{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T20:26:06Z","timestamp":1783542366336,"version":"3.55.0"},"reference-count":37,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2018,6,27]],"date-time":"2018-06-27T00:00:00Z","timestamp":1530057600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Methadone has the potential to assist in the management of pain in children with life-limiting illness, but its use is limited by its complex pharmacokinetic profile and limited research on its use in children. This is a retrospective review of the use of methadone as an analgesic in 16 children with life-limiting illness. Efficacy, dosing and side effect profile were analysed. Fifteen (94%) patients had improvements in their analgesia with minimal observed adverse effects. Patients were either rapidly converted from a prior opioid in one change or received methadone as an adjunct medication. Conversions were calculated using ratios frequently in the range of 10:1 to 20:1 from the oral morphine equivalent total daily dose (MEDD). Adjunct initial dosing was a low dose trial, often beginning with 1 mg at night. Only two patients required a dose adjustment due to side effects attributed to methadone. This was despite the cohort having significant underlying illnesses, extensive concurrent medications, and high methadone dosing where needed. Analysis of dosing and ratios indicates that an individualised approach is required. Based on this and on the infrequency of methadone use in this population, specialist assistance with dosing is recommended. Further research, including prospective and pharmacokinetic studies, is recommended.<\/jats:p>","DOI":"10.3390\/children5070086","type":"journal-article","created":{"date-parts":[[2018,6,27]],"date-time":"2018-06-27T11:02:05Z","timestamp":1530097325000},"page":"86","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Methadone for Analgesia in Children with Life-Limiting Illness: Experience from a Tertiary Children\u2019s Health Service"],"prefix":"10.3390","volume":"5","author":[{"given":"Christine","family":"Mott","sequence":"first","affiliation":[{"name":"Lady Cilento Children\u2019s Hospital, Brisbane 4069, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7965-6624","authenticated-orcid":false,"given":"Amrita","family":"Sarpal","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital London Health Sciences Centre, London, ON N6A 5W9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krista","family":"Moss","sequence":"additional","affiliation":[{"name":"Alder Hey Children\u2019s Hospital, Liverpool L12 2AP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9777-1105","authenticated-orcid":false,"given":"Anthony","family":"Herbert","sequence":"additional","affiliation":[{"name":"Lady Cilento Children\u2019s Hospital, Brisbane 4069, Australia"},{"name":"Centre for Children\u2019s Health Research at Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane 4069, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0885-3924(97)00020-1","article-title":"Plasma morphine and glucuronide (M3G and M6G) concentrations in hospice inpatients","volume":"14","author":"Ashby","year":"1997","journal-title":"J. Pain Symptom Manag."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1177\/1049909107312597","article-title":"Methadone","volume":"25","author":"Chhabra","year":"2008","journal-title":"Am. J. Hosp. Palliat. Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1093\/bja\/80.1.92","article-title":"Use of methadone in the morphine-tolerant burned paediatric patient","volume":"80","author":"Williams","year":"1998","journal-title":"Br. J. Anaesth."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/S0165-0173(99)00020-X","article-title":"NMDA and opioid receptors: Their interactions in antinociception, tolerance and neuroplasticity","volume":"30","author":"Mao","year":"1999","journal-title":"Brain Res. Brain Res. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1155\/2007\/730785","article-title":"Pharmacological Management of Chronic Neuropathic Pain: Consensus Statement and Guidelines from the Canadian Pain Society","volume":"12","author":"Moulin","year":"2007","journal-title":"Pain Res. Manag."},{"key":"ref_6","first-page":"60","article-title":"Revisiting methadone: Pharmacokinetics, pharmacodynamics and clinical indication","volume":"16","author":"Garcia","year":"2015","journal-title":"Rev. Dor"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1111\/pan.12385","article-title":"The pharmacokinetics of methadone and its metabolites in neonates, infants, and children","volume":"24","author":"Ward","year":"2014","journal-title":"Paediatr. Anaesth."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1097\/ALN.0b013e318238fec5","article-title":"Perioperative pharmacokinetics of methadone in adolescents","volume":"115","author":"Sharma","year":"2011","journal-title":"Anesthesiology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1002\/pbc.26207","article-title":"Pharmacokinetics and analgesic effects of methadone in children and adults with sickle cell disease","volume":"63","author":"Horst","year":"2016","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1002\/cpt1975182180","article-title":"Methadone in man: Pharmacokinetic and excretion studies in acute and chronic treatment","volume":"18","author":"Verebely","year":"1975","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1002\/pbc.25392","article-title":"Extreme doses of intravenous methadone for severe pain in two children with cancer","volume":"62","author":"Rasmussen","year":"2015","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1002\/pbc.21584","article-title":"Methadone analgesia for children with advanced cancer","volume":"51","author":"Davies","year":"2008","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_13","first-page":"22","article-title":"The merits of methadone","volume":"100","author":"McCaffery","year":"2000","journal-title":"Am. J. Nurs."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/S0885-3924(98)00366-2","article-title":"Pain Medication During Terminal Care of Children with Cancer","volume":"15","author":"Hovi","year":"1998","journal-title":"J. Pain Symptom Manag."