瑞马唑仑在临床中的应用与研究进展
Clinical Application and Research Progress of Remimazolam
DOI: 10.12677/ACM.2022.12101357, PDF,   
作者: 贺占芳：青海大学研究生院，青海 西宁；甘桂芬*：青海大学附属医院重症医学科，青海 西宁
关键词: 瑞马唑仑；苯二氮?类药物；镇静；临床；Remimazolam； Benzodiazepine； Sedation； Clinical
摘要: 瑞马唑仑是一种新型超短效苯二氮䓬类药物，作用于γ氨基丁酸(GABA)受体，独立器官代谢通过组织酯酶快速代谢为无活性的羧酸代谢物，起效快、恢复迅速，不依赖肝肾功能代谢，对血流动力学及呼吸影响较轻，长时间输注不容易发生蓄积，且可以被氟马西尼逆转。目前，瑞马唑仑在临床上主要应用于无痛诊疗的程序性镇静与全身麻醉的诱导和维持，对于重症监护病房(ICU)的重症患者，瑞马唑仑可能是ICU镇静药物的新选择，是一种非常有应用前景的镇静剂。本文就瑞马唑仑的临床应用和研究进展作一综述，为其临床用药提供参考。
Abstract: Remimazolam is a new type of ultra short acting benzodiazepine that acts on GABA receptors. It undergoes organ-independent metabolism by tissue esterases into an inactive carboxylic acid me-tabolite. It has a fast onset of action, rapid recovery, independent of liver and kidney function me-tabolism and less impact on hemodynamics and respiration. It is not easy to accumulate after long-term infusion, and its sedative effects can be reversed using flumazenil. At present, its main clinical uses include the induction and maintenance of general anesthesia and procedural sedation for endoscopic procedures. For critically ill patients in intensive care unit (ICU), remimazolam may be a new choice of sedative drugs in ICU, and it is a sedative with great application prospect. In this paper, the clinical application and research progress of remimazolam, providing reference for its clinical application.
文章引用：贺占芳, 甘桂芬. 瑞马唑仑在临床中的应用与研究进展[J]. 临床医学进展, 2022, 12(10): 9384-9391. https://doi.org/10.12677/ACM.2022.12101357

参考文献

[1] 中华医学会重症医学分会. 中国成人ICU镇痛和镇静治疗指南[J]. 中华危重病急救医学, 2018, 30(6): 497-514.
[2] Chanques, G., Jaber, S., Barbotte, E., et al. (2006) Impact of Systematic Evaluation of Pain and Agitation in an Intensive Care Unit. Critical Care Medicine, 34, 1691-1699. [Google Scholar] [CrossRef] 
[3] Tate, J.A., Devito Dabbs, A., Hoffman, L.A., et al. (2012) Anxiety and Agitation in Mechanically Ventilated Patients. Qualitative Health Research, 22, 157-173. [Google Scholar] [CrossRef] [PubMed]
[4] 中华医学会重症医学分会. 中国重症加强治疗病房患者镇痛和镇静治疗指导意见(2006) [J]. 中华外科杂志, 2006(17): 1158-1166.
