A hybrid implementation-effectiveness randomized trial of CYP2D6 -guided postoperative pain management

Purpose Cytochrome P450 2D6 ( CYP2D6 ) genotype–guided opioid prescribing is limited. The purpose of this type 2 hybrid implementation-effectiveness trial was to evaluate the feasibility of clinically implementing CYP2D6 - guided postsurgical pain management and determine that such an approach did not worsen pain control. Methods Adults undergoing total joint arthroplasty were randomized 2:1 to genotype-guided or usual pain management. For participants in the genotype-guided arm with a CYP2D6 poor (PM), intermediate (IM), or ultrarapid (UM) metabolizer phenotype, recommendations were to avoid hydrocodone, tramadol, codeine, and oxycodone. The primary endpoints were feasibility metrics and opioid use; pain intensity was a secondary endpoint. Effectiveness outcomes were collected 2 weeks postsurgery. Results Of 282 patients approached, 260 (92%) agreed to participate. In the genotype-guided arm, 20% had a high-risk (IM/PM/UM) phenotype, of whom 72% received an alternative opioid versus 0% of usual care participants ( p < 0.001). In an exploratory analysis, there was less opioid consumption (200 [104–280] vs. 230 [133–350] morphine milligram equivalents; p = 0.047) and similar pain intensity (2.6 ± 0.8 vs. 2.5 ± 0.7; p = 0.638) in the genotype-guided vs. usual care arm, respectively. Conclusion Implementing CYP2D6 to guide postoperative pain management is feasible and may lead to lower opioid use without compromising pain control.