Rheumatology 2014;53:1752–1758 doi:10.1093/rheumatology/ket443 Advance Access publication 22 January 2014

RHEUMATOLOGY

Concise report Predictors of pain medication use for arthroplasty pain after revision total knee arthroplasty Jasvinder A. Singh1,2,3 and David G. Lewallen2 Abstract

Methods. We examined whether demographic (gender, age) and clinical characteristics [BMI, co-morbidity measured by the Deyo–Charlson index (a 5-point increase), anxiety and depression] predict the use of NSAIDs and narcotic pain medications 2 and 5 years after revision TKA. Multivariable logistic regression adjusted for these predictors as well as operative diagnosis, American Society of Anesthesiologists class and distance from the medical centre. Results. A total of 1533 patients responded to the 2-year questionnaire and 881 responded to the 5-year questionnaire. NSAID use was reported by 13.4% (206/1533) of patients at 2 years and 16.7% (147/881) at 5 years. Narcotic medication use was reported by 5.4% (83/1533) of patients at 2 years and 5.9% (52/ 881) at 5 years. Significant predictors of the use of NSAIDs for index TKA pain at 2 and 5 years were age >60–70 years [odds ratio (OR) 0.62 (95% CI 0.39, 0.98) and 0.46 (0.25, 0.85)] compared with age 460 years and a higher Deyo–Charlson index [OR 0.51 (95% CI 0.28, 0.93)] per 5-point increase at 5-year after revision TKA. Significant predictors of narcotic pain medication use for index TKA pain were age >60–70 years [OR 0.41 (0.21, 0.78)] and >70–80 years [0.40 (95% CI 0.22, 0.73)] at 2 years and depression [OR 4.58 (95% CI 1.58, 13.18)] at 5 years.

CLINICAL SCIENCE

Conclusion. Younger age and depression were risk factors for the use of NSAIDs and narcotic pain medications for index TKA pain at 2- and 5-years after revision TKA. Key words: total knee replacement, pain medication, narcotic, NSAIDs, predictors, revision TKA, opioid.

Introduction Revision total knee arthroplasty (TKA) is associated with significant improvements in pain and function [1, 2]. In the USA, the annual rate of revision TKA is predicted to double by 2015 [3]. According to recent estimates, >60 000 revision TKAs were performed in 2006 in the

1 Medicine Service and Center for Surgical Medical Acute Care Research and Transitions (C-SMART), Birmingham VA Medical Center, 2 Department of Medicine, School of Medicine and Division of Epidemiology, School of Public Health, University of Alabama, Birmingham, AL and 3Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA.

Submitted 13 February 2013; revised version accepted 14 November 2013. Correspondence to: Jasvinder A. Singh, Department of Medicine, School of Medicine and Division of Epidemiology, School of Public Health, University of Alabama at Birmingham, Faculty Office Tower 805B, 510 20th Street S, Birmingham, AL 35294, USA. E-mail: [email protected]

USA using the National Inpatient Sample (NIS) [4]; a more recent study of the US Medicare population (565 years only) reported >19 000 revision TKAs in 2010 [5]. In recent years, several studies have examined pain and function outcomes after revision TKA [1, 2, 6–8]. Patients undergo revision TKA for refractory pain and/or functional limitation associated with mechanical loosening, wear or implant osteolysis and, less commonly, infection. While most patients have a favourable outcome after revision TKA, some patients may continue to have significant index arthroplasty pain. It is important to characterize these patients and to examine the outcomes in these poor responders. The use of pain medications after arthroplasty has been examined in patients with primary TKA [9, 10] and primary total hip arthroplasty (THA) [11], but not in revision TKA. Only one previous study examined the use of pain medications for the treatment of persistent/refractory index primary THA pain [11]. Outcomes of revision TKA are not as optimal and costs are higher

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Objective. Our objective was to study the use of pain medications for persistent knee pain and their predictors after revision total knee arthroplasty (TKA).

Pain medication use after revision knee arthroplasty

Materials and methods Data source We used the data from patients who underwent revision TKA between 1993 and 2005, collected prospectively in the Mayo Clinic Total Joint Registry [14, 15]. Since 1993, this joint registry has electronically captured patientreported outcomes (PROs) including pain and function assessments for every patient who has undergone arthroplasty (knee, hip, shoulder and others). PROs were captured using a validated knee questionnaire [16] that has face and construct validity and reliability. Analyses related to pain and functional limitations have been reported previously [17–20]. Patients were followed prospectively after their arthroplasty, with follow-up questionnaires at 2 and 5 years after arthroplasty by mail or in person at the clinical follow-up visit. The questionnaire included assessments of pain, function and the use of pain medications. Dedicated registry staff administered the questionnaire on the telephone to patients who did not return mailed surveys and failed to return for follow-up clinic visits. The Institutional Review Board at the Mayo Clinic, Rochester, MN, USA approved the study and waived the requirement for informed consent for these existing data. All investigations were conducted in conformity with the ethical principles of research.

