Polypharmacy as a Predictor of Opioid Dependence and Misuse Post-Orthopaedic Surgery

RESEARCH ANALYSIS

Polypharmacy as a Predictor of Opioid Dependence and Misuse Post-Orthopaedic Surgery

JACOB SPRING, BA

Sidney Kimmel Medical College at Thomas Jefferson University

SUMMARY POINTS

-        Orthopedics needs new predictors for ensuring short-term, responsible, and safe opioid use in post-surgical patients

-        Polypharmacy is the concurrent use of five or more medications. Patients with polypharmacy have notably increased odds of developing and sustaining chronic opioid use

-        Those with a history of using multiple substances are more likely to report misuse and abuse of opioid analgesics for pain management

ANALYSIS

Background

Orthopedic surgeons rank third on the list of highest opioid prescribers in healthcare (1). This makes sense considering their practice often involves surgeries with potentially painful recovery periods. However, opioid prescription is not without risks, as 6-10% of opioid-naïve patients go on to develop new persistent opioid use each year after surgery (2, 3). While many experts agree that overdose from prescription opioids is not a leading cause of death in post-surgical populations, there is concern that blanket efforts to curb opioid prescribing have fueled the recent rise in the use of illicitly produced synthetic opioids, such as fentanyl, as patients look for alternative methods of pain management (4). Hence, there is a current push to uncover the patterns of patient opioid use in the months following orthopedic procedures. If providers can identify which patients are predisposed to opioid misuse or long-term dependence, prescriptions can be tailored in a manner that can reduce risk in susceptible patients while still being able to provide effective relief to those not at risk.  

One predictor that has been heavily scrutinized by orthopedic surgeons looking to improve post-surgical patient outcomes is the concurrent use of multiple medications—termed “polypharmacy,” defined as the concurrent use of five or more prescription medications. In past analyses, several authors have noted that preoperative polypharmacy is linked to poor functional outcomes in patients recovering from surgery (5, 6). Moreover, in the field of pain management, incidence of polypharmacy is as high as 71.4% in patients suffering from chronic pain (7). This analysis will primarily explore the small subset of literature surrounding polypharmacy as it relates to opioid use, as well as attempt to synthesize findings in an orthopedic surgery context.

Findings

A recent study published in Perioperative Medicine identified predictors of patients having at least three ongoing opioid prescriptions in the 24-month period following hip surgery (8). Notably, among the variables identified as being statistically predictive of receiving many opioid prescriptions, high preoperative health-seeking behavior—defined by a high number of health visits—had one of the strongest effects (8). Intuitively, surgical patients who see providers more frequently likely possess some form of preoperative comorbidity or at least show a greater concern for their health. Considering this, it is valid to pose the question whether polypharmacy could be classified as a health-seeking behavior, or rather a predisposing factor for continued opioid use.

Existing literature on patterns of chronic opioid use in elderly patients suggests that a positive association does in fact exist if high health-seeking behavior is replaced with a patient’s total number of prescription medications (9). When stratified by chronic use versus no use, there was an adjusted odds ratio of 4.89 [1.53, 15.65] that patients on five or more non-opioid medications would display prevalent chronic use of opioids over no use of opioid (9). Notably, the patient group on one to four medications showed an odds ratio of 2.59 [0.79, 8.45] in favor of prevalent chronic opioid use, posing the possibility that there may be a linear correlation if a larger data set is collected (9).

Further research on Medicare Part D claims found that the average opioid user fills fifty-two prescriptions annually from 10 different drug classes (10). This suggests that polypharmacy, as a proxy for poor health and prescription variety, is present in patients who rely on opioids for pain management. Furthermore, a population-based cohort study of orthopedic patients receiving hip fracture surgery revealed the individual predictive power of certain preoperative medications for new chronic opioid use post-surgery (11). Drugs including NSAIDs, SSRIs, antipsychotics, statins, corticosteroids, antibiotics, antiosteoporotics, and antiplatelets all individually increased risk of new chronic opioid use when used consistently in the year before surgery (Figure 1) (11).

