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October 21, 2008
3:00 PM - 4:30 PM
Room Room 230A
Impact of CYP2D6 Genotype on the Analgesic Effect of Oxycodone in Postoperative Pain
Stine T. Zwisler, M.D., Thomas P. Enggaard, M.D., Ph.D., Soeren S. Mikkelsen, M.D., Kim Brosen, M.D., Ph.D., Soeren H. Sindrup, M.D., Ph.D.
Anesthesiology and Intensive Care Medicine, Odense University Hospital, Odense C, Denmark
Introduction: Oxycodone is a semi-synthetic opioid with a µ-receptor agonist-mediated effect in several pain conditions, e.g. postoperative pain. Oxycodone is metabolized to its active metabolite oxymorphone by O-demethylation via CYP2D6. A genetic polymorphism divides a Caucasian population in two clinically important groups: 8% poor metabolizers (PMs) with impaired or no function of CYP2D6 and over 90% extensive metabolizers (EMs) with preserved function of CYP2D6.

Aim: To investigate if PMs obtain the same analgesia postoperatively from oxycodone as EMs.

Methods: 268 patients undergoing thyroid surgery, parathyroid surgery or hysterectomy were included and followed for 24 hours postoperatively. The CYP2D6 genotype was blinded to both the patient and the investigator until inclusion of all patients had ended.

All patients received oxycodone as pain treatment for 24 hours postoperatively. Initially, 5 mg i.v. was given approximately 30 min. before surgery ended. Upon request, oxycodone 5 mg i.v. was given in the recovery room once or twice. At discharge from the recovery room, patient-controlled analgesia with oxycodone 2 mg boluses i.v. was initiated. Intravenous morphine 5 mg was used as escape medicine.

When entering the recovery room and after 1, 2, 3, 4, 6, 8, 12, 18 and 24 hours, the patients rated their pain level on a Numeric Rating Scale (NRS, 0=no pain, 10=worst possible pain). After 24 hours, the patients completed a questionnaire to evaluate their satisfaction with the postoperative pain management.

A responder was characterized as a patient without need for escape medication and a positive evaluation in the questionnaire.

Results: 23 patients were categorized as PM (8.6%) and 245 were EM (91.4%). 22 PM were responders and 1 PM was non-responder (4.4%). 202 EM were responders and 43 EM were non-responders (17.1%).

There was no difference in the responder rate (p= 0.14) between the two genotypes.

Comparing the AUC0-24 hours of NRS at rest (EM mean 1.51 vs PM mean 1.67) and during movement (EM mean 2.41 vs PM mean 2.39) we found no difference between the genotypes (p=0.59 and p=0.88).

There was no difference in the total consumption of oxycodone between the two genotypic groups (EM = 14.9 mg and PM = 13.3 mg, p = 0.46).

Discussion: Our distribution of genotype was comparable to earlier findings in the Caucasian population, and therefore the patient population is representative.

In general, the patients included in the study did not suffer from severe postoperative pain, and it would have been ideal to study a group with more intense pain to demonstrate any differences.

An earlier study (not yet published) has shown that PMs in human experimental pain experience less pain relief from oxycodone than EMs and that PMs had a lower oxymorphone/oxycodone plasma ratio than EM, indicating that the CYP2D6 genotype may be of importance in patients with more intense postoperative pain.

With only 1 PM non-responder, our findings suggest that there is no relation between CYP2D6 genotype and efficacy of oxycodone in postoperative pain.

Conclusion: This study found no difference in the analgesic effect of oxycodone between CYP2D6 genotypes.

Acknowledgements: The study was supported financially by the Lundbeck foundation and University of Southern Denmark.

Anesthesiology 2008; 109 A1588