What's Tramadol Got to Do with It? A Case Report of Rebound Hypoglycemia, a Reappraisal and Review of Potential Mechanisms.

BACKGROUND Tramadol has gained traction as an analgesic of choice among pain practicing physicians. However some concerns regarding a previously unlabeled adverse reaction - hypoglycemia - have cast it in a dim light. Prior reports have noted an associated risk of hospitalization for hypoglycemia after tramadol use, but whether tramadol is the main causal agent is poorly understood and the underlying mechanisms are not well delineated. We present a unique case of rebound hypoglycemia as a variation of the theme of tramadol's adverse effect profile in a patient with type 1 diabetes mellitus, and reappraise potential mechanisms underlying this underappreciated phenomenon. CASE PRESENTATION A 71-year-old woman presented with right buttock pain and right lateral leg discomfort of 9-month duration. Her physical exam suggested sacroiliac joint (SIJ) etiology, confirmed by magnetic resonance imaging (MRI). She was scheduled for an SIJ-diagnostic and therapeutic block and started on tramadol 50 mg 3 times daily on as needed basis. The patient subsequently developed severe hypoglycemia initially resistant to euglycemia restorative interventions with a rebound episode. Hypoglycemia resolved with oral ingestion of high levels of glucose and the patient was taken off tramadol. Fortunately, she did not require hospitalization. DISCUSSION The clinical scenario described is a case of rebound hypoglycemia after tramadol use in a patient with type-1 diabetes naïve to opioid analgesics. The episodes of hypoglycemia aligned perfectly with the anticipated pharmacodynamic and pharmacokinetic properties of tramadol. The specificity and temporality of events after tramadol use in this patient fulfilled causality criteria. Tramadol may cause rebound hypoglycemia in patients via interference of the intrinsic euglycemia-restoration pathways and a blunted autonomic counter-regulatory response to antecedent hypoglycemia. Its use must be tempered by this underappreciated adverse effect profile.Key words: Tramadol, hypoglycemia, sacroiliac joint arthritis, type 1 diabetes mellitus, serotonin uptake inhibitors, glutamate receptor 4.