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Preoperative Reduction of Opioid Use Before Total Joint Arthroplasty
The Journal of Arthroplasty xxx (2016) 1e6
Contents lists available at ScienceDirect
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AAHKS Supplement paper
Preoperative Reduction of Opioid Use Before Total Joint Arthroplasty Long-Co L. Nguyen, BA, BS a, David C. Sing, BS a, Kevin J. Bozic, MD, MBA b, * a b
University of California San Francisco School of Medicine, San Francisco, California Department of Surgery and Perioperative Care, Dell Medical School, University of Texas at Austin, Austin, Texas
a r t i c l e i n f o
a b s t r a c t
Article history: Received 30 November 2015 Received in revised form 5 January 2016 Accepted 13 January 2016 Available online xxx
Background: The purpose of this study was to assess whether weaning of opioid use in the preoperative period improved total joint arthroplasty (TJA) outcomes. Methods: Forty-one patients who regularly used opioids and successfully weaned (defined as a 50% reduction in morphine-equivalent dose) before a primary total knee or hip arthroplasty were matched with a group of TJA patients who did not wean and a matched control group of TJA patients who did not use opioids preoperatively. The difference between preoperative and postoperative (at 6-12 months follow-up) patient-reported outcomes were assessed using the change in University of California, Los Angeles (UCLA) activity score, SF12v2, and The Western Ontario and McMaster Universities Arthritis Index (WOMAC). Paired t tests and 1-way repeated measures analysis of variance were performed to assess differences in TJA outcomes between groups. Results: Patients using opioids who successfully weaned had greater improvements in both diseasespecific and generic measures of health outcomes than patients who did not wean (WOMAC 43.7 vs 17.8, P < .001; SF12v2 Physical Component Score 10.5 vs 1.85, P ¼ .003; UCLA activity score 1.49 vs 0, P < .001). There was no statistical difference between the 2 groups on SF12v2 Mental Component Score 2.48 vs 4.21, P ¼ .409. Patients who successfully weaned from opioids had similar outcomes to control patients who did not use opioids: WOMAC 39.0 vs 43.7, P ¼ .31; SF12v2 Physical Component Score 12.5 vs 10.5, P ¼ .35; SF12v2 Mental Component Score 3.08 vs 2.48, P ¼ .82; UCLA activity 1.90 vs 1.49, P ¼ .23. Conclusion: Patients with a history of chronic opioid use who successfully decreased their use of opioids before surgery had substantially improved clinical outcomes that were comparable to patients who did not use opioids at all. © 2016 Elsevier Inc. All rights reserved.
Keywords: opioids patient-reported outcomes total hip arthroplasty total knee arthroplasty pain management
Osteoarthritis (OA) is a leading cause of disability, and its prevalence continues to rise due to the increasing obese and elderly population. Worldwide, OA affects almost 10% of men and 18% of women older than 60 years, increasing to around 30% for those older than 70 years [1,2]. About 40%-60% of patients with radiologically confirmed knee OA experience pain, stiffness, and decreased mobility, with more than half stating that pain causes the most burden above all other arthritic symptomology [3]. OA 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 http://dx.doi.org/10.1016/j.arth.2016.01.068. Funding: None. * Reprint requests: Kevin J. Bozic, MD, MBA, Department of Surgery and Perioperative Care, Dell Medical School at the University of Texas at Austin, 1400 Barbara Jordan Blvd, Suite 1.114, Austin, TX 78723. http://dx.doi.org/10.1016/j.arth.2016.01.068 0883-5403/© 2016 Elsevier Inc. All rights reserved.
can cause decreased quality of life by interfering with activities of daily living, impairing cognition, reducing productivity, and increasing mood symptoms. Therefore, pain control is an essential part of managing OA. Analgesics, including nonopioid (eg, nonsteroidal anti-inflammatory drugs) and opioid pain medications, are the most common type of pharmacotherapy used in the treatment of OA. Previously, opioids were limited to managing predominantly acute pain and chronic cancer pain; however, opioids are now more liberally prescribed for chronic noncancer pain syndromes such as OA [4]. In a sample of elderly Medicare patients with knee OA, a study demonstrated that opioid use has increased from 31% to 40% between 2003 and 2009 [5]. Several clinical practice guidelines are currently available for the management of OA. The 2012 American College of Rheumatology guidelines on management of osteoarthritis recommends the use of opioids in management of osteoarthritis after failed medical therapy if the patient is not willing or has contraindications for total joint arthroplasty [6]. National Institute of Clinical Excellence
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guidelines also propose opioids if inadequate pain control with nonsteroidal anti-inflammatory drugs or paracetamol [7]. The American Academy of Orthopedic Surgeons provide inconclusive recommendations for the use of opioids in the treatment of OA [8], whereas other organizations, including the American Geriatrics Society and the OA Research Society International, remain unclear on how and when to use opioids in managing OA [9,10]. Although opiates have emerged as potential agents for select patients with symptomatic OA who are unresponsive or have contraindications to antiinflammatory medication, the association with adverse effects has highlighted the potential harms of chronic opiate use. As prolonged use of opioids to manage chronic pain associated with OA becomes more prevalent, a growing body of evidence has amassed that suggests that such exposure may affect outcomes of total joint arthroplasty. Long-term use of opioid medications may lead to dependence or hyperalgesia, both of which might adversely affect perioperative and postoperative pain management, risk of complications, rehabilitation, and clinical outcomes after a total joint arthroplasty [11-14]. Although several studies have