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Preoperative Pain Management: Is Tramadol a Safe Alternative to Traditional Opioids Before Total Hip Arthroplasty?
The Journal of Arthroplasty xxx (2020) 1e6
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The Journal of Arthroplasty journal homepage: www.arthroplastyjournal.org
Preoperative Pain Management: Is Tramadol a Safe Alternative to Traditional Opioids Before Total Hip Arthroplasty? Joshua E. Bell, MD, Sean B. Sequeira, BS, Dennis Q. Chen, MD, Emanuel C. Haug, MD, Brian C. Werner, MD, James A. Browne, MD * Department of Orthopaedic Surgery, University of Virginia, Charlottesville, VA
a r t i c l e i n f o
a b s t r a c t
Article history: Received 19 February 2020 Received in revised form 26 April 2020 Accepted 28 April 2020 Available online xxx
Background: Preoperative opioid use has been associated with worse clinical outcomes and higher rates of prolonged opioid use following lower extremity arthroplasty. Tramadol has been recommended for management of osteoarthritis-related pain; however, outcomes following total hip arthroplasty (THA) in patients taking tramadol in the preoperative period have not been well described. The aim of this study is to examine the effect of preoperative tramadol use on postoperative outcomes in patients undergoing elective THA. Methods: A total of 5304 patients who underwent primary THA for degenerative hip pathology from 2008 to 2014 were identified using the Humana Claims Database. Patients were grouped by preoperative pain management modality into 3 mutually exclusive populations including tramadol, traditional opioid, or nonopioid only. A multivariate logistic regression was used to evaluate all postsurgical outcomes of interest. Results: Tramadol users had an increased risk of developing prolonged narcotic use (odds ratio [OR], 2.17; confidence interval [CI], 1.89-2.49; P < .001) following surgery compared to nonopioid-only users. When compared to traditional opioid use, tramadol use was associated with decreased risk of subsequent 90day minor medical complications (OR, 0.75; CI, 0.62-0.90; P ¼ .002), emergency department visits (OR, 0.70; CI, 0.57-0.85; P < .001), and prolonged narcotic use (OR, 0.43; CI, 0.37-0.49; P < .001). Traditional opioid use significantly increased length of stay by 0.20 days (P ¼ .001) when compared to tramadol use. Conclusion: Preoperative tramadol use is associated with prolonged opioid use following THA but is not associated with other postoperative complications. Patients taking tramadol preoperatively appear to have a lower risk of postoperative complications compared to patients taking traditional opioids preoperatively. © 2020 Elsevier Inc. All rights reserved.
Keywords: arthroplasty preoperative pain management hip postoperative complications opioids tramadol
Hip osteoarthritis (OA) is one of the most common musculoskeletal conditions treated worldwide [1e3]. The current gold standard treatment for end-stage hip OA is total hip arthroplasty (THA), which has excellent patient outcomes and the ability to restore function and improve quality of life following surgery [4e6]. Before surgical management, conservative management including physical therapy, lifestyle modification, and pain
One or more of the authors of this paper have disclosed potential or pertinent conflicts of interest, which may include receipt of payment, either direct or indirect, institutional support, or association with an entity in the biomedical field which may be perceived to have potential conflict of interest with this work. For full disclosure statements refer to https://doi.org/10.1016/j.arth.2020.04.093. * Reprint requests: James A. Browne, MD, Department of Orthopaedic Surgery, University of Virginia, Box 800159 HSC, Charlottesville, VA 22908. https://doi.org/10.1016/j.arth.2020.04.093 0883-5403/© 2020 Elsevier Inc. All rights reserved.
management is utilized for symptomatic treatment of OA. Although traditional opioids are not recommended by the AAOS, many patients are prescribed them for pain management before arthroplasty. However, as the opioid epidemic in the United States continues to incur a significant health and economic burden on patients and healthcare institutions, perioperative opioid consumption has come under greater scrutiny [7e9]. The use of preoperative opioids has been associated with prolonged narcotic use in the postoperative period, in addition to worse postoperative pain management and increased risk of postoperative complications [10e13]. Tramadol is considered an “atypical” opioid analgesic; when compared to other narcotics, it exhibits weaker opioid receptor agonism and has additional effects on the serotonergic and noradrenergic pathways [14e17]. Tramadol is also perceived to present a lower risk of addiction and respiratory
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depression compared to other opioids. As a result, tramadol has grown in popularity as an alternative to traditional opioids for the management of moderate to severe OA [18,19]. Although the AAOS Clinical Practice Guidelines do not comment on the use of tramadol for hip OA, tramadol was given a strong recommendation for the management of symptomatic knee OA [20]. Additionally, the American College of Rheumatology advocates for the use of tramadol for the initial management of hip OA [21]. There is a paucity of literature evaluating the impact of preoperative tramadol use on postoperative outcomes following THA. This study aims to evaluate the use of preoperative tramadol on postoperative outcomes including minor and major medical complications, prolonged opioid use, dislocation, periprosthetic fracture (PF), periprosthetic joint infection (PJI), revision THA (rTHA), emergency department (ED) visits, readmissions, and length of stay (LOS) following THA. We hypothesized that tramadol would be associated with an increased risk of prolonged opioid use postoperatively but would not be associated with the risk of postoperative complications. Methods Data Source A retrospective database review was conducted utilizing the commercially available PearlDiver Patient Records Database (www. pearldiverinc.com; PearlDiver Inc, Colorado Springs, CO), which contains all Humana Private/Commercial and Medicare patients from 2007 to 2017Q1, searchable by International Classification of Diseases, Current Procedural Terminology (CPT), and National Drug Codes among others. Queried data are de-identified and Health Insurance Portability and Accountability Act compliant; therefore, institutional review board approval was waived for this study. Study Population The study population included all Humana patients from the years of 2008 to 2014 aged 20 to 85 who underwent elective THA (CPT-27130) for degenerative pathology. Patients undergoing same-day revision and those with a history of hip trauma, infection, or neoplasm were excluded from the population using CPT and International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes (Appendix Table 1). The population was then grouped into 3 mutually exclusive cohorts based on the patient’s preoperative pain management modality: (1) tramadol, (2) traditional opioid, and (3) nonopioid only. Patients using both tramadol and traditional opioids in the preoperative period were excluded from the study. This was determined by filled outpatient prescriptions within 4 months of the index surgery. Using the National Drug Code Directory, the following brand name and generic opioid formulations were included in the traditional opioid group: hydrocodone, hydromorphone, morphine, fentanyl, oxymorphone, propoxyphene, oxycodone, and oxycontin. Tramadol use was defined as any generic formulations of tramadol and the name brand equivalent, Ultram (Janssen Pharmaceuticals, Inc, Beerse, Belgium).
