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PATIENT SAFETY

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

Ulrike M. Stamer, MD^*, Frank Stüber, MD^*, Thomas Muders, MD^*, and Frank Musshoff, PhD

From the *Department of Anesthesiology and Intensive Care Medicine, and Institute of Forensic Medicine, University of Bonn, Bonn, Germany.

Address correspondence and reprint requests to Ulrike M. Stamer, Department of Anesthesiology and Intensive Care Medicine, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany. Address e-mail to ulrike.stamer{at}ukb.uni-bonn.de.

Abstract

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.