{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:34:47Z","timestamp":1759970087227,"version":"build-2065373602"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"DOI":"10.1186\/s13063-025-09159-0","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:18:53Z","timestamp":1759918733000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Determination of the 50% and 95% effective dose of esketamine combined with propofol for intravenous sedation in pediatric circumcision: study protocol for a randomized controlled, double-blind, dose-finding clinical trial"],"prefix":"10.1186","volume":"26","author":[{"given":"Junqin","family":"Mao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kang","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3806-9620","authenticated-orcid":false,"given":"Zhimin","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"issue":"2","key":"9159_CR1","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1024\/1661-8157\/a001532","volume":"103","author":"T AQDrake","year":"2014","unstructured":"AQDrake T, Rustom J, Davies M. Kindliche Phimose [Pediatric phimosis]. Praxis (Bern 1994). 2014;103(2):105\u20137.","journal-title":"Praxis (Bern 1994)"},{"issue":"2","key":"9159_CR2","first-page":"396","volume":"96","author":"WY Choi","year":"2003","unstructured":"Choi WY, Irwin MG, Hui TW, Lim HH, Chan KL. EMLA cream versus dorsal penile nerve block for postcircumcision analgesia in children. Anesth Analg. 2003;96(2):396\u20139.","journal-title":"Anesth Analg"},{"issue":"5","key":"9159_CR3","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1177\/0310057X1504300517","volume":"43","author":"X Qian","year":"2015","unstructured":"Qian X, Jin X, Chen L, Pan Y, Wu B, Li J. A new ultrasound-guided dorsal penile nerve block technique for circumcision in children. Anaesth Intensive Care. 2015;43(5):662\u20133.","journal-title":"Anaesth Intensive Care"},{"issue":"1","key":"9159_CR4","doi-asserted-by":"publisher","first-page":"75","DOI":"10.15537\/smj.2017.1.15632","volume":"38","author":"C Alta\u015f","year":"2017","unstructured":"Alta\u015f C, K\u00fc\u00e7\u00fckosman G, Yurtlu BS, Okyay RD, Ayd\u0131n BG, Pi\u015fkin \u00d6, et al. Anesthesia methods used by anesthetic specialists for circumcision cases. National survey study for Turkey. Saudi Med J. 2017;38(1):75\u201381.","journal-title":"Saudi Med J"},{"issue":"8","key":"9159_CR5","doi-asserted-by":"publisher","DOI":"10.3390\/children8080678","volume":"8","author":"LE Gilbertson","year":"2021","unstructured":"Gilbertson LE, Patel C, De S, Lo W, Garcia-Roig M, Austin TM. The utilization of an opioid-free anesthetic for pediatric circumcision in an ambulatory surgery center. Children. 2021;8(8):678.","journal-title":"Children"},{"issue":"5","key":"9159_CR6","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1016\/j.bja.2018.01.018","volume":"120","author":"DJ Eleveld","year":"2018","unstructured":"Eleveld DJ, Colin P, Absalom AR, Struys MMRF. Pharmacokinetic-pharmacodynamic model for propofol for broad application in anaesthesia and sedation. Br J Anaesth. 2018;120(5):942\u201359.","journal-title":"Br J Anaesth"},{"issue":"2","key":"9159_CR7","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1097\/00000542-200202000-00022","volume":"96","author":"EG Pfenninger","year":"2002","unstructured":"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(2):357\u201366.","journal-title":"Anesthesiology"},{"issue":"12","key":"9159_CR8","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1111\/j.1460-9592.2004.01358.x","volume":"14","author":"F Weber","year":"2004","unstructured":"Weber F, Wulf H, Gruber M, Biallas R. S-ketamine and s-norketamine plasma concentrations after nasal and i.v. administration in anesthetized children. Paediatr Anaesth. 2004;14(12):983\u20138.","journal-title":"Paediatr Anaesth"},{"issue":"1","key":"9159_CR9","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1186\/s13063-017-2197-8","volume":"18","author":"S Eberl","year":"2017","unstructured":"Eberl S, Koers L, van Hooft JE, de Jong E, Schneider T, Hollmann MW, et al. Sedation with propofol during ERCP: is the combination with esketamine more effective and safer than with alfentanil? Study protocol for a randomized controlled trial. Trials. 