raised concerns about the association of preoperative opioid use with worse clinical outcomes after surgery, it has yet to be explored whether this risk factor is modifiable with weaning of opioid dose before surgery. The purpose of this study was to evaluate whether weaning of opioid dose in patients with a history of chronic opioid use before undergoing a total joint arthroplasty would improve clinical outcomes compared to patients who did not wean. Methods A retrospective matched cohort study design was used to define 3 cohorts of patients: (1) Intervention group, which included patients who successfully weaned their opioid dose before surgery, which was defined as weaning their morphine equivalent dose by 50% after recommending the patient to self-wean, referring patient to pain management to help wean, or suggesting they wean under the supervision of their primary care provider; (2) Opioiddependent control group, which included patients with chronic opioid use, defined as continued use for at least 4 weeks, based on Chu et al [15] who reported that hyperalgesia was achieved after chronic use of morphine for 4 weeks; and (3) opioid naïve control group, which included patients with no prior narcotic history. A review of all patients who underwent unilateral primary hip or knee arthroplasty at a single institution between 2007 and 2014 was conducted using multiple sources including clinical office notes and referral notes to identify a study group of 41 patients with a history of chronic opioid use before a primary hip or knee arthroplasty who successfully weaned their dose before their surgery. All opioid medications and dosages were converted to a morphine-equivalent dose [16]. Patients were excluded if they had a bilateral or revision procedure. Postoperative pain management protocol (gabapentin 200 mg three times a day, acetaminophen 1000 mg three times a day, celebrex 200 mg twice a day, oxycodone 5-15 mg as needed for moderate pain, Dilaudid IV 0.2-0.8 mg as needed for severe pain) was followed for all patients barring any contraindications. Patients undergoing a total knee arthroplasty also received an adductor canal block. Patients from the study group were individually pair-matched 1:1:1 with patients who met the definition for chronic opioid use, however did not wean, and patients who managed their pain without narcotics. Patients in the control group were selected from a list of all patients who received a total joint arthroplasty at the same institution over the same period of time at random using a random number generator. Patients were matched based on primary diagnosis, affected joint (hip/knee), American Society of Anaesthesiologists' classification of physical health, sex, body mass
Table 1 Demographics of Patient Cohorts. Characteristics
Intervention Group
Opioid-Dependent Control Group
Opioid Naïve Control Group
Mean age Sex Female Male Primary diagnosis Primary OA Osteonecrosis Posttraumatic
59
60
58
27 (66%) 14 (34%)
27 (66%) 14 (34%)
27 (66%) 14 (34%)
34 (83%) 4 (10%) 3 (7%)
34 (83%) 4 (10%) 3 (7%)
34 (83%) 4 (10%) 3 (7%)
OA, osteoarthritis.
index (BMI) (þ/ 10), age (þ/ 10), and daily morphine equivalent group. Opioid subgroups were based on methodology published by Kidner et al [17] and was divided as follows: low (<30 mg), medium (31-60 mg), high (61-120 mg), and very high (>120 mg). An a priori power analysis was performed and indicates that 41 matches of subjects were needed for a power of 80% to detect a real clinical difference between the subjects and 2 control groups at a P-value of <.05. Primary outcome studied was the delta of patientreported outcomes (PRO) from baseline to 6-12 month follow-up as measured by University of California at Los Angeles Activity Score, SF12v2, and The Western Ontario and McMaster Universities Arthritis Index (WOMAC). Outcomes data were taken from a database of prospectively collected PROs. The continuous outcomes of PRO change were analyzed using a paired 2-tailed Student t test and 1-way analysis of variance. Categorical variables were compared utilizing chi-squared test. Statics were performed using STATA. Results There were 41 patients in each group. Mean age of the intervention, opioid dependent, and opioid naive groups were 59.0, 60.1, and 58.2, respectively. Mean BMI was 29.5 (range, 21.6-47.5), 32.8 (20.6-54.9), and 29.4 (21.4-42.89), respectively. Each group was comprised of 34% males and 66% females. The primary diagnoses of each group were distributed as follows: 34 primary osteoarthritis (83%), 4 osteonecrosis (10%), 3 posttraumatic osteoarthritis (7%) (Table 1). There were 14 patients using a low morphine equivalent (34%), 7 taking medium morphine equivalent (17%), 6 taking high morphine equivalent (15%), and 14 taking very high morphine equivalent in each of the groups (34%). There were no differences in baseline University of California, Los Angeles (UCLA) activity and SF12v2 mental component scores between the groups, (P-value ¼ .052, P-value ¼ .057, respectively). The intervention group had significantly lower mean WOMAC and SF12v2 physical component scores than the two control groups, (P-value < .01) (Table 2). The opioid naïve control group had significantly higher increases from their baseline to their postoperative UCLA, WOMAC, SF12v2 physical component scores than the opioid-dependent control group (P < .01 for all 3 measures). The change in SF12v2 mental component score between the opioid naïve and opioiddependent control groups was not significant (P ¼ .63) (Fig. 1). The opioid naïve group had significantly higher final PROs at 6-12 Table 2 Differences in Patient-Reported Outcomes Between Patient Groups. Patient Reported Intervention Opioid-Dependent Opioid Naïve P-value Outcome Measure Group Control Group Control Group UCLA WOMAC SF12v2-P SF12v2-M
3.1 32 24.7 47.5
3.6 47.5 28.8 42.8
4.1 44.1 30.9 49.1
.052 <.01 <.01 .057
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3
Fig. 1. Opioid naïve vs opioid dependent (change in patient-reported outcomes). * Indicates the comparison was statistically significant (P < .01).
