Présenté par Charles LELANDAIS sous la direction du Dr Nicolas COURTIN explorant les nouveaux hypnotiques en anesthésie.
Présenté en mai 2025.
le résumé sous forme pdf :
Nouveaux-hypotiques-topo-05_2025La présentation au téléchargement :
Références :
[1] Egan TD. The story of propofol: an interview with John (Iain) B. Glen. Br J Anaesth 2024;132:196. https://doi.org/10.1016/j.bja.2023.09.033.
[2] Sahinovic MM, Struys MMRF, Absalom AR. Clinical Pharmacokinetics and Pharmacodynamics of Propofol. Clin Pharmacokinet 2018;57:1539–58. https://doi.org/10.1007/s40262-018-0672-3.
[3] Qin L, Ren L, Wan S, Liu G, Luo X, Liu Z, et al. Design, Synthesis, and Evaluation of Novel 2,6- Disubstituted Phenol Derivatives as General Anesthetics. J Med Chem 2017;60:3606–17.
https://doi.org/10.1021/acs.jmedchem.7b00254.
[4] Lu M, Liu J, Wu X, Zhang Z. Ciprofol: A Novel Alternative to Propofol in Clinical Intravenous Anesthesia? Biomed Res Int 2023;2023:7443226. https://doi.org/10.1155/2023/7443226.
[5] Liao J, Li M, Huang C, Yu Y, Chen Y, Gan J, et al. Pharmacodynamics and Pharmacokinetics of HSK3486, a Novel 2,6-Disubstituted Phenol Derivative as a General Anesthetic. Front Pharmacol
2022;13:830791. https://doi.org/10.3389/fphar.2022.830791.
[6] Teng Y, Ou M-C, Wang X, Zhang W-S, Liu X, Liang Y, et al. Pharmacokinetic and pharmacodynamic properties of ciprofol emulsion in Chinese subjects: a single center, open-label,
single-arm dose-escalation phase 1 study. Am J Transl Res 2021;13:13791–802.
[7] Hu C, Ou X, Teng Y, Shu S, Wang Y, Zhu X, et al. Sedation Effects Produced by a Ciprofol Initial Infusion or Bolus Dose Followed by Continuous Maintenance Infusion in Healthy Subjects: A Phase 1
Trial. Adv Ther 2021;38:5484–500. https://doi.org/10.1007/s12325-021-01914-4.
[8] Ludbrook G, Li F, Sleigh J, Liang Y. Assessments of Onset and Duration of Drug Effects and Pharmacokinetics by Dose Level of HSK3486, a New Sedative-Hypnotic Agent, in Healthy
Female/Male Subjects: A Phase I Multiarm Randomized Controlled Clinical Trial [Retracted]. Anesthesia & Analgesia 2022:10.1213/ANE.0000000000005343. https://doi.org/10.1213/ANE.0000000000005343.
[9] Teng Y, Ou M, Wang X, Zhang W, Liu X, Liang Y, et al. Efficacy and safety of ciprofol for the sedation/anesthesia in patients undergoing colonoscopy: Phase IIa and IIb multi-center clinical trials.
Eur J Pharm Sci 2021;164:105904. https://doi.org/10.1016/j.ejps.2021.105904.
[10] Zeng Y, Wang D-X, Lin Z-M, Liu J, Wei X-C, Deng J, et al. Efficacy and safety of HSK3486 for the induction and maintenance of general anesthesia in elective surgical patients: a multicenter,
randomized, open-label, propofol-controlled phase 2 clinical trial. Eur Rev Med Pharmacol Sci 2022;26:1114–24. https://doi.org/10.26355/eurrev_202202_28101.
[11] Chen B, Yin X, Jiang L, Liu J, Shi Y, Yuan B. The efficacy and safety of ciprofol use for the induction of general anesthesia in patients undergoing gynecological surgery: a prospective randomized controlled study. BMC Anesthesiology 2022;22:245. https://doi.org/10.1186/s12871- 022-01782-7.
[12] Wang X, Wang X, Liu J, Zuo Y-X, Zhu Q-M, Wei X-C, et al. Effects of ciprofol for the induction of general anesthesia in patients scheduled for elective surgery compared to propofol: a phase 3,
multicenter, randomized, double-blind, comparative study. Eur Rev Med Pharmacol Sci 2022;26:1607–17. https://doi.org/10.26355/eurrev_202203_28228.
[13] Liang P, Dai M, Wang X, Wang D, Yang M, Lin X, et al. Efficacy and safety of ciprofol vs. propofol for the induction and maintenance of general anaesthesia: A multicentre, single-blind,
randomised, parallel-group, phase 3 clinical trial. Eur J Anaesthesiol 2023;40:399–406. https://doi.org/10.1097/EJA.0000000000001799.
[14] Gan TJ, Bertoch T, Habib AS, Yan P, Zhou R, Lai Y-L, et al. Comparison of the Efficacy of HSK3486 and Propofol for Induction of General Anesthesia in Adults: A Multicenter, Randomized,
Double-blind, Controlled, Phase 3 Noninferiority Trial. Anesthesiology 2024;140:690–700. https://doi.org/10.1097/ALN.0000000000004886.
[15] Li J, Wang X, Liu J, Wang X, Li X, Wang Y, et al. Comparison of ciprofol (HSK3486) versus propofol for the induction of deep sedation during gastroscopy and colonoscopy procedures: A multi-
centre, non-inferiority, randomized, controlled phase 3 clinical trial. Basic Clin Pharmacol Toxicol 2022;131:138–48. https://doi.org/10.1111/bcpt.13761.
[16] Gao S-H, Tang Q-Q, Wang C-M, Guan Z-Y, Wang L-L, Zhang J, et al. The efficacy and safety of ciprofol and propofol in patients undergoing colonoscopy: A double-blind, randomized, controlled
trial. J Clin Anesth 2024;95:111474. https://doi.org/10.1016/j.jclinane.2024.111474.
[17] Duan G, Lan H, Shan W, Wu Y, Xu Q, Dong X, et al. Clinical effect of different doses of ciprofol for induction of general anesthesia in elderly patients: A randomized, controlled trial. Pharmacol Res
Perspect 2023;11:e01066. https://doi.org/10.1002/prp2.1066.
[18] Liang Z, Liu J, Chen S, Zhao X, Chen G, Xie Y, et al. Postoperative quality of recovery comparison between ciprofol and propofol in total intravenous anesthesia for elderly patients
undergoing laparoscopic major abdominal surgery: A randomized, controlled, double-blind, noninferiority trial. J Clin Anesth 2024;99:111660. https://doi.org/10.1016/j.jclinane.2024.111660.
[19] Liu Z, Jin Y, Wang L, Huang Z. The Effect of Ciprofol on Postoperative Delirium in Elderly Patients Undergoing Thoracoscopic Surgery for Lung Cancer: A Prospective, Randomized, Controlled
Trial. Drug Des Devel Ther 2024;18:325–39. https://doi.org/10.2147/DDDT.S441950.
[20] Hung K-C, Chen J-Y, Wu S-C, Huang P-Y, Wu J-Y, Liu T-H, et al. A systematic review and metaanalysis comparing the efficacy and safety of ciprofol (HSK3486) versus propofol for anesthetic
induction and non-ICU sedation. Front Pharmacol 2023;14:1225288. https://doi.org/10.3389/fphar.2023.1225288.
[21] Currò JM, Santonocito C, Merola F, Messina S, Sanfilippo M, Brancati S, et al. Ciprofol as compared to propofol for sedation and general anesthesia: a systematic review of randomized
controlled trials. J Anesth Analg Crit Care 2024;4:24. https://doi.org/10.1186/s44158-024-00159-1.
