Chronic Opioid Use Prior to Total Knee Arthroplasty Michael G. Zywiel, MD; D. Alex Stroh, BS; Seung Yong Lee, MD; Peter M. Bonutti, MD; Michael A. Mont, MD The Journal of Bone & Joint Surgery. 2011 Background: Chronic use of opioid medications may lead to dependence or hyperalgesia (increased sensitivity to pain), both of which might adversely affect perioperative and postoperative pain management, rehabilitation, and clinical outcomes after total knee arthroplasty. The purpose of this study was to evaluate patients who underwent total knee arthroplasty following six or more weeks of chronic opioid use for pain control and to compare them with a matched group who did not use opioids preoperatively. Forty-nine knees in patients who had a mean age of fifty-six years and who had regularly used opioid medications for pain control prior to total knee arthroplasty were compared with a group of patients who had not used them. Length of hospitalization, aseptic complications requiring reoperation, requirement for specialized pain management, and clinical outcomes were assessed for both groups. Results: Knee Society scores were significantly lower in the patients who regularly used opioid medications at the time of final follow-up; the opioid group had a mean of 79 points as compared with a mean of 92 points in the non-opioid group. A significantly higher prevalence of complications was seen in the opioid group, with five arthroscopic evaluations and eight revisions for persistent stiffness and/or pain, compared with none in the matched group. Ten patients in the opioid group were referred for outpatient pain management, compared with one patient in the non-opioid group. Conclusions: Patients who chronically use opioid medications prior to total knee arthroplasty may be at a substantially greater risk for complications and painful prolonged recoveries. Alternative non-opioid pain medications and/or earlier referral to an orthopaedic surgeon prior to habitual opioid use should be considered for patients with painful degenerative disease of the knee. Introduction Osteoarthritis of the knee has a chronic course, with gradually increasing pain and decreasing quality of life prior to reaching the end stage of disease that may be amenable to arthroplasty treatment. A number of guidelines and consensus statements have been released regarding the management of this disease. While the American Academy of Orthopaedic Surgeons clinical practice guidelines on the treatment of osteoarthritis of the knee do not address the use of opioid medications, most reports recommend that mild analgesics such as acetaminophen be used initially, followed by nonsteroidal anti-inflammatory drugs and opioids. Examples of prescribed opioids include: Tylenol #3 (codeine and acetaminophen), Percocet (oxycodone and acetaminophen), Percodan (oxycodone and acetylsalicylic acid), OxyContin (oxycodone timed-release formulation), Dilaudid (hydromorphone), Vicodin (hydrocodone and acetaminophen), and methadone. Surgical treatment, including total knee arthroplasty, is typically considered after nonoperative methods have failed. Recently, an increase in the use of these medications for the treatment of chronic musculoskeletal conditions has been reported with opioid medications becoming the second or even the first-line treatment of choice for primary-care providers for the management of osteoarthritis-associated pain. In 2009, the updated guidelines for the management of chronic pain in elderly patients recommended against the use of nonsteroidal anti-inflammatory medications due to the high risk of gastric bleeding and suggested the use of opioid analgesics instead. However, several authors have raised concerns about the use of these medications, specifically with regard to the development of tolerance and hyperalgesia and the potential association of opioids with worse treatment outcomes in association with a variety of musculoskeletal conditions affecting the neck, lower back, and knee. The purpose of this study was to compare the perioperative course, complication rates, and clinical outcomes of patients who underwent total knee arthroplasty and were or were not treated with chronic preoperative oral opioid analgesic medications. Materials and Methods Databases of patients who underwent operation at either of two specialized centers were used to identify all primary total knee arthroplasties that were performed for end-stage degenerative joint disease. Subjects were identified who had documented treatment with oral opioid medications for knee pain for a minimum of six weeks prior to the arthroplasty procedure. This threshold for chronic use was based on the report by Chu et al on the development of hyperalgesia in human volunteers following one month of daily oral opioid medication use. Only those patients using a minimum equivalent dose of 20 mg/day were included in the preoperative opioid group (equivalent to approximately four hydrocodone or three oxycodone tablets per day). Forty-nine knees were identified in fourteen men and thirty-one women (including forty-one unilateral procedures and four bilateral arthroplasties) who had a minimum of twenty-four months follow-up. Specific demographic characteristics reviewed included patient age, sex and BMI. Preoperative and perioperative factors examined included the specific opioid medication(s) used and duration of preoperative use; preoperative diagnosis leading to degenerative joint disease; history of substantial knee trauma; number and type of previous knee surgical procedures; history of chronic back pain and/or back surgery; smoking status; neuroleptic, antidepressant, and/or anxiolytic medication use; alcohol abuse; systemic corticosteroid use; preoperative University of California Los Angeles (UCLA) activity scores; Knee Society objective scores; knee range of motion; and number of days until discharge following surgery. Clinical outcomes evaluated were the Knee Society objective score, knee range of motion, and the prevalence of arthroscopic and/or revision surgery for unexplained knee stiffness and/or pain. Patients were also evaluated for the need for referral to a pain management specialist. This is routinely done at both study centers if patients continue to experience substantial pain ninety days following the most recent surgical procedure and the pain is unexplained by implant factors and requires narcotic medication. Perioperative analgesia was provided through patient-controlled intravenous analgesia, continuous