{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T19:59:27Z","timestamp":1793217567115,"version":"4.5.0"},"reference-count":25,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012285","name":"BC Children's Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012285","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000245","name":"Michael Smith Health Research BC","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000245","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Anesthesia"],"published-print":{"date-parts":[[2025,12]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Propofol is a commonly used intravenous sedative and general anesthetic, with rapid onset and short duration of action. It has a narrow therapeutic index and significant interindividual variability in dosing requirements, which may elevate risks of its use, particularly in children.<\/jats:p>\n <\/jats:sec>\n \n Aims<\/jats:title>\n We aimed to quantify the doses required to induce loss of consciousness and apnea in children by age and sex to contribute to tailored propofol dosing recommendations for improved safety and efficacy in pediatric anesthesia.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n In this stratified\u2010 and purposive\u2010sampling study, we enrolled children in six groups based on sex and age (3\u2010 to 5\u2010year\u2010olds, 6\u2010 to 10\u2010year\u2010olds, 11\u2010 to 18\u2010year\u2010olds), targeting 60 participants per group. For induction of anesthesia, we administered propofol at a constant rate until apnea was reached (absence of end\u2010tidal CO\n 2<\/jats:sub>\n for 20\u2009s) up to a maximum dose of 10\u2009mg\/kg. We measured the propofol dose required to reach pharmacodynamic endpoints, including loss of eyelash reflex (LOER) and apnea, and estimated the effect of sex and age on these doses.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Data were available for 318 participants, with 162 females and a median (interquartile range) age of 8.1 (5.3\u201312.9) years. The mean (SD) propofol dose to LOER was 2.65 (0.69) mg\/kg with no effect of sex (\u22120.10\u2009mg\/kg for male, 95% confidence interval (CI) \u20130.26 to 0.05,\n p<\/jats:italic>\n \u2009=\u20090.183) or age (0.0\u2009mg\/kg per year, 95% CI \u20130.02 to 0.02,\n p<\/jats:italic>\n \u2009=\u20090.876). The mean (SD) propofol dose to apnea was 6.82 (1.64) mg\/kg, with significant effects of both sex (+0.67\u2009mg\/kg for male, 95% CI 0.30 to 1.03,\n p<\/jats:italic>\n \u2009<\u20090.001) and age (\u22120.14\u2009mg\/kg per year, 95% CI \u20130.19 to \u22120.1,\n p<\/jats:italic>\n \u2009<\u20090.001). Apnea was not reached in 62 participants.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Older and female children exhibited narrower therapeutic indices for the margin between LOER and apnea. This requires heightened vigilance, especially when maintaining spontaneous respiration. A planned genome\u2010wide association study may identify pharmacogenetic\u2010pharmacodynamic relationships and correlations with genetic ancestry.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n The trial was registered on\n clinicaltrials.gov<\/jats:ext-link>\n before enrolment (NCT04164264; date of registration 2019\u201011\u201015)\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/pan.70031","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T12:53:20Z","timestamp":1754916800000},"page":"1071-1079","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacodynamic Safety Endpoints for Propofol Anesthesia in Children by Age and Sex: A Multicohort Observational Study"],"prefix":"10.1111","volume":"35","author":[{"given":"Lindy","family":"Moxham","sequence":"first","affiliation":[{"name":"Faculty of Medicine University of British Columbia Vancouver British Columbia Canada"},{"name":"Research Institute, BC Children's Hospital Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aanisah","family":"Golam","sequence":"additional","affiliation":[{"name":"Department of Anesthesia BC Children's Hospital Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8382-5136","authenticated-orcid":false,"given":"Nicholas C.","family":"West","sequence":"additional","affiliation":[{"name":"Research Institute, BC Children's Hospital Vancouver British Columbia Canada"},{"name":"Department of Anesthesia BC Children's Hospital Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2193-178X","authenticated-orcid":false,"given":"Matthias","family":"G\u00f6rges","sequence":"additional","affiliation":[{"name":"Research Institute, BC Children's Hospital Vancouver British Columbia Canada"},{"name":"Department of Anesthesiology, Pharmacology & Therapeutics University of British Columbia Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8590-3916","authenticated-orcid":false,"given":"Simon D.","family":"Whyte","sequence":"additional","affiliation":[{"name":"Research Institute, BC Children's Hospital Vancouver British Columbia Canada"},{"name":"Department of Anesthesia BC Children's Hospital Vancouver British Columbia Canada"},{"name":"Department of Anesthesiology, Pharmacology & Therapeutics University of British Columbia Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010018\u20100672\u20103"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263\u2010015\u20100259\u20106"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.809393"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0000000000006196"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460\u20109592.2010.03269.x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.12746\/swrccc.v11i47.1119"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460\u20109592.2007.02285.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aem294"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aei245"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.716"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1213\/ane.0b013e31818fc334"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40272\u2010017\u20100241\u20105"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/PCC.0000000000000273"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/PCC.0000000000000504"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed"},{"key":"e_1_2_10_17_1","unstructured":"Statistics Canada \u201cVisible Minority and Population Group by Generation Status: Canada Provinces and Territories Census Metropolitan Areas and Census Agglomerations With Parts.\u201dTable: 98\u201010\u20100324\u201001. 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