[22] Liu Y, Peng Z, Liu S, Yu X, Zhu D, Zhang L, et al. Efficacy and Safety of Ciprofol Sedation in ICU Patients Undergoing Mechanical Ventilation: A Multicenter, Single-Blind, Randomized, Noninferiority
Trial. Crit Care Med 2023;51:1318–27. https://doi.org/10.1097/CCM.0000000000005920.
[23] Haisco Pharmaceutical Group Co., Ltd. A Multi-Center, Randomized, Open-Label, PropofolControlled Exploratory Clinical Study Evaluating Sedation of Intravenous Administration of HSK3486
Injectable Emulsion in ICU Patients Undergoing Long-Term Mechanical Ventilation. clinicaltrials.gov; 2022.
[24] Yu L, Liu X, Zhao X, Shan X, Bischof E, Lu H-H. Ciprofol versus propofol for anesthesia induction in cardiac surgery: a randomized double-blind controlled clinical trial. BMC Anesthesiol 2024;24:412. https://doi.org/10.1186/s12871-024-02795-0.
[25] Lan L, Liao J, Qin L, Wang X, Qin T, Chen Y, et al. The effects of ciprofol on haemodynamics under general anaesthesia during thoracoscopic surgery: a randomised, double-blind, controlled trial.
BMC Anesthesiol 2025;25:168. https://doi.org/10.1186/s12871-025-03054-6.
[26] Qi J, Zhang L, Meng F, Yang X, Chen B, Gao L, et al. Comparative effects of ciprofol and propofol on perioperative outcomes: a systematic review and meta-analysis of randomized controlled trials. Braz J Anesthesiol 2025;75:844578. https://doi.org/10.1016/j.bjane.2024.844578.
[27] Chen W, Xu Y, Zeng Y, Xing G. A meta-analysis and systematic review based on perioperative management of elderly patients: is ciprofol an alternative to propofol? Eur J Clin Pharmacol 2025;81:111–21. https://doi.org/10.1007/s00228-024-03782-7.
[28] Ni T, Zhou X, Wu S, Lv T, Hu Y, Gao Q, et al. Hemodynamic Impact of Cipepofol vs Propofol During Anesthesia Induction in Patients With Severe Aortic Stenosis: A Randomized Clinical Trial. JAMA Surg 2025:e251299. https://doi.org/10.1001/jamasurg.2025.1299.
[29] Lu Y-F, Wu J-M, Lan H-Y, Xu Q-M, Shi S-Q, Duan G-C. Efficacy and Safety of General Anesthesia Induction with Ciprofol in Hip Fracture Surgery of Elderly Patients: A Randomized Controlled Trial. Drug Des Devel Ther 2024;18:3951–8. https://doi.org/10.2147/DDDT.S475176.
[30] Tan CH, Onsiong MK. Pain on injection of propofol. Anaesthesia 1998;53:468–76. https://doi.org/10.1046/j.1365-2044.1998.00405.x.
[31] Jalota L, Kalira V, George E, Shi Y-Y, Hornuss C, Radke O, et al. Prevention of pain on injection of propofol: systematic review and meta-analysis. BMJ 2011;342:d1110. https://doi.org/10.1136/bmj.d1110.
[32] Euasobhon P, Dej-Arkom S, Siriussawakul A, Muangman S, Sriraj W, Pattanittum P, et al. Lidocaine for reducing propofol-induced pain on induction of anaesthesia in adults. Cochrane Database Syst Rev 2016;2:CD007874. https://doi.org/10.1002/14651858.CD007874.pub2.
[33] Wang M, Wang Q, Yu YY, Wang WS. An effective dose of ketamine for eliminating pain during injection of propofol: a dose response study. Ann Fr Anesth Reanim 2013;32:e103-106. https://doi.org/10.1016/j.annfar.2013.06.013.
[34] Mion G, Himmelseher S. Esketamine: Less Drowsiness, More Analgesia. Anesth Analg 2024;139:78–91. https://doi.org/10.1213/ANE.0000000000006851.
[35] Mathisen LC, Skjelbred P, Skoglund LA, Øye I. Effect of ketamine, an NMDA receptor inhibitor, in acute and chronic orofacial pain. Pain 1995;61:215–20. https://doi.org/10.1016/0304- 3959(94)00170-J.
[36] Arendt-Nielsen L, Nielsen J, Petersen-Felix S, Schnider TW, Zbinden AM. Effect of racemic mixture and the (S+)-isomer of ketamine on temporal and spatial summation of pain. Br J Anaesth 1996;77:625–31. https://doi.org/10.1093/bja/77.5.625.
[37] Zanos P, Moaddel R, Morris PJ, Riggs LM, Highland JN, Georgiou P, et al. Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms. Pharmacol Rev 2018;70:621–60. https://doi.org/10.1124/pr.117.015198.
[38] Kokkinou M, Ashok AH, Howes OD. The effects of ketamine on dopaminergic function: metaanalysis and review of the implications for neuropsychiatric disorders. Mol Psychiatry 2018;23:59–69.
https://doi.org/10.1038/mp.2017.190.
[39] Negre I. Kétamine : quoi de neuf en France ? EM-Consulte 2025. https://www.emconsulte.com/article/1728790/ketamine-quoi-de-neuf-en-france- (accessed June 30, 2025).
[40] White PF, Ham J, Way WL, Trevor AJ. Pharmacology of ketamine isomers in surgical patients. Anesthesiology 1980;52:231–9. https://doi.org/10.1097/00000542-198003000-00008.
[41] Pfenninger EG, Durieux ME, Himmelseher S. Cognitive impairment after small-dose ketamine isomers in comparison to equianalgesic racemic ketamine in human volunteers. Anesthesiology 2002;96:357–66. https://doi.org/10.1097/00000542-200202000-00022.
[42] Liu T, Zhang X, Li A, Liu T, Yang X, Zhang H, et al. Effects of intra-operative administration of subanesthetic s-ketamine on emergence from sevoflurane anesthesia: a randomized double-blind
placebo-controlled study. BMC Anesthesiol 2023;23:221. https://doi.org/10.1186/s12871-023- 02170-5.
[43] Wang J, Huang J, Yang S, Cui C, Ye L, Wang S-Y, et al. Pharmacokinetics and Safety of Esketamine in Chinese Patients Undergoing Painless Gastroscopy in Comparison with Ketamine: A
Randomized, Open-Label Clinical Study. Drug Des Devel Ther 2019;13:4135–44. https://doi.org/10.2147/DDDT.S224553.
[44] Kamp J, Jonkman K, van Velzen M, Aarts L, Niesters M, Dahan A, et al. Pharmacokinetics of ketamine and its major metabolites norketamine, hydroxynorketamine, and dehydronorketamine: a
model-based analysis. Br J Anaesth 2020;125:750–61. https://doi.org/10.1016/j.bja.2020.06.067.
[45] Ihmsen H, Geisslinger G, Schüttler J. Stereoselective pharmacokinetics of ketamine: R(-)- ketamine inhibits the elimination of S(+)-ketamine. Clin Pharmacol Ther 2001;70:431–8.
https://doi.org/10.1067/mcp.2001.119722.
[46] Trimmel H, Helbok R, Staudinger T, Jaksch W, Messerer B, Schöchl H, et al. S(+)-ketamine : Current trends in emergency and intensive care medicine. Wien Klin Wochenschr 2018;130:356–66.
https://doi.org/10.1007/s00508-017-1299-3.
[47] Kamp J, van Velzen M, Aarts L, Niesters M, Dahan A, Olofsen E. Stereoselective ketamine effect on cardiac output: a population pharmacokinetic/pharmacodynamic modelling study in
healthy volunteers. Br J Anaesth 2021;127:23–31. https://doi.org/10.1016/j.bja.2021.02.034.
[48] Kunst G, Martin E, Graf BM, Hagl S, Vahl CF. Actions of ketamine and its isomers on contractility and calcium transients in human myocardium. Anesthesiology 1999;90:1363–71. https://doi.org/10.1097/00000542-199905000-00021.