[5] Devlin, J.W., Skrobik, Y., Gélinas, C., et al. (2018) Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immo-bility, and Sleep Disruption in Adult Patients in the ICU. Critical Care Medicine, 46, E825-E873. [Google Scholar] [CrossRef] 
[6] Mirrakhimov, A.E., Voore, P., Halytskyy, O., Khan, M. and Ali, A.M. (2015) Propofol Infusion Syndrome in Adults: A Clinical Update. Critical Care Research and Practice, 2015, Article ID: 260385. [Google Scholar] [CrossRef] [PubMed]
[7] Saari, T.I., Uusi-Oukari, M., Ahonen, J. and Olkkola, K.T. (2011) En-hancement of GABAergic Activity: Neuropharmacological Effects of Benzodiazepines and Therapeutic Use in Anesthe-siology. Pharmacological Reviews, 63, 243-267. [Google Scholar] [CrossRef] [PubMed]
[8] Kilpatrick, G.J., McIntyre, M.S., Cox, R.F., et al. (2007) CNS 7056: A Novel Ultrashort-Acting Benzodiazepine. Anesthesiology, 107, 60-66. [Google Scholar] [CrossRef] [PubMed]
[9] Goudra, B.G. and Singh, P.M. (2014) Remimazolam: The Future of Its Sedative Potential. Saudi Journal of Anaesthesia, 8, 388-391. [Google Scholar] [CrossRef] 
[10] Pambianco, D.J. and Cash, B.D. (2016) New Horizons for Seda-tion: the Ultrashort Acting Benzodiazepine Remimazolam. Techniques in Gastrointestinal Endoscopy, 18, 22-28. [Google Scholar] [CrossRef] 
[11] Chen, X., Sang, N., Song, K., et al. (2020) Psychomotor Recovery Following Remimazolam-Induced Sedation and the Effectiveness of Flumazenil as an Antidote. Clinical Therapeutics, 42, 614-624. [Google Scholar] [CrossRef] [PubMed]
[12] Jacob, T.C., Moss, S.J. and Jurd, R. (2008) GABA(A) Re-ceptor Trafficking and Its Role in the Dynamic Modulation of Neuronal Inhibition. Nature Reviews Neuroscience, 9, 331-343. [Google Scholar] [CrossRef] [PubMed]
[13] Freyer, N., Knöspel, F., Damm, G., et al. (2019) Metabolism of Remimazolam in Primary Human Hepatocytes during Continuous Long-Term Infusion in a 3-D Bioreactor System. Drug Design, Development and Therapy, 13, 1033-1047. [Google Scholar] [CrossRef] 
[14] Zhou, Y., Hu, P. and Jiang, J. (2017) Metabolite Characterization of a Novel Sedative Drug, Remimazolam in Human Plasma and Urine Using Ultra High-Performance Liquid Chromatog-raphy Coupled with Synapt High-Definition Mass Spectrometry. Journal of Pharmaceutical and Biomedical Analysis, 137, 78-83. [Google Scholar] [CrossRef] [PubMed]
[15] Antonik, L.J., Goldwater, D.R., Kilpatrick, G.J., et al. (2012) 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. Anesthesia & Analgesia, 115, 274-283. [Google Scholar] [CrossRef] 
[16] Sheng, X.Y., Liang, Y., Yang, X.Y., et al. (2020) Safety, Pharmacokinetic and Pharmacodynamic Properties of Single Ascending Dose and Continuous Infusion of Remimazolam Besylate in Healthy Chinese Volunteers. European Journal of Clinical Pharmacology, 76, 383-391. [Google Scholar] [CrossRef] [PubMed]
[17] Schüttler, J., Eisenried, A., Lerch, M., et al. (2020) Pharmacoki-netics and Pharmacodynamics of Remimazolam (CNS 7056) After Continuous Infusion in Healthy Male Volunteers: Part I. Pharmacokinetics and Clinical Pharmacodynamics. Anesthesiology, 132, 636-651. [Google Scholar] [CrossRef] 
[18] Worthington, M.T., Antonik, L.J., Goldwater, D.R., et al. (2013) A Phase Ib, Dose-Finding Study of Multiple Doses of Remimazolam (CNS 7056) in Volunteers Undergoing Colonoscopy. Anesthesia & Analgesia, 117, 1093-1100. [Google Scholar] [CrossRef] 
[19] Pambianco, D.J., Borkett, K.M., Riff, D.S., et al. (2016) A Phase IIb Study Comparing the Safety and Efficacy of Remimazolam and Midazolam in Patients Undergoing Colonos-copy. Gastrointestinal Endoscopy, 83, 984-992. [Google Scholar] [CrossRef] [PubMed]
[20] Rex, D.K., Bhandari, R., Desta, T., et al. (2018) A Phase III Study Evaluating the Efficacy and Safety of Remimazolam (CNS 7056) Compared with Placebo and Midazolam in Patients Undergoing Colonoscopy. Gastrointestinal Endoscopy, 88, 427-437.e6. [Google Scholar] [CrossRef] [PubMed]
[21] Chen, S., Wang, J., Xu, X., et al. (2020) The Efficacy and Safety of Remimazolam Tosylate versus Propofol in Patients Undergoing Colonoscopy: A Multicentered, Randomized, Posi-tive-Controlled, Phase III Clinical Trial. American Journal of Translational Research, 12, 4594-4603.
