Postoperative Opioid Dependence/Addiction

1. Dr. Obumneke Amadi-Onuoha Scripts
Research Question:
Are there genes that can play a role in increasing the risk of developing postoperative opioid
dependence/addiction?
Disease/Condition:
Postoperative Opioid Dependence/Addiction
Background: There are several studies showing that patients who undergo surgical procedures
are at increased risk of developing opioid dependence, and one study showed the risk of
developing postoperative opioid dependence to be 5.9% after minor surgical procedures
(Brummett, Waljee, & Goesling, 2017). In a retrospective study of 39,000 postoperative
patients, 3.1% of patients still required opioids 90 days after discharge (Clarke, Soneji, Ko, Yun,
& Wijeysundera, 2014). Typically, the duration of postoperative pain is less than 6 weeks, so
why are there a significant number of patients who require opioids after this period (Dunn,
Durieux, Nemergut, & Naik, 2017)? The answer to this question is likely multifactorial, and
some risk factors discovered to date include age, gender, comorbidities, surgical factors and
etcetera (Ip, Abrishami, Peng, Wong, & Chung, 2009).
Rationale: One overlooked factor from this equation may be the genetics of the patients.
CYP2D6 is a highly polymorphic gene whose polymorphism results in different degrees of
metabolism of many drugs including analgesics (Dean, 2012). For example, when a commonly
used opioid such as oxycodone is given to a poor metabolizer, the plasma concentration of this
drug will be significantly higher than an ultra-rapid metabolizer (Stamer, et al., 2013). Surgeons
commonly prescribe the same opioids postoperatively, but patients have different response to
them based on their genetics of metabolizing the drug.
Gene of Interest: Cytochrome P450 family 2 subfamily D member 6 (CYP2D6)
Hypothesis
Patients with poor metabolizer phenotypic variants of CYP2D6 will have increased incidence of
postoperative opioid addiction compared with ultra-rapid metabolizers.
Methods
Subjects: Patients admitted for elective laparoscopic cholecystectomy
Design: Cohort Study
• Enrolled patients are genotyped for CYP2D6 (blind). Postoperatively prior to discharge,
all patients receive a prescription for 6 pills (5 mg oxycodone).

2. • Data from Vermont Prescription Monitoring System (VPMS) will be gathered for the
next 1 year to assess further opioids prescribed for the patients.
• Patient’s genotypic variations will be compared with development of opioid
dependence/addiction.
• Experimental Protocol Development
Literature Review:
Experimental data on CYP2D6 variants and associated response to medications metabolized by
this cytochrome
Possible use of phenotypic marker instead of genotyping to decrease cost
Bioinformatics:
Genomic data analysis on patients previously genotyped with CYP2D6 polymorphism and
postoperative opioid use
References
Brummett, C. M., Waljee, J. F., & Goesling, J. (2017). New persistent opioid use after minor and
major surgical procedures in US adults. JAMA, 152:e170504.
Clarke, H., Soneji, N., Ko, D. T., Yun, L., & Wijeysundera, D. N. (2014). Rates and risk factors for
prolonged opioid use after major surgery: population based cohort study. British Medical
Journal, 348:g1251.
Dean, L. (2012, September 20). Codeine Therapy and CYP2D6 Genotype. Retrieved from
https://www.ncbi.nlm.nih.gov/books/NBK100662/pdf/Bookshelf_NBK100662.pdf
Dunn, L. K., Durieux, M. E., Nemergut, E. C., & Naik, B. I. (2017). Surgery-induced opioid
dependence: Adding fuel to the fire? Anesthesia & Analgesia, 125(5), 1806-8.
Ip, H. Y., Abrishami, A., Peng, P. W., Wong, J., & Chung, F. (2009). Predictors of postoperative
pain and analgesic consumption: a qualitative systematic review. Anesthesiology, 111, 657-677.
Stamer, U. M., Zhang, L., Book, M., Lehmann, L. E., Stuber, F., & Musshoff, F. (2013). CYP2D6
genotype dependent oxycodone metabolism in postoperative patients. PLoS One, 8(3).