months post operation than the opioid-dependent group: UCLA (P < .01), WOMAC (P < .01), SF12v2 physical component (P < .01), SF12v2 mental component (P ¼ .015) (Table 3). Patients with history of chronic opioid use who reduced their dose by half preoperatively had significantly higher changes in UCLA, WOMAC, SF12v2 physical component scores than the opioiddependent control group (P < .01 for all 3 measures). There were no significant differences in change of SF12v2 mental component scores (P-value ¼ .41) (Fig. 2). The intervention group had significantly higher postoperative final physical function scores than the opioid-dependent groups for UCLA (P < .01), WOMAC (P ¼ .022), and SF12v2 physical component (P ¼ .048). The final SF12v2 mental component score was not significantly different between the 2 groups (P ¼ .14) (Table 4). There were no significant differences in change scores for all PROs between the intervention group and the opioid naïve control group (UCLA, P-value ¼ .24; SF12v2 mental, P-value ¼ .82; SF12v2 physical, P-value ¼ .35; and WOMAC, P-value ¼ .31) (Fig. 3). However, the opioid naïve group had significantly higher final UCLA (P < .01), WOMAC (P ¼ .049), and SF12v2 physical component (P < .01). There was no difference in the final SF12v2 mental component scores between the 2 groups (P ¼ .22) (Table 5). Discussion Patients on chronic opioid therapy present certain challenges to orthopedic surgeons. There is accumulating evidence that suggests that chronic opioid use is associated with poor clinical outcomes after orthopedic surgery. In a study by Chapman et al [18], patients who reported chronic opioid use before an orthopedic surgery Table 3 Opioid Naïve vs Opioid Dependent: Final PROs at 6-12 Months Follow-Up. Patient Reported Outcome Measure
Opioid Naïve
Opioid Dependent
Baseline
6-12 mo Postoperatively
Baseline
6-12 mo Postoperatively
UCLA WOMAC SF12-P SF12-M
4.1 44.1 30.9 49.1
6 83.1 42.4 52.2
3.6 47.5 28.8 42.8
3.6 65.3 30.6 47
P-value
<.01 <.01 <.01 .015
use experienced greater severity of acute pain and slower pain resolution despite adjustments made for additional opioid administration. Zywiel et al [11] found that those with preoperative exposure to opioids were likely to have a longer length of stay, increased risk of complications and additional surgical procedures, greater need to be referred for pain management after total knee arthroplasty, along with lower clinical scores compared with those without prolonged exposure to opioids before surgery. A study by Pivec et al [12] comparing the clinical outcomes of patients taking chronic narcotics before undergoing total hip arthroplasty to those not taking narcotics similarly showed worse long-term clinical results, higher in-hospital opioid dose requirements, and greater levels of continued narcotic use after surgery. Lawrence et al [19] found that chronic narcotic users had worse outcomes after cervical arthrodesis procedures when compared to other patients. This present study further supports the hypothesis that chronic opioid use clinical outcomes in patients undergoing a total joint arthroplasty. However, the novel finding in this study is that opioid users who taper their dose before surgery achieved significantly improved outcomes compared with those who did not taper, therefore, suggesting that chronic opioid use is in fact a modifiable risk factor. Chronic opioid users who reduced their dose by at least 50% had improved functional outcome scores compared to those that did not wean as measured by WOMAC 43.7 vs 17.8, (P-value < .001), SF12v2 physical, 10.5 vs 1.85 (P-value ¼ .003), UCLA activity score, with a mean delta score of 1.49 vs 0 (P-value < .001). Although the group that reduced their opioid use achieved the same delta scores in their functional outcomes as those that are narcotic naïve, given that their baseline functional scores were lower they did not achieve the same postoperative functional status as those that did not use opioids initially. Therefore, chronic opioid users who wean their dose of opioids before TJA can expect greater improvements in functional status and better overall functional status than chronic opioid users who do not wean, they should still be counseled to expect lower functional abilities than TJA patients who have not had chronic exposure to opioids. Why chronic opioid use affects outcomes is not well understood but is thought to be multifactorial and may result from opioidinduced hyperalgesia (OIH) [20,21]. OIH is defined as nociceptive sensitization caused by exposure to opioids. This neuropharmacological phenomenon is characterized by a paradoxical adverse
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Fig. 2. Intervention vs opioid dependent (change in patient-reported outcomes). * Indicates the comparison was statistically significant (P < .01).
