AbstractAimsParenteral oxycodone is increasingly used worldwide to manage perioperative pain. Oxycodone doses required for adequate analgesia vary significantly between individuals. Our study investigated whether an analgesic plasma concentration could be determined for oxycodone and which factors affect it.Methods1000 women undergoing breast cancer surgery were recruited to the study. Demographic data were collected and their cold and heat pain sensitivity and anxiety scores were measured preoperatively. After surgery, rest and motion pain intensities were measured. Intravenous oxycodone was administered until the patients reported satisfactory pain relief (NRS <4/10). At this point, plasma concentrations of oxycodone and its metabolites were determined. A second plasma sample for oxycodone deter-mination was taken when the patient requested a new dose of oxycodone. Genomic DNA was extracted from whole blood samples and the patients were genotyped for CYP2D6, CYP3A4 and CYP3A5 variants.ResultsThe two oxycodone concentrations showed a strong correlation (r =0.84). The pain intensity measured during motion before oxycodone dosing correlated significantly with the plasma oxycodone concentration (geometric mean 35.3 ng/ml and CV % 66.4) required to achieve satisfactory analgesia (r = 0.38, p = 1.5 x 10-33). The most important factors associating with postoperative pain intensity were type of surgery (breast conserving or mastectomy with or without axillary clearance) and the age of the patient. Older patients reported lower pain scores and required smaller oxycodone concentrations for satisfactory analgesia. CYP2D6, CYP3A5 or CYP3A4 genotypes did not significantly affect the oxycodone concentrations, but CYP2D6 genotype significantly affected the formation of the metabolites oxymorphone and noroxymorphone. CYP3A4 and CYP3A5 genotypes did not affect the metabolite formation.ConclusionsOur results indicate that the more pain the patient experiences postoperatively the greater her minimum plasma oxycodone concentration must be to achieve satisfactory analgesia. Type of surgery and age significantly affect postoperative pain intensity.
Scandinavian Journal of Pain – de Gruyter
Published: Jul 1, 2016
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