Use of pharmacogenetic data to guide individualized opioid prescribing after surgery

Despite the current strategies aimed at avoiding opioid overprescription by implementing institutional guidelines, the use of opioids after surgical procedures remains highly variable. It is well known that opioids are activated by the cytochrome p450 CYP2D6 enzyme to exert pharmacologic effect. Individual variation in CYP2D6 activity affects drug metabolism, and genotyping can be performed to predict an individual's ability to metabolize CYP2D6 substrates. We postulate that the pharmacogenomic identification of patients with different opioid metabolism capacity may allow for the individualization of postsurgical opioid prescription.

This study was generated by the unison of data from 2 prior initiatives taking place at our Institution. In the first study, patients undergoing 1 of 25 elective surgical procedures were prospectively identified as part of a quality initiative and surveyed by phone 21 to 35 days after hospital discharge to complete a 29-question survey regarding opioid utilization and pain experience. Additional chart abstraction was conducted to obtain prescribing data and pain scores during the hospitalization. The second study was the Mayo Clinic Right Drug, Right Dose, Right Time study protocol, in which 5 pharmacogenes, including CYP2D6, were genotyped for 1,000 Mayo Clinic Biobank participants. The goal of this study was to implement preemptive pharmacogenomics in an academic health care setting and to generate data for further pharmacogenomic research. Patients were classified by their predicted CYP2D6 activity based on their CYP2D6 genotype.

Of the 2,486 patients with prospective opioid utilization data, 21 had pharmacogenetic data available and were included in the analysis. These patients were classified according to their activity as opioid metabolizers, with 10 patients (48%) classified as intermediate, 4 patients (19%) as intermediate to normal, and 7 patients (33%) as normal or extensive. Compared with the intermediate to normal and intermediate phenotypes, normal or extensive patients had the highest percentages of preoperative opioid naivety and recorded pain scores throughout the surgical experience. The percentage of unused opioids for intermediate, intermediate to normal, and normal or extensive categories was 79%, 63%, and 46%, respectively. Moreover, of the 14 patients declaring the highest level of satisfaction for their pain control after discharge, 60% belonged to intermediate, 100% to intermediate to normal, and 57% to the normal or extensive group.

This study outlines a possible correlation between genetically controlled metabolism and opioid requirements after surgery. In this setting, an increased CYP2D6 enzymatic activity was associated to a greater opioid consumption, lesser amount of unused opioids, and a lower satisfaction level from opioid prescription.