Predictors of pain and use of pain medications following primary Total Hip Arthroplasty (THA): 5,707 THAs at 2-years and 3,289 THAs at 5-years

Primary Total Hip Arthroplasty (THA) is an extremely successful surgery [1] associated with significant pain relief and improvement in function and quality of life [2]. Implant survival studies indicate a very low failure rate of <1% per year [3, 4]. While important clinical outcomes/complications such as fracture, infection and revision have been studied well, well-designed studies assessing patient-reported outcomes have been getting more attention in the last decade [5]. Pain is the number one reason for patients undergoing these procedures and therefore recurrence and/or persistence of significant hip pain after THA is of great concern for both patients and surgeons. While several important unmodifiable patient characteristics such as age and gender can impact pain outcomes following primary THA, it is important to know whether modifiable factors such as Body Mass Index and comorbidity impact pain following primary THA.

Are Body mass index (BMI) and comorbidity associated with pain outcomes after THA? The evidence is contradictory. BMI was associated with more pain at 6-12 months post-primary THA in one study [6], but not in others [7–9]. Comorbidity was found to be associated with pain outcomes post-THA in all studies [7, 9–11] except one [6]. The main limitation of most previous studies is a small sample size that makes them underpowered to detect significant associations, thereby leading to false negative results. These studies also differed in measures of pain outcomes, length of follow-up and confounders adjusted in the analyses.

Non-modifiable factors of interest, such as gender have also been studied. Some studies have reported that female gender is associated with worse pain outcomes post-primary THA [7, 9, 12], while other studies found no gender association [10, 11, 13, 14]. Similarly, younger age was associated with more pain 1-15 years post-THA [9, 12–14], while others found no difference in pain outcomes by age, at 6-12 months [6, 7, 10, 11, 15]. A recent systematic review assessing prognostic factors for patient outcomes in THA studies up to 2001 reported that female gender was associated with less post-operative pain, after THA [16].

We hypothesized that at 2- and 5-years post-THA: (1) higher body mass index and comorbidity will be associated with worse pain outcomes; (2) pre-operative depression and anxiety, female gender and younger age will be associated with worse pain outcomes and higher use of pain medications.

We used the data collected prospectively in the Mayo Total Joint Registry, detailed in previous studies [17, 18]. Starting in 1993, all patients who underwent hip arthroplasty at the Mayo Clinic received a hip questionnaire that included questions regarding hip pain and function [19]. This validated questionnaire was administered at 2- and 5-years post-operatively by mail or in person at the clinical follow-up visit [20, 21]. Patients who did not return the mailed survey and failed to return for follow-up clinic visits, had the questionnaire administered on the telephone by experienced registry staff. The study was approved by the Mayo Clinic Institutional Review Board. Several studies using these questionnaires and outcomes in knee and hip arthroplasty patients have been published or are in press [22–25]. The study cohort consisted of all patients who underwent primary THA at the Mayo Clinic, Rochester between 1993 and 2005 and were alive at the 2- or 5-year follow-up. We did not restrict by age group or diagnosis. A total of 9,154 THAs at 2- and 6,243 THAs at 5-year were eligible for the study.

In this study, we found that higher body mass index was associated with significantly higher odds of moderate-severe hip pain and use of NSAID medications 2-years after primary THA. At 2-years post-primary THA, female gender was associated with higher odds of NSAID and opioid medication use. Depression was associated with higher odds of moderate-severe pain and opioid medication use at 2-years post-primary THA. Most of these associations were still significant at 5-years.

Our study has many novel findings that merit further discussion. We believe our study is among the first to provide the estimates of NSAIDs and opioid medication use after primary THA in a large sample of patients. Despite several studies of pain after THA, quite surprisingly, the prevalence of pain medication use at intermediate- or long-term follow-up after THA has not been described. In this large sample of patients, we provide estimates of moderate-severe pain at intermediate-term follow-up after primary THA. This information can be provided at pre-operative counseling so that patients have realistic expectations from the procedure. Studies are needed to examine use of these mediations at long-term follow-up after THA.