[49] Zhou N, Liang X, Gong J, Li H, Liu W, Zhou S, et al. S-ketamine used during anesthesia induction increases the perfusion index and mean arterial pressure after induction: A randomized,
double-blind, placebo-controlled trial. Eur J Pharm Sci 2022;179:106312. https://doi.org/10.1016/j.ejps.2022.106312.
[50] Song N, Yang Y, Zheng Z, Shi W-C, Tan A-P, Shan X-S, et al. Effect of Esketamine Added to Propofol Sedation on Desaturation and Hypotension in Bidirectional Endoscopy: A Randomized
Clinical Trial. JAMA Netw Open 2023;6:e2347886. https://doi.org/10.1001/jamanetworkopen.2023.47886.
[51] Lian X, Lin Y, Luo T, Jing Y, Yuan H, Guo Y. Efficacy and safety of esketamine for sedation among patients undergoing gastrointestinal endoscopy: a systematic review and meta-analysis. BMC
Anesthesiol 2023;23:204. https://doi.org/10.1186/s12871-023-02167-0.
[52] Zhu T, Zhao X, Sun M, An Y, Kong W, Ji F, et al. Opioid-reduced anesthesia based on esketamine in gynecological day surgery: a randomized double-blind controlled study. BMC
Anesthesiol 2022;22:354. https://doi.org/10.1186/s12871-022-01889-x.
[53] Hou N-N, Zhang M-Y, Zhang Y-W, Wu H-J, Luo H, Yang H. Safety and efficacy of low-dose esketamine weakly opioidized anesthesia in elderly patients with lumbar spinal stenosis undergoing
surgery: a prospective, double-blind randomized controlled trial. BMC Anesthesiol 2025;25:57. https://doi.org/10.1186/s12871-025-02908-3.
[54] Yang H, Zhao Q, Chen H-Y, Liu W, Ding T, Yang B, et al. The median effective concentration of propofol with different doses of esketamine during gastrointestinal endoscopy in elderly patients: A
randomized controlled trial. Br J Clin Pharmacol 2022;88:1279–87. https://doi.org/10.1111/bcp.15072.
[55] Zheng L, Wang Y, Ma Q, Liang W, Zhang X, Ren Z, et al. Efficacy and Safety of a Subanesthetic Dose of Esketamine Combined with Propofol in Patients with Obesity Undergoing Painless
Gastroscopy: A Prospective, Double-Blind, Randomized Controlled Trial. Drug Des Devel Ther 2023;17:1347–56. https://doi.org/10.2147/DDDT.S408076.
[56] Yang T, Mudabbar MS, Xu M, Xiang Q, Liu B, Fu Q. The effects of esketamine on blood pressure and hypotension incidence during induction of bariatric surgery: A randomized controlled
trial. Medicine (Baltimore) 2023;102:e36754. https://doi.org/10.1097/MD.0000000000036754.
[57] Liu C, Zhang T, Cao L, Lin W. Comparison of esketamine versus dexmedetomidine for attenuation of cardiovascular stress response to double-lumen tracheal tube intubation: a
randomized controlled trial. Front Cardiovasc Med 2023;10:1289841. https://doi.org/10.3389/fcvm.2023.1289841.
[58] Zickmann B, Kling D, Quis S. [S-(+)-ketamine versus ketamine racemic mixture: hemodynamic studies]. Anasthesiol Intensivmed Notfallmed Schmerzther 2000;35:333–9. https://doi.org/10.1055/s-2000-322.
[59] Gorlin AW, Rosenfeld DM, Ramakrishna H. Intravenous sub-anesthetic ketamine for perioperative analgesia. J Anaesthesiol Clin Pharmacol 2016;32:160–7. https://doi.org/10.4103/0970-9185.182085.
[60] Jonkman K, van Rijnsoever E, Olofsen E, Aarts L, Sarton E, van Velzen M, et al. Esketamine counters opioid-induced respiratory depression. Br J Anaesth 2018;120:1117–27. https://doi.org/10.1016/j.bja.2018.02.021.
[61] Sheikh S, Hendry P. The Expanding Role of Ketamine in the Emergency Department. Drugs 2018;78:727–35. https://doi.org/10.1007/s40265-018-0904-8.
[62] Chen H, Ding X, Xiang G, Xu L, Liu Q, Fu Q, et al. Analysis of the efficacy of subclinical doses of esketamine in combination with propofol in non-intubated general anesthesia procedures – a systematic review and meta-analysis. BMC Anesthesiol 2023;23:245. https://doi.org/10.1186/s12871-023-02135-8.
[63] Hirota K, Sato T, Rabito SF, Zsigmond EK, Matsuki A. Relaxant effect of ketamine and its isomers on histamine-induced contraction of tracheal smooth muscle. Br J Anaesth 1996;76:266–70. https://doi.org/10.1093/bja/76.2.266.
[64] Pabelick CM, Rehder K, Jones KA, Shumway R, Lindahl SG, Warner DO. Stereospecific effects of ketamine enantiomers on canine tracheal smooth muscle. Br J Pharmacol 1997;121:1378–82.
https://doi.org/10.1038/sj.bjp.0701280.
[65] Epperson J, Athar ZM, Arshad M, Chen EY. Ketamine as an Adjunct Therapy in Acute Severe Asthma: An In-Depth Review of Efficacy and Clinical Implications. Cureus 2024;16:e62483. https://doi.org/10.7759/cureus.62483.
[66] La Via L, Sanfilippo F, Cuttone G, Dezio V, Falcone M, Brancati S, et al. Use of ketamine in patients with refractory severe asthma exacerbations: systematic review of prospective studies. Eur J
Clin Pharmacol 2022;78:1613–22. https://doi.org/10.1007/s00228-022-03374-3.
[67] Binsaeedu AS, Prabakar D, Ashkar M, Joseph C, Alsabri M. Evaluating the Safety and Efficacy of Ketamine as a Bronchodilator in Pediatric Patients With Acute Asthma Exacerbation: A Review.
Cureus 2023;15:e40789. https://doi.org/10.7759/cureus.40789.
[68] Le Conte P, Terzi N, Mortamet G. Prise en charge de l’exacerbation sévère d’asthme. Recommandations de la SFMU / Société Française de Médecine d’Urgence – SFMU 2018.
https://www.sfmu.org/fr/publications/recommandations-de-la-sfmu/prise-en-charge-de-lexacerbation-severe-d-asthme-recommandations-formalisees-d-experts/con_id/466 (accessed May 26, 2025).
[69] Dahan A, Olofsen E, Sigtermans M, Noppers I, Niesters M, Aarts L, et al. Population pharmacokinetic-pharmacodynamic modeling of ketamine-induced pain relief of chronic pain. Eur J Pain 2011;15:258–67. https://doi.org/10.1016/j.ejpain.2010.06.016.
[70] Miziara LE de PG, Simoni RF, Esteves LO, Cangiani LH, Grillo-Filho GFR, Paula AGLE. Efficacy of Continuous S(+)-Ketamine Infusion for Postoperative Pain Control: A Randomized Placebo-Controlled
Trial. Anesthesiol Res Pract 2016;2016:6918327. https://doi.org/10.1155/2016/6918327.
[71] Yuan J, Chen S, Xie Y, Wang Z, Xing F, Mao Y, et al. Intraoperative Intravenous Infusion of Esmketamine Has Opioid-Sparing Effect and Improves the Quality of Recovery in Patients Undergoing Thoracic Surgery: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Pain Physician 2022;25:E1389–97.
[72] Xie M, Liang Y, Deng Y, Li T. Effect of S-ketamine on Postoperative Pain in Adults PostAbdominal Surgery: A Systematic Review and Meta-analysis. Pain Physician 2023;26:327–35.