response whereby a patient receiving opioids for the treatment of pain might actually become more sensitive to painful stimuli. This concept was observed as early as the 19th century in patients receiving morphine for pain. It was recognized that a potent analgesic such as morphine could actually result in an increase in pain [22]. Since then, there has been substantial basic science as well as clinical evidence supporting the concept of OIH [15,23-28]. Among the more important human studies documenting this effect are those demonstrating hyperalgesia in former opioid addicts maintained on methadone when compared with matched controls not receiving methadone or other opioids [29]. In addition, OIH appears to be a definable phenomenon that could lead to the loss of opioid efficacy and difficulty with treating postoperative pain. Patients with severe pain that is not appropriately managed postoperatively have been shown to have worse outcomes, which may also contribute to the lower functional scores seen in this study [30,31]. Although not assessed in the present study, dose and duration appear to be important factors in the relationship between opioids and adverse effects. A small number of studies have looked at the clinical characteristics of this relationship. Kidner et al reported that, in patients admitted for rehabilitation of a chronic musculoskeletal disorder, increased opioid medication dosages were associated with an increased rate of program noncompletion, a lower rate of return to work, and an increased likelihood of receiving disability or social security supplemental income 1 year after treatment [17]. It was also found that exposure to larger doses of opioids seems to be associated with OIH [23,26,32-34]. Some studies have demonstrated that larger doses of intraoperative remifentanil induced an increase in postoperative pain [33,35]. However, there are studies that reported observing OIH after interruption of even small doses of opiates [15,36]. On the contrary,
Table 4 Intervention vs Opioid Dependent: Final PROs at 6-12 Months Follow-Up.
UCLA WOMAC SF12-P SF12-M
Intervention Group
Opioid Dependent
Baseline
6-12 mo Postoperatively
Baseline
6-12 mo Postoperatively
3.1 32 24.7 47.5
4.6 75.7 35.1 50
3.6 47.5 28.8 42.8
3.6 65.3 30.6 47
P-value
<.01 .022 .048 .14
a study by Cortinez et al [37] failed to demonstrate an increase in postoperative opioid consumption with increased doses of intraoperative remifentanil. This study only looks at short-term intraoperative opioid use, and it could be that longer anesthesia is required to develop clinically significant opioid tolerance effect. Studies have shown that OIH is more evident with prolonged duration of use [24,38]. However, reports on the duration required to attain OIH is inconsistent. In a prospective study by Chu et al [15], it was found that chronic use of oral morphine for 4 weeks in previously narcotic naïve patients with chronic back pain resulted in hyperalgesia. Another study demonstrated increased pain sensitivity in patients undergoing eye surgery who only used opioids intraoperatively [35]. Few studies have investigated the effect of reducing opioid doses on pain, although one retrospective study of patients undergoing detoxification for opioid addiction found a significant decrease in pain when patients were converted onto nonsteroidal antiinflammatory drugs for their pain [39]. Further research is needed to define clinical factors such as duration and dose to achieve symptoms and critical dose to mitigate the hyperalgesic effect. The strengths of the present study are related to the design and the selection of the cohorts. Matching the cases and controls with respect to age, gender, American Society of Anaesthesiologists' classification of physical health, BMI, primary diagnosis, affected joint, and morphine equivalent reduces the possibility of confounding from these factors because of their potential associated with the outcome indices studied. In addition, there were no significant differences in baseline functional scores as measured by UCLA scores and SF12v2 mental clinical scores. Although there were, however, differences between the baseline functional scores as measured by SF12v2 physical component score and WOMAC; the baseline scores were lower in the group of chronic narcotic users who were able to wean. The random selection of controls from an administrative database of all patients that have received primary joint arthroplasty reduces selection bias. Some limitations of the investigation were also noted. Reliance on self-reported preoperative opioid use may underreport the true opioid use in the study population. We did not have access to pharmacy records and were unable to confirm the duration or dosing of preoperative or postoperative opioids. We also did not assess certain other preoperative risk factors such as smoking, chronic back pain, or concomitant mood disorder.
L.-C.L. Nguyen et al. / The Journal of Arthroplasty xxx (2016) 1e6
5
Fig. 3. Intervention vs opioid naïve (change in patient-reported outcomes).
Table 5 Intervention vs Opioid Naïve: Final PROs at 6-12 Months Follow-Up.
UCLA WOMAC SF12-P SF12-M
Intervention Group
Opioid Naïve
Baseline
6-12 mo Postoperatively
Baseline
6-12 mo Postoperatively
3.1 32 24.7 47.5
4.6 75.7 35.1 50
4.1 44.1 30.9 49.1
6 83.1 42.4 52.2
P-value
<.01 .049 <.01 .22
In conclusion, this retrospective cohort study demonstrates that patients who reduce their opioid dose by at least 50% before undergoing TJA achieved improved functional outcomes compared to patients using chronic opioids who did not wean. The syndrome of OIH may explain this association. Another explanation could be that weaning is acting as a surrogate for a patient characteristic that is known to portend to more favorable outcomes such as patient activation and compliance with postoperative care [40]. Larger prospective studies are required to evaluate this association further. Given the findings of this study, opioid use before TJA may be a modifiable risk factor. Early discussions with patients using opioids before TJA about expectations and the possible benefits of weaning should be initiated to optimize preoperative management. Providers should consider referring opiate tolerant patients to a pain management specialist or primary care provider to help patients wean before TJA to potentially improve postoperative outcomes. References 1. Zhang Y, Jordan JM. Epidemiology of osteoarthritis. Clin Geriatr Med 2010;26(3):355. 2. Woolf A, Pfleger B. Burden of major musculoskeletal conditions. Bull World Health Organ 2003;81(9):646. 3. Mordarski S. Pain management in the elderly: transdermal fentanyl for the treatment of pain caused by osteoarthritis of the knee and hip. Biomed Res Int 2014;2014:262961. 4. Goodwin JL, Kraemer JJ, Bajwa ZH. The use of opioids in the treatment of osteoarthritis: when, why, and how? Curr Rheumatol Rep 2009;11(1):5. 5. Wright EA, Katz JN, Abrams S, et al. Trends in prescription of opioids from 20032009 in persons with knee osteoarthritis. Arthritis Care Res 2014;66(10):1489. 6. Hochberg MC, Altman RD, April KT, et al. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res 2012;64(4):465.