use. Matching was performed on a 1:1:1 ratiodevery patient in the tramadol use cohort was matched with 1 patient in the both the traditional opioid and nonopioid-only use cohorts. Postoperative Outcomes Following THA Study groups were evaluated for LOS and the following 90-day outcomes: minor medical complication, major medical complications, ED visits, readmissions, and reimbursement. Minor medical complications included deep vein thrombosis, urinary tract infection, acute kidney injury, wound complications, and need for transfusion. Likewise, major medical complications included pulmonary embolism, pneumonia, myocardial infarction, cerebrovascular accident, sepsis, and death. The following complications within 1 year of surgery were also analyzed: hip dislocation, PF, PJI, and rTHA (Appendix Table 2). Finally, prolonged postoperative opioid use was compared among the 3 groups. Prolonged opioid use was defined as opioid use within the 3- to 6-month postoperative window following index surgery. By 3 months patients should not require opioid prescriptions for the management of postoperative THA pain. Likewise, 6 months was selected to minimize crossover with future planned surgeries or procedures that may require postoperative narcotic prescriptions. Statistical Analysis Pearson’s chi-square analysis was used to compare all outcomes of interest in addition to baseline demographics and comorbidities. Multivariate logistic regression was used to determine the independent effect each preoperative pain management modality had on postoperative outcomes after adjusting for age, gender, and preexisting comorbidities/substance abuse as covariates. Mean LOS was compared using Welch’s t-test. Linear regression was used to determine the independent effect of each preoperative pain management modality on LOS using the previously mentioned covariates. All statistical analyses were performed using R Project for Statistical Computing, which is embedded in the PearlDiver software. Significance was determined by a P value < .05. Results Patient Demographics and Comorbidities Following application of inclusion and exclusion criteria and successful 1:1:1 matching, 5304 patients were identified as undergoing THA during the study period. Of those, 1768 utilized tramadol, 1768 utilized traditional opioids, and 1768 utilized nonopioids only preoperatively. Analysis of preoperative hip pathology diagnosis revealed that an overwhelming majority of patients had preexisting hip OA. The highest rates of OA were within the tramadol (96%) and traditional opioid users (96%); however, nonopioid users had a clinically similar rate of hip OA (94%). The next most common diagnosis was avascular necrosis of the femoral head, which was more prevalent among tramadol users (8%) compared to traditional opioid (6%) and nonopioid-only users (4%). No differences existed between the 3 cohorts in terms of age, sex, and preexisting comorbidities (Table 1).
Patient Matching The resulting 3 cohorts (tramadol users, traditional opioid users, and nonopioid-only users) were matched based on age, sex, and the following preexisting comorbidities: obesity, chronic kidney disease, peripheral vascular disease, chronic obstructive pulmonary disease, diabetes mellitus, hyperlipidemia, hypertension, coronary artery disease, congestive heart failure, depression, and tobacco
Postoperative Outcomes Between Tramadol Users and NonopioidOnly Users Following adjusted multivariate regression, tramadol was associated with increased odds of prolonged postoperative narcotic use (48% vs 30%; odds ratio [OR], 2.17; confidence interval [CI],1.89-2.49; P < .001) when compared to nonopioid-only users. Between the 2
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Table. 1 Patient Demographics. Patient Demographics Age (y) <65 65-69 70-74 75-79 80-84 Male sex Female sex Comorbidities Obesity (BMI > 30 kg/m2) Chronic kidney disease PVD Diabetes mellitus COPD CHF Coronary artery disease Hyperlipidemia Hypertension Depression Tobacco use Preoperative degenerative pathology Osteoarthritis Avascular necrosis Rheumatoid arthritis SLE Psoriatic arthritis Ankylosing spondylitis
Tramadol (N ¼ 1768)
Traditional Opioid (N ¼ 1768)
Nonopioid Only (N ¼ 1768)
P Value
336 436 500 324 172 588 1180
19% 25% 28% 18% 10% 33% 67%
336 436 500 324 172 588 1180
19% 25% 28% 18% 10% 33% 67%
336 436 500 324 172 588 1180
19% 25% 28% 18% 10% 33% 67%
1.000
201 115 74 403 311 44 300 1270 1348 176 180
11% 7% 4% 23% 18% 2% 17% 72% 76% 10% 10%
201 115 74 403 311 44 300 1270 1348 176 180
11% 7% 4% 23% 18% 2% 17% 72% 76% 10% 10%
201 115 74 403 311 44 300 1270 1348 176 180
11% 7% 4% 23% 18% 2% 17% 72% 76% 10% 10%
1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000
1692 99 99 19 6 5
96% 6% 6% 1% <1% <1%
1693 134 88 15 5 3
96% 8% 5% 1% <1% <1%
1655 71 70 13 3 6
94% 4% 4% 1% <1% <1%
.004 <.001 .072 .659 .606 .606
1.000
BMI, body mass index; PVD, peripheral vascular disease; COPD, chronic obstructive pulmonary disease; CHF, congestive heart failure; SLE, systemic lupus erythematosus.
cohorts, there was no significant difference in odds of postoperative minor medical complications (P ¼ .544), major medical complications (P ¼.243), ED visit (P ¼.915), readmission (P ¼.631), dislocation (P ¼ .893), PF (P ¼ .287), PJI (P ¼ .703), and rTHA (P ¼ .164). When compared to nonopioid-only users, tramadol use did not attribute to a significant change in LOS (P ¼ .727; Tables 2 and 3).
PJI (P ¼ .150), and rTHA (P ¼ .706). When compared to nonopioidonly users, traditional opioid use was independently associated with a 0.18-day increase in LOS (P ¼ .005; Tables 2 and 3).
Postoperative Outcomes Between Opioid Users and Nonopioid-Only Users
Patients using preoperative tramadol, when compared to traditional opioid users, were associated with decreased risk of subsequent minor medical complications (13% vs 17%; OR, 0.75; CI, 0.62-0.90; P ¼ .002), ED visit (11% vs 15%; OR, 0.70; CI, 0.57-0.85; P < .001), and prolonged postoperative narcotic use (48% vs 68%; OR, 0.43; CI, 0.37-0.49; P < .001). There was no significant difference in risk of postoperative major medical complications (P ¼ .280), readmission (P ¼ .073). dislocation (P ¼ .215), PF (P ¼ .841), PJI (P ¼ .072), and rTHA (P ¼ .080). When compared to the traditional opioid cohort, preoperative tramadol use was associated with a 0.20-day decrease in LOS (P ¼ .001; Tables 2 and 4).