[73] Zhang T, Yue Z, Yu L, Li S, Xie Y, Wei J, et al. S-ketamine promotes postoperative recovery of gastrointestinal function and reduces postoperative pain in gynecological abdominal surgery patients: a randomized controlled trial. BMC Surg 2023;23:74. https://doi.org/10.1186/s12893-023- 01973-0.
[74] Hou N-N, Zhang M-Y, Zhang Y-W, Wu H-J, Luo H, Yang H. Safety and efficacy of low-dose esketamine weakly opioidized anesthesia in elderly patients with lumbar spinal stenosis undergoing surgery: a prospective, double-blind randomized controlled trial. BMC Anesthesiol 2025;25:57. https://doi.org/10.1186/s12871-025-02908-3.
[75] Zhang Q, Wang X, Wang Z, Sun H. Low-dose esketamine improves acute postoperative pain in patients undergoing thoracoscopic surgery. APS 2024;2:5. https://doi.org/10.1007/s44254-023-
00039-x.
[76] Wang X, Lin C, Lan L, Liu J. Perioperative intravenous S-ketamine for acute postoperative pain in adults: A systematic review and meta-analysis. J Clin Anesth 2021;68:110071. https://doi.org/10.1016/j.jclinane.2020.110071.
[77] Brinck ECV, Maisniemi K, Kankare J, Tielinen L, Tarkkila P, Kontinen VK. Analgesic Effect of Intraoperative Intravenous S-Ketamine in Opioid-Naïve Patients After Major Lumbar Fusion Surgery Is Temporary and Not Dose-Dependent: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Anesth Analg 2021;132:69–79. https://doi.org/10.1213/ANE.0000000000004729.
[78] Kozek-Langenecker SA, Marhofer P, Sator-Katzenschlager SM, Dieckmann K. S(+)-ketamine for long-term sedation in a child with retinoblastoma undergoing interstitial brachytherapy. Paediatr
Anaesth 2005;15:248–50. https://doi.org/10.1111/j.1460-9592.2005.01423.x.
[79] Tao J-C, Huang B, Luo G, Zhang Z-Q, Xin B-Y, Yao M. Trigeminal extracranial thermocoagulation along with patient-controlled analgesia with esketamine for refractory postherpetic neuralgia after herpes zoster ophthalmicus: A case report. World J Clin Cases 2022;10:4220–5. https://doi.org/10.12998/wjcc.v10.i13.4220.
[80] Zhao J, Wang Y, Wang D. The Effect of Ketamine Infusion in the Treatment of Complex Regional Pain Syndrome: a Systemic Review and Meta-analysis. Curr Pain Headache Rep 2018;22:12. https://doi.org/10.1007/s11916-018-0664-x.
[81] Mangnus TJP, Dirckx M, Bharwani KD, de Vos CC, Frankema SPG, Stronks DL, et al. Effect of intravenous low-dose S-ketamine on pain in patients with Complex Regional Pain Syndrome: A
retrospective cohort study. Pain Pract 2021;21:890–7. https://doi.org/10.1111/papr.13056.
[82] Juan S, Lu X, Zhou J, Wu G, Yuan Y. Efficacy of esketamine for chronic post-thoracotomy pain: protocol for a systematic review and meta-analysis. BMJ Open 2024;14:e092131. https://doi.org/10.1136/bmjopen-2024-092131.
[83] Noppers IM, Niesters M, Aarts LPHJ, Bauer MCR, Drewes AM, Dahan A, et al. Drug-induced liver injury following a repeated course of ketamine treatment for chronic pain in CRPS type 1 patients: a report of 3 cases. Pain 2011;152:2173–8. https://doi.org/10.1016/j.pain.2011.03.026.
[84] Information de sécurité – Kétamine : une utilisation prolongée. ANSM n.d. https://ansm.sante.fr/informations-de-securite/ketamine-une-utilisation-prolongee-entraine-desatteintes-graves-hepatiques-et-uronephrologiques (accessed May 20, 2025).
[85] Nielsen RV, Fomsgaard JS, Siegel H, Martusevicius R, Nikolajsen L, Dahl JB, et al. Intraoperative ketamine reduces immediate postoperative opioid consumption after spinal fusion
surgery in chronic pain patients with opioid dependency: a randomized, blinded trial. Pain 2017;158:463–70. https://doi.org/10.1097/j.pain.0000000000000782.
[86] Nielsen RV, Fomsgaard JS, Nikolajsen L, Dahl JB, Mathiesen O. Intraoperative S-ketamine for the reduction of opioid consumption and pain one year after spine surgery: A randomized clinical
trial of opioid-dependent patients. Eur J Pain 2019;23:455–60. https://doi.org/10.1002/ejp.1317.
[87] Tan M, Zhang C, Zeng W, Chen M, Huang Z, Huang D. Determining the effective dose of esketamine for mitigating pain during propofol injection by Dixon’s up-and-down method: a doubleblind, prospective clinical study of drug dose response. BMC Anesthesiol 2022;22:368. https://doi.org/10.1186/s12871-022-01914-z.
[88] Shinohara R, Aghajanian GK, Abdallah CG. Neurobiology of the Rapid-Acting Antidepressant Effects of Ketamine: Impact and Opportunities. Biol Psychiatry 2021;90:85–95. https://doi.org/10.1016/j.biopsych.2020.12.006.
[89] Kang MJY, Hawken E, Vazquez GH. The Mechanisms Behind Rapid Antidepressant Effects of Ketamine: A Systematic Review With a Focus on Molecular Neuroplasticity. Front Psychiatry 2022;13.
https://doi.org/10.3389/fpsyt.2022.860882.
[90] Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 2000;47:351–4. https://doi.org/10.1016/s0006-3223(99)00230-9.
[91] Zarate CA, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen
Psychiatry 2006;63:856–64. https://doi.org/10.1001/archpsyc.63.8.856.
[92] Fava M, Freeman MP, Flynn M, Judge H, Hoeppner BB, Cusin C, et al. Double-blind, placebocontrolled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant
depression (TRD). Mol Psychiatry 2020;25:1592–603. https://doi.org/10.1038/s41380-018-0256-5.
[93] Marcantoni WS, Akoumba BS, Wassef M, Mayrand J, Lai H, Richard-Devantoy S, et al. A systematic review and meta-analysis of the efficacy of intravenous ketamine infusion for treatment resistant depression: January 2009 – January 2019. J Affect Disord 2020;277:831–41. https://doi.org/10.1016/j.jad.2020.09.007.
[94] Wilkinson ST, Ballard ED, Bloch MH, Mathew SJ, Murrough JW, Feder A, et al. The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis. Am J Psychiatry 2018;175:150–8. https://doi.org/10.1176/appi.ajp.2017.17040472.
[95] Research C for DE and. FDA warns patients and health care providers about potential risks associated with compounded ketamine products, including oral formulations, for the treatment of psychiatric disorders. FDA 2023.
[96] Dépression résistante : SPRAVATO, nouvel antidépresseur à base d’eskétamine en solution pour pulvérisation nasale. VIDAL 2020. https://www.vidal.fr/actualites/25942-depression-resistantespravato-nouvel-antidepresseur-a-base-d-esketamine-en-solution-pour-pulverisation-nasale.html (accessed May 26, 2025).
[97] Fedgchin M, Trivedi M, Daly EJ, Melkote R, Lane R, Lim P, et al. Efficacy and Safety of FixedDose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1). Int J Neuropsychopharmacol 2019;22:616–30. https://doi.org/10.1093/ijnp/pyz039.
[98] Daly EJ, Trivedi MH, Janik A, Li H, Zhang Y, Li X, et al. Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry 2019;76:893–903. https://doi.org/10.1001/jamapsychiatry.2019.1189.