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1097\/00002508-199812000-00013","article-title":"Oral methadone for the treatment of severe pain in hospitalized children: A report of five cases","volume":"14","author":"Shir","year":"1998","journal-title":"Clin. J. Pain"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"353","DOI":"10.5055\/jom.2011.0076","article-title":"Methadone use in children and young adults at a cancer center: A retrospective study","volume":"7","author":"Anghelescu","year":"2011","journal-title":"J. Opioid Manag."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1093\/bja\/70.4.414","article-title":"Ventilatory effects of morphine, pethidine and methadone in children","volume":"70","author":"Hamunen","year":"1993","journal-title":"Br. J. Anaesth."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/S0022-3476(05)81054-6","article-title":"Comparison of morphine and methadone for prevention of postoperative pain in 3- to 7-year-old children","volume":"119","author":"Berde","year":"1991","journal-title":"J. Pediatr."},{"key":"ref_19","first-page":"1353","article-title":"Methadone treatment for pain states","volume":"71","author":"Toombs","year":"2005","journal-title":"Am. Fam. Phys."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0885-3924(01)00389-X","article-title":"Patient-controlled analgesia with intravenous L-methadone in a child with cancer pain refractory to high-dose morphine","volume":"23","author":"Sabatowski","year":"2002","journal-title":"J. Pain Symptom Manag."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S0885-3924(99)00083-4","article-title":"Methadone: Outpatient titration and monitoring strategies in cancer patients","volume":"18","author":"Hagen","year":"1999","journal-title":"J. Pain Symptom Manag."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.jpainsymman.2015.02.029","article-title":"Methods of Rotation from Another Strong Opioid to Methadone for the Management of Cancer Pain: A Systematic Review of the Available Evidence","volume":"50","author":"McLean","year":"2015","journal-title":"J. Pain Symptom Manag."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1111\/j.1526-4637.2008.00461.x","article-title":"A systematic review of opioid conversion ratios used with methadone for the treatment of pain","volume":"9","author":"Weschules","year":"2008","journal-title":"Pain Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/ppul.22539","article-title":"Severe central sleep apnea in a child with leukemia on chronic methadone therapy","volume":"48","author":"Amos","year":"2013","journal-title":"Pediatr. Pulmonol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"131","DOI":"10.5055\/jom.2016.0325","article-title":"Methadone prolongs cardiac conduction in young patients with cancer-related pain","volume":"12","author":"Anghelescu","year":"2016","journal-title":"J. Opioid Manag."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/S0304-3959(03)00205-7","article-title":"QTc interval prolongation associated with intravenous methadone","volume":"105","author":"Kornick","year":"2003","journal-title":"Pain"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/j.1521-0391.2009.00002.x","article-title":"Methadone and buprenorphine toxicity in children","volume":"19","author":"Boyer","year":"2010","journal-title":"Am. J. Addict."},{"key":"ref_28","unstructured":"Irving, H., Liebke, K., Lockwood, L., Noyes, M., Pfingst, D., and Rogers, T. (2014). A Practical Guide to Palliative Care in Paediatrics, Children\u2019s Health Queensland Hospital and Health Service. Available online: https:\/\/www.caresearch.com.au\/QuoCCA\/Portals\/6\/Documents\/A-Practical-guide-to-Palliative-Care-in-Paediatrics.pdf."},{"key":"ref_29","unstructured":"(2018, June 17). Eastern Metropolitan Region Palliative Care Consortium, Opioid Conversion Ratios Guide to Palliative Care Practice: Rangeview, Australia,. Available online: http:\/\/www.emrpcc.org.au\/wp-content\/uploads\/2016\/05\/Opioid-Conversions-May-3-2016-final.pdf."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/S0022-3476(95)70370-5","article-title":"Control of severe pain in children with terminal malignancy","volume":"126","author":"Collins","year":"1995","journal-title":"J. Pediatr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1136\/heart.89.11.1363","article-title":"Drug induced QT prolongation and torsades de pointes","volume":"89","author":"Yap","year":"2003","journal-title":"Heart"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1046\/j.1460-9592.2003.01153.x","article-title":"Methadone dosage for prevention of opioid withdrawal in children","volume":"13","author":"Siddappa","year":"2003","journal-title":"Paediatr. Anaesth."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1016\/j.ejpn.2016.07.021","article-title":"Effective treatment of spasticity using dronabinol in pediatric palliative care","volume":"20","author":"Kuhlen","year":"2016","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"123","DOI":"10.5055\/jom.2016.0324","article-title":"Methadone conversion in infants and children: Retrospective cohort study of 199 pediatric inpatients","volume":"12","author":"Fife","year":"2016","journal-title":"J. Opioid Manag."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1111\/j.1445-5994.2005.00888.x","article-title":"Effects of opioids and sedatives on survival in an Australian inpatient palliative care population","volume":"35","author":"Good","year":"2005","journal-title":"Intern. Med. J."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Sathornviriyapong, A., Nagaviroj, K., and Anothaisintawee, T. (2016). The association between different opioid doses and the survival of advanced cancer patients receiving palliative care. BMC Palliat. Care, 15.","DOI":"10.1186\/s12904-016-0169-5"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/S1470-2045(03)01079-9","article-title":"The use of opioids and sedatives at the end of life","volume":"4","author":"Sykes","year":"2003","journal-title":"Lancet Oncol."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/5\/7\/86\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:10:18Z","timestamp":1760195418000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/5\/7\/86"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,27]]},"references-count":37,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2018,7]]}},"alternative-id":["children5070086"],"URL":"https:\/\/doi.org\/10.3390\/children5070086","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,27]]}}}