Patients with preoperative traditional opioid use had increased odds of minor medical complications (17% vs 13%; OR, 1.42; CI, 1.181.72; P < .001), ED visit (15% vs 11%; OR, 1.41; CI, 1.16-1.72; P ¼ .001), readmission (8% vs 6%; OR, 1.35; CI, 1.04-1.75; P ¼ .023), and prolonged postoperative narcotic use (68% vs 30%; OR, 5.06; CI, 4.385.85; P < .001) when compared to nonopioid-only users. There were no significant differences in risk of postoperative major medical complications (P ¼ .931), dislocation (P ¼ .266), PF (P ¼ .207),
Postoperative Outcomes Between Tramadol Users and Traditional Opioid Users
Table. 2 Rates of Postoperative Outcomes Between Tramadol, Traditional Opioid, and Nonopioid-Only Users. Postoperative Outcomes
90-d Minor medical complications 90-d Major medical complications 90-d Emergency department visit 90-d Readmissions 1-y Hip dislocation 1-y Periprosthetic fracture 1-y Periprosthetic infection 1-y Revision arthroplasty Prolonged narcotic use Length of stay (d)
Tramadol (N ¼ 1768)
Traditional Opioid (N ¼ 1768)
Nonopioid Only (N ¼ 1768)
P Value Tramadol vs Nonopioid Only
Traditional Opioid vs Nonopioid Only
Tramadol vs Traditional Opioid
234 (13%) 59 (3%) 201 (11%) 118 (7%) 28 (2%) 13 (1%) 13 (1%) 21 (1%) 853 (48%) 3.07 ± 1.66
298 (17%) 71 (4%) 272 (15%) 146 (8%) 38 (2%) 12 (1%) 24 (1%) 34 (2%) 1203 (68%) 3.27 ± 1.96
222 (13%) 72 (4%) 203 (11%) 111 (6%) 29 (2%) 19 (1%) 15 (1%) 31 (2%) 539 (30%) 3.09 ± 0.92
.581 .285 .958 .682 1.000 .375 .850 .209 <.001 .729
<.001 1.000 .001 .028 .324 .279 .198 .802 <.001 .005
.003 .326 .001 .084 .263 1.000 .098 .103 <.001 .001
Values in bold denote significance determined as P < .05.
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Table. 3 Adjusted Odds Ratios (OR) of Postoperative Outcomes of Tramadol Users and Traditional Opioid Users Compared to Nonopioid-Only Users. Postoperative Outcomes
Tramadol vs Nonopioid Only Adjusted OR (95% CI)
P Value
Traditional Opioid vs Nonopioid Only Adjusted OR (95% CI)
P Value
90-d Minor medical complications 90-d Major medical complications 90-d Emergency department visit 90-d Readmissions 1-y Hip dislocation 1-y Periprosthetic fracture 1-y Periprosthetic infection 1-y Revision arthroplasty Prolonged narcotic use Length of stay (d)
1.33 0.81 0.99 1.07 0.96 0.68 0.86 0.67 2.17 a 0.02
.544 .243 .915 .631 .893 .287 .703 .164 <.001 .727
1.42 0.99 1.41 1.35 1.32 0.62 1.61 1.10 5.06 a 0.18
<.001 .931 .001 .023 .266 .207 .150 .706 <.001 .005
(0.87-1.30) (0.57-1.15) (0.80-1.22) (0.82-1.40) (0.57-1.63) (0.33-1.37) (0.40-1.83) (0.38-1.17) (1.89-2.49) (0.14 b 0.10)
(1.18-1.72) (0.70-1.38) (1.16-1.72) (1.04-1.75) (0.81-2.17) (0.40-1.28) (0.85-3.16) (0.67-1.80) (4.38-5.85) (0.06 ≤ b ≤ 0.31)
Values in bold denote significance determined as P < .05. CI, confidence interval. a Standardized beta (b) coefficient.
Discussion The use of tramadol for OA pain has gained steady traction in the clinical setting, given its potential to achieve improved pain relief with a lower perceived adverse effect and addictive profile compared to traditional opioids. The present study found that preoperative tramadol use was associated with over a 2-fold increased risk of prolonged narcotic use postoperatively but was not associated with an increased risk of any other postoperative complication or increased LOS when compared to nonopioid-only users. When compared to preoperative traditional opioid use, tramadol use was associated with a decreased risk of minor medical complications, ED visits, prolonged narcotic use, and shorter LOS. A major concern surrounding preoperative opioid use is the high risk of dependence and hyperalgesia following arthroplasty, making the management of postoperative pain and ability to properly rehabilitate more difficult [8]. The use of opioids in the preoperative period and the associated poorer outcomes following THA have been well documented in the literature; many studies have demonstrated that preoperative opioid use leads to significantly worse pain scores, greater LOS, and increased risk of revision [13,22e24]. This was consistent with our findings; preoperative traditional opioid use was associated with increased risk of subsequent minor medical complications, ED visits, readmission, prolonged narcotic use, and longer LOS when compared to nonopioidonly users. These complications may be attributable to the side effect profile of opioids and hyperalgesia associated with chronic use. Increased risk of falls, oversedation, gastrointestinal
Table. 4 Adjusted Odds Ratios (OR) of Postoperative Outcomes of Tramadol Users Compared to Traditional Opioid Users. Postoperative Outcomes
Tramadol vs Traditional Opioid Adjusted OR (95% CI)
P Value
90-d Minor medical complications 90-d Major medical complications 90-d Emergency department visit 90-d Readmissions 1-y Hip dislocation 1-y Periprosthetic fracture 1-y Periprosthetic infection 1-y Revision arthroplasty Prolonged narcotic use Length of stay (d)
0.75 0.82 0.70 0.79 0.73 1.08 0.54 0.61 0.43 a 0.20
.002 .280 <.001 .073 .215 .841 .072 .080 <.001 .001
(0.62-0.90) (0.58-1.17) (0.57-0.85) (0.62-1.02) (0.44-1.19) (0.49-2.42) (0.26-1.04) (0.35-1.05) (0.37-0.49) (¡0.32 ≤ b ≤ ¡0.09)
Values in bold denote significance determined as P < .05. CI, confidence interval. a Standardized beta (b) coefficient.
