{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:49:53Z","timestamp":1790887793906,"version":"4.1.0"},"reference-count":36,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2018,6,1]],"date-time":"2018-06-01T00:00:00Z","timestamp":1527811200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T00:00:00Z","timestamp":1559347200000},"content-version":"vor","delay-in-days":365,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Taiwan Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST-104-2314-B-075-008"],"award-info":[{"award-number":["MOST-104-2314-B-075-008"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Taiwan Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST 103-2314-B-075-030"],"award-info":[{"award-number":["MOST 103-2314-B-075-030"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011912","name":"Taipei Veterans General Hospital","doi-asserted-by":"crossref","award":["V100C-172"],"award-info":[{"award-number":["V100C-172"]}],"id":[{"id":"10.13039\/501100011912","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100011912","name":"Taipei Veterans General Hospital","doi-asserted-by":"crossref","award":["V107C-101"],"award-info":[{"award-number":["V107C-101"]}],"id":[{"id":"10.13039\/501100011912","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["British Journal of Anaesthesia"],"published-print":{"date-parts":[[2018,6]]},"DOI":"10.1016\/j.bja.2018.01.041","type":"journal-article","created":{"date-parts":[[2018,4,17]],"date-time":"2018-04-17T12:45:31Z","timestamp":1523969131000},"page":"1209-1218","source":"Crossref","is-referenced-by-count":25,"title":["Adaptation of non-linear mixed amount with zero amount response surface model for analysis of concentration-dependent synergism and safety with midazolam, alfentanil, and propofol sedation"],"prefix":"10.1016","volume":"120","author":[{"given":"J.-Y.","family":"Liou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.-K.","family":"Ting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.-N.","family":"Teng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.S.","family":"Mandell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.-Y.","family":"Tsou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bja.2018.01.041_bib1","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/S0031-6997(25)06847-4","article-title":"The search for synergy: a critical review from a response surface perspective","volume":"47","author":"Greco","year":"1995","journal-title":"Pharmacol Rev"},{"key":"10.1016\/j.bja.2018.01.041_bib2","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1097\/00000542-200006000-00017","article-title":"Response surface model for anesthetic drug interactions","volume":"92","author":"Minto","year":"2000","journal-title":"Anesthesiology"},{"key":"10.1016\/j.bja.2018.01.041_bib3","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.aat.2015.06.005","article-title":"Response surface models in the field of anesthesia: a crash course","volume":"53","author":"Liou","year":"2015","journal-title":"Acta Anaesthesiol Taiwan"},{"key":"10.1016\/j.bja.2018.01.041_bib4","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1213\/ANE.0000000000001299","article-title":"Predicting the best fit: a comparison of response surface models for midazolam and alfentanil sedation in procedures with varying stimulation","volume":"123","author":"Liou","year":"2016","journal-title":"Anesth Analg"},{"key":"10.1016\/j.bja.2018.01.041_bib5","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1097\/ALN.0b013e318242a2ec","article-title":"Sevoflurane remifentanil interaction: comparison of different response surface models","volume":"116","author":"Heyse","year":"2012","journal-title":"Anesthesiology"},{"key":"10.1016\/j.bja.2018.01.041_bib6","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1097\/00000542-200608000-00009","article-title":"Opioid-volatile anesthetic synergy: a response surface model with remifentanil and sevoflurane as prototypes","volume":"105","author":"Manyam","year":"2006","journal-title":"Anesthesiology"},{"key":"10.1016\/j.bja.2018.01.041_bib7","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1097\/ALN.0b013e3181b799ef","article-title":"Response surface modeling of the interaction between propofol and sevoflurane","volume":"111","author":"Schumacher","year":"2009","journal-title":"Anesthesiology"},{"key":"10.1016\/j.bja.2018.01.041_bib8","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1111\/j.1460-9592.2011.03644.x","article-title":"Explaining the acetaminophen-ibuprofen analgesic interaction using a response surface model","volume":"21","author":"Hannam","year":"2011","journal-title":"Paediatr Anaesth"},{"key":"10.1016\/j.bja.2018.01.041_bib9","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/S0022-3565(24)38100-5","article-title":"Response surface analysis of synergism between morphine and clonidine","volume":"289","author":"Tallarida","year":"1999","journal-title":"J\u00a0Pharmacol