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29. Doverty M, White JM, Somogyi AA, et al. Hyperalgesic responses in methadone maintenance patients. Pain 2001;90(1-2):91. 30. Ready LB. Postoperative pain managementebeyond basics. Can J Anaesth 1996;43(2):193. 31. Jamison RN, Taft K, O'Hara JP, et al. Psychosocial and pharmacologic predictors of satisfaction with intravenous patient-controlled analgesia. Anesth Analg 1993;77(1):121. 32. Vanderah TW, Ossipov MH, Lai J, et al. Mechanisms of opioid-induced pain and antinociceptive tolerance: descending facilitation and spinal dynorphin. Pain 2001;92(1-2):5. 33. Joly V, Richebe P, Guignard B, et al. Remifentanil-induced postoperative hyperalgesia and its prevention with small-dose ketamine. Anesthesiology 2005;103(1):147. 34. Celerier E, Rivat C, Jun Y, et al. Long-lasting hyperalgesia induced by fentanyl in rats: preventive effect of ketamine. Anesthesiology 2000;92(2):465.
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Contents lists available at ScienceDirect
The Journal of Arthroplasty journal homepage: www.arthroplastyjournal.org
AAHKS Supplement paper
Preoperative Reduction of Opioid Use Before Total Joint Arthroplasty Long-Co L. Nguyen, BA, BS a, David C. Sing, BS a, Kevin J. Bozic, MD, MBA b, * a b
University of California San Francisco School of Medicine, San Francisco, California Department of Surgery and Perioperative Care, Dell Medical School, University of Texas at Austin, Austin, Texas
a r t i c l e i n f o
a b s t r a c t
Article history: Received 30 November 2015 Received in revised form 5 January 2016 Accepted 13 January 2016 Available online xxx
Background: The purpose of this study was to assess whether weaning of opioid use in the preoperative period improved total joint arthroplasty (TJA) outcomes. Methods: Forty-one patients who regularly used opioids and successfully weaned (defined as a 50% reduction in morphine-equivalent dose) before a primary total knee or hip arthroplasty were matched with a group of TJA patients who did not wean and a matched control group of TJA patients who did not use opioids preoperatively. The difference between preoperative and postoperative (at 6-12 months follow-up) patient-reported outcomes were assessed using the change in University of California, Los Angeles (UCLA) activity score, SF12v2, and The Western Ontario and McMaster Universities Arthritis Index (WOMAC). Paired t tests and 1-way repeated measures analysis of variance were performed to assess differences in TJA outcomes between groups. Results: Patients using opioids who successfully weaned had greater improvements in both diseasespecific and generic measures of health outcomes than patients who did not wean (WOMAC 43.7 vs 17.8, P < .001; SF12v2 Physical Component Score 10.5 vs 1.85, P ¼ .003; UCLA activity score 1.49 vs 0, P < .001). There was no statistical difference between the 2 groups on SF12v2 Mental Component Score 2.48 vs 4.21, P ¼ .409. Patients who successfully weaned from opioids had similar outcomes to control patients who did not use opioids: WOMAC 39.0 vs 43.7, P ¼ .31; SF12v2 Physical Component Score 12.5 vs 10.5, P ¼ .35; SF12v2 Mental Component Score 3.08 vs 2.48, P ¼ .82; UCLA activity 1.90 vs 1.49, P ¼ .23. Conclusion: Patients with a history of chronic opioid use who successfully decreased their use of opioids before surgery had substantially improved clinical outcomes that were comparable to patients who did not use opioids at all. © 2016 Elsevier Inc. All rights reserved.
Keywords: opioids patient-reported outcomes total hip arthroplasty total knee arthroplasty pain management
Osteoarthritis (OA) is a leading cause of disability, and its prevalence continues to rise due to the increasing obese and elderly population. Worldwide, OA affects almost 10% of men and 18% of women older than 60 years, increasing to around 30% for those older than 70 years [1,2]. About 40%-60% of patients with radiologically confirmed knee OA experience pain, stiffness, and decreased mobility, with more than half stating that pain causes the most burden above all other arthritic symptomology [3]. OA 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 http://dx.doi.org/10.1016/j.arth.2016.01.068. Funding: None. * Reprint requests: Kevin J. Bozic, MD, MBA, Department of Surgery and Perioperative Care, Dell Medical School at the University of Texas at Austin, 1400 Barbara Jordan Blvd, Suite 1.114, Austin, TX 78723. http://dx.doi.org/10.1016/j.arth.2016.01.068 0883-5403/© 2016 Elsevier Inc. All rights reserved.