dysfunction (including postoperative ileus and constipation), respiratory depression, and sleep apnea are all associated with chronic opioid and could be potential contributors to the increased number of complications, healthcare visits, and greater LOS observed among opioid users in this study [8,25e28]. Tramadol, while defined as an opioid by its mechanism of action, has been prescribed for preoperative pain before total joint arthroplasty in lieu of conventional opioids, although there is a paucity of described outcomes following THA in tramadol-using patients. One prior study found that preoperative tramadol users who underwent total knee arthroplasty (TKA) had significantly worse clinical improvement at 3-month follow-up compared to opioid users (TKA) [29]. Conversely, several recent studies have demonstrated similar outcomes between preoperative tramadol and opioid users, noting no difference in risk of mortality, readmission, poorer clinical outcomes, manipulation under anesthesia, and persistent opioid use following TKA [30e32]. We propose that tramadol’s improved outcomes when compared to opioid users following THA are attributed to its multimechanistic approach to analgesia. The analgesic effects of tramadol stem from the ability to modulate serotonergic and noradrenergic receptors, in addition to weak agonism of opioid receptors [14,17]. As such, the likelihood of deleterious side effects and adverse events is lower than that of traditional opioids which exhibit stronger agonism for opioid receptors [14e17]. The additional modulation of noradrenergic and serotonergic receptors provides a secondary and tertiary dimension to tramadol’s pain management capacity that lessens the dependence on opioid receptor stimulation [14,17]. Studies have concluded that tramadol is an adequate antinociceptive analgesic agent for osteoarthritic flares while demonstrating decreased gastrointestinal side effects as compared to others in the opioid family [28,33,34]. Tramadol users when compared to traditional opioid users had significantly shorter LOS, lower risk of minor medical complications, ED visits, and most notably prolonged narcotic use. Multiple studies have shown the side effect profile of tramadol to be favorable to that of traditional opioids. Not only is the potential for abuse lower, but tramadol has a lower risk of causing respiratory depression, gastrointestinal impairment, and sedation compared to traditional opioids [17,35e37]. These complications in the postoperative setting can prolong LOS and may result in higher postoperative medical complications requiring additional healthcare visits. Tramadol appears to be a superior option, when compared to traditional opioids, for the conservative management of OA before surgical management. A favorable complication profile and decreased risk of prolonged narcotic use favor the use of tramadol over traditional opioids. Tramadol users were found to be similar to nonopioid-only users in terms of postoperative complications; however, the
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addition of preoperative tramadol was associated with a significantly increased risk of prolonged postoperative narcotic use when compared to nonopioid-only users. Similar associations between preoperative tramadol use and prolonged postoperative narcotic use have been reported following orthopedic surgery [10e12]. While the risk of prolonged opioid use in tramadol patients compared to naïve patients is lower than traditional opioid users, tramadol use in the preoperative setting should be done judiciously to curb potential postoperative narcotic dependence. Interestingly, Zeng et al found that tramadol use among osteoarthritic patients increased the risk of 1-year mortality compared to nonsteroidal anti-inflammatory drug users [32]. Although our study did not assess 1-year mortality associated with preoperative tramadol use, risk of 90-day major and minor medical complications, including mortality, was similar between tramadol and nonopioid-only cohorts. Our findings may be in part to the utilization of exact 1:1:1 matching, which eliminated demographic differences that could have influenced risk of complications among tramadol users. Additionally, there is some evidence that tramadol use, when compared to nonopioid-only users, has been associated with poorer patient-reported outcomes (PROs) following TKA, which may manifest in the prolonged usage of postoperative narcotics [29]. While this study did not evaluate PROs, there was no evidence, outside of increased risk of prolonged narcotic use, that suggested these patients’ clinical outcomes were inferior to those of nonopioid-only users. This study possesses inherent strengths that make it a worthwhile addition to the growing body of literature concerning preoperative pain management in THA patients. The Humana claims database offers a comprehensive assessment of the US population with the inclusion of both private payer and Medicare patients. This large and diverse population of approximately 38,000 patients ensures that not only is our study adequately powered but it allows for a greater generalizability of the results. In addition, the utilization of multivariate regression models allows for a robust and comprehensive analysis of the independent effect of each preoperative pain modality. By controlling for patient demographics and potential confounding comorbidities, we can better ensure the accuracy of our conclusions when assessing the utility of each modality. Likewise, the utilization of both traditional opioid and nonopioid-only users as positive and negative controls allows the study to better delineate the effects of tramadol use in our patient population. Nevertheless, the utilization of large databases has limitations, namely the accuracy of data entry. As with all medical coding, entry is subject to the potential for human error [38]. However, this error is only reported to be 1.1% of all code entries and any potential confounding effects are controlled through thorough regression analysis [39]. In addition, despite our ability to tract filled prescription, we were unable to verify how much of the medication was taken. Over-the-counter medications like nonsteroidal anti-inflammatory drugs and acetaminophen could not be accurately tracked in the database and could potentially be confounding variables if not distributed evenly among the 3 patient groups. Finally, while comprehensive, the study lacked the ability to track and analyze PROs, including pain score, following THA. The lack of quantitative pain scoring limits any conclusions regarding the adequacy of the differing pain management modalities, with the study instead relying on indirect evaluation of pain management through other clinical outcomes. Despite this, the study was able to demonstrate significant differences between the 3 preoperative pain regimen cohorts, which may help to further develop a safe and effective approach to preoperative pain management in patients who require eventual THA.
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Conclusion The present study suggests that patients taking tramadol may have a lower risk of negative postoperative outcomes compared to patients taking traditional opioids. However, preoperative tramadol should be used judiciously in the preoperative setting given the association with increased risk of prolonged postoperative narcotic use.
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[22] Bonner BE, Castillo TN, Fitz DW, Zhao JZ, Klemt C, Kwon Y-M. Preoperative opioid use negatively affects patient-reported outcomes after primary total hip arthroplasty. J Am Acad Orthop Surg 2019;27:e1016e20. https://doi.org/ 10.5435/JAAOS-D-18-00658. [23] Prentice HA, Inacio MCS, Singh A, Namba RS, Paxton EW. Preoperative risk factors for opioid utilization after total hip arthroplasty. J Bone Joint Surg Am 2019;101:1670. https://doi.org/10.2106/JBJS.18.01005. [24] Weick J, Bawa H, Dirschl DR, Luu HH. Preoperative opioid use is associated with higher readmission and revision rates in total knee and total hip arthroplasty. J Bone Joint Surg Am 2018;100:1171e6. https://doi.org/10.2106/ JBJS.17.01414. [25] Baldini A, Von Korff M, Lin EHB. A review of potential adverse effects of longterm opioid therapy: a practitioner’s guide. Prim Care Companion CNS Disord 2012;14. https://doi.org/10.4088/PCC.11m01326. [26] Lo-Ciganic W-H, Floden L, Lee JK, Ashbeck EL, Zhou L, Chinthammit C, et al. Analgesic use and risk of recurrent falls in participants with or at risk of knee osteoarthritis: data from the Osteoarthritis Initiative. Osteoarthritis Cartilage 2017;25:1390e8. https://doi.org/10.1016/j.joca.2017.03.017. [27] O’Neil CK, Hanlon JT, Marcum ZA. Adverse effects of analgesics commonly used by older adults with osteoarthritis: focus on non-opioid and opioid analgesics. Am J Geriatr Pharmacother 2012;10:331e42. https://doi.org/ 10.1016/j.amjopharm.2012.09.004. [28] Wilder-Smith CH, Schimke J, Osterwalder B, Senn HJ. Oral tramadol, a muopioid agonist and monoamine reuptake-blocker, and morphine for strong cancer-related pain. Ann Oncol 1994;5:141e6. https://doi.org/10.1093/ oxfordjournals.annonc.a058765. [29] Driesman A, Kaplan D, Feng JE, Waren DP, Vigdorchik J, Meere P, et al. Tramadol in knee osteoarthritis: does preoperative use affect patient-reported outcomes after total knee arthroplasty? J Arthroplasty 2019;34:1662e6. https://doi.org/10.1016/j.arth.2019.03.056. [30] Hernandez NM, Parry JA, Mabry TM, Taunton MJ. Patients at risk: preoperative opioid use affects opioid prescribing, refills, and outcomes after total knee
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Appendix
Appendix Table 1 Inclusion and Exclusion Codes. Hip trauma Hip neoplasm Hip infection
ICD-9-CM: 716.5, 820.00-03, 820.09-13, 820.19-22, 820.30-32, 820.80, 820.90, 821.00-01, 821.10-11, 827.0-1, 928.00-01, 905.3-4 ICD-9-CM: 170.7, 170.9, 171.3, 213.7, 213.9 ICD-9-CM: 711.05, 711.45, 711.85, 711.95
ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification.
