(107) Perioperative Buprenorphine Use Protects Against Long-Term Opioid Use

Background & Introduction: One of the highest risks for surgeries include persistent postoperative opioid use (PPOU), misuse, and diversion.1 Research shows 70-80% of surgical procedures result in mu opioid prescriptions in perioperative periods.2,3 Use of opioids in surgery for general anesthesia and analgesia contribute to PPOU and related problems.2

Benign prostatic hyperplasia (BPH) affects older men older and significantly impacts quality of life related to lower urinary tract symptoms. Initial therapies include medications at onset of bothersome symptoms. Urological surgical intervention is recommended for individuals who fail to respond adequately to medication.4

Despite recognized risks associated with mu opioid pain medication use, current literature does not address how different perioperative pathways impact persistent and/or long-term opioid use, misuse and opioid use disorders. Little is known about how buprenorphine (partial mu opioid agonist/kappa opioid antagonist)—with a superior safety profile versus traditional mu opioid agonists administered on the day of surgery—might influence PPOU outcomes in men for elective BPH surgery.5 Additionally, no research explores PPOU in elderly men. Therefore, this study compared incidence of PPOU postoperatively among opioid-naïve versus opioid-exposed men who had elective BPH procedure and received buprenorphine or mu agonists opioids on the day of surgery.

Methods: This retrospective cohort study utilized deidentified electronic health records from the TriNetX database, exempted from informed consent. Data searched came from 84 healthcare organizations between 2011 and 2024. Inclusion criteria were men aged 60 or older who underwent BPH surgery identified by specific Common Procedural Terminology (CPT) codes. Individuals were excluded if they underwent another surgical procedure requiring anesthesia 30–180 days after BPH surgery.

Mu opioid exposure status was determined by reviewing prescription records from one month to one day before the procedure or any diagnosis of an opioid-related disorder. Men who met either criterion were categorized as opioid-exposed and compared to opioid-naïve. After classification, both groups were further subdivided based on whether they received buprenorphine or opioids on the day of surgery, using International Classification of Diseases–Tenth Revision (ICD-10) codes.

The primary outcome—PPOU—was defined as any opioid prescription filled 90–180 days following the index BPH surgery. These criteria resulted in four distinct cohorts, enabling propensity score matching (PSM) through TriNetX Analytics to control for demographic and clinical confounders, performed two cohorts at a time.

Results: In the opioid-exposed group, 37 men received perioperative buprenorphine and 40,791 received perioperative opioids. After propensity score matching (PSM) 36 matched men were in the opioid exposed cohort. In contrast, the opioid-naïve group initially included 194 perioperative buprenorphine exposed and 121,129 perioperative mu-opioid exposed men who were matched to 193 men in each group.

Among opioid-naïve patients, PSM balancing yielded a statistically significant difference (p=0.0078) in demographic and clinical risk factors between buprenorphine and opioid users. PPOU occurred in 25 men within the mu opioid cohort, versus fewer than 10 patients in the buprenorphine cohort. Risk of PPOU was 12.95% for those who received opioids on day of surgery and 5.18% for those who received buprenorphine, with a risk difference of 7.77 percentage points (95% CI 2.10%~13.45%, p=0.0078). The risk ratio (RR) was 2.72 (95% CI 1.27~5.84), indicating that opioid-naïve patients undergoing BPH surgery were more than twice as likely to develop PPOU if they received perioperative mu opioid agonists instead of buprenorphine.

By contrast, in the opioid-exposed cohorts, the difference in PPOU rates was not statistically significant (p=0.22).

These findings suggest that for opioid-naïve individuals, perioperative buprenorphine may significantly reduce the likelihood of PPOU relative to conventional perioperative mu opioid use.

Conclusion & Discussion: This study is an initial step in research aimed to improve safety in elective surgeries by understanding and mitigating risks of opioid exposure among elderly patients who undergo BPH surgeries. Identifying how and which opioids (buprenorphine vs mu opioids) are prescribed for perioperative pain could reveal key opportunities for interventions to reduce development of persistent opioid use, misuse, dependence, and/or opioid use disorders.

Moreover, a broader analysis within large-scale databases, such as TRINETX, could be invaluable in exploring correlations between various disease states, concurrent medications, and the risk of PPOU, offering more comprehensive understanding of individual-specific vulnerability. Comparative studies with younger/young adult populations may also be considered. In addition, studies comparing younger and older populations may further clarify the impact of age-related physiological changes on the incidence and severity of opioid use disorders, potentially guiding age-specific recommendations for surgical care and pain management.

By examining alternative approaches to perioperative day of surgery pain control, this research aligns with ongoing endeavors to refine opioid prescribing practices while ensuring adequate analgesia. Ultimately, these findings underscore the importance of individualized strategies that minimize opioid-related harms.

References: (1.) Jivraj, N. K., Raghavji, F., Bethell, J., Wijeysundera, D. N., Ladha, K. S., Bateman, B. T., Neuman, M. D., & Wunsch, H. (2020). Persistent Postoperative Opioid Use: A Systematic Literature Search of Definitions and Population-based Cohort Study. Anesthesiology, 132(6), 1528-1539. https://doi.org/10.1097/ALN.0000000000003265

(2.) Ladha, K. S., Neuman, M. D., Broms, G., Bethell, J., Bateman, B. T., Wijeysundera, D. N., Bell, M., Hallqvist, L., Svensson, T., Newcomb, C. W., Brensinger, C. M., Gaskins, L. J., & Wunsch, H. (2019). Opioid Prescribing After Surgery in the United States, Canada, and Sweden. JAMA Netw Open, 2(9), e1910734. https://doi.org/10.1001/jamanetworkopen.2019.10734

(3.) Page, M. G., Kudrina, I., Zomahoun, H. T. V., Croteau, J., Ziegler, D., Ngangue, P., Martin, E., Fortier, M., Boisvert, E. E., Beaulieu, P., Charbonneau, C., Cogan, J., Daoust, R., Martel, M. O., Neron, A., Richebe, P., & Clarke, H. (2020). A Systematic Review of the Relative Frequency and Risk Factors for Prolonged Opioid Prescription Following Surgery and Trauma Among Adults. Ann Surg, 271(5), 845-854. https://doi.org/10.1097/SLA.0000000000003403

(4.) Smetana GW, Smith CC, Singla A, Libman H. How Would You Manage This Patient With Benign Prostatic Hyperplasia?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center. Ann Intern Med. 2023 Apr;176(4):545-555. doi: 10.7326/M23-0113.

(5.) T. R. Hickey, G. P. A. Costa, D. Oliveira, A. Podosek, A. Abelleira, V. J. Avila-Quintero, et al. Buprenorphine versus full agonist opioids for acute postoperative pain management: a systematic review and meta-analysis of randomized controlled trials Regional Anesthesia & Pain Medicine 2025 Pages rapm-2024-106014. DOI: 10.1136/rapm-2024-106014 https://rapm.bmj.com/content/rapm/early/2025/01/01/rapm-2024-106014.full.pdf