{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:12:37Z","timestamp":1781669557754,"version":"3.54.5"},"reference-count":37,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2014,3,26]],"date-time":"2014-03-26T00:00:00Z","timestamp":1395792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Anesthesia"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Propofol mixed with racemic ketamine (or \u2018ketofol\u2019) is popular for short procedural sedation and analgesia. Use is creeping into anesthesia, yet neither the optimal combination nor infusion rate is known. The<jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content><jats:sub>50<\/jats:sub>of propofol's antiemetic effect is reported to be 0.343\u00a0mg\u00b7l<jats:sup>\u22121<\/jats:sup>, while ketamine analgesia is thought to persist with concentrations above 0.2\u00a0mg\u00b7l<jats:sup>\u22121<\/jats:sup>. We aimed to determine a ketofol dosing regimen for anesthesia 30\u2010min and 1.5\u2010h duration in a healthy child that did not unduly compromise recovery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Pharmacokinetic\u2013pharmacodynamic parameters were used to simulate drug concentration and effect profiles over time for different ratios of propofol to ketamine ratios (1\u00a0:\u00a01 to 10\u00a0:\u00a01) and rates. The target effect was the 95% probability of loss of response to a 5\u2010s transcutaneous tetanus (P<jats:sub>05<\/jats:sub>). Combined effects were additive, with a propofol<jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content><jats:sub>50<\/jats:sub>of 3.1\u00a0mg\u00b7l<jats:sup>\u22121<\/jats:sup>, ketamine<jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content><jats:sub>50<\/jats:sub>of 0.64\u00a0mg\u00b7l<jats:sup>\u22121<\/jats:sup>, and slope of 5.4. The time to predicted 50% probability of return of this response after ceasing infusion (P<jats:sub>50<\/jats:sub>) was determined for a 5\u2010year\u2010old 20\u2010kg healthy child.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The addition of ketamine to propofol infused using a manual infusion regimen (loading dose 3\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>, then 15\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7h<jats:sup>\u22121<\/jats:sup>for 15\u00a0min, 13\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7h<jats:sup>\u22121<\/jats:sup>for 15\u00a0min, 11\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7h<jats:sup>\u22121<\/jats:sup>for 30\u00a0min, and 10\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7h<jats:sup>\u22121<\/jats:sup>for 1\u20132\u00a0h) caused prolonged postoperative sedation. The P<jats:sub>50<\/jats:sub>after a 1.5\u2010h infusion using a 1\u00a0:\u00a01 mixture was 4.5\u00a0h, 2\u00a0:\u00a01 mixture was 3.25\u00a0h, 5\u00a0:\u00a01 mixture was 1.6\u00a0h, and 10\u00a0:\u00a01 mixture was 40\u00a0min. These P<jats:sub>50<\/jats:sub>estimates could be reduced by slowing administration infusion rates to 20%, 33%, 50%, 67%, 80%, and 90% for mixtures 1\u00a0:\u00a01, 2\u00a0:\u00a01, 3\u00a0:\u00a01, 5\u00a0:\u00a01, 6.7\u00a0:\u00a01, and 10\u00a0:\u00a01, respectively. These rates achieve a P<jats:sub>50<\/jats:sub>of approximately 20\u00a0min for 30\u2010min duration anesthesia and 60\u00a0min for 1.5\u2010h duration anesthesia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The addition of ketamine to propofol infusion will prolong recovery unless infusion rates are decreased. We suggest an optimal ratio of racemic ketamine to propofol of 1\u00a0:\u00a05 for 30\u2010min anesthesia and 1\u00a0:\u00a06.7 for 90\u2010min anesthesia. Delivery of these ratios achieves propofol concentrations above an antiemetic threshold for longer than the ketamine concentration above the analgesic threshold during, potentially reducing postoperative nausea incidence.<\/jats:p><\/jats:sec>","DOI":"10.1111\/pan.12386","type":"journal-article","created":{"date-parts":[[2014,3,26]],"date-time":"2014-03-26T06:26:43Z","timestamp":1395815203000},"page":"806-812","source":"Crossref","is-referenced-by-count":40,"title":["Ketofol simulations for dosing in pediatric anesthesia"],"prefix":"10.1111","volume":"24","author":[{"given":"Finn L. S.","family":"Coulter","sequence":"first","affiliation":[{"name":"Paediatric Intensive Care Unit Starship Children's Hospital Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline A.","family":"Hannam","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,3,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1093\/ajhp\/54.11.1287","article-title":"Compatibility of propofol injectable emulsion with selected drugs during simulated Y\u2010site administration","volume":"54","author":"Trissel LA","year":"1997","journal-title":"Am J Health Syst Pharm"},{"key":"e_1_2_8_3_1","first-page":"426","article-title":"Stability of ketamine\u2010propofol mixtures for procedural sedation and analgesia in the emergency department","volume":"61","author":"Donnelly RF","year":"2008","journal-title":"Can J Hosp Pharm"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.jvca.2005.07.018"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9592.2007.02206.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-004-0707-4"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2005.04.011"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.jvca.2003.09.008"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9592.2006.02177.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2044.1991.tb09308.x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1213\/00000539-200004000-00016"},{"key":"e_1_2_8_12_1","first-page":"31","article-title":"Propofol and ketamine for dressing in burnt patients","volume":"43","author":"Escarment J","year":"1995","journal-title":"Cah Anesthesiol"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/PEC.0000000000000222"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9592.2008.02665.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9592.2009.02962.x"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9592.2010.03488.x"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/pan.12246"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199503000-00005"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1213\/ane.0b013e31817b859e"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199401000-00018"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9592.2007.02257.x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.48.113006.094708"},{"key":"e_1_2_8_23_1","first-page":"36","article-title":"Investigating the pharmacodynamics of ketamine in children","volume":"18","author":"Herd DW","year":"2008","journal-title":"PediatrAnesth"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e31821a8d80"},{"key":"e_1_2_8_25_1","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 WR","year":"1995","journal-title":"Pharmacol Rev"},{"key":"e_1_2_8_26_1","first-page":"5318","article-title":"Application of a new approach for the quantitation of drug synergism to the combination of cis\u2010diamminedichloroplatinum and 1\u2010beta\u2010D\u2010arabinofuranosylcytosine","volume":"50","author":"Greco WR","year":"1990","journal-title":"Cancer Res"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199710000-00010"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/53.1.27"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/51.12.1167"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9592.1999.00364.x"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1053-0770(00)90053-3"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2005.02445.x"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9592.2007.02380.x"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annemergmed.2010.11.030"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annemergmed.2009.04.004"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annemergmed.2010.08.032"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9592.2006.02145.x"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-6576.1999.430216.x"}],"container-title":["Pediatric Anesthesia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fpan.12386","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pan.12386","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T04:48:46Z","timestamp":1746161326000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pan.12386"}},"subtitle":[],"editor":[{"given":"Jerrold","family":"Lerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,3,26]]},"references-count":37,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2014,8]]}},"alternative-id":["10.1111\/pan.12386"],"URL":"https:\/\/doi.org\/10.1111\/pan.12386","archive":["Portico"],"relation":{},"ISSN":["1155-5645","1460-9592"],"issn-type":[{"value":"1155-5645","type":"print"},{"value":"1460-9592","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,3,26]]}}}