Appendix Table 2 Postoperative Outcome Codes. Major medical complication Pulmonary embolus Pneumonia CVA Myocardial infarction Sepsis Minor medical complication AKI UTI Wound complications Transfusion DVT Periprosthetic fracture Periprosthetic infection Dislocation Revision arthroplasty
ICD-9-CM: ICD-9-CM: ICD-9-CM: ICD-9-CM: ICD-9-CM:
415.11-415.13, 415.19 480.0-3, 480.8-9, 481, 482.0-2, 482.30-32, 482.39-42, 482.49, 482.81-84, 482.89, 482.9, 483.0-1, 483.8, 485, 486, 997.31-32 434.01, 434.11, 434.91, 436, 997.02 410.00-01, 410.10-11, 410.20-21, 410.30-31, 410.40-41, 410.50-51, 410.60-61, 410.70-71, 410.80-81, 410.90-91, 997.1 995.91-92
ICD-9-CM: 584.5, 584.9 ICD-9-CM: 599.0 ICD-9-CM: 998.12-13, 998.30-32, 998.51, 998.59, 998.83 ICD-9-CM: 99.00-09 ICD-9-CM: 453.40-42 ICD-9-CM: 996.44 ICD-9-CM: 996.66 ICD-9-CM: 718.35, 835.00-03, 996.42, 79.75, 79.85 CPT: 27134, 27137, 27138
ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification; CVA, cerebrovascular accident; AKI, acute kidney injury; UTI, urinary tract infection DVT, deep vein thrombosis.
Contents lists available at ScienceDirect
The Journal of Arthroplasty journal homepage: www.arthroplastyjournal.org
Preoperative Pain Management: Is Tramadol a Safe Alternative to Traditional Opioids Before Total Hip Arthroplasty? Joshua E. Bell, MD, Sean B. Sequeira, BS, Dennis Q. Chen, MD, Emanuel C. Haug, MD, Brian C. Werner, MD, James A. Browne, MD * Department of Orthopaedic Surgery, University of Virginia, Charlottesville, VA
a r t i c l e i n f o
a b s t r a c t
Article history: Received 19 February 2020 Received in revised form 26 April 2020 Accepted 28 April 2020 Available online xxx
Background: Preoperative opioid use has been associated with worse clinical outcomes and higher rates of prolonged opioid use following lower extremity arthroplasty. Tramadol has been recommended for management of osteoarthritis-related pain; however, outcomes following total hip arthroplasty (THA) in patients taking tramadol in the preoperative period have not been well described. The aim of this study is to examine the effect of preoperative tramadol use on postoperative outcomes in patients undergoing elective THA. Methods: A total of 5304 patients who underwent primary THA for degenerative hip pathology from 2008 to 2014 were identified using the Humana Claims Database. Patients were grouped by preoperative pain management modality into 3 mutually exclusive populations including tramadol, traditional opioid, or nonopioid only. A multivariate logistic regression was used to evaluate all postsurgical outcomes of interest. Results: Tramadol users had an increased risk of developing prolonged narcotic use (odds ratio [OR], 2.17; confidence interval [CI], 1.89-2.49; P < .001) following surgery compared to nonopioid-only users. When compared to traditional opioid use, tramadol use was associated with decreased risk of subsequent 90day minor medical complications (OR, 0.75; CI, 0.62-0.90; P ¼ .002), emergency department visits (OR, 0.70; CI, 0.57-0.85; P < .001), and prolonged narcotic use (OR, 0.43; CI, 0.37-0.49; P < .001). Traditional opioid use significantly increased length of stay by 0.20 days (P ¼ .001) when compared to tramadol use. Conclusion: Preoperative tramadol use is associated with prolonged opioid use following THA but is not associated with other postoperative complications. Patients taking tramadol preoperatively appear to have a lower risk of postoperative complications compared to patients taking traditional opioids preoperatively. © 2020 Elsevier Inc. All rights reserved.
Keywords: arthroplasty preoperative pain management hip postoperative complications opioids tramadol
Hip osteoarthritis (OA) is one of the most common musculoskeletal conditions treated worldwide [1e3]. The current gold standard treatment for end-stage hip OA is total hip arthroplasty (THA), which has excellent patient outcomes and the ability to restore function and improve quality of life following surgery [4e6]. Before surgical management, conservative management including physical therapy, lifestyle modification, and pain
One or more of the authors of this paper have disclosed potential or pertinent conflicts of interest, which may include receipt of payment, either direct or indirect, institutional support, or association with an entity in the biomedical field which may be perceived to have potential conflict of interest with this work. For full disclosure statements refer to https://doi.org/10.1016/j.arth.2020.04.093. * Reprint requests: James A. Browne, MD, Department of Orthopaedic Surgery, University of Virginia, Box 800159 HSC, Charlottesville, VA 22908. https://doi.org/10.1016/j.arth.2020.04.093 0883-5403/© 2020 Elsevier Inc. All rights reserved.
management is utilized for symptomatic treatment of OA. Although traditional opioids are not recommended by the AAOS, many patients are prescribed them for pain management before arthroplasty. However, as the opioid epidemic in the United States continues to incur a significant health and economic burden on patients and healthcare institutions, perioperative opioid consumption has come under greater scrutiny [7e9]. The use of preoperative opioids has been associated with prolonged narcotic use in the postoperative period, in addition to worse postoperative pain management and increased risk of postoperative complications [10e13]. Tramadol is considered an “atypical” opioid analgesic; when compared to other narcotics, it exhibits weaker opioid receptor agonism and has additional effects on the serotonergic and noradrenergic pathways [14e17]. Tramadol is also perceived to present a lower risk of addiction and respiratory
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depression compared to other opioids. As a result, tramadol has grown in popularity as an alternative to traditional opioids for the management of moderate to severe OA [18,19]. Although the AAOS Clinical Practice Guidelines do not comment on the use of tramadol for hip OA, tramadol was given a strong recommendation for the management of symptomatic knee OA [20]. Additionally, the American College of Rheumatology advocates for the use of tramadol for the initial management of hip OA [21]. There is a paucity of literature evaluating the impact of preoperative tramadol use on postoperative outcomes following THA. This study aims to evaluate the use of preoperative tramadol on postoperative outcomes including minor and major medical complications, prolonged opioid use, dislocation, periprosthetic fracture (PF), periprosthetic joint infection (PJI), revision THA (rTHA), emergency department (ED) visits, readmissions, and length of stay (LOS) following THA. We hypothesized that tramadol would be associated with an increased risk of prolonged opioid use postoperatively but would not be associated with the risk of postoperative complications. Methods Data Source A retrospective database review was conducted utilizing the commercially available PearlDiver Patient Records Database (www. pearldiverinc.com; PearlDiver Inc, Colorado Springs, CO), which contains all Humana Private/Commercial and Medicare patients from 2007 to 2017Q1, searchable by International Classification of Diseases, Current Procedural Terminology (CPT), and National Drug Codes among others. Queried data are de-identified and Health Insurance Portability and Accountability Act compliant; therefore, institutional review board approval was waived for this study. Study Population The study population included all Humana patients from the years of 2008 to 2014 aged 20 to 85 who underwent elective THA (CPT-27130) for degenerative pathology. Patients undergoing same-day revision and those with a history of hip trauma, infection, or neoplasm were excluded from the population using CPT and International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes (Appendix Table 1). The population was then grouped into 3 mutually exclusive cohorts based on the patient’s preoperative pain management modality: (1) tramadol, (2) traditional opioid, and (3) nonopioid only. Patients using both tramadol and traditional opioids in the preoperative period were excluded from the study. This was determined by filled outpatient prescriptions within 4 months of the index surgery. Using the National Drug Code Directory, the following brand name and generic opioid formulations were included in the traditional opioid group: hydrocodone, hydromorphone, morphine, fentanyl, oxymorphone, propoxyphene, oxycodone, and oxycontin. Tramadol use was defined as any generic formulations of tramadol and the name brand equivalent, Ultram (Janssen Pharmaceuticals, Inc, Beerse, Belgium).