Second, depression predicted moderate-severe pain and higher opioid medication use 2-years post-primary THA. Previous studies in primary knee arthroplasty patients have reported that depression predicts pain at 1- [32], 2- [33] and 5-years [34]. To our knowledge, there are no published studies that have examined whether depression is associated with pain or pain medication use after primary THA. Our findings suggest that screening for depression prior to surgery may help identify patients at-risk for poorer pain outcomes and opioid use 2-years after THA. A potential explanation of association of baseline depression with 2-year outcomes may be higher pain perception and reporting by those with depression than those without depression. Further studies need to examine if treatment of depression in the pre- or post-operative period improves pain outcomes and opioid medication use 2-years after THA. At 5-years, these associations were not significant. The lack of significance with 5-year outcomes may be due to smaller sample size at 5-years compared to 2-years, longer duration since depression diagnosis or simple lack of any association at 5-years.

The third important finding in this study is that higher BMI significantly predicted a higher risk of moderate-severe hip pain at 2- and 5-years. This finding confirms a similar finding in one other study of 193 patients at 6-12 months post-primary THA [6], but is in contrast to three multivariable-adjusted studies that found no such association at 0.5-years [7] or at 15-years [8, 9]. All previous studies were multivariable-adjusted, similar to our study. Previous studies had examined BMI as a continuous [6, 7] or three-level categorical variable (<25, 25-30, >30) [8, 9], compared to 5-level categorical variable in our study, as per the WHO classification [27]. The main reason for two of the previous studies being negative was small sample size, making them liable to type II error, i.e., missing an effect when one exists due to a small sample size. We categorized BMI as per WHO classification [27], since our sample size was large enough to not restrict us to fewer categories. Another interesting observation was a dose-relationship of increasing BMI with moderate-severe pain at 5-year follow-up.

Fourth, the association of female gender with NSAID use and opioid medication use at 2- and 5-years, but not moderate-severe pain merits some discussion. Lack of gender-pain associations in our study is similar to many studies [10, 11, 13, 14], but in contrast to others [7, 9, 12]. Higher odds of use of NSAIDs and opioid medications in women versus men with primary THA is similar to higher analgesic use reported for women in national cohorts of patients in US and Sweden [35, 36]; our study extends this finding to THA cohorts. Our finding of lack of gender and pain severity in THA patients is also interesting, since we have reported higher prevalence of pain in women at 2- and 5-year post-TKA from the same dataset [22]. Thus, gender has different impact on pain outcomes after THA versus TKA.

Lastly, the lack of association of older age with pain outcomes confirmed similar findings in studies of primary THA [6, 7, 10, 11], in contrast to others [9, 12–14]. Again, it is interesting that age associations we noted in post-TKA outcomes from the same dataset were not true for post-THA [22].

Our study has several strengths. We examined the NSAID and opioid medication use alongside pain assessment at both 2- and 5-years after primary THA in a large cohort. This is the most important contribution of this study. Most previous studies were limited to 1-2 year follow-up and had not included study of use of pain medications for residual pain after THA. The study of use of pain medications is an important outcome, which is under-studied in the arthroplasty literature. We controlled for several important confounders and covariates and our estimates of association were robust i.e., changed very little between univariate and multivariable models.

Our study has several limitations. Non-response and referral bias may limit generalizability to general populations. The response rate of 62% at 2-years and 53% at 5-years, is similar to the average response rate of 60% in large surveys of this size [37]. A higher response rate is always more desirable. The estimates of association in this study are conservative, since non-responders were more likely to be younger, have ASA class III-IV and live >100 miles away from the medical center and the same categories that also reported more pain. Residual confounding is possible in this cohort study due to our inability to control for pre-operative pain in the main analyses, since this would have led to selection bias with only less than half subjects eligible in each category. We were unable to adjust for acute pain management after THA, which may impact chronic postoperative pain [38]. Depression and anxiety would be best captured by examination by a psychologist or use of validated instruments such as Center for Epidemiological Studies Depression (CES-D) scale or Beck's Depression Inventory. This was a retrospective analysis of prospectively collected data of all-comers for THA over a 12-year period that did not include depression questionnaires; and psychiatric evaluation of every patient undergoing THA is neither feasible nor clinically appropriate. Currently there is no National U.S. Joint Registry, and therefore an analysis of data collected over a considerable time-period from a large volume medical center (such as this) is the next best approach. Future studies can examine the predictors of moderate and severe categories separately, if it is clinically indicated.

In summary, we studied pain severity and use of pain medications 2- and 5-years after primary THA in a large cohort of patients. We noted significant impact of BMI on moderate-severe pain and use of pain medications 2- and 5-years after THA. Associations with depression with moderate-severe pain were significant at 2-years, but not at 5-year follow-up. Female gender was associated with more pain medication use, but similar pain outcome. This study identifies modifiable factors for pain outcomes, which can be targeted with pre- or post-operative interventions in future studies.