{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T21:47:11Z","timestamp":1790113631635,"version":"4.0.1"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2022,1,9]],"date-time":"2022-01-09T00:00:00Z","timestamp":1641686400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2022,1,9]],"date-time":"2022-01-09T00:00:00Z","timestamp":1641686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Anesth"],"published-print":{"date-parts":[[2022,4]]},"DOI":"10.1007\/s00540-021-03030-7","type":"journal-article","created":{"date-parts":[[2022,1,9]],"date-time":"2022-01-09T00:03:07Z","timestamp":1641686587000},"page":"194-200","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":92,"title":["Neurological sedative indicators during general anesthesia with remimazolam"],"prefix":"10.1007","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2290-3764","authenticated-orcid":false,"given":"Kazuhiro","family":"Shirozu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Nobukuni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shota","family":"Tsumura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Imura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Nakashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinnosuke","family":"Takamori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Midoriko","family":"Higashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Yamaura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,9]]},"reference":[{"issue":"1","key":"3030_CR1","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1097\/01.anes.0000267503.85085.c0","volume":"107","author":"GJ Kilpatrick","year":"2007","unstructured":"Kilpatrick GJ, McIntyre MS, Cox RF, Stafford JA, Pacofsky GJ, Lovell GG, Wiard RP, Feldman PL, Collins H, Waszczak BL, Tilbrook GS. CNS 7056: a novel ultra-short-acting Benzodiazepine. Anesthesiology. 2007;107(1):60\u20136.","journal-title":"Anesthesiology"},{"issue":"2","key":"3030_CR2","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1213\/ANE.0b013e318241f68a","volume":"115","author":"HR Wiltshire","year":"2012","unstructured":"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(2):284\u201396.","journal-title":"Anesth Analg"},{"issue":"6","key":"3030_CR3","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1093\/bja\/aeq260","volume":"105","author":"RN Upton","year":"2010","unstructured":"Upton RN, Somogyi AA, Martinez AM, Colvill J, Grant C. Pharmacokinetics and pharmacodynamics of the short-acting sedative CNS 7056 in sheep. Br J Anaesth. 2010;105(6):798\u2013809.","journal-title":"Br J Anaesth"},{"issue":"1","key":"3030_CR4","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.chest.2018.09.015","volume":"155","author":"NJ Pastis","year":"2019","unstructured":"Pastis NJ, Yarmus LB, Schippers F, Ostroff R, Chen A, Akulian J, Wahidi M, Shojaee S, Tanner NT, Callahan SP, Feldman G, Lorch DG Jr, Ndukwu I, Pritchett MA, Silvestri GA, Investigators P. Safety and efficacy of remimazolam compared with placebo and midazolam for moderate sedation during bronchoscopy. Chest. 2019;155(1):137\u201346.","journal-title":"Chest"},{"issue":"8","key":"3030_CR5","first-page":"4594","volume":"12","author":"S Chen","year":"2020","unstructured":"Chen S, Wang J, Xu X, Huang Y, Xue S, Wu A, Jin X, Wang Q, Lyu J, Wang S, Li Y, Yu Y, Ai D, Luo A, Min S, Li L, Zou X, Liu J, Lv P, Chai X, Sun X, Zhao Z, Zhang J. 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(8):4594\u2013603.","journal-title":"Am J Transl Res"},{"issue":"3","key":"3030_CR6","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/j.gie.2018.04.2351","volume":"88","author":"DK Rex","year":"2018","unstructured":"Rex DK, Bhandari R, Desta T, DeMicco MP, Schaeffer C, Etzkorn K, Barish CF, Pruitt R, Cash BD, Quirk D, Tiongco F, Sullivan S, Bernstein D. 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(3):427\u201337.","journal-title":"Gastrointest Endosc"},{"issue":"4","key":"3030_CR7","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1213\/ANE.0000000000000548","volume":"120","author":"KM Borkett","year":"2015","unstructured":"Borkett KM, Riff DS, Schwartz HI, Winkle PJ, Pambianco DJ, Lees JP, Wilhelm-Ogunbiyi K. A Phase IIa, randomized, double-blind study of remimazolam (CNS 7056) versus midazolam for sedation in upper gastrointestinal endoscopy. Anesth Analg. 