use. Matching was performed on a 1:1:1 ratiodevery patient in the tramadol use cohort was matched with 1 patient in the both the traditional opioid and nonopioid-only use cohorts. Postoperative Outcomes Following THA Study groups were evaluated for LOS and the following 90-day outcomes: minor medical complication, major medical complications, ED visits, readmissions, and reimbursement. Minor medical complications included deep vein thrombosis, urinary tract infection, acute kidney injury, wound complications, and need for transfusion. Likewise, major medical complications included pulmonary embolism, pneumonia, myocardial infarction, cerebrovascular accident, sepsis, and death. The following complications within 1 year of surgery were also analyzed: hip dislocation, PF, PJI, and rTHA (Appendix Table 2). Finally, prolonged postoperative opioid use was compared among the 3 groups. Prolonged opioid use was defined as opioid use within the 3- to 6-month postoperative window following index surgery. By 3 months patients should not require opioid prescriptions for the management of postoperative THA pain. Likewise, 6 months was selected to minimize crossover with future planned surgeries or procedures that may require postoperative narcotic prescriptions. Statistical Analysis Pearson’s chi-square analysis was used to compare all outcomes of interest in addition to baseline demographics and comorbidities. Multivariate logistic regression was used to determine the independent effect each preoperative pain management modality had on postoperative outcomes after adjusting for age, gender, and preexisting comorbidities/substance abuse as covariates. Mean LOS was compared using Welch’s t-test. Linear regression was used to determine the independent effect of each preoperative pain management modality on LOS using the previously mentioned covariates. All statistical analyses were performed using R Project for Statistical Computing, which is embedded in the PearlDiver software. Significance was determined by a P value < .05. Results Patient Demographics and Comorbidities Following application of inclusion and exclusion criteria and successful 1:1:1 matching, 5304 patients were identified as undergoing THA during the study period. Of those, 1768 utilized tramadol, 1768 utilized traditional opioids, and 1768 utilized nonopioids only preoperatively. Analysis of preoperative hip pathology diagnosis revealed that an overwhelming majority of patients had preexisting hip OA. The highest rates of OA were within the tramadol (96%) and traditional opioid users (96%); however, nonopioid users had a clinically similar rate of hip OA (94%). The next most common diagnosis was avascular necrosis of the femoral head, which was more prevalent among tramadol users (8%) compared to traditional opioid (6%) and nonopioid-only users (4%). No differences existed between the 3 cohorts in terms of age, sex, and preexisting comorbidities (Table 1).
Patient Matching The resulting 3 cohorts (tramadol users, traditional opioid users, and nonopioid-only users) were matched based on age, sex, and the following preexisting comorbidities: obesity, chronic kidney disease, peripheral vascular disease, chronic obstructive pulmonary disease, diabetes mellitus, hyperlipidemia, hypertension, coronary artery disease, congestive heart failure, depression, and tobacco
Postoperative Outcomes Between Tramadol Users and NonopioidOnly Users Following adjusted multivariate regression, tramadol was associated with increased odds of prolonged postoperative narcotic use (48% vs 30%; odds ratio [OR], 2.17; confidence interval [CI],1.89-2.49; P < .001) when compared to nonopioid-only users. Between the 2
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3
Table. 1 Patient Demographics. Patient Demographics Age (y) <65 65-69 70-74 75-79 80-84 Male sex Female sex Comorbidities Obesity (BMI > 30 kg/m2) Chronic kidney disease PVD Diabetes mellitus COPD CHF Coronary artery disease Hyperlipidemia Hypertension Depression Tobacco use Preoperative degenerative pathology Osteoarthritis Avascular necrosis Rheumatoid arthritis SLE Psoriatic arthritis Ankylosing spondylitis
Tramadol (N ¼ 1768)
Traditional Opioid (N ¼ 1768)
Nonopioid Only (N ¼ 1768)
P Value
336 436 500 324 172 588 1180
19% 25% 28% 18% 10% 33% 67%
336 436 500 324 172 588 1180
19% 25% 28% 18% 10% 33% 67%
336 436 500 324 172 588 1180
19% 25% 28% 18% 10% 33% 67%
1.000
201 115 74 403 311 44 300 1270 1348 176 180
11% 7% 4% 23% 18% 2% 17% 72% 76% 10% 10%
201 115 74 403 311 44 300 1270 1348 176 180
11% 7% 4% 23% 18% 2% 17% 72% 76% 10% 10%
201 115 74 403 311 44 300 1270 1348 176 180
11% 7% 4% 23% 18% 2% 17% 72% 76% 10% 10%
1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000
1692 99 99 19 6 5
96% 6% 6% 1% <1% <1%
1693 134 88 15 5 3
96% 8% 5% 1% <1% <1%
1655 71 70 13 3 6
94% 4% 4% 1% <1% <1%
.004 <.001 .072 .659 .606 .606
1.000
BMI, body mass index; PVD, peripheral vascular disease; COPD, chronic obstructive pulmonary disease; CHF, congestive heart failure; SLE, systemic lupus erythematosus.
cohorts, there was no significant difference in odds of postoperative minor medical complications (P ¼ .544), major medical complications (P ¼.243), ED visit (P ¼.915), readmission (P ¼.631), dislocation (P ¼ .893), PF (P ¼ .287), PJI (P ¼ .703), and rTHA (P ¼ .164). When compared to nonopioid-only users, tramadol use did not attribute to a significant change in LOS (P ¼ .727; Tables 2 and 3).
PJI (P ¼ .150), and rTHA (P ¼ .706). When compared to nonopioidonly users, traditional opioid use was independently associated with a 0.18-day increase in LOS (P ¼ .005; Tables 2 and 3).
Postoperative Outcomes Between Opioid Users and Nonopioid-Only Users
Patients using preoperative tramadol, when compared to traditional opioid users, were associated with decreased risk of subsequent minor medical complications (13% vs 17%; OR, 0.75; CI, 0.62-0.90; P ¼ .002), ED visit (11% vs 15%; OR, 0.70; CI, 0.57-0.85; P < .001), and prolonged postoperative narcotic use (48% vs 68%; OR, 0.43; CI, 0.37-0.49; P < .001). There was no significant difference in risk of postoperative major medical complications (P ¼ .280), readmission (P ¼ .073). dislocation (P ¼ .215), PF (P ¼ .841), PJI (P ¼ .072), and rTHA (P ¼ .080). When compared to the traditional opioid cohort, preoperative tramadol use was associated with a 0.20-day decrease in LOS (P ¼ .001; Tables 2 and 4).
