Methadone for Analgesia in Children with Life-Limiting Illness: Experience from a Tertiary Children’s Health Service

Abstract

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.

Old Drug, New Pain. Roles and Challenges of Methadone Therapy in Pediatric Palliative Care: A Systematic Review

“…In a bicentric retrospective study ( 18 ), 16 children with a life-limiting disease (cancer, n = 12; neurological conditions, n = 3; cardiac diagnosis, n = 1) received methadone for incomplete analgesia on other high-potency opioids ( n = 9), adverse events from other opioids ( n = 6) and desire to use oral analgesic ( n = 3). Their mean age was 7.4 (1.3–16) years.…”

“…Both Davies et al ( 20 ) and Mott et al ( 18 ) reported data on methadone use in patients previously exposed to other high-potency opioid medications. In these cases, the strategies used for opioids to methadone conversion were specifically analyzed.…”

“…In the study by Mott et al ( 18 ), one patient started methadone as a first-line therapy and the dose was calculated pro kg. Three patients began methadone as adjuvant (initial dose 1 mg) therapy and moved to methadone monotherapy over a few days/weeks, and 12 patients rapidly switched from high-dose opioids to methadone.…”

“…Indeed, in the studies by Hall et al and Davies et al ( 17 , 20 ), the efficacy of methadone was defined only as “improvement of pain,” without the use of dedicated scales. In the study by Mott et al ( 18 ) when the patient was incapable of expressing pain, symptoms were evaluated by parents and clinicians as proxy measures. However, some of these symptoms, such as irritability and agitation, may be due to causes other than pain.…”

Accidental Methadone Poisoning in a Four-Year-Old Child Reversed With Continuous Intravenous Infusion of Naloxone

“…Methadone toxicity in children can be deadly if antidote and supportive measures are not instituted in time [8]. Usual initial dose of methadone for moderate to severe pain relief in children ranged between 50 -100 µg/kg/dose [9][10][11][12]. In reported cases of acute methadone poisoning, dosage as low as 0.5 -1 mg/kg have been reported to potentially cause lifethreatening toxicity (i.e., respiratory depression) in children [13][14][15].…”