Respiratory Depression with Tramadol in a Patient with Renal Impairment and CYP2D6 Gene Duplication

In Brief We observed opioid-related respiratory depression in a patient receiving tramadol via patient-controlled analgesia. Predisposing factors were the patient's genetic background and renal impairment. Complete recovery occurred after naloxone administration, thus confirming opioid intoxication. Analysis of the patient's genotype revealed a CYP2D6 gene duplication resulting in ultra-rapid metabolism of tramadol to its active metabolite (+)O-desmethyltramadol. Concomitant renal impairment resulting in decreased metabolite clearance enhanced opioid toxicity. This genetic CYP2D6 variant is particularly common in specific ethnic populations and should be a future diagnostic target whenever administration of tramadol or codeine is anticipated, as both drugs are subject to a comparable CYP2D6-dependent metabolism. IMPLICATIONS: Predisposing factors for opioid-related respiratory depression in patients receiving tramadol include renal impairment and the genetic CYP2D6 variant that results in its ultra-rapid metabolism and accumulation of its active metabolite.