[99] Ochs-Ross R, Daly EJ, Zhang Y, Lane R, Lim P, Morrison RL, et al. Efficacy and Safety of Esketamine Nasal Spray Plus an Oral Antidepressant in Elderly Patients With Treatment-Resistant Depression-TRANSFORM-3. Am J Geriatr Psychiatry 2020;28:121–41. https://doi.org/10.1016/j.jagp.2019.10.008.
[100] Popova V, Daly EJ, Trivedi M, Cooper K, Lane R, Lim P, et al. Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment Resistant Depression: A Randomized Double-Blind Active-Controlled Study. Am J Psychiatry 2019;176:428–38. https://doi.org/10.1176/appi.ajp.2019.19020172.
[101] Jiang M, Wang M-H, Wang X-B, Liu L, Wu J-L, Yang X-L, et al. Effect of intraoperative application of ketamine on postoperative depressed mood in patients undergoing elective
orthopedic surgery. J Anesth 2016;30:232–7. https://doi.org/10.1007/s00540-015-2096-7.
[102] Mashour GA, Ben Abdallah A, Pryor KO, El-Gabalawy R, Vlisides PE, Jacobsohn E, et al. Intraoperative ketamine for prevention of depressive symptoms after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial. Br J Anaesth 2018;121:1075–83. https://doi.org/10.1016/j.bja.2018.03.030.
[103] Wang J, Echevarria GC, Doan L, Ekasumara N, Calvino S, Chae F, et al. Effects of a single subanaesthetic dose of ketamine on pain and mood after laparoscopic bariatric surgery: A randomised double-blind placebo controlled study. Eur J Anaesthesiol 2019;36:16–24. https://doi.org/10.1097/EJA.0000000000000860.
[104] Wang J, Sun Y, Ai P, Cui V, Shi H, An D, et al. The effect of intravenous ketamine on depressive symptoms after surgery: A systematic review. J Clin Anesth 2022;77:110631. https://doi.org/10.1016/j.jclinane.2021.110631.
[105] Guo J, Qiu D, Gu H-W, Wang X-M, Hashimoto K, Zhang G-F, et al. Efficacy and safety of perioperative application of ketamine on postoperative depression: A meta-analysis of randomized
controlled studies. Mol Psychiatry 2023;28:2266–76. https://doi.org/10.1038/s41380-023-01945-z.
[106] Wei Q, Li M, Jiang Y, Liu X. Efficacy of perioperatively application of ketamine on postoperative depressive symptoms in adult patients: A systematic review and meta-analysis with
trial sequential analysis. J Affect Disord 2024;353:27–35. https://doi.org/10.1016/j.jad.2024.02.085.
[107] Gan S-L, Long Y-Q, Wang Q-Y, Feng C-D, Lai C-X, Liu C-T, et al. Effect of esketamine on postoperative depressive symptoms in patients undergoing thoracoscopic lung cancer surgery: A
randomized controlled trial. Front Psychiatry 2023;14:1128406. https://doi.org/10.3389/fpsyt.2023.1128406.
[108] Wei Q, Li M, Du Q, Zhang H, Liang Y, Cheng C, et al. Effect of esketamine on postoperative depression in women with breast cancer and preoperative depressive symptoms: The EASE
randomized trial. J Clin Anesth 2025;103:111821. https://doi.org/10.1016/j.jclinane.2025.111821.
[109] Qiu D, Wang X-M, Yang J-J, Chen S, Yue C-B, Hashimoto K, et al. Effect of Intraoperative Esketamine Infusion on Postoperative Sleep Disturbance After Gynecological Laparoscopy: A
Randomized Clinical Trial. JAMA Netw Open 2022;5:e2244514. https://doi.org/10.1001/jamanetworkopen.2022.44514.
[110] Li H-Y, Xu W-J, Wang Y-M, Xie S, Wang H-L. Efficacy of perioperative esketamine on postoperative depression: a systematic review and meta-analysis. Front Psychiatry 2025;16:1476449.
https://doi.org/10.3389/fpsyt.2025.1476449.
[111] Wen Y, Mao M, Jiang M, Liu Q, Li Q, Wang X, et al. Efficacy and safety of perioperative application of esketamine on postoperative depression: a meta-analysis of randomized controlled
studies. Int J Surg 2025;111:1191–202. https://doi.org/10.1097/JS9.0000000000001870.
[112] Lee S, Xue Y, Petricca J, Kremic L, Xiao MZX, Pivetta B, et al. The impact of pre-operative depression on pain outcomes after major surgery: a systematic review and meta-analysis.
Anaesthesia 2024;79:423–34. https://doi.org/10.1111/anae.16188.
[113] Tu W, Yuan H, Zhang S, Lu F, Yin L, Chen C, et al. Influence of anesthetic induction of propofol combined with esketamine on perioperative stress and inflammatory responses and postoperative
cognition of elderly surgical patients. Am J Transl Res 2021;13:1701–9.
[114] Gohari J, Grosman-Rimon L, Arazi M, Caspi-Avissar N, Granot D, Gleitman S, et al. Clinical factors and pre-surgical depression scores predict pain intensity in cardiac surgery patients. BMC
Anesthesiol 2022;22:204. https://doi.org/10.1186/s12871-022-01740-3.
[115] Wang Y, Zhang Q, Dai X, Xiao G, Luo H. Effect of low-dose esketamine on pain control and postpartum depression after cesarean section: a retrospective cohort study. Ann Palliat Med
2022;11:45–57. https://doi.org/10.21037/apm-21-3343.
[116] Xu S, Yang J, Li J, Zhang M, Sun J, Liu Q, et al. Esketamine pretreatment during cesarean section reduced the incidence of postpartum depression: a randomized controlled trail. BMC
Anesthesiol 2024;24:20. https://doi.org/10.1186/s12871-023-02398-1.
[117] Wang S, Deng C-M, Zeng Y, Chen X-Z, Li A-Y, Feng S-W, et al. Efficacy of a single low dose of esketamine after childbirth for mothers with symptoms of prenatal depression: randomised clinical
trial. BMJ 2024;385:e078218. https://doi.org/10.1136/bmj-2023-078218.
[118] Ma S, Dou Y, Wang W, Wei A, Lan M, Liu J, et al. Association between esketamine interventions and postpartum depression and analgesia following cesarean delivery: a systematic
review and meta-analysis. Am J Obstet Gynecol MFM 2024;6:101241. https://doi.org/10.1016/j.ajogmf.2023.101241.
[119] Li S, Zhou W, Li P, Lin R. Effects of ketamine and esketamine on preventing postpartum depression after cesarean delivery: A meta-analysis. J Affect Disord 2024;351:720–8.
https://doi.org/10.1016/j.jad.2024.01.202.
[120] Wang J, Liu H, Wei X. Effect of intraoperative and/or postoperative esketamine administration on preventing postpartum depression: A systematic review and meta-analysis.
Psychiatry Res 2024;335:115890. https://doi.org/10.1016/j.psychres.2024.115890.
[121] Li S, Zhuo Z, Li R, Guo K. Efficacy of esketamine for the treatment of postpartum depression and pain control following cesarean section: a randomized, double-blind, controlled clinical trial.
BMC Anesthesiol 2024;24:52. https://doi.org/10.1186/s12871-024-02436-6.
[122] Nestor CC, Ng C, Sepulveda P, Irwin MG. Pharmacological and clinical implications of local anaesthetic mixtures: a narrative review. Anaesthesia 2022;77:339–50. https://doi.org/10.1111/anae.15641.
[123] Xiang J, Cao C, Chen J, Kong F, Nian S, Li Z, et al. Efficacy and safety of ketamine as an adjuvant to regional anesthesia: A systematic review and meta-analysis of randomized controlled
trials. J Clin Anesth 2024;94:111415. https://doi.org/10.1016/j.jclinane.2024.111415.