Exp Ther"},{"key":"10.1016\/j.bja.2018.01.041_bib10","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1002\/bimj.201500021","article-title":"Nonlinear response surface in the study of interaction analysis of three combination drugs","volume":"59","author":"Wan","year":"2017","journal-title":"Biom J"},{"key":"10.1016\/j.bja.2018.01.041_bib11","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1080\/10799890701417576","article-title":"Nonlinear blending: a useful general concept for the assessment of combination drug synergy","volume":"27","author":"Peterson","year":"2007","journal-title":"J\u00a0Recept Signal Transduct Res"},{"key":"10.1016\/j.bja.2018.01.041_bib12","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1128\/AAC.00873-06","article-title":"Concentration-dependent synergy and antagonism within a triple antifungal drug combination against Aspergillus species: analysis by a new response surface model","volume":"51","author":"Meletiadis","year":"2007","journal-title":"Antimicrob Agents Chemother"},{"key":"10.1016\/j.bja.2018.01.041_bib13","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1093\/bja\/69.2.162","article-title":"Hypnotic and anaesthetic interactions between midazolam, propofol and alfentanil","volume":"69","author":"Short","year":"1992","journal-title":"Br J Anaesth"},{"key":"10.1016\/j.bja.2018.01.041_bib14","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1213\/00000539-199402000-00026","article-title":"Triple anesthetic combination: propofol-midazolam-alfentanil","volume":"78","author":"Vinik","year":"1994","journal-title":"Anesth Analg"},{"key":"10.1016\/j.bja.2018.01.041_bib15","doi-asserted-by":"crossref","first-page":"399","DOI":"10.2174\/1389200033489316","article-title":"A\u00a0new nonlinear mixture response surface paradigm for the study of synergism: a three drug example","volume":"4","author":"White","year":"2003","journal-title":"Curr Drug Metab"},{"key":"10.1016\/j.bja.2018.01.041_bib16","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1097\/00000542-200202000-00027","article-title":"Efficient trial design for eliciting a pharmacokinetic-pharmacodynamic model-based response surface describing the interaction between two intravenous anesthetic drugs","volume":"96","author":"Short","year":"2002","journal-title":"Anesthesiology"},{"key":"10.1016\/j.bja.2018.01.041_bib17","first-page":"244","article-title":"Validity and reliability of the observer's assessment of alertness\/sedation scale: study with intravenous midazolam","volume":"10","author":"Chernik","year":"1990","journal-title":"J\u00a0Clin Psychopharmacol"},{"key":"10.1016\/j.bja.2018.01.041_bib18","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1213\/ANE.0000000000000548","article-title":"A\u00a0Phase IIa, randomized, double-blind study of remimazolam (CNS 7056) versus midazolam for sedation in upper gastrointestinal endoscopy","volume":"120","author":"Borkett","year":"2015","journal-title":"Anesth Analg"},{"key":"10.1016\/j.bja.2018.01.041_bib19","doi-asserted-by":"crossref","first-page":"e3520","DOI":"10.1097\/MD.0000000000003520","article-title":"A\u00a0response surface model exploration of dosing strategies in gastrointestinal endoscopies using midazolam and opioids","volume":"95","author":"Liou","year":"2016","journal-title":"Medicine (Baltimore)"},{"key":"10.1016\/j.bja.2018.01.041_bib20","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1213\/ane.0b013e31817b7140","article-title":"Additivity versus synergy: a theoretical analysis of implications for anesthetic mechanisms","volume":"107","author":"Shafer","year":"2008","journal-title":"Anesth Analg"},{"key":"10.1016\/j.bja.2018.01.041_bib21","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1097\/00000542-198701000-00002","article-title":"Population pharmacokinetics of alfentanil: the average dose-plasma concentration relationship and interindividual variability in patients","volume":"66","author":"Maitre","year":"1987","journal-title":"Anesthesiology"},{"key":"10.1016\/j.bja.2018.01.041_bib22","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1097\/00000542-199812000-00020","article-title":"Population pharmacokinetics of midazolam administered by target controlled infusion for sedation following coronary artery bypass grafting","volume":"89","author":"Zomorodi","year":"1998","journal-title":"Anesthesiology"},{"issue":"5","key":"10.1016\/j.bja.2018.01.041_bib23","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1097\/00000542-199805000-00006","article-title":"The influence of method of administration and covariates on the pharmacokinetics of propofol in adult volunteers","volume":"88","year":"1998","journal-title":"Anesthesiology"},{"key":"10.1016\/j.bja.2018.01.041_bib24","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1097\/00000542-198503000-00005","article-title":"EEG quantitation of narcotic effect: the comparative pharmacodynamics of fentanyl and