can cause decreased quality of life by interfering with activities of daily living, impairing cognition, reducing productivity, and increasing mood symptoms. Therefore, pain control is an essential part of managing OA. Analgesics, including nonopioid (eg, nonsteroidal anti-inflammatory drugs) and opioid pain medications, are the most common type of pharmacotherapy used in the treatment of OA. Previously, opioids were limited to managing predominantly acute pain and chronic cancer pain; however, opioids are now more liberally prescribed for chronic noncancer pain syndromes such as OA [4]. In a sample of elderly Medicare patients with knee OA, a study demonstrated that opioid use has increased from 31% to 40% between 2003 and 2009 [5]. Several clinical practice guidelines are currently available for the management of OA. The 2012 American College of Rheumatology guidelines on management of osteoarthritis recommends the use of opioids in management of osteoarthritis after failed medical therapy if the patient is not willing or has contraindications for total joint arthroplasty [6]. National Institute of Clinical Excellence
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guidelines also propose opioids if inadequate pain control with nonsteroidal anti-inflammatory drugs or paracetamol [7]. The American Academy of Orthopedic Surgeons provide inconclusive recommendations for the use of opioids in the treatment of OA [8], whereas other organizations, including the American Geriatrics Society and the OA Research Society International, remain unclear on how and when to use opioids in managing OA [9,10]. Although opiates have emerged as potential agents for select patients with symptomatic OA who are unresponsive or have contraindications to antiinflammatory medication, the association with adverse effects has highlighted the potential harms of chronic opiate use. As prolonged use of opioids to manage chronic pain associated with OA becomes more prevalent, a growing body of evidence has amassed that suggests that such exposure may affect outcomes of total joint arthroplasty. Long-term use of opioid medications may lead to dependence or hyperalgesia, both of which might adversely affect perioperative and postoperative pain management, risk of complications, rehabilitation, and clinical outcomes after a total joint arthroplasty [11-14]. Although several studies have raised concerns about the association of preoperative opioid use with worse clinical outcomes after surgery, it has yet to be explored whether this risk factor is modifiable with weaning of opioid dose before surgery. The purpose of this study was to evaluate whether weaning of opioid dose in patients with a history of chronic opioid use before undergoing a total joint arthroplasty would improve clinical outcomes compared to patients who did not wean. Methods A retrospective matched cohort study design was used to define 3 cohorts of patients: (1) Intervention group, which included patients who successfully weaned their opioid dose before surgery, which was defined as weaning their morphine equivalent dose by 50% after recommending the patient to self-wean, referring patient to pain management to help wean, or suggesting they wean under the supervision of their primary care provider; (2) Opioiddependent control group, which included patients with chronic opioid use, defined as continued use for at least 4 weeks, based on Chu et al [15] who reported that hyperalgesia was achieved after chronic use of morphine for 4 weeks; and (3) opioid naïve control group, which included patients with no prior narcotic history. A review of all patients who underwent unilateral primary hip or knee arthroplasty at a single institution between 2007 and 2014 was conducted using multiple sources including clinical office notes and referral notes to identify a study group of 41 patients with a history of chronic opioid use before a primary hip or knee arthroplasty who successfully weaned their dose before their surgery. All opioid medications and dosages were converted to a morphine-equivalent dose [16]. Patients were excluded if they had a bilateral or revision procedure. Postoperative pain management protocol (gabapentin 200 mg three times a day, acetaminophen 1000 mg three times a day, celebrex 200 mg twice a day, oxycodone 5-15 mg as needed for moderate pain, Dilaudid IV 0.2-0.8 mg as needed for severe pain) was followed for all patients barring any contraindications. Patients undergoing a total knee arthroplasty also received an adductor canal block. Patients from the study group were individually pair-matched 1:1:1 with patients who met the definition for chronic opioid use, however did not wean, and patients who managed their pain without narcotics. Patients in the control group were selected from a list of all patients who received a total joint arthroplasty at the same institution over the same period of time at random using a random number generator. Patients were matched based on primary diagnosis, affected joint (hip/knee), American Society of Anaesthesiologists' classification of physical health, sex, body mass
Table 1 Demographics of Patient Cohorts. Characteristics
Intervention Group
Opioid-Dependent Control Group
Opioid Naïve Control Group
Mean age Sex Female Male Primary diagnosis Primary OA Osteonecrosis Posttraumatic
59
60
58
27 (66%) 14 (34%)
27 (66%) 14 (34%)
27 (66%) 14 (34%)
34 (83%) 4 (10%) 3 (7%)
34 (83%) 4 (10%) 3 (7%)
34 (83%) 4 (10%) 3 (7%)
OA, osteoarthritis.