[124] Hussain SY, Jain D, Kumar S. OP040 Analgesic efficacy of perineural ketamine as an adjuvant to local anesthetic solution for peripheral nerve blocks: a systematic review and meta analysis. Reg
Anesth Pain Med 2024;49:A34–5. https://doi.org/10.1136/rapm-2024-ESRA.39.
[125] Sohnen S, Dowling O, Shore-Lesserson L. Single dose perioperative intrathecal ketamine as an adjuvant to intrathecal bupivacaine: A systematic review and meta-analysis of adult human
randomized controlled trials. J Clin Anesth 2021;73:110331. https://doi.org/10.1016/j.jclinane.2021.110331.
[126] Schnabel A, Poepping DM, Kranke P, Zahn PK, Pogatzki-Zahn EM. Efficacy and adverse effects of ketamine as an additive for paediatric caudal anaesthesia: a quantitative systematic review of
randomized controlled trials. Br J Anaesth 2011;107:601–11. https://doi.org/10.1093/bja/aer258.
[127] Haeseler G, Tetzlaff D, Bufler J, Dengler R, Münte S, Hecker H, et al. Blockade of voltageoperated neuronal and skeletal muscle sodium channels by S(+)- and R(-)-ketamine. Anesth Analg 2003;96:1019–26. https://doi.org/10.1213/01.ANE.0000052513.91900.D5.
[128] Martindale SJ, Dix P, Stoddart PA. Double-blind randomized controlled trial of caudal versus intravenous S(+)-ketamine for supplementation of caudal analgesia in children. Br J Anaesth
2004;92:344–7. https://doi.org/10.1093/bja/aeh076.
[129] Togal T, Demirbilek S, Koroglu A, Yapici E, Ersoy O. Effects of S(+) ketamine added to bupivacaine for spinal anaesthesia for prostate surgery in elderly patients. Eur J Anaesthesiol 2004;21:193–7. https://doi.org/10.1017/s0265021504003059.
[130] Unlugenc H, Ozalevli M, Gunes Y, Olguner S, Evrüke C, Ozcengiz D, et al. A double-blind comparison of intrathecal S(+) ketamine and fentanyl combined with bupivacaine 0.5% for Caesarean
delivery. Eur J Anaesthesiol 2006;23:1018–24. https://doi.org/10.1017/S0265021506000950.
[131] Desai N, Albrecht E, El-Boghdadly K. Perineural adjuncts for peripheral nerve block. BJA Educ 2019;19:276–82. https://doi.org/10.1016/j.bjae.2019.05.001.
[132] Nestor CC, Ng C, Sepulveda P, Irwin MG. Pharmacological and clinical implications of local anaesthetic mixtures: a narrative review. Anaesthesia 2022;77:339–50. https://doi.org/10.1111/anae.15641.
[133] Vranken JH, Troost D, de Haan P, Pennings FA, van der Vegt MH, Dijkgraaf MGW, et al. Severe toxic damage to the rabbit spinal cord after intrathecal administration of preservative-free S(+)-
ketamine. Anesthesiology 2006;105:813–8. https://doi.org/10.1097/00000542-200610000-00028.
[134] Vranken JH, Troost D, Wegener JT, Kruis MR, van der Vegt MH. Neuropathological findings after continuous intrathecal administration of S(+)-ketamine for the management of neuropathic cancer pain. Pain 2005;117:231–5. https://doi.org/10.1016/j.pain.2005.06.014.
[135] Werdehausen R, Braun S, Hermanns H, Kremer D, Küry P, Hollmann MW, et al. The influence of adjuvants used in regional anesthesia on lidocaine-induced neurotoxicity in vitro. Reg Anesth Pain Med 2011;36:436–43. https://doi.org/10.1097/AAP.0b013e318226ba62.
[136] Carles M. Mise au point – Adjuvants en anesthésie locorégionale péri nerveuse (ALR-pn) : que reste-t-il de nos amours ? SFAR; 2016.
[137] RCP – KETAMINE PANPHARMA 10 mg/mL, solution injectable (I.V.-I.M.) – 62768665 – BDM ANSM n.d. https://m.base-donnees-publique.medicaments.gouv.fr/rcp-62768665- 2? tm_source=chatgpt.com#!rcp-67101800-4 (accessed May 23, 2025).
[138] ESKESIA (eskétamine) – Anesthésie. Haute Autorité de Santé n.d. https://www.hassante.fr/jcms/p_3428300/fr/eskesia-esketamine-anesthesie (accessed May 23, 2025).
[139] Boussofara M, Raucoules-Aimé M. EMC Anesthésie-Réanimation – Pharmacologie des benzodiazépines utilisées en anesthésie-réanimation 2016.
[140] Kilpatrick GJ. Remimazolam: Non-Clinical and Clinical Profile of a New Sedative/Anesthetic Agent. Front Pharmacol 2021;12:690875. https://doi.org/10.3389/fphar.2021.690875.
[141] Kilpatrick GJ, McIntyre MS, Cox RF, Stafford JA, Pacofsky GJ, Lovell GG, et al. CNS 7056: a novel ultra-short-acting Benzodiazepine. Anesthesiology 2007;107:60–6. https://doi.org/10.1097/01.anes.0000267503.85085.c0.
[142] Antonik LJ, Goldwater DR, Kilpatrick GJ, Tilbrook GS, Borkett KM. A placebo- and midazolamcontrolled 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;115:274–83. https://doi.org/10.1213/ANE.0b013e31823f0c28.
[143] Kim KM. Remimazolam: pharmacological characteristics and clinical applications in anesthesiology. Anesth Pain Med (Seoul) 2022;17:1–11. https://doi.org/10.17085/apm.21115.
[144] Sheng X-Y, Liang Y, Yang X-Y, Li L-E, 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;76:383–91. https://doi.org/10.1007/s00228-019-02800-3.
[145] Abcejo AS, Teixera MT. Remimazolam: Patient Safety Considerations of a Novel, PracticeChanging Drug in Perioperative Medicine. Anesthesia Patient Safety Foundation 2023.
https://www.apsf.org/article/remimazolam-patient-safety-considerations-of-a-novel-practicechanging-drug-in-perioperative-medicine/ (accessed June 8, 2025).
[146] Shimamoto Y, Sanuki M, Kurita S, Ueki M, Kuwahara Y, Matsumoto A. Factors affecting prolonged time to extubation in patients given remimazolam. PLoS One 2022;17:e0268568.
https://doi.org/10.1371/journal.pone.0268568.
[147] Stöhr T, Colin PJ, Ossig J, Pesic M, Borkett K, Winkle P, et al. Pharmacokinetic properties of remimazolam in subjects with hepatic or renal impairment. Br J Anaesth 2021;127:415–23.
https://doi.org/10.1016/j.bja.2021.05.027.
[148] Keam SJ. Remimazolam: First Approval. Drugs 2020;80:625–33. https://doi.org/10.1007/s40265-020-01299-8.
[149] BYFAVO (rémimazolam) – Sédation / anesthésie générale. Haute Autorité de Santé n.d. https://www.has-sante.fr/jcms/p_3518111/fr/byfavo-remimazolam-sedation-/-anesthesie-generale (accessed June 23, 2025).
[150] Borkett KM, Riff DS, Schwartz HI, Winkle PJ, Pambianco DJ, Lees JP, et al. A Phase IIa, randomized, double-blind study of remimazolam (CNS 7056) versus midazolam for sedation in upper gastrointestinal endoscopy. Anesth Analg 2015;120:771–80. https://doi.org/10.1213/ANE.0000000000000548.
[151] Pambianco DJ, Borkett KM, Riff DS, Winkle PJ, Schwartz HI, Melson TI, et al. A phase IIb study comparing the safety and efficacy of remimazolam and midazolam in patients undergoing colonoscopy. Gastrointest Endosc 2016;83:984–92. https://doi.org/10.1016/j.gie.2015.08.062.