2017;18(1):472.","journal-title":"Trials"},{"issue":"5","key":"9159_CR10","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/j.bjane.2014.03.002","volume":"65","author":"H Gulec","year":"2015","unstructured":"Gulec H, Sahin S, Ozayar E, Degerli S, Bercin F, Ozdemir O. Ketamine-propofol sedation in circumcision. Brazilian Journal of Anesthesiology (English Edition). 2015;65(5):367\u201370.","journal-title":"Brazilian Journal of Anesthesiology (English Edition)"},{"issue":"1","key":"9159_CR11","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1186\/s12871-022-01885-1","volume":"22","author":"J Wang","year":"2022","unstructured":"Wang J, Hu W, Zhao X, Ren W, Huang X, Zhang B. Sedative effect and safety of different doses of S-ketamine in combination with propofol during gastro-duodenoscopy in school-aged children: a prospective, randomized study. BMC Anesthesiol. 2022;22(1):346.","journal-title":"BMC Anesthesiol"},{"issue":"7","key":"9159_CR12","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1111\/jcpt.13635","volume":"47","author":"XS Zheng","year":"2022","unstructured":"Zheng XS, Shen Y, Yang YY, He P, Wang YT, Tao YY, et al. ED50 and ED95 of propofol combined with different doses of esketamine for children undergoing upper gastrointestinal endoscopy: a prospective dose-finding study using up-and-down sequential allocation method. J Clin Pharm Ther. 2022;47(7):1002\u20139.","journal-title":"J Clin Pharm Ther"},{"issue":"1","key":"9159_CR13","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1186\/s40001-022-00890-x","volume":"27","author":"SX Xu","year":"2022","unstructured":"Xu SX, Shan XS, Gao JM, Liu HX, Chen WR, Gao SS, et al. Effect of esketamine vs dexmedetomidine adjunct to propofol sedation for pediatric 3Tesla magnetic resonance imaging: a randomized, double-blind, controlled trial. Eur J Med Res. 2022;27(1):258.","journal-title":"Eur J Med Res"},{"issue":"44","key":"9159_CR14","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000031624","volume":"101","author":"W Liu","year":"2022","unstructured":"Liu W, Xu F, Guo L, Li H, Zhao L, Ma J. Anaesthesia administered as S(+)-ketamine for cardiac intervention in children with common congenital heart disease. Medicine (Baltimore). 2022;101(44):e31624.","journal-title":"Medicine (Baltimore)"},{"issue":"3","key":"9159_CR15","doi-asserted-by":"publisher","first-page":"200","DOI":"10.7326\/0003-4819-158-3-201302050-00583","volume":"358","author":"AW Chan","year":"2013","unstructured":"Chan AW, Tetzlaf JM, Altman DG, Laupacis A, G\u00f8tzsche PC, Krle\u017ea-Jeri\u0107 K, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013;358(3):200\u20137.","journal-title":"Ann Intern Med"},{"issue":"7","key":"9159_CR16","first-page":"1893","volume":"109","author":"J Wang","year":"2023","unstructured":"Wang J, Zeng J, Zhao N, Chen S, Chen Z, Liao J, et al. Intranasal esketamine combined with oral midazolam provides adequate sedation for outpatient pediatric dental procedures: a prospective cohort study. Int J Surg. 2023;109(7):1893\u20139.","journal-title":"Int J Surg"},{"issue":"12","key":"9159_CR17","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1001\/jamapediatrics.2019.3351","volume":"173","author":"V Giordano","year":"2019","unstructured":"Giordano V, Edobor J, Deindl P, Wildner B, Goeral K, Steinbauer P, et al. Pain and sedation scales for neonatal and pediatric patients in a preverbal stage of development: a systematic review. JAMA Pediatr. 2019;173(12):1186\u201397.","journal-title":"JAMA Pediatr"},{"issue":"1","key":"9159_CR18","doi-asserted-by":"publisher","first-page":"83","DOI":"10.4103\/ijo.IJO_457_20","volume":"69","author":"S Sethi","year":"2021","unstructured":"Sethi S, Joshi G, Bloria SD, Kaushik S, Chauhan R, Meena S, et al. Safety and efficacy of oral triclofos in the ophthalmic evaluation of children with pediatric glaucoma: an observational study. Indian J Ophthalmol. 