index (BMI) (þ/ 10), age (þ/ 10), and daily morphine equivalent group. Opioid subgroups were based on methodology published by Kidner et al [17] and was divided as follows: low (<30 mg), medium (31-60 mg), high (61-120 mg), and very high (>120 mg). An a priori power analysis was performed and indicates that 41 matches of subjects were needed for a power of 80% to detect a real clinical difference between the subjects and 2 control groups at a P-value of <.05. Primary outcome studied was the delta of patientreported outcomes (PRO) from baseline to 6-12 month follow-up as measured by University of California at Los Angeles Activity Score, SF12v2, and The Western Ontario and McMaster Universities Arthritis Index (WOMAC). Outcomes data were taken from a database of prospectively collected PROs. The continuous outcomes of PRO change were analyzed using a paired 2-tailed Student t test and 1-way analysis of variance. Categorical variables were compared utilizing chi-squared test. Statics were performed using STATA. Results There were 41 patients in each group. Mean age of the intervention, opioid dependent, and opioid naive groups were 59.0, 60.1, and 58.2, respectively. Mean BMI was 29.5 (range, 21.6-47.5), 32.8 (20.6-54.9), and 29.4 (21.4-42.89), respectively. Each group was comprised of 34% males and 66% females. The primary diagnoses of each group were distributed as follows: 34 primary osteoarthritis (83%), 4 osteonecrosis (10%), 3 posttraumatic osteoarthritis (7%) (Table 1). There were 14 patients using a low morphine equivalent (34%), 7 taking medium morphine equivalent (17%), 6 taking high morphine equivalent (15%), and 14 taking very high morphine equivalent in each of the groups (34%). There were no differences in baseline University of California, Los Angeles (UCLA) activity and SF12v2 mental component scores between the groups, (P-value ¼ .052, P-value ¼ .057, respectively). The intervention group had significantly lower mean WOMAC and SF12v2 physical component scores than the two control groups, (P-value < .01) (Table 2). The opioid naïve control group had significantly higher increases from their baseline to their postoperative UCLA, WOMAC, SF12v2 physical component scores than the opioid-dependent control group (P < .01 for all 3 measures). The change in SF12v2 mental component score between the opioid naïve and opioiddependent control groups was not significant (P ¼ .63) (Fig. 1). The opioid naïve group had significantly higher final PROs at 6-12 Table 2 Differences in Patient-Reported Outcomes Between Patient Groups. Patient Reported Intervention Opioid-Dependent Opioid Naïve P-value Outcome Measure Group Control Group Control Group UCLA WOMAC SF12v2-P SF12v2-M
3.1 32 24.7 47.5
3.6 47.5 28.8 42.8
4.1 44.1 30.9 49.1
.052 <.01 <.01 .057
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Fig. 1. Opioid naïve vs opioid dependent (change in patient-reported outcomes). * Indicates the comparison was statistically significant (P < .01).
months post operation than the opioid-dependent group: UCLA (P < .01), WOMAC (P < .01), SF12v2 physical component (P < .01), SF12v2 mental component (P ¼ .015) (Table 3). Patients with history of chronic opioid use who reduced their dose by half preoperatively had significantly higher changes in UCLA, WOMAC, SF12v2 physical component scores than the opioiddependent control group (P < .01 for all 3 measures). There were no significant differences in change of SF12v2 mental component scores (P-value ¼ .41) (Fig. 2). The intervention group had significantly higher postoperative final physical function scores than the opioid-dependent groups for UCLA (P < .01), WOMAC (P ¼ .022), and SF12v2 physical component (P ¼ .048). The final SF12v2 mental component score was not significantly different between the 2 groups (P ¼ .14) (Table 4). There were no significant differences in change scores for all PROs between the intervention group and the opioid naïve control group (UCLA, P-value ¼ .24; SF12v2 mental, P-value ¼ .82; SF12v2 physical, P-value ¼ .35; and WOMAC, P-value ¼ .31) (Fig. 3). However, the opioid naïve group had significantly higher final UCLA (P < .01), WOMAC (P ¼ .049), and SF12v2 physical component (P < .01). There was no difference in the final SF12v2 mental component scores between the 2 groups (P ¼ .22) (Table 5). Discussion Patients on chronic opioid therapy present certain challenges to orthopedic surgeons. There is accumulating evidence that suggests that chronic opioid use is associated with poor clinical outcomes after orthopedic surgery. In a study by Chapman et al [18], patients who reported chronic opioid use before an orthopedic surgery Table 3 Opioid Naïve vs Opioid Dependent: Final PROs at 6-12 Months Follow-Up. Patient Reported Outcome Measure
Opioid Naïve
Opioid Dependent
Baseline
6-12 mo Postoperatively
Baseline
6-12 mo Postoperatively
UCLA WOMAC SF12-P SF12-M
4.1 44.1 30.9 49.1
6 83.1 42.4 52.2
3.6 47.5 28.8 42.8
3.6 65.3 30.6 47
P-value
<.01 <.01 <.01 .015
use experienced greater severity of acute pain and slower pain resolution despite adjustments made for additional opioid administration. Zywiel et al [11] found that those with preoperative exposure to opioids were likely to have a longer length of stay, increased risk of complications and additional surgical procedures, greater need to be referred for pain management after total knee arthroplasty, along with lower clinical scores compared with those without prolonged exposure to opioids before surgery. A study by Pivec et al [12] comparing the clinical outcomes of patients taking chronic narcotics before undergoing total hip arthroplasty to those not taking narcotics similarly showed worse long-term clinical results, higher in-hospital opioid dose requirements, and greater levels of continued narcotic use after surgery. Lawrence et al [19] found that chronic narcotic users had worse outcomes after cervical arthrodesis procedures when compared to other patients. This present study further supports the hypothesis that chronic opioid use clinical outcomes in patients undergoing a total joint arthroplasty. However, the novel finding in this study is that opioid users who taper their dose before surgery achieved significantly improved outcomes compared with those who did not taper, therefore, suggesting that chronic opioid use is in fact a modifiable risk factor. Chronic opioid users who reduced their dose by at least 50% had improved functional outcome scores compared to those that did not wean as measured by WOMAC 43.7 vs 17.8, (P-value < .001), SF12v2 physical, 10.5 vs 1.85 (P-value ¼ .003), UCLA activity score, with a mean delta score of 1.49 vs 0 (P-value < .001). Although the group that reduced their opioid use achieved the same delta scores in their functional outcomes as those that are narcotic naïve, given that their baseline functional scores were lower they did not achieve the same postoperative functional status as those that did not use opioids initially. Therefore, chronic opioid users who wean their dose of opioids before TJA can expect greater improvements in functional status and better overall functional status than chronic opioid users who do not wean, they should still be counseled to expect lower functional abilities than TJA patients who have not had chronic exposure to opioids. Why chronic opioid use affects outcomes is not well understood but is thought to be multifactorial and may result from opioidinduced hyperalgesia (OIH) [20,21]. OIH is defined as nociceptive sensitization caused by exposure to opioids. This neuropharmacological phenomenon is characterized by a paradoxical adverse
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Fig. 2. Intervention vs opioid dependent (change in patient-reported outcomes). * Indicates the comparison was statistically significant (P < .01).