[152] 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. https://doi.org/10.1016/j.gie.2018.04.2351.
[153] Pastis NJ, Yarmus LB, Schippers F, Ostroff R, Chen A, Akulian J, et al. Safety and Efficacy of Remimazolam Compared With Placebo and Midazolam for Moderate Sedation During Bronchoscopy.
Chest 2019;155:137–46. https://doi.org/10.1016/j.chest.2018.09.015.
[154] 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. https://doi.org/10.1016/j.dld.2020.10.039.
[155] 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;12:4594–603.
[156] Chen S-H, Yuan T-M, Zhang J, Bai H, Tian M, Pan C-X, et al. Remimazolam tosilate in upper gastrointestinal endoscopy: A multicenter, randomized, non-inferiority, phase III trial. J Gastroenterol
Hepatol 2021;36:474–81. https://doi.org/10.1111/jgh.15188.
[157] Barbosa EC, Espírito Santo PA, Baraldo S, Meine GC. Remimazolam versus propofol for sedation in gastrointestinal endoscopic procedures: a systematic review and meta-analysis. Br J Anaesth 2024;132:1219–29. https://doi.org/10.1016/j.bja.2024.02.005.
[158] Tan Y, Ouyang W, Tang Y, Fang N, Fang C, Quan C. Effect of remimazolam tosilate on early cognitive function in elderly patients undergoing upper gastrointestinal endoscopy. J Gastroenterol
Hepatol 2022;37:576–83. https://doi.org/10.1111/jgh.15761.
[159] Yao Y, Guan J, Liu L, Fu B, Chen L, Zheng X. Discharge readiness after remimazolam versus propofol for colonoscopy: A randomised, double-blind trial. Eur J Anaesthesiol 2022;39:911–7.
https://doi.org/10.1097/EJA.0000000000001715.
[160] Lee JH, Lee J, Park SH, Han S-H, Kim J-H, Park J-W. Comparison between remimazolam and propofol anaesthesia for interventional neuroradiology: a randomised controlled trial. Anaesth Crit Care Pain Med 2024;43:101337. https://doi.org/10.1016/j.accpm.2023.101337.
[161] Zhang J, Zhang J, Wang Y, Bai X, Guo Q, Liu W, et al. Effect of remimazolam vs propofol on emergence from general anesthesia in patients undergoing cerebral endovascular procedures: A randomized controlled, non-inferiority trial. J Clin Anesth 2024;93:111356. https://doi.org/10.1016/j.jclinane.2023.111356.
[162] 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;34:543–53. https://doi.org/10.1007/s00540-020- 02788-6.
[163] Doi M, Hirata N, Suzuki T, Morisaki H, Morimatsu H, Sakamoto A. Safety and efficacy 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. J Anesth 2020;34:491–501. https://doi.org/10.1007/s00540-020-02776-w.
[164] Tang F, Yi J-M, Gong H-Y, Lu Z-Y, Chen J, Fang B, et al. Remimazolam benzenesulfonate anesthesia effectiveness in cardiac surgery patients under general anesthesia. World J Clin Cases 2021;9:10595–603. https://doi.org/10.12998/wjcc.v9.i34.10595.
[165] Xiao Y-Y, Zou H-D, Qin X-N, Zhu R, Dai R-P. A Comparison of Remimazolam versus Propofol on Blood Pressure Changes During Therapeutic Endoscopic Retrograde Cholangiopancreatography: A
Randomized Controlled Trial. Anesth Analg 2024;141:90–9. https://doi.org/10.1213/ANE.0000000000007309.
[166] Peng X, Liu C, Zhu Y, Peng L, Zhang X, Wei W, et al. Hemodynamic Influences of Remimazolam Versus Propofol During the Induction Period of General Anesthesia: A Systematic Review and Metaanalysis of Randomized Controlled Trials. Pain Physician 2023;26:E761–73.
[167] Ko C-C, Hung K-C, Illias AM, Chiu C-C, Yu C-H, Lin C-M, et al. The use of remimazolam versus propofol for induction and maintenance of general anesthesia: A systematic review and metaanalysis. Front Pharmacol 2023;14:1101728. https://doi.org/10.3389/fphar.2023.1101728.
[168] Choi JY, Lee HS, Kim JY, Han DW, Yang JY, Kim MJ, et al. Comparison of remimazolam-based and propofol-based total intravenous anesthesia on postoperative quality of recovery: A randomized
non-inferiority trial. J Clin Anesth 2022;82:110955. https://doi.org/10.1016/j.jclinane.2022.110955.
[169] Fechner J, El-Boghdadly K, Spahn DR, Motsch J, Struys MMRF, Duranteau O, et al. Anaesthetic efficacy and postinduction hypotension with remimazolam compared with propofol: a multicentre
randomised controlled trial. Anaesthesia 2024;79:410–22. https://doi.org/10.1111/anae.16205.
[170] Hu B, Zhang M, Wu Z, Zhang X, Zou X, Tan L, et al. Comparison of Remimazolam Tosilate and Etomidate on Hemodynamics in Cardiac Surgery: A Randomised Controlled Trial. Drug Des Devel Ther
2023;17:381–8. https://doi.org/10.2147/DDDT.S401969.
[171] 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 (Baltimore) 2021;100:e28209. https://doi.org/10.1097/MD.0000000000028209.
[172] Petkus H, Willer BL, Tobias JD. Remimazolam in a Pediatric Patient With a Suspected Family History of Malignant Hyperthermia. J Med Cases 2022;13:386–90. https://doi.org/10.14740/jmc3977.
[173] 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. https://doi.org/10.1186/s40981-022-00564-x.
[174] 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. https://doi.org/10.3390/jcm12123930.
[175] Kuklin V, Hansen TG. Remimazolam for sedation and anesthesia in children: A scoping review. Acta Anaesthesiol Scand 2024;68:862–70. https://doi.org/10.1111/aas.14439.
[176] 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;16:3413–20. https://doi.org/10.2147/DDDT.S381611.
[177] Tang Y, Yang X, Yu Y, Shu H, Yuan Y, Liu H, et al. Remimazolam besylate versus propofol for long-term sedation during invasive mechanical ventilation: a pilot study. Crit Care 2022;26:279.
https://doi.org/10.1186/s13054-022-04168-w.
[178] 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. https://doi.org/10.1186/s13054-023-04760-8.
[179] Grillot N, Vourc’h M, Hourmant Y, Bouras M, Rozec B, Rouhani A, et al. A phase 2 open-label pilot study of Remimazolam for sedation in critically ill patients. Anaesth Crit Care Pain Med 2025;44:101510. https://doi.org/10.1016/j.accpm.2025.101510.
[180] Choi B-M, Lee J-S, Kim KM, Bang J-Y, Lee E-K, Noh G-J. Frequency and characteristics of patients with bispectral index values of 60 or higher during the induction and maintenance of general
anesthesia with remimazolam. Sci Rep 2023;13:9992. https://doi.org/10.1038/s41598-023-37150-9.
[181] Park I, Cho M, Nam SW, Hwang J-W, Do S-H, Na H-S. Total intravenous anesthesia induced and maintained by a combination of remimazolam and remifentanil without a neuromuscular
blocking agent: a prospective, observational pilot study. BMC Anesthesiol 2022;22:237. https://doi.org/10.1186/s12871-022-01779-2.
[182] Shirozu K, Nobukuni K, Tsumura S, Imura K, Nakashima K, Takamori S, et al. Neurological sedative indicators during general anesthesia with remimazolam. J Anesth 2022;36:194–200.
https://doi.org/10.1007/s00540-021-03030-7.
[183] Yang C, Jiao J, Nie Y, Shao W, Zhang H, Huang S. Comparison of the bispectral indices of patients receiving remimazolam and propofol for general anesthesia: a randomized crossover trial.
