol 2023; 40: 841-453. DOI: https://doi.org/10.1097/EJA.00....
72.
Hanley D, Pozo M. Treatment of status epilepticus with midazolam in the critical care setting. Int J Clin Pract 2000; 54: 30-35. DOI: https://doi.org/10.1111/j.1742....
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