response whereby a patient receiving opioids for the treatment of pain might actually become more sensitive to painful stimuli. This concept was observed as early as the 19th century in patients receiving morphine for pain. It was recognized that a potent analgesic such as morphine could actually result in an increase in pain [22]. Since then, there has been substantial basic science as well as clinical evidence supporting the concept of OIH [15,23-28]. Among the more important human studies documenting this effect are those demonstrating hyperalgesia in former opioid addicts maintained on methadone when compared with matched controls not receiving methadone or other opioids [29]. In addition, OIH appears to be a definable phenomenon that could lead to the loss of opioid efficacy and difficulty with treating postoperative pain. Patients with severe pain that is not appropriately managed postoperatively have been shown to have worse outcomes, which may also contribute to the lower functional scores seen in this study [30,31]. Although not assessed in the present study, dose and duration appear to be important factors in the relationship between opioids and adverse effects. A small number of studies have looked at the clinical characteristics of this relationship. Kidner et al reported that, in patients admitted for rehabilitation of a chronic musculoskeletal disorder, increased opioid medication dosages were associated with an increased rate of program noncompletion, a lower rate of return to work, and an increased likelihood of receiving disability or social security supplemental income 1 year after treatment [17]. It was also found that exposure to larger doses of opioids seems to be associated with OIH [23,26,32-34]. Some studies have demonstrated that larger doses of intraoperative remifentanil induced an increase in postoperative pain [33,35]. However, there are studies that reported observing OIH after interruption of even small doses of opiates [15,36]. On the contrary,
Table 4 Intervention vs Opioid Dependent: Final PROs at 6-12 Months Follow-Up.
UCLA WOMAC SF12-P SF12-M
Intervention Group
Opioid Dependent
Baseline
6-12 mo Postoperatively
Baseline
6-12 mo Postoperatively
3.1 32 24.7 47.5
4.6 75.7 35.1 50
3.6 47.5 28.8 42.8
3.6 65.3 30.6 47
P-value
<.01 .022 .048 .14
a study by Cortinez et al [37] failed to demonstrate an increase in postoperative opioid consumption with increased doses of intraoperative remifentanil. This study only looks at short-term intraoperative opioid use, and it could be that longer anesthesia is required to develop clinically significant opioid tolerance effect. Studies have shown that OIH is more evident with prolonged duration of use [24,38]. However, reports on the duration required to attain OIH is inconsistent. In a prospective study by Chu et al [15], it was found that chronic use of oral morphine for 4 weeks in previously narcotic naïve patients with chronic back pain resulted in hyperalgesia. Another study demonstrated increased pain sensitivity in patients undergoing eye surgery who only used opioids intraoperatively [35]. Few studies have investigated the effect of reducing opioid doses on pain, although one retrospective study of patients undergoing detoxification for opioid addiction found a significant decrease in pain when patients were converted onto nonsteroidal antiinflammatory drugs for their pain [39]. Further research is needed to define clinical factors such as duration and dose to achieve symptoms and critical dose to mitigate the hyperalgesic effect. The strengths of the present study are related to the design and the selection of the cohorts. Matching the cases and controls with respect to age, gender, American Society of Anaesthesiologists' classification of physical health, BMI, primary diagnosis, affected joint, and morphine equivalent reduces the possibility of confounding from these factors because of their potential associated with the outcome indices studied. In addition, there were no significant differences in baseline functional scores as measured by UCLA scores and SF12v2 mental clinical scores. Although there were, however, differences between the baseline functional scores as measured by SF12v2 physical component score and WOMAC; the baseline scores were lower in the group of chronic narcotic users who were able to wean. The random selection of controls from an administrative database of all patients that have received primary joint arthroplasty reduces selection bias. Some limitations of the investigation were also noted. Reliance on self-reported preoperative opioid use may underreport the true opioid use in the study population. We did not have access to pharmacy records and were unable to confirm the duration or dosing of preoperative or postoperative opioids. We also did not assess certain other preoperative risk factors such as smoking, chronic back pain, or concomitant mood disorder.
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5
Fig. 3. Intervention vs opioid naïve (change in patient-reported outcomes).
Table 5 Intervention vs Opioid Naïve: Final PROs at 6-12 Months Follow-Up.
UCLA WOMAC SF12-P SF12-M
Intervention Group
Opioid Naïve
Baseline
6-12 mo Postoperatively
Baseline
6-12 mo Postoperatively
3.1 32 24.7 47.5
4.6 75.7 35.1 50
4.1 44.1 30.9 49.1
6 83.1 42.4 52.2
P-value
<.01 .049 <.01 .22
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