Patients with preoperative traditional opioid use had increased odds of minor medical complications (17% vs 13%; OR, 1.42; CI, 1.181.72; P < .001), ED visit (15% vs 11%; OR, 1.41; CI, 1.16-1.72; P ¼ .001), readmission (8% vs 6%; OR, 1.35; CI, 1.04-1.75; P ¼ .023), and prolonged postoperative narcotic use (68% vs 30%; OR, 5.06; CI, 4.385.85; P < .001) when compared to nonopioid-only users. There were no significant differences in risk of postoperative major medical complications (P ¼ .931), dislocation (P ¼ .266), PF (P ¼ .207),
Postoperative Outcomes Between Tramadol Users and Traditional Opioid Users
Table. 2 Rates of Postoperative Outcomes Between Tramadol, Traditional Opioid, and Nonopioid-Only Users. Postoperative Outcomes
90-d Minor medical complications 90-d Major medical complications 90-d Emergency department visit 90-d Readmissions 1-y Hip dislocation 1-y Periprosthetic fracture 1-y Periprosthetic infection 1-y Revision arthroplasty Prolonged narcotic use Length of stay (d)
Tramadol (N ¼ 1768)
Traditional Opioid (N ¼ 1768)
Nonopioid Only (N ¼ 1768)
P Value Tramadol vs Nonopioid Only
Traditional Opioid vs Nonopioid Only
Tramadol vs Traditional Opioid
234 (13%) 59 (3%) 201 (11%) 118 (7%) 28 (2%) 13 (1%) 13 (1%) 21 (1%) 853 (48%) 3.07 ± 1.66
298 (17%) 71 (4%) 272 (15%) 146 (8%) 38 (2%) 12 (1%) 24 (1%) 34 (2%) 1203 (68%) 3.27 ± 1.96
222 (13%) 72 (4%) 203 (11%) 111 (6%) 29 (2%) 19 (1%) 15 (1%) 31 (2%) 539 (30%) 3.09 ± 0.92
.581 .285 .958 .682 1.000 .375 .850 .209 <.001 .729
<.001 1.000 .001 .028 .324 .279 .198 .802 <.001 .005
.003 .326 .001 .084 .263 1.000 .098 .103 <.001 .001
Values in bold denote significance determined as P < .05.
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Table. 3 Adjusted Odds Ratios (OR) of Postoperative Outcomes of Tramadol Users and Traditional Opioid Users Compared to Nonopioid-Only Users. Postoperative Outcomes
Tramadol vs Nonopioid Only Adjusted OR (95% CI)
P Value
Traditional Opioid vs Nonopioid Only Adjusted OR (95% CI)
P Value
90-d Minor medical complications 90-d Major medical complications 90-d Emergency department visit 90-d Readmissions 1-y Hip dislocation 1-y Periprosthetic fracture 1-y Periprosthetic infection 1-y Revision arthroplasty Prolonged narcotic use Length of stay (d)
1.33 0.81 0.99 1.07 0.96 0.68 0.86 0.67 2.17 a 0.02
.544 .243 .915 .631 .893 .287 .703 .164 <.001 .727
1.42 0.99 1.41 1.35 1.32 0.62 1.61 1.10 5.06 a 0.18
<.001 .931 .001 .023 .266 .207 .150 .706 <.001 .005
(0.87-1.30) (0.57-1.15) (0.80-1.22) (0.82-1.40) (0.57-1.63) (0.33-1.37) (0.40-1.83) (0.38-1.17) (1.89-2.49) (0.14 b 0.10)
(1.18-1.72) (0.70-1.38) (1.16-1.72) (1.04-1.75) (0.81-2.17) (0.40-1.28) (0.85-3.16) (0.67-1.80) (4.38-5.85) (0.06 ≤ b ≤ 0.31)
Values in bold denote significance determined as P < .05. CI, confidence interval. a Standardized beta (b) coefficient.
Discussion The use of tramadol for OA pain has gained steady traction in the clinical setting, given its potential to achieve improved pain relief with a lower perceived adverse effect and addictive profile compared to traditional opioids. The present study found that preoperative tramadol use was associated with over a 2-fold increased risk of prolonged narcotic use postoperatively but was not associated with an increased risk of any other postoperative complication or increased LOS when compared to nonopioid-only users. When compared to preoperative traditional opioid use, tramadol use was associated with a decreased risk of minor medical complications, ED visits, prolonged narcotic use, and shorter LOS. A major concern surrounding preoperative opioid use is the high risk of dependence and hyperalgesia following arthroplasty, making the management of postoperative pain and ability to properly rehabilitate more difficult [8]. The use of opioids in the preoperative period and the associated poorer outcomes following THA have been well documented in the literature; many studies have demonstrated that preoperative opioid use leads to significantly worse pain scores, greater LOS, and increased risk of revision [13,22e24]. This was consistent with our findings; preoperative traditional opioid use was associated with increased risk of subsequent minor medical complications, ED visits, readmission, prolonged narcotic use, and longer LOS when compared to nonopioidonly users. These complications may be attributable to the side effect profile of opioids and hyperalgesia associated with chronic use. Increased risk of falls, oversedation, gastrointestinal
Table. 4 Adjusted Odds Ratios (OR) of Postoperative Outcomes of Tramadol Users Compared to Traditional Opioid Users. Postoperative Outcomes
Tramadol vs Traditional Opioid Adjusted OR (95% CI)
P Value
90-d Minor medical complications 90-d Major medical complications 90-d Emergency department visit 90-d Readmissions 1-y Hip dislocation 1-y Periprosthetic fracture 1-y Periprosthetic infection 1-y Revision arthroplasty Prolonged narcotic use Length of stay (d)
0.75 0.82 0.70 0.79 0.73 1.08 0.54 0.61 0.43 a 0.20
.002 .280 <.001 .073 .215 .841 .072 .080 <.001 .001
(0.62-0.90) (0.58-1.17) (0.57-0.85) (0.62-1.02) (0.44-1.19) (0.49-2.42) (0.26-1.04) (0.35-1.05) (0.37-0.49) (¡0.32 ≤ b ≤ ¡0.09)
Values in bold denote significance determined as P < .05. CI, confidence interval. a Standardized beta (b) coefficient.