Outcomes of interest The outcomes of interest were the patient-reported use of pain medications, NSAIDs and narcotics for index revision TKA pain at 2 and 5 years after revision TKA, assessed by a single question: Do you use any of the following medications for the pain in your operated knee? Responses included none, NSAIDs, narcotics and oral steroids. The use of NSAIDs and narcotics was analysed separately, with none/steroids as the reference category.

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Predictors of interest We examined important socio-demographic and clinical characteristics as potential predictors. These included age, gender, BMI, medical co-morbidity, depression and anxiety. Age was categorized into 460, 61–70, 71–80 and >80 years, as in previous studies [17, 21]. BMI was categorized into 425, 25.1–29.9, 30–34.9, 35–39.9 and 540, as recommended by the World Health Organization, and used widely in other studies [22]. The categorization of these variables was based on the clinical relevance of these categories, commonly used previously in several studies and for ease of interpretation by clinicians. Co-morbidity was measured by the Deyo–Charlson score, a validated co-morbidity measure based on medical records documentation of diagnostic codes [23], treated as a continuous variable. The Deyo–Charlson index is the most commonly used co-morbidity measure, consisting of a weighted scale of 17 co-morbidities (including cardiac, pulmonary, renal, hepatic disease, diabetes, cancer and HIV), expressed as a summative score [24, 25]; a higher score indicates more medical co-morbidity. Depression and anxiety were assessed by the presence or absence of the respective International Classification of Diseases, 9th revision (ICD-9) codes.

Statistical analyses We compared baseline clinical and demographic characteristics using the Student’s t-test for continuous variables and the chi-square test for categorical measures. We used logistic regression analyses to compare responder and non-responder characteristics. We performed multivariable-adjusted logistic regression analyses to assess predictors of NSAID use and narcotic medication use at 2 and 5 years after primary TKA. A generalized estimating equations averaged logistic regression model was used to adjust for clustering of knees within patients (due to replacement of both knees; >65% were sequential bilateral TKAs). All logistic regression analyses were adjusted for primary predictors of interest (i.e. age, gender, BMI, medical co-morbidity, anxiety and depression) and important covariates such as operative diagnosis, American Society of Anesthesiologists (ASA) class (class I or II vs III or IV) [26], median household income level (4$35 000, >$35 000–45 000, >$45 000) determined using the patients’ zip code, and the median household income for geographical areas using the census data for the respective year of the survey, as previously [20, 27], and distance from the medical centre (500 miles/ overseas) [27–29]. We then calculated the odds ratio (OR) and the 95% CI. A P-value 0.10 for all comparisons). As expected, the prevalence of moderate to severe pain was higher in patients using NSAIDs or narcotics at both 2 and 5 years (supplementary Table S4, available at Rheumatology Online; P < 0.001 for all comparisons).

Predictors of NSAID use after revision TKA Two years after revision TKA, significantly lower odds of NSAID use were noted in patients ages >60–70 years compared with patients 460 years (Table 1). Patients with a higher Deyo–Charlson index score had lower odds of NSAID use 2 years after revision TKA. Gender,

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Predictors of the use of narcotic pain medications after revision TKA At 2 years after revision TKA, patients ages >60–70 and >70-80 years had lower odds (compared with those 460 years) of using narcotic medications (Table 2). At 5 years after revision TKA, depression was associated with significantly higher odds of using narcotic pain medications (Table 2). Sensitivity analyses that had no pain medications as a reference category showed a minimal change in the OR and no change in interpretation for age >60–70 years and depression; age >70-80 years was no longer significantly associated at 2 years. Sensitivity analyses additionally adjusting for two-way interactions between age, Deyo–Charlson index score and depression were unstable for narcotic use at 2 years and failed to converge at 5 years. Sensitivity analyses that examined the 2-year outcomes in patients without moderate to severe pain (n = 1162) confirmed that the ORs for age associations were similar, but not statistically significant, as expected, due to a smaller sample (supplementary Table S6, available at Rheumatology Online); the model did not converge for patients with moderate to severe pain (n = 332).

