Symptomatic hypoglycemia due to escalating doses of intravenous methadone

Several case reports exist linking propoxyphene, a drug structurally related to methadone, to hypoglycemia. Morphine-induced hypoglycemia in mice has been shown to be inhibited by co-administration of naloxone. Blunted responses to insulin-induced hypoglycemia as well as delayed and inhibited insulin responses to food ingestion have been demonstrated in methadone maintenance patients. However, there are no published reports of methadone causing or contributing to symptomatic hypoglycemia. In this case, a 46 year old non-diabetic man with stage IV rectosigmoid cancer and renal failure that improved after nephrostomy tubes placement presented with severe abdominal pain due to a rapidly growing right pelvic wall mass. The patient required TPN and parenteral opioids due to the malabsorption. When his fentanyl PCA was changed to methadone the patient developed symptomatic hypoglycemia that resolved only after methadone infusion was stopped. A dose-dependent relationship between the degree of the patient's hypoglycemia and the dose of his intravenous methadone was established in this case. In addition to a stable TPN infusion for 18 hours a day, which was being infused at the times that the patient experienced symptomatic hypoglycemia, the patient received dextrose infusions for his recurrent hypoglycemic episodes. Despite TPN and dextrose infusions, the hypoglycemia persisted and resolved only after intravenous methadone was changed back to fentanyl. After a thorough endocrine evaluation, the high-dose intravenous methadone infusion was implicated as the cause of this patient's profound hypoglycemia. To the best of our knowledge, this is the first report of symptomatic hypoglycemia associated with intravenous methadone dose escalation. This case has important clinical applications for a patient who develops fatigue, agitation or lethargy on increasing doses of intravenous methadone because hypoglycemia and not opioid overdose may be the underlying cause of the patient's change in mental status. Blood sugar monitoring may be helpful in these situations.