2021;69(1):83\u20136.","journal-title":"Indian J Ophthalmol"},{"issue":"1","key":"9159_CR19","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1186\/s12871-022-01897-x","volume":"22","author":"H Gu","year":"2022","unstructured":"Gu H, Miao L, Bai J, Lu G, Lei Q, Yang L, et al. Combined use of intranasal dexmedetomidine and an oral novel formulation of midazolam for sedation of young children during brain MRI examination: a prospective, single-center, randomized controlled trial. BMC Anesthesiol. 2022;22(1):357.","journal-title":"BMC Anesthesiol"},{"issue":"9","key":"9159_CR20","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1056\/NEJMsa1012065","volume":"364","author":"DA AQZarin","year":"2011","unstructured":"AQZarin DA, Tse T, Williams RJ, Califf RM, Ide NC. The clinicaltrials.gov results database-update and key issues. N Engl J Med. 2011;364(9):852\u201360.","journal-title":"N Engl J Med"},{"issue":"10","key":"9159_CR21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0109400","volume":"9","author":"IJ Saldanha","year":"2014","unstructured":"Saldanha IJ, Dickersin K, Wang X, Li T. Outcomes in Cochrane systematic reviews addressing four common eye conditions: an evaluation of completeness and comparability. PLoS ONE. 2014;9(10):e109400.","journal-title":"PLoS ONE"},{"issue":"3","key":"9159_CR22","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/j.giec.2016.02.004","volume":"26","author":"HK Chung","year":"2016","unstructured":"Chung HK, Lightdale JR. Sedation and monitoring in the pediatric patient during gastrointestinal endoscopy. Gastrointest Endosc Clin N Am. 2016;26(3):507\u201325.","journal-title":"Gastrointest Endosc Clin N Am"},{"key":"9159_CR23","doi-asserted-by":"crossref","unstructured":"Alletag MJ, Auerbach MA, Baum CR. Ketamine, propofol, and ketofol use for pediatric sedation. Pediatr Emerg Care. 2012;28(12):1391\u20135; quiz 1396\u20138.","DOI":"10.1097\/PEC.0b013e318276fde2"},{"key":"9159_CR24","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/6501215","volume":"2018","author":"N Narula","year":"2018","unstructured":"Narula N, Masood S, Shojaee S, McGuinness B, Sabeti S, Buchan A. Safety of propofol versus nonpropofol-based sedation in children undergoing gastrointestinal endoscopy: a systematic review and meta-analysis. Gastroenterol Res Pract. 2018;2018:6501215.","journal-title":"Gastroenterol Res Pract"},{"key":"9159_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2021.113651","volume":"418","author":"JC Maraschin","year":"2022","unstructured":"Maraschin JC, Frias AT, Hernandes PM, Batistela MF, Martinez LM, Joca SRL, et al. Antipanic-like effect of esketamine and buprenorphine in rats exposed to acute hypoxia. Behav Brain Res. 2022;418:113651.","journal-title":"Behav Brain Res"},{"issue":"7","key":"9159_CR26","volume":"9","author":"S Apostolidou","year":"2022","unstructured":"Apostolidou S, Kintscher M, Sch\u00f6n G, Ebenebe CU, Bartz HJ, Singer D, et al. The impact of a dedicated sedation team on the incidence of complications in pediatric procedural analgosedation. Children (Basel). 2022;9(7):998.","journal-title":"Children (Basel)"},{"issue":"5","key":"9159_CR27","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1213\/01.ANE.0000134810.60270.E8","volume":"99","author":"JP Cravero","year":"2004","unstructured":"Cravero JP, Blike GT. Review of pediatric sedation. Anesth Analg. 2004;99(5):1355\u201364.","journal-title":"Anesth Analg"},{"issue":"3","key":"9159_CR28","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1111\/j.0006-341X.2001.00886.x","volume":"57","author":"HH M\u00fcller","year":"2001","unstructured":"M\u00fcller HH, Sch\u00e4fer H. Adaptive group sequential designs for clinical trials: combining the advantages of adaptive and of classical group sequential approaches. Biometrics. 