Moderate to severe pain and the use of NSAIDs vs narcotic pain medications after revision TKA At both 2 and 5 years, narcotic pain medications were used less commonly than NSAIDs (supplementary Table S7, available at Rheumatology Online). In unadjusted models, the presence of moderate to severe pain was associated with significantly higher odds of the use of narcotics at 2 years but not at 5 years, with ORs of 2.93

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Of the 2800 revision TKA patients, 2695 were alive and eligible for the 2-year follow-up. Fifteen hundred and thirty-three (57%) completed a 2-year questionnaire. A total of 1842 patients were alive and eligible for the 5-year follow-up, with 881 (48%) having completed a 5-year questionnaire. Patients responding to either follow-up questionnaire (2- or 5-year) constituted the study cohort. At 2 years, responders had a mean age of 69 years (range 26–92), a mean BMI of 30.8 (range 15.6–62.4), >90% had a BMI >25 (the cut-off for overweight), with an equal male:female distribution (supplementary Table S1, available as supplementary data at Rheumatology Online). Loosening, wear or osteolysis was the underlying diagnosis in the majority of the patients. Almost 50% of the patients undergoing revision TKA had an ASA class of III or IV. Similar characteristics were noted for the 5-year cohort. Non-responders were more likely to be men, younger and have a higher Deyo–Charlson co-morbidity index score, higher ASA class and diagnoses other than loosening, osteolysis or wear (supplementary Table S2, available as supplementary data at Rheumatology Online).

BMI, depression and anxiety were not significantly associated with NSAID use after revision TKA. Five years after revision TKA, age >60–70 years (compared with age 460 years) was associated with significantly lower odds of NSAID use (Table 1). BMI, gender, co-morbidity and anxiety were not significantly associated. Sensitivity analyses that had no pain medications as a reference category showed minimal change in the OR and no change in interpretation: (i) both age >60–70 years and higher Deyo–Charlson index score were significantly associated with lower odds of NSAID use at 2 years and (ii) age >60–70 years was significantly associated with lower odds of NSAID use at 2 years. Sensitivity analyses additionally adjusting for two-way interactions between age, Deyo–Charlson index score and depression showed no significant interactions for NSAIDs use at 2 years (P > 0.20 for all) and did not converge for NSAIDs use at 2 years. Sensitivity analyses that examined the 2-year outcomes in patients without (n = 1162) and with (n = 332) moderate to severe pain confirmed that the OR for the Deyo–Charlson score and age were similar to the overall sample (supplementary Table S5, available at Rheumatology Online). As expected, some P-values for age associations lost statistical significance.

Pain medication use after revision knee arthroplasty

TABLE 1 Multivariable predictors of the use of NSAID medications after revision TKA Multivariable-adjusteda 2-year OR

95% CI

P-value

OR

95% CI

P-value

0.78

0.55, 1.10

0.16

0.74

0.48, 1.15

0.19

0.62 0.66 1.15

0.39, 0.98 0.43, 1.03 0.61, 2.15

0.04 0.07 0.66

0.46 0.73 0.49

0.25, 0.85 0.42, 1.27 0.19, 1.23

0.01 0.27 0.13

1.01 1.22 0.92 1.61 0.51 1.65 1.00

0.58, 0.69, 0.47, 0.74, 0.28, 0.87, 0.47,

0.97 0.50 0.81 0.23 0.03 0.13 0.99

1.01 1.01 2.10 1.48 0.70 0.86 0.49

0.50, 0.47, 0.92, 0.51, 0.28, 0.29, 0.11,

0.98 0.98 0.08 0.47 0.45 0.78 0.36

1.77 2.16 1.81 3.51 0.93 3.13 2.15

2.05 2.20 4.77 4.31 1.76 2.56 2.22

a

Adjusted for American Society of Anesthesiologists score, distance from the medical centre, income and operative diagnosis in addition to all the variables in the table. Numbers in bold indicate significant odds ratio (OR) and P-value. Goodness-of-fit statistics as assessed by quasi-likelihood under the independence model criterion (QIC; smaller is better) were 993.48 for the 2-year and 609.88 for the 5-year follow-up. Ref.: reference.