[22] Rex, D.K., Bhandari, R., Lorch, D.G., et al. (2021) Safety and Efficacy of Remimazolam in High Risk Colonoscopy: A Randomized Trial. Digestive and Liver Disease, 53, 94-101. [Google Scholar] [CrossRef] [PubMed]
[23] Borkett, K.M., Riff, D.S., Schwartz, H.I., et al. (2015) A Phase IIa, Randomized, Double-Blind Study of Remimazolam (CNS 7056) versus Midazolam for Sedation in Upper Gastrointestinal Endoscopy. Anesthesia & Analgesia, 120, 771-780. [Google Scholar] [CrossRef] 
[24] Chen, S.H., Yuan, T.M., Zhang, J., et al. (2021) Remima-zolam Tosilate in Upper Gastrointestinal Endoscopy: A Multicenter, Randomized, Non-Inferiority, Phase III Trial. Jour-nal of Gastroenterology and Hepatology, 36, 474-481. [Google Scholar] [CrossRef] [PubMed]
[25] Ichijima, R., Ikehara, H., Maeda, T., et al. (2022) The First Dose-Ranging Study of Remimazolam in Japanese Patients Undergoing Gastrointestinal Endoscopy: A Phase II Investigator-Initiated Clinical Trial. Digestive Endoscopy. (Preprint) [Google Scholar] [CrossRef] [PubMed]
[26] Pastis, N.J., Yarmus, L.B., Schippers, F., et al. (2019) Safety and Efficacy of Remimazolam Compared with Placebo and Midazolam for Moderate Sedation during Bronchoscopy. Chest, 155, 137-146. [Google Scholar] [CrossRef] [PubMed]
[27] 贾真, 任丽霞, 范叶铁, 谭志明. 甲苯磺酸瑞马唑仑用于纤维支气管镜检查中深度镇静的有效剂量观察[J]. 中华医学杂志, 2021, 101(11): 813-816.
[28] Zhang, X., Li, S. and Liu, J. (2021) Efficacy and Safety of Remimazolam Besylate versus Propofol during Hysteroscopy: Single-Centre Ran-domized Controlled Trial [Published Correction Appears in BMC Anesthesiol. 2021 Jun 18; 21, 173]. BMC Anesthesi-ology, 21, Article No. 156. [Google Scholar] [CrossRef] [PubMed]
[29] Zhang, S., Wang, J., Ran, R., Peng, Y. and Xiao, Y. (2022) Efficacy and Safety of Remimazolam Tosylate in Hysteroscopy: A Randomized, Single-Blind, Parallel Controlled Trial. Journal of Clinical Pharmacy and Therapeutics, 47, 55-60. [Google Scholar] [CrossRef] [PubMed]
[30] Doi, M., Morita, K., Takeda, J., Sakamoto, A., Yamakage, M. and Suzuki, T. (2020) Efficacy and Safety of Remimazolam versus Propofol for General Anesthesia: A Multicenter, Single-Blind, Randomized, Parallel-Group, Phase IIb/III Trial. Journal of Anesthesia, 34, 543-553. [Google Scholar] [CrossRef] [PubMed]
[31] Dai, G., Pei, L., Duan, F., et al. (2021) Safety and Efficacy of Remimazolam Compared with Propofol in Induction of General Anesthesia. Minerva Anestesiologica, 87, 1073-1079.
