{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T16:32:16Z","timestamp":1759336336783,"version":"3.40.5"},"reference-count":15,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T00:00:00Z","timestamp":1589932800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014364","name":"National Children's Research Centre","doi-asserted-by":"publisher","award":["F\/12\/4"],"award-info":[{"award-number":["F\/12\/4"]}],"id":[{"id":"10.13039\/100014364","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Titrating analgesic and sedative drugs in pediatric intensive care remains a challenge for caregivers due to the lack of pharmacodynamic knowledge in this population. The aim of the current study is to explore the concentration\u2010effect relationship for morphine\u2010associated oversedation after cardiac surgery in children aged 3 months to 3 years. Data on morphine dosing, as well as morphine plasma concentrations, were available from a previous study on the pharmacokinetics of morphine after cardiac surgery in children. Oversedation was defined as scores below 11 on the validated COMFORT\u2013behavioral scale. Population pharmacokinetic\u2010pharmacodynamic modeling was performed in NONMEM 7.3. The probability of oversedation as a function of morphine concentration was best described using a step function in which the EC<jats:sub>50<\/jats:sub> was 46.3 ng\/mL. At morphine concentrations below the EC<jats:sub>50<\/jats:sub>, the probability of oversedation was 2.9% (0.4&amp; to 18%), whereas above the EC<jats:sub>50<\/jats:sub> percentages were 13% (1.9% to 52%) (median value [95% prediction interval from interindividual variability]). Additionally, the risk of oversedation was found to be increased during the first hours after surgery (<jats:italic>P<\/jats:italic> &lt; .001) and was significantly lower during mechanical ventilation (<jats:italic>P<\/jats:italic> &lt; .005). We conclude that morphine concentrations above approximately 45 ng\/mL may increase the probability of oversedation in children after cardiac surgery. The clinician must evaluate, on a case\u2010by\u2010case basis, whether the analgesic benefits arising from dosing regimen associated with such concentrations outweigh the risks.<\/jats:p>","DOI":"10.1002\/jcph.1620","type":"journal-article","created":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T22:14:07Z","timestamp":1590012847000},"page":"1231-1236","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Exploring the Relationship Between Morphine Concentration and Oversedation in Children After Cardiac Surgery"],"prefix":"10.1002","volume":"60","author":[{"given":"Abraham J.","family":"Valkenburg","sequence":"first","affiliation":[{"name":"Department of Intensive Care Erasmus University Medical Center  Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3369-6107","authenticated-orcid":false,"given":"Sebastiaan C.","family":"Goulooze","sequence":"additional","affiliation":[{"name":"Division of Systems Biomedicine and Pharmacology Leiden Academic Centre for Drug Research Leiden University  Leiden the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun Yin","family":"Ng","sequence":"additional","affiliation":[{"name":"Division of Systems Biomedicine and Pharmacology Leiden Academic Centre for Drug Research Leiden University  Leiden the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cormac V.","family":"Breatnach","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia and Critical Care Medicine Our Lady's Children's Hospital  Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dick","family":"Tibboel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Erasmus University Medical Center\u2013Sophia Children's Hospital  Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monique","family":"van Dijk","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Erasmus University Medical Center\u2013Sophia Children's Hospital  Rotterdam the Netherlands"},{"name":"Division of Nursing Science Department of Internal Medicine Erasmus University Medical Center\u2013Sophia Children's Hospital  Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherijne A. J.","family":"Knibbe","sequence":"additional","affiliation":[{"name":"Division of Systems Biomedicine and Pharmacology Leiden Academic Centre for Drug Research Leiden University  Leiden the Netherlands"},{"name":"St. Antonius Hospital Department of Clinical Pharmacy  Nieuwegein the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elke H.J.","family":"Krekels","sequence":"additional","affiliation":[{"name":"Division of Systems Biomedicine and Pharmacology Leiden Academic Centre for Drug Research Leiden University  Leiden the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,5,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(98)00028-3"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjpo-2017-000046"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/PCC.0000000000000904"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200948060-00003"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-016-0398-z"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-013-2971-3"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci4020321"},{"key":"e_1_2_8_9_1","first-page":"885066619871432","article-title":"Postoperative pain management in pediatric patients undergoing cardiac surgery: where are we heading?","author":"Pollak U","year":"2019","journal-title":"J Intensive Care Med"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000446-200501000-00019"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.PCC.0000149318.40279.1A"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2011.05.001"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(99)00239-0"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/jpepsy\/17.1.95"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200612000-00013"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200603000-00013"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.1620","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.1620","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.1620","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T23:19:44Z","timestamp":1693955984000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.1620"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,20]]},"references-count":15,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["10.1002\/jcph.1620"],"URL":"https:\/\/doi.org\/10.1002\/jcph.1620","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"type":"print","value":"0091-2700"},{"type":"electronic","value":"1552-4604"}],"subject":[],"published":{"date-parts":[[2020,5,20]]},"assertion":[{"value":"2020-01-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}