alfentanil","volume":"62","author":"Scott","year":"1985","journal-title":"Anesthesiology"},{"key":"10.1016\/j.bja.2018.01.041_bib25","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/clpt.1990.192","article-title":"Electroencephalographic effects of benzodiazepines. II. Pharmacodynamic modeling of the electroencephalographic effects of midazolam and diazepam","volume":"48","author":"Buhrer","year":"1990","journal-title":"Clin Pharmacol Ther"},{"key":"10.1016\/j.bja.2018.01.041_bib26","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1093\/bja\/aew060","article-title":"Probability to tolerate laryngoscopy and noxious stimulation response index as general indicators of the anaesthetic potency of sevoflurane, propofol, and remifentanil","volume":"116","author":"Hannivoort","year":"2016","journal-title":"Br J Anaesth"},{"key":"10.1016\/j.bja.2018.01.041_bib27","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1213\/ANE.0000000000000094","article-title":"Response surface model predictions of wake-up time during scoliosis surgery","volume":"118","author":"Ting","year":"2014","journal-title":"Anesth Analg"},{"key":"10.1016\/j.bja.2018.01.041_bib28","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1097\/ALN.0000000000000180","article-title":"A\u00a0response surface model approach for continuous measures of hypnotic and analgesic effect during sevoflurane-remifentanil interaction: quantifying the pharmacodynamic shift evoked by stimulation","volume":"120","author":"Heyse","year":"2014","journal-title":"Anesthesiology"},{"key":"10.1016\/j.bja.2018.01.041_bib29","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/0160-5402(90)90058-S","article-title":"Statistical modeling of the effects of drug combinations","volume":"23","author":"Plummer","year":"1990","journal-title":"J\u00a0Pharmacol Meth"},{"key":"10.1016\/j.bja.2018.01.041_bib30","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1097\/ALN.0b013e3182860486","article-title":"Interaction between nitrous oxide, sevoflurane, and opioids: a response surface approach","volume":"118","author":"Vereecke","year":"2013","journal-title":"Anesthesiology"},{"key":"10.1016\/j.bja.2018.01.041_bib31","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1213\/ane.0b013e3181606c62","article-title":"An evaluation of remifentanil propofol response surfaces for loss of responsiveness, loss of response to surrogates of painful stimuli and laryngoscopy in patients undergoing elective surgery","volume":"106","author":"Johnson","year":"2008","journal-title":"Anesth Analg"},{"key":"10.1016\/j.bja.2018.01.041_bib32","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1097\/00000542-200406000-00006","article-title":"Pharmacodynamic interaction between propofol and remifentanil regarding hypnosis, tolerance of laryngoscopy, bispectral index, and electroencephalographic approximate entropy","volume":"100","author":"Bouillon","year":"2004","journal-title":"Anesthesiology"},{"key":"10.1016\/j.bja.2018.01.041_bib33","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1097\/00000542-200302000-00008","article-title":"Response surface modeling of remifentanil-propofol interaction on cardiorespiratory control and bispectral index","volume":"98","author":"Nieuwenhuijs","year":"2003","journal-title":"Anesthesiology"},{"key":"10.1016\/j.bja.2018.01.041_bib34","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1213\/ANE.0b013e318210fc45","article-title":"An exploration of remifentanil-propofol combinations that lead to a loss of response to esophageal instrumentation, a loss of responsiveness, and\/or onset of intolerable ventilatory depression","volume":"113","author":"LaPierre","year":"2011","journal-title":"Anesth Analg"},{"key":"10.1016\/j.bja.2018.01.041_bib35","doi-asserted-by":"crossref","first-page":"18S","DOI":"10.1016\/S0952-8180(97)00122-0","article-title":"Drug interactions: volatile anesthetics and opioids","volume":"9","author":"Glass","year":"1997","journal-title":"J\u00a0Clin Anesth"},{"key":"10.1016\/j.bja.2018.01.041_bib36","first-page":"1207","article-title":"The effects of large-dose flumazenil on midazolam-induced ventilatory depression","volume":"77","author":"Flogel","year":"1993","journal-title":"Anesth Analg"}],"container-title":["British Journal of Anaesthesia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S000709121830223X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S000709121830223X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T18:46:37Z","timestamp":1751568397000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S000709121830223X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6]]},"references-count":36,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,6]]}},"alternative-id":["S000709121830223X"],"URL":"https:\/\/doi.org\/10.1016\/j.bja.2018.01.041","relation":{},"ISSN":["0007-0912"],"issn-type":[{"value":"0007-0912","type":"print"}],"subject":[],"published":{"date-parts":[[2018,6]]}}}