Abstract
Introduction
Insufficient pain control following lower extremity surgery can increase length of stay, readmission rates, and impair postoperative outcome. It has been shown that CYP2D6 genotypes predict function of the enzyme responsible for conversion of hydrocodone to hydromorphone (active metabolite) and plasma concentration of hydromorphone best predicted analgesic response. Purpose of this study was to evaluate relationship of CYP2D6 genotypes, drug-drug interactions, and plasma drug concentrations in patients undergoing lower extremity surgery.
Methods
A prospective cohort of 271 orthopedic patients undergoing lower extremity surgery including TKA, THA and trauma were queried. Patients treated with hydrocodone were enrolled and tested for plasma concentrations of hydrocodone and hydromorphone. CYP2D6 genotyping was performed. Medications co-administered with hydrocodone during perioperative and postoperative periods were queried.
Results
Out of 271 patients enrolled, only 41 (15%) had detectable hydromorphone (i.e. >0.5 ng/mL). 86% were extensive (normal) metabolizers, 7% were intermediate metabolizers, 5% poor metabolizers and 2% were ultra rapid metabolizers. 179 subjects were not administered any inhibitors of CYP2D6 whereas 92 were on at least one inhibitor. 33 (18%) with no pharmacological inhibitors had detectable hydromorphone, whereas only 7 (7.6%) on inhibitors had hydromorphone detected above the lower limit of quantification (0.5ng/mL), p=0.033. Diphenhydramine, fluoxetine, hydralazine, duloxetine, bupropion and sertraline, were the most common CYP2D6 inhibitors co-administered with hydrocodone in this cohort.
Conclusions
Patients' home medications and selection of various drugs in the postoperative setting could impact the pharmacokinetics and pharmacodynamics of hydrocodone leading to a diminished analgesic response. We conclude that health care providers should become familiar with the inhibitors of CYP2D6 to obtain the best response with the use of hydrocodone following lower extremity surgery. Additional work is required to determine the ideal opioid for an individual patient's genotype following lower extremity orthopedic surgery.
For figures, tables, or references, please contact authors directly.
