Respiratory depression with tramadol in a patient with renal impairment and CYP2D6 gene duplication.
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.
Stamer
Ulrike M
UM
Department of Anesthesiology and Intensive Care Medicine, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany. ulrike.stamer@ukb.uni-bonn.de
Stüber
Frank
F
Muders
Thomas
T
Musshoff
Frank
F
D000368:Aged; D000698:Analgesia; D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000378:metabolism*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D020440:Gene Duplication; D005786:Gene Expression Regulation; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D010597:Pharmacogenetics / Q000379:methods; D012119:Respiration; D012131:Respiratory Insufficiency / Q000139:chemically induced* / Q000235:genetics*; D014147:Tramadol / Q000009:adverse effects*
D000701:Analgesics, Opioid; D014147:Tramadol; D019389:Cytochrome P-450 CYP2D6