2015;120(4):771\u201380.","journal-title":"Anesth Analg"},{"issue":"4","key":"3030_CR8","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1007\/s00540-020-02788-6","volume":"34","author":"M Doi","year":"2020","unstructured":"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(4):543\u201353.","journal-title":"J Anesth"},{"issue":"4","key":"3030_CR9","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1097\/ALN.0000000000003103","volume":"132","author":"J Schuttler","year":"2020","unstructured":"Schuttler 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(4):636\u201351.","journal-title":"Anesthesiology"},{"issue":"4","key":"3030_CR10","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1007\/s00540-020-02776-w","volume":"34","author":"M Doi","year":"2020","unstructured":"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(4):491\u2013501.","journal-title":"J Anesth"},{"key":"3030_CR11","doi-asserted-by":"publisher","first-page":"109899","DOI":"10.1016\/j.jclinane.2020.109899","volume":"66","author":"J Zhou","year":"2020","unstructured":"Zhou J, Leonowens C, Ivaturi VD, Lohmer LL, Curd L, Ossig J, Schippers F, Petersen KU, Stoehr T, Schmith V. Population pharmacokinetic\/pharmacodynamic modeling for remimazolam in the induction and maintenance of general anesthesia in healthy subjects and in surgical subjects. J Clin Anesth. 2020;66:109899.","journal-title":"J Clin Anesth"},{"issue":"4","key":"3030_CR12","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1002\/jcph.1552","volume":"60","author":"LL Lohmer","year":"2020","unstructured":"Lohmer LL, Schippers F, Petersen KU, Stoehr T, Schmith VD. Time-to-event modeling for remimazolam for the indication of induction and maintenance of general anesthesia. J Clin Pharmacol. 2020;60(4):505\u201314.","journal-title":"J Clin Pharmacol"},{"issue":"1","key":"3030_CR13","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1097\/00000542-199107000-00011","volume":"75","author":"MD Larson","year":"1991","unstructured":"Larson MD, Sessler DI, McGuire J, Hynson JM. Isoflurane, but not mild hypothermia, depresses the human pupillary light reflex. Anesthesiology. 1991;75(1):62\u20137.","journal-title":"Anesthesiology"},{"issue":"1","key":"3030_CR14","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1097\/00000542-199601000-00006","volume":"84","author":"K Leslie","year":"1996","unstructured":"Leslie K, Sessler DI, Smith WD, Larson MD, Ozaki M, Blanchard D, Crankshaw DP. Prediction of movement during propofol\/nitrous oxide anesthesia. Performance of concentration, electroencephalographic, pupillary, and hemodynamic indicators. Anesthesiology. 1996;84(1):52\u201363.","journal-title":"Anesthesiology"},{"issue":"2","key":"3030_CR15","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1007\/s10877-016-9839-3","volume":"31","author":"K Shirozu","year":"2017","unstructured":"Shirozu K, Setoguchi H, Tokuda K, Karashima Y, Ikeda M, Kubo M, Nakamura K, Hoka S. The effects of anesthetic agents on pupillary function during general anesthesia using the automated infrared quantitative pupillometer. J Clin Monit Comput. 2017;31(2):291\u20136.","journal-title":"J Clin Monit Comput"},{"key":"3030_CR16","doi-asserted-by":"publisher","DOI":"10.3791\/59488","author":"K Shirozu","year":"2019","unstructured":"Shirozu K, Murayama K, Yamaura K. Pupillary response as assessment of effective seizure induction by electroconvulsive therapy. J Vis Exp. 2019. https:\/\/doi.org\/10.3791\/59488.","journal-title":"J Vis Exp"},{"issue":"1","key":"3030_CR17","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1097\/00000542-199701000-00005","volume":"86","author":"CF Minto","year":"1997","unstructured":"Minto CF, Schnider TW, Shafer SL. Pharmacokinetics and pharmacodynamics of remifentanil. II. Model application. Anesthesiology. 1997;86(1):24\u201333.","journal-title":"Anesthesiology"},{"issue":"6","key":"3030_CR18","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1093\/bja\/aep269","volume":"103","author":"RN Upton","year":"2009","unstructured":"Upton RN, Martinez AM, Grant C. Comparison of the sedative properties of CNS 7056, midazolam, and propofol in sheep. Br J Anaesth. 