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

Abstract

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.

Figure 1.

CONSORT Flow Diagram

Figure 2.

Implementation Outcomes: Opioid Use Among Study Participants Stratified by Treatment Assignment and CYP2D6 Phenotype High-risk phenotype defined as CYP2D6 IM (intermediate metabolizer), PM (poor metabolizer), UM (ultrarapid metabolizer), or NM-UM (range from NM to UM).

Figure 3.

Effectiveness Outcomes: Opioid Consumption and Composite Pain Intensity at 2-weeks Post-op by Study Arm (a) Opioid consumption and (b) composite pain intensity. Boxes represent the median values and upper and lower quartiles. Whiskers extend to show the rest of the distribution, except for outliers which are represented by diamonds.