Methadone: Best Practices for Weaning Pediatric Patients
Weaning from continuous opioid infusion can result in withdrawal and associated adverse effects, including respiratory, neurologic, and cardiovascular sequelae.
Practices pertaining to the use of methadone to facilitate opioid weaning in pediatric patients are widely heterogeneous, according to a recent systematic review and meta-analysis published in Pediatric Anesthesia.1
Weaning from continuous opioid infusion can result in withdrawal and associated adverse effects, including respiratory, neurologic, and cardiovascular sequelae. A 2015 randomized trial found withdrawal rates of 27% among pediatric critical care patients undergoing usual-care weaning management.2 Although methadone therapy is commonly used to facilitate this process, optimal protocols for use have not been clearly defined.
"Methadone has complicated pharmacokinetics, and choosing a dose and taper regimen that will reliably prevent withdrawal but avoid side effects can be challenging, as evidenced by the relatively high proportion of children who continue to experience opioid withdrawal despite methadone therapy in large studies," explained lead author Leslie A. Dervan, MD, a pediatric critical care intensivist from Seattle Children's Hospital and assistant professor at the University of Washington.
In the current study, Dr Dervan and colleagues aimed to identify best practices in the use of methadone for weaning pediatric patients from long-term opioid infusion. They examined the results of 12 studies involving a total of 459 intensive care patients aged 0 to 18 years in medical, cardiac, and surgical intensive care units (ICUs).
The results of the literature review show that premethadone drug exposure, methadone dosing, and taper regimens varied widely across studies, as did methadone taper times (from 4.3 to 26.2 days). The most common adverse event was excessive sedation, which affected 2% to 16% of patients. The meta-analysis revealed that the introduction of a new methadone protocol was associated with a lower proportion of patients experiencing withdrawal (standardized mean difference, −0.60; 95% CI, −0.998 to −0.195; P =.004).
The authors deemed the evidence insufficient to recommend specific strategies pertaining to the use of methadone for long-term opioid weaning in this setting. However, they discerned practices that may increase the likelihood of successful therapy, including the use of an ICU pharmacist and an institutional protocol for prescribing and tapering.
"Several different prescribing decisions should be considered, such as ensuring an appropriate methadone loading period, adequate initial dosing based on dose and duration of opioid exposure, and appropriate taper regimen based on duration of exposure and tolerance of ongoing weaning," Dr Dervan told Clinical Pain Advisor.
Future research in this area should compare methadone therapy with other weaning approaches, compare various methadone dosing and taper strategies, include thorough reporting of adverse effects, and evaluate potential benefits of methadone weaning in terms of time and cost savings and symptom control. "Ultimately, research comparing these different options will help providers choose an opioid weaning and discontinuation strategy that will reduce patients' symptoms while reducing ICU exposures and costs of care," said Dr Dervan.
Summary and Clinical Applicability
Additional research is needed to inform best practices regarding methadone therapy as a strategy for weaning pediatric ICU patients from continuous opioid infusion.
The main study limitation was that, because of the substantial heterogeneity of the evidence, the authors were unable to derive clear clinical implications from their findings.
- Dervan LA, Yaghmai B, Watson RS, Wolf FM. The use of methadone to facilitate opioid weaning in pediatric critical care patients: a systematic review of the literature and meta-analysis [published online January 20, 2017]. Paediatr Anaesth. doi: 10.1111/pan.13056
- Curley MA, Wypij D, Watson RS, et al. Protocolized sedation vs usual care in pediatric patients mechanically ventilated for acute respiratory failure: a randomized clinical trial. JAMA. 2015;313(4):379-389. doi: 10.1001/jama.2014.18399