2009;103(6):848\u201357.","journal-title":"Br J Anaesth"},{"issue":"4","key":"3030_CR19","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1097\/ALN.0000000000003102","volume":"132","author":"A Eisenried","year":"2020","unstructured":"Eisenried A, Schuttler 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(4):652\u201366.","journal-title":"Anesthesiology"},{"issue":"3","key":"3030_CR20","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1007\/s00540-010-0907-4","volume":"24","author":"W Miyake","year":"2010","unstructured":"Miyake W, Oda Y, Ikeda Y, Hagihira S, Iwaki H, Asada A. Electroencephalographic response following midazolam-induced general anesthesia: relationship to plasma and effect-site midazolam concentrations. J Anesth. 2010;24(3):386\u201393.","journal-title":"J Anesth"},{"issue":"4","key":"3030_CR21","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1038\/clpt.1989.41","volume":"45","author":"DJ Greenblatt","year":"1989","unstructured":"Greenblatt DJ, Ehrenberg BL, Gunderman J, Locniskar A, Scavone JM, Harmatz JS, Shader RI. Pharmacokinetic and electroencephalographic study of intravenous diazepam, midazolam, and placebo. Clin Pharmacol Ther. 1989;45(4):356\u201365.","journal-title":"Clin Pharmacol Ther"},{"issue":"5","key":"3030_CR22","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1016\/j.bja.2019.07.021","volume":"123","author":"J Sleigh","year":"2019","unstructured":"Sleigh J, Pullon RM, Vlisides PE, Warnaby CE. Electroencephalographic slow wave dynamics and loss of behavioural responsiveness induced by ketamine in human volunteers. Br J Anaesth. 2019;123(5):592\u2013600.","journal-title":"Br J Anaesth"},{"issue":"6","key":"3030_CR23","doi-asserted-by":"publisher","first-page":"1530","DOI":"10.1213\/00000539-200206000-00028","volume":"94","author":"T Koitabashi","year":"2002","unstructured":"Koitabashi T, Johansen JW, Sebel PS. Remifentanil dose\/electroencephalogram bispectral response during combined propofol\/regional anesthesia. Anesth Analg. 2002;94(6):1530\u20133 (Table of contents).","journal-title":"Anesth Analg"},{"issue":"2","key":"3030_CR24","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1093\/bja\/78.2.180","volume":"78","author":"M Doi","year":"1997","unstructured":"Doi M, Gajraj RJ, Mantzaridis H, Kenny GN. Relationship between calculated blood concentration of propofol and electrophysiological variables during emergence from anaesthesia: comparison of bispectral index, spectral edge frequency, median frequency and auditory evoked potential index. Br J Anaesth. 1997;78(2):180\u20134.","journal-title":"Br J Anaesth"},{"issue":"4","key":"3030_CR25","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1097\/00000542-199710000-00007","volume":"87","author":"RA Veselis","year":"1997","unstructured":"Veselis RA, Reinsel RA, Feshchenko VA, Wronski M. The comparative amnestic effects of midazolam, propofol, thiopental, and fentanyl at equisedative concentrations. Anesthesiology. 1997;87(4):749\u201364.","journal-title":"Anesthesiology"},{"issue":"3","key":"3030_CR26","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1093\/bja\/aei040","volume":"94","author":"R Bulach","year":"2005","unstructured":"Bulach R, Myles PS, Russnak M. Double-blind randomized controlled trial to determine extent of amnesia with midazolam given immediately before general anaesthesia. Br J Anaesth. 2005;94(3):300\u20135.","journal-title":"Br J Anaesth"}],"container-title":["Journal of Anesthesia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00540-021-03030-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00540-021-03030-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00540-021-03030-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T03:20:49Z","timestamp":1649647249000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00540-021-03030-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,9]]},"references-count":26,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,4]]}},"alternative-id":["3030"],"URL":"https:\/\/doi.org\/10.1007\/s00540-021-03030-7","relation":{},"ISSN":["0913-8668","1438-8359"],"issn-type":[{"value":"0913-8668","type":"print"},{"value":"1438-8359","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,9]]},"assertion":[{"value":"16 September 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 January 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"No external funding and no competing interests declared.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}