dysfunction (including postoperative ileus and constipation), respiratory depression, and sleep apnea are all associated with chronic opioid and could be potential contributors to the increased number of complications, healthcare visits, and greater LOS observed among opioid users in this study [8,25e28]. Tramadol, while defined as an opioid by its mechanism of action, has been prescribed for preoperative pain before total joint arthroplasty in lieu of conventional opioids, although there is a paucity of described outcomes following THA in tramadol-using patients. One prior study found that preoperative tramadol users who underwent total knee arthroplasty (TKA) had significantly worse clinical improvement at 3-month follow-up compared to opioid users (TKA) [29]. Conversely, several recent studies have demonstrated similar outcomes between preoperative tramadol and opioid users, noting no difference in risk of mortality, readmission, poorer clinical outcomes, manipulation under anesthesia, and persistent opioid use following TKA [30e32]. We propose that tramadol’s improved outcomes when compared to opioid users following THA are attributed to its multimechanistic approach to analgesia. The analgesic effects of tramadol stem from the ability to modulate serotonergic and noradrenergic receptors, in addition to weak agonism of opioid receptors [14,17]. As such, the likelihood of deleterious side effects and adverse events is lower than that of traditional opioids which exhibit stronger agonism for opioid receptors [14e17]. The additional modulation of noradrenergic and serotonergic receptors provides a secondary and tertiary dimension to tramadol’s pain management capacity that lessens the dependence on opioid receptor stimulation [14,17]. Studies have concluded that tramadol is an adequate antinociceptive analgesic agent for osteoarthritic flares while demonstrating decreased gastrointestinal side effects as compared to others in the opioid family [28,33,34]. Tramadol users when compared to traditional opioid users had significantly shorter LOS, lower risk of minor medical complications, ED visits, and most notably prolonged narcotic use. Multiple studies have shown the side effect profile of tramadol to be favorable to that of traditional opioids. Not only is the potential for abuse lower, but tramadol has a lower risk of causing respiratory depression, gastrointestinal impairment, and sedation compared to traditional opioids [17,35e37]. These complications in the postoperative setting can prolong LOS and may result in higher postoperative medical complications requiring additional healthcare visits. Tramadol appears to be a superior option, when compared to traditional opioids, for the conservative management of OA before surgical management. A favorable complication profile and decreased risk of prolonged narcotic use favor the use of tramadol over traditional opioids. Tramadol users were found to be similar to nonopioid-only users in terms of postoperative complications; however, the
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addition of preoperative tramadol was associated with a significantly increased risk of prolonged postoperative narcotic use when compared to nonopioid-only users. Similar associations between preoperative tramadol use and prolonged postoperative narcotic use have been reported following orthopedic surgery [10e12]. While the risk of prolonged opioid use in tramadol patients compared to naïve patients is lower than traditional opioid users, tramadol use in the preoperative setting should be done judiciously to curb potential postoperative narcotic dependence. Interestingly, Zeng et al found that tramadol use among osteoarthritic patients increased the risk of 1-year mortality compared to nonsteroidal anti-inflammatory drug users [32]. Although our study did not assess 1-year mortality associated with preoperative tramadol use, risk of 90-day major and minor medical complications, including mortality, was similar between tramadol and nonopioid-only cohorts. Our findings may be in part to the utilization of exact 1:1:1 matching, which eliminated demographic differences that could have influenced risk of complications among tramadol users. Additionally, there is some evidence that tramadol use, when compared to nonopioid-only users, has been associated with poorer patient-reported outcomes (PROs) following TKA, which may manifest in the prolonged usage of postoperative narcotics [29]. While this study did not evaluate PROs, there was no evidence, outside of increased risk of prolonged narcotic use, that suggested these patients’ clinical outcomes were inferior to those of nonopioid-only users. This study possesses inherent strengths that make it a worthwhile addition to the growing body of literature concerning preoperative pain management in THA patients. The Humana claims database offers a comprehensive assessment of the US population with the inclusion of both private payer and Medicare patients. This large and diverse population of approximately 38,000 patients ensures that not only is our study adequately powered but it allows for a greater generalizability of the results. In addition, the utilization of multivariate regression models allows for a robust and comprehensive analysis of the independent effect of each preoperative pain modality. By controlling for patient demographics and potential confounding comorbidities, we can better ensure the accuracy of our conclusions when assessing the utility of each modality. Likewise, the utilization of both traditional opioid and nonopioid-only users as positive and negative controls allows the study to better delineate the effects of tramadol use in our patient population. Nevertheless, the utilization of large databases has limitations, namely the accuracy of data entry. As with all medical coding, entry is subject to the potential for human error [38]. However, this error is only reported to be 1.1% of all code entries and any potential confounding effects are controlled through thorough regression analysis [39]. In addition, despite our ability to tract filled prescription, we were unable to verify how much of the medication was taken. Over-the-counter medications like nonsteroidal anti-inflammatory drugs and acetaminophen could not be accurately tracked in the database and could potentially be confounding variables if not distributed evenly among the 3 patient groups. Finally, while comprehensive, the study lacked the ability to track and analyze PROs, including pain score, following THA. The lack of quantitative pain scoring limits any conclusions regarding the adequacy of the differing pain management modalities, with the study instead relying on indirect evaluation of pain management through other clinical outcomes. Despite this, the study was able to demonstrate significant differences between the 3 preoperative pain regimen cohorts, which may help to further develop a safe and effective approach to preoperative pain management in patients who require eventual THA.
5
Conclusion The present study suggests that patients taking tramadol may have a lower risk of negative postoperative outcomes compared to patients taking traditional opioids. However, preoperative tramadol should be used judiciously in the preoperative setting given the association with increased risk of prolonged postoperative narcotic use.
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Appendix
Appendix Table 1 Inclusion and Exclusion Codes. Hip trauma Hip neoplasm Hip infection
ICD-9-CM: 716.5, 820.00-03, 820.09-13, 820.19-22, 820.30-32, 820.80, 820.90, 821.00-01, 821.10-11, 827.0-1, 928.00-01, 905.3-4 ICD-9-CM: 170.7, 170.9, 171.3, 213.7, 213.9 ICD-9-CM: 711.05, 711.45, 711.85, 711.95
ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification.
Appendix Table 2 Postoperative Outcome Codes. Major medical complication Pulmonary embolus Pneumonia CVA Myocardial infarction Sepsis Minor medical complication AKI UTI Wound complications Transfusion DVT Periprosthetic fracture Periprosthetic infection Dislocation Revision arthroplasty
ICD-9-CM: ICD-9-CM: ICD-9-CM: ICD-9-CM: ICD-9-CM:
415.11-415.13, 415.19 480.0-3, 480.8-9, 481, 482.0-2, 482.30-32, 482.39-42, 482.49, 482.81-84, 482.89, 482.9, 483.0-1, 483.8, 485, 486, 997.31-32 434.01, 434.11, 434.91, 436, 997.02 410.00-01, 410.10-11, 410.20-21, 410.30-31, 410.40-41, 410.50-51, 410.60-61, 410.70-71, 410.80-81, 410.90-91, 997.1 995.91-92
ICD-9-CM: 584.5, 584.9 ICD-9-CM: 599.0 ICD-9-CM: 998.12-13, 998.30-32, 998.51, 998.59, 998.83 ICD-9-CM: 99.00-09 ICD-9-CM: 453.40-42 ICD-9-CM: 996.44 ICD-9-CM: 996.66 ICD-9-CM: 718.35, 835.00-03, 996.42, 79.75, 79.85 CPT: 27134, 27137, 27138
ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification; CVA, cerebrovascular accident; AKI, acute kidney injury; UTI, urinary tract infection DVT, deep vein thrombosis.