TABLE 2 Multivariable predictors of the use of narcotic pain medications after revision TKA Multivariable-adjusteda 2-year

Male gender (Ref., female) Age, years (Ref., 460 years) >60–70 >70–80 >80 BMI, kg/m2 (Ref., 60–70 >70–80 >80 BMI, kg/m2 (Ref., 60–70 years old reported a lower risk of NSAID use at 2 and 5 years and patients >60–70 and >70–80 years of age reported a lower risk of narcotic pain medication use for index arthroplasty pain 2 years after revision TKA. This finding adds to the current knowledge. To our knowledge, this is the first study to make this interesting observation. We have previously shown that younger patients report a much higher prevalence of moderate to severe pain 2 and 5 years after revision TKA [35], which is consistent with a greater need for pain medication for persistent index knee arthroplasty pain. An interesting finding was that higher co-morbidity (Deyo–Charlson index) was a predictor of lower odds of NSAID use. This OR of 0.5 mirrors a similar finding in a previous study where a 5-point increase in the Deyo–Charlson index score was associated with an OR of 0.8 for NSAID use for index joint pain in patients who had undergone revision hip arthroplasty [35]. We postulate that patients with higher co-morbidity may be less likely to get a physician’s recommendation to use NSAIDs, due either to the perceived risk or presence of significant renal, gastrointestinal and/or cardiac disease, which are risks with the long-term use of NSAIDs [36–40]. An important aspect of this study was that we studied the use of pain medications specifically for the index revision arthroplasty, and not general pain medication use for pain in other joints or other chronic pain states (e.g. low back pain, fibromyalgia, etc.). Another key aspect of our study was that we decided to use patient-reported use of pain medications as our study outcome rather than using

Pain medication use after revision knee arthroplasty

Rheumatology key messages NSAIDs were used by 13–17% of patients for persistent joint pain at the 2- and 5-year follow-ups after revision TKA and 5–6% reported using narcotic medications. . Patients >60–70 years of age have a lower chance of using either NSAIDs or narcotic pain medications for persistent knee pain 2 years after revision TKA compared with younger patients. .

Funding: This material is the result of work supported by research grants from the Mayo Clinic Orthopedic Surgery research funds, National Institutes of Health (NIH) Clinical Translational Science Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research) and the resources and use of facilities at the Birmingham VA Medical Center, Birmingham, AL, USA. J.A.S. is also supported by grants from the Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs), National Institute of Aging and National Cancer Institute. Disclosure statement: D.L. has received royalties from Zimmer, has been a paid consultant to Zimmer, Pipeline Biomedical and Ketai Medical Devices and owns stock in

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Pipeline Biomedical and Ketai Medical Devices. His institution has received research funds from DePuy, Stryker, Biomet and Zimmer. J.A.S. has received investigatorinitiated research grants from Takeda and Savient; consultant fees from Takeda, Savient, Allergan and Regeneron and is a member of the executive board of OMERACT, an organization that develops outcome measures in rheumatology and receives arms-length funding from 36 companies. J.A.S. is also a member of the American College of Rheumatology’s Guidelines Subcommittee of the Quality of Care Committee and Veterans Affairs Rheumatology Field Advisory Committee. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the US government.

Supplementary data Supplementary data are available at Rheumatology Online.

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explain outcomes after revision TKA, since these data are not available in our joint registry. Future studies should collect these data and assess if the appropriateness of primary and revision TKA are associated with persistent pain and pain medication use. Our response rate of 57% at 2 years is similar to the average survey response rate of 60% for large surveys such as ours [41]; however, our 48% 5-year response rate is lower. The major rationale for inclusion of the 5-year follow-up, despite the lower response rate, was to provide an assessment of pain medication use at longer-term follow-up after revision TKA, due to the absence of any studies to date that have assessed this outcome at 5 years. In summary, in a large cohort of patients undergoing revision TKA, we describe the prevalence of the use of pain medications for persistent index knee arthroplasty pain. The use of NSAIDs and narcotics was noted in 13% and 5% of patients at the 2-year follow-up and 17% and 6% at the 5-year follow-up after revision TKA, respectively. Age 460 years was associated with a higher risk of the use of NSAIDs and narcotic pain medications for persistent index knee arthroplasty pain. Depression was associated with a greater use of narcotic pain medications for persistent index knee arthroplasty pain. These findings should serve as useful guides to surgeons and patients in high-risk groups to improve their pain outcomes through close follow-up, optimized physical rehabilitation and screening and treatment of depression. Empiric evidence from well-designed studies is needed to assess which of these interventions may be effective in improving pain outcomes and reducing the use of chronic pain medications for persistent index knee arthroplasty pain after revision TKA.

Jasvinder A. Singh and David G. Lewallen

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