2001;57(3):886\u201391.","journal-title":"Biometrics"},{"issue":"2","key":"9159_CR29","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1128\/br.11.2.115-145.1947","volume":"11","author":"WR Aqthompson","year":"1947","unstructured":"Aqthompson WR. Use of moving averages and interpolation to estimate median-effective dose; fundamental formulas, estimation of error, and relation to other methods. Bacteriol Rev. 1947;11(2):115\u201345.","journal-title":"Bacteriol Rev"},{"issue":"2","key":"9159_CR30","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/S0022-3565(25)03549-9","volume":"96","author":"JT Litchfield Jr","year":"1949","unstructured":"Litchfield JT Jr, Wilcoxon F. A simplified method of evaluating dose-effect experiments. J Pharmacol Exp Ther. 1949;96(2):99\u2013113.","journal-title":"J Pharmacol Exp Ther"},{"issue":"3","key":"9159_CR31","doi-asserted-by":"publisher","first-page":"e461","DOI":"10.1542\/peds.2006-2577","volume":"120","author":"S Malviya","year":"2007","unstructured":"Malviya S, Voepel-Lewis T, Tait AR, Watcha MF, Sadhasivam S, Friesen RH. Effect of age and sedative agent on the accuracy of bispectral index in detecting depth of sedation in children. Pediatrics. 2007;120(3):e461\u201370.","journal-title":"Pediatrics"},{"issue":"9","key":"9159_CR32","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1007\/s40262-016-0383-6","volume":"55","author":"MA Peltoniemi","year":"2016","unstructured":"Peltoniemi MA, Hagelberg NM, Olkkola KT, Saari TI. Ketamine: a review of clinical pharmacokinetics and pharmacodynamics in anesthesia and pain therapy. Clin Pharmacokinet. 2016;55(9):1059\u201377.","journal-title":"Clin Pharmacokinet"},{"issue":"2","key":"9159_CR33","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1097\/00000542-200408000-00008","volume":"101","author":"F Weber","year":"2004","unstructured":"Weber F, Bein T, Hobbhahn J, Taeger K. Evaluation of the Alaris Auditory Evoked Potential Index as an indicator of anesthetic depth in preschool children during induction of anesthesia with sevoflurane and remifentanil. Anesthesiology. 2004;101(2):294\u20138.","journal-title":"Anesthesiology"},{"issue":"1","key":"9159_CR34","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1186\/s12871-023-02238-2","volume":"23","author":"J Luo","year":"2023","unstructured":"Luo J, Yin K, Zhao D, Zhang Z, Sun R. Effect of intravenous induction with different doses of Esketamine combined with propofol and sufentanil on intraocular pressure among pediatric strabismus surgery: a randomized clinical trial. BMC Anesthesiol. 2023;23(1):275.","journal-title":"BMC Anesthesiol"},{"issue":"2","key":"9159_CR35","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1016\/j.bja.2018.03.037","volume":"121","author":"J Hayes","year":"2018","unstructured":"Hayes J, Matava C, Pehora C, El-Beheiry H, Jarvis S, Finkelstein Y. Determination of the median effective dose of propofol in combination with different doses of ketamine during gastro-duodenoscopy in children: a randomised controlled trial. Br J Anaesth. 2018;121(2):453\u201361.","journal-title":"Br J Anaesth"}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-025-09159-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13063-025-09159-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-025-09159-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:18:54Z","timestamp":1759918734000},"score":1,"resource":{"primary":{"URL":"https:\/\/trialsjournal.biomedcentral.com\/articles\/10.1186\/s13063-025-09159-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,8]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["9159"],"URL":"https:\/\/doi.org\/10.1186\/s13063-025-09159-0","relation":{},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,8]]},"assertion":[{"value":"13 November 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The trial was approved by the IRB of Wenling Maternity and Child Health Care Hospital (approval number: 2024-IRB-103). Before inclusion in the study, relevant information will be provided to the legal guardians of the participants and obtain written informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethic approval and consent to participate {24}"}},{"value":"All authors consent to the publication and participants will provide consent for publication of anonymized data and study findings.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication {32}"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests {28}"}}],"article-number":"393"}}