Figure 1. Adjusted risk factors for new chronic opioid use following hip surgery. Included patients report no preoperative opioid  use. Reprinted from Edwards NM, Varnum C, Overgaard S, Nikolajsen L, Christiansen CF, Pedersen AB. Risk factors for new chronic opioid use after hip fracture surgery: a Danish nationwide cohort study from 2005 to 2016 using the Danish multidisciplinary hip fracture registry. BMJ Open. 2021;11(3):e039238. doi:https://doi.org/10.1136/bmjopen-2020-039238

Interestingly, it is also possible that a history of medical polysubstance use can predict patient behaviors and adherence to opioid use protocols. A multi-level analysis published in 2017 showed that patients who endorsed using multiple substances—including both prescription benzodiazepines and illicit drugs—were three times more likely to report misuse of their opioid prescription and five times more likely to report overall opioid abuse (Figure 2) (12). 

Figure 2. Reported misuse and abuse of opioid analgesics classified by reported degree of multiple substance abuse. Reprinted from Morley KI, Ferris JA, Winstock AR, Lynskey MT. Polysubstance use and misuse or abuse of prescription opioid analgesics. PAIN. 2017;158(6):1138-1144. doi:https://doi.org/10.1097/j.pain.0000000000000892

Discussion

Amidst the opioid epidemic, it is a surgeon’s duty to determine the potential for long-term opioid dependence or misuse in those they operate on. Research shows that orthopedic surgeons could benefit from considering the polypharmacy history of their patients when deciding if it is safe to offer opioids as a method of post-surgical pain management. Considering that medication lists are easily accessible for most providers, future investigations are feasible and warranted to explore polypharmacy as it relates to more descriptive characteristics of post-surgical opioid use, such as length of prescription, number of refills, and dosage changes. 

REFERENCES

1. Wyles CC, Hevesi M, Ubl DS, et al. Implementation of Procedure-Specific Opioid Guidelines. JB & JS Open Access. 2020;5(1):e0050-e0050. doi:https://doi.org/10.2106/jbjs.oa.19.00050

2. Hinds S, Miller J, Maccani M, et al. Patient risk screening to improve transitions of care in surgical opioid prescribing: a qualitative study of provider perspectives. Regional Anesthesia & Pain Medicine. 2022;47(8):475-483. doi:https://doi.org/10.1136/rapm-2021-103304

3. Brummett CM, Waljee JF, Goesling J, et al. New Persistent Opioid Use After Minor and Major Surgical Procedures in US Adults. JAMA surgery. 2017;152(6):e170504. doi:https://doi.org/10.1001/jamasurg.2017.0504

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6. Mangoni AA, Russell P, Jarmuzewska EA. Preoperative polypharmacy assessment for risk stratification and management. British Journal of Clinical Pharmacology. 2022;88(5):1952-1954. doi:https://doi.org/10.1111/bcp.15271

7. Zahlan G, Clifford-Faugère GD, Nguefack HLN, et al. Polypharmacy and Excessive Polypharmacy Among Persons Living with Chronic Pain: A Cross-Sectional Study on the Prevalence and Associated Factors. Journal of Pain Research. 2023;16:3085-3100. doi:https://doi.org/10.2147/JPR.S411451

8. Rhon DI, Snodgrass SJ, Cleland JA, Sissel CD, Cook CE. Predictors of chronic prescription opioid use after orthopedic surgery: derivation of a clinical prediction rule. Perioperative Medicine. 2018;7(1). doi:https://doi.org/10.1186/s13741-018-0105-8

9. Oh Gy, Abner EL, Fardo DW, Freeman PR, Moga DC. Patterns and predictors of chronic opioid use in older adults: A retrospective cohort study. Gnjidic D, ed. PLOS ONE. 2019;14(1):e0210341. doi:https://doi.org/10.1371/journal.pone.0210341

10. Matos A, Bankes DL, Bain KT, Ballinghoff T, Turgeon J. Opioids, Polypharmacy, and Drug Interactions: A Technological Paradigm Shift Is Needed to Ameliorate the Ongoing Opioid Epidemic. Pharmacy: Journal of Pharmacy Education and Practice. 2020;8(3). doi:https://doi.org/10.3390/pharmacy8030154

11. Edwards NM, Varnum C, Overgaard S, Nikolajsen L, Christiansen CF, Pedersen AB. Risk factors for new chronic opioid use after hip fracture surgery: a Danish nationwide cohort study from 2005 to 2016 using the Danish multidisciplinary hip fracture registry. BMJ Open. 2021;11(3):e039238. doi:https://doi.org/10.1136/bmjopen-2020-039238

12. Morley KI, Ferris JA, Winstock AR, Lynskey MT. Polysubstance use and misuse or abuse of prescription opioid analgesics. PAIN. 2017;158(6):1138-1144. doi:https://doi.org/10.1097/j.pain.0000000000000892