From Tramadol to Methadone Opioids in the Treatment of Pain and Dyspnea in Pediatric Palliative Care

Background: More than 15,000 children die annually in the United States due to an underlying life-limiting disease and the majority of those children experience distressing symptoms, which are not adequately relieved, such as pain and dyspnea. Multimodal analgesia, that is multiple agents, interventions, rehabilitation, psychological modalities, and integrative (nonpharmacologic) therapies, act synergistically for more effective pediatric pain and symptom control with fewer side effects than a single analgesic or modality. However, opioids, such as morphine, fentanyl, hydromorphone, oxycodone, and methadone (in the United Kingdom: diamorphine) remain the mainstay medication to effectively treat pain and dyspnea in children with serious illness. Methods: This article reviews commonly used opioids in Pediatric Palliative Care, which a special emphasis on 2 potentially particularly effective multimechanistic opioids: tramadol and methadone. Results: Methadone, due to its multimechanistic action profile, is possibly among the most effective and most underutilized opioid analgesics in children with severe unrelieved pain at end of life. However, methadone should not be prescribed by those unfamiliar with its use: Its effects should be closely monitored for several days, particularly when it is first started and after any dose changes. Conclusions: Tramadol appears to play a key role in treating episodes of inconsolability in children with progressive neurologic, metabolic, or chromosomally based condition with impairment of the central nervous system. However, the recent 2017 United States Food and Drug Administration (FDA) warning against pediatric use of tramadol does not seem to be based on clinical evidence, and therefore puts children at risk for unrelieved pain or increased respiratory depression.