[32] Doi, M., Hirata, N., Suzuki, T., Morisaki, H., Morimatsu, H. and Sakamoto, A. (2020) Safety and Ef-ficacy of Remimazolam in Induction and Maintenance of General Anesthesia in High-Risk Surgical Patients (ASA Class III): Results of a Multicenter, Randomized, Double-Blind, Parallel-Group Comparative Trial. Journal of Anesthesia, 34, 491-501. [Google Scholar] [CrossRef] [PubMed]
[33] Sato, T., Kato, Y., Yamamoto, M. and Nishiwaki, K. (2020) Novel Anesthetic Agent Remimazolam as an Alternative for the Asleep-Awake-Asleep Technique of Awake Craniotomy. JA Clinical Reports, 6, Article No. 92. [Google Scholar] [CrossRef] [PubMed]
[34] Tachibana, S., Hayamizu, K. and Yamakage, M. (2021) Remi-mazolam Use for Awake Craniotomy. JA Clinical Reports, 7, Article No. 25. [Google Scholar] [CrossRef] [PubMed]
[35] Kondo, T., Toyota, Y., Narasaki, S., et al. (2020) Intraoperative Responses of Motor Evoked Potentials To the Novel Intravenous Anesthetic Remimazolam during Spine Surgery: A Report of Two Cases. JA Clinical Reports, 6, Article No. 97. [Google Scholar] [CrossRef] [PubMed]
[36] Saito, K., Ohno, S., Maeda, M., Hirata, N. and Yamakage, M. (2021) Remimazolam Anesthesia for Cardiac Surgery with Cardiopulmonary Bypass: A Case Report. JA Clinical Re-ports, 7, Article No. 21. [Google Scholar] [CrossRef] [PubMed]
[37] Fukuda, M., Tachibana, S., Nishihara, N. and Yamakage, M. (2021) Remimazolam for a Patient with Myotonic Dystrophy Type 1 Who Underwent Endoscopic Retrograde Cholangi-opancreatography Under General Anesthesia: A Case Report. JA Clinical Reports, 7, Article No. 17. [Google Scholar] [CrossRef] [PubMed]
[38] Suzuki, Y., Doi, M. and Nakajima, Y. (2021) General Anesthe-sia with Remimazolam in a Patient with Mitochondrial Encephalomyopathy: A Case Report. JA Clinical Reports, 7, Arti-cle No. 51. [Google Scholar] [CrossRef] [PubMed]
[39] Furuta, M., Ito, H. and Yamazaki, M. (2021) Anaesthetic Man-agement Using Remimazolam in a Patient with Severe Aortic Stenosis: A Case Report. BMC Anesthesiology, 21, Article No. 202. [Google Scholar] [CrossRef] [PubMed]
[40] Nakayama, J., Ogihara, T., Yajima, R., Innami, Y. and Ouchi, T. (2021) Anesthetic Management of Super-Elderly Patients with Remimazolam: A Report of Two Cases. JA Clinical Re-ports, 7, Article No. 71. [Google Scholar] [CrossRef] [PubMed]
[41] Arashiro, A., Shinzato, H., Kamizato, K. and Kakinohana, M. (2021) Spinal Fusion with Motor Evoked Potential Monitoring Using Remimazolam in Alström Syndrome: A Case Re-port. Medicine, 100, e27990. [Google Scholar] [CrossRef] 
[42] 叶冲冲, 谢永鹏, 骆继业, 陈晓兵, 王静, 陆思烨, 王言理. 不同剂量瑞马唑仑在ICU机械通气患者中的镇静效果及对血流动力学的影响[J]. 中国医药导报, 2021, 18(22): 121-124.
[43] Kleiman, R.B., Darpo, B., Thorn, M., Stoehr, T. and Schippers, F. (2020) Potential Strategy for Assessing QT/QTc Interval for Drugs That Produce Rapid Changes in Heart Rate: Electrocardiographic Assessment of the Effects of Intravenous Remimazolam On Cardiac Repolarization. British Journal of Clinical Pharmacology, 86, 1600-1609. [Google Scholar] [CrossRef] [PubMed]
[44] Schippers, F., Pesic, M., Saunders, R., et al. (2020) Randomized Crossover Trial to Compare Abuse Liability of Intravenous Remimazolam versus Intravenous Midazolam and Placebo in Recrea-tional Central Nervous System Depressant Users. The Journal of Clinical Pharmacology, 60, 1189-1197. [Google Scholar] [CrossRef] [PubMed]

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