Anaesth Crit Care Pain Med 2024;43:101377. https://doi.org/10.1016/j.accpm.2024.101377.
[184] Johansen JW, Sebel PS. Development and clinical application of electroencephalographic bispectrum monitoring. Anesthesiology 2000;93:1336–44. https://doi.org/10.1097/00000542-
200011000-00029.
[185] Park I, Cho M, Nam SW, Hwang J-W, Do S-H, Na H-S. Total intravenous anesthesia induced and maintained by a combination of remimazolam and remifentanil without a neuromuscular
blocking agent: a prospective, observational pilot study. BMC Anesthesiol 2022;22:237. https://doi.org/10.1186/s12871-022-01779-2.
[186] Kim KM, Bang J-Y, Choi B-M, Noh G-J. Assessment of explicit and implicit memories during remimazolam anaesthesia using the process dissociation procedure: A prospective cohort study. Eur J
Anaesthesiol 2023;40:833–40. https://doi.org/10.1097/EJA.0000000000001904.
[187] Kuang Q, Zhong N, Ye C, Zhu X, Wei F. Propofol Versus Remimazolam on Cognitive Function, Hemodynamics, and Oxygenation During One-Lung Ventilation in Older Patients Undergoing
Pulmonary Lobectomy: A Randomized Controlled Trial. J Cardiothorac Vasc Anesth 2023;37:1996– https://doi.org/10.1053/j.jvca.2023.06.027.
[188] Yang J-J, Lei L, Qiu D, Chen S, Xing L-K, Zhao J-W, 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;17:143–53. https://doi.org/10.2147/DDDT.S392569.
[189] Aoki Y, Kurita T, Nakajima M, Imai R, Suzuki Y, Makino H, et al. Association between remimazolam and postoperative delirium in older adults undergoing elective cardiovascular surgery:
a prospective cohort study. J Anesth 2023;37:13–22. https://doi.org/10.1007/s00540-022-03119-7.
[190] 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;89:553–64. https://doi.org/10.23736/S0375- 9393.23.17034-9.
[191] Huang Q, Zou Y, Kong G. Hiccup, a neglected side-effect of remimazolam bolus? Minerva Anestesiol 2022;88:193–4. https://doi.org/10.23736/S0375-9393.21.16086-9.
[192] Ye E, Wu K, Ye H, Zhang W, Chu L, Zhang K, et al. Comparison of 95% effective dose of remimazolam besylate and propofol for gastroscopy sedation on older patients: A single-centre
randomized controlled trial. Br J Clin Pharmacol 2023;89:3401–10. https://doi.org/10.1111/bcp.15839.
[193] Kempenaers S, Hansen TG, Van de Velde M. Remimazolam and serious adverse events: A scoping review. Eur J Anaesthesiol 2023;40:841–53. https://doi.org/10.1097/EJA.0000000000001902.
[194] Laizure SC, Parker RB. Is genetic variability in carboxylesterase-1 and carboxylesterase-2 drug metabolism an important component of personalized medicine? Xenobiotica 2020;50:92–100.
https://doi.org/10.1080/00498254.2019.1678078.
[195] Oh EJ, Chung YJ, Lee J-H, Kwon EJ, Choi EA, On YK, et al. Comparison of propofol vs. remimazolam on emergence profiles after general anesthesia: A randomized clinical trial. J Clin Anesth 2023;90:111223. https://doi.org/10.1016/j.jclinane.2023.111223.
[196] Shi F, Chen Y, Li H, Zhang Y, Zhao T. Efficacy and Safety of Remimazolam Tosilate versus Propofol for General Anesthesia in Cirrhotic Patients Undergoing Endoscopic Variceal Ligation. Int J
Gen Med 2022;15:583–91. https://doi.org/10.2147/IJGM.S345390.
[197] Lee J, Kim DH, Ju J-W, Nam K, Cho YJ, Jeon Y, et al. Comparison of recovery profiles between total intravenous anaesthesia with propofol or remimazolam reversed with flumazenil in patients
undergoing breast surgery: A randomised controlled trial. Eur J Anaesthesiol 2024;41:199–207. https://doi.org/10.1097/EJA.0000000000001951.
[198] 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. https://doi.org/10.3390/jcm12237316.
[199] Lauven PM, Schwilden H, Stoeckel H, Greenblatt DJ. The effects of a benzodiazepine antagonist Ro 15-1788 in the presence of stable concentrations of midazolam. Anesthesiology
1985;63:61–4. https://doi.org/10.1097/00000542-198507000-00009.
[200] Masui K. Caution!! Reappearance of remimazolam effect after a flumazenil bolus: a larger bolus of flumazenil and a lower total remimazolam clearance are higher risks. J Anesth 2023;37:1–5.
https://doi.org/10.1007/s00540-022-03107-x.
[201] Teixeira MT, Brinkman NJ, Pasternak JJ, Abcejo AS. The Role of Remimazolam in Neurosurgery and in Patients With Neurological Diseases: A Narrative Review. J Neurosurg Anesthesiol 2024;36:11–9. https://doi.org/10.1097/ANA.0000000000000917.
[202] Yoshida A, Kurata S, Kida K, Tsubokawa T. Anesthetic management for the sleep-awake-sleep technique of awake craniotomy using a novel benzodiazepine remimazolam and its antagonist
flumazenil. JA Clin Rep 2021;7:14. https://doi.org/10.1186/s40981-021-00417-z.
[203] Cinotti R. An update on remimazolam and anaphylaxis. Eur J Anaesthesiol 2023;40:153–4. https://doi.org/10.1097/EJA.0000000000001794.
[204] Kim KM, Lee H, Bang J-Y, Choi B-M, Noh G-J. Anaphylaxis following remimazolam administration during induction of anaesthesia. Br J Anaesth 2022;129:e122–4. https://doi.org/10.1016/j.bja.2022.07.047.
[205] Tsurumi K, Takahashi S, Hiramoto Y, Nagumo K, Takazawa T, Kamiyama Y. Remimazolam anaphylaxis during anesthesia induction. J Anesth 2021;35:571–5. https://doi.org/10.1007/s00540-
021-02934-8.
[206] Nucera E, Parrinello G, Buonomo A, Aruanno A, Rizzi A. Allergic reactions to midazolam: A case series from an Italian allergy unit. Allergol Immunopathol (Madr) 2021;49:167–70.
https://doi.org/10.15586/aei.v49i4.238.
[207] Olafuyi O, Parekh N, Wright J, Koenig J. Inter-ethnic differences in pharmacokinetics-is there more that unites than divides? Pharmacol Res Perspect 2021;9:e00890. https://doi.org/10.1002/prp2.890.
[208] Wang D, Zou L, Jin Q, Hou J, Ge G, Yang L. Human carboxylesterases: a comprehensive review. Acta Pharm Sin B 2018;8:699–712. https://doi.org/10.1016/j.apsb.2018.05.005.
[209] Zhang J, Wang X, Zhang Q, Wang Z, Zhu S. Application effects of remimazolam and propofol on elderly patients undergoing hip replacement. BMC Anesthesiol 2022;22:118. https://doi.org/10.1186/s12871-022-01641-5.
[210] 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;16:1199–209. https://doi.org/10.2147/DDDT.S359496.
[211] Takaki R, Yokose M, Mihara T, Saigusa Y, Tanaka H, Yamamoto N, et al. Hypotension after general anaesthesia induction using remimazolam or propofol in geriatric patients undergoing
sevoflurane anaesthesia with remifentanil: a single-centre, double-blind, randomised controlled trial. Br J Anaesth 2024;133:24–32. https://doi.org/10.1016/j.bja.2024.04.013.
[212] Chae D, Kim H-C, 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. https://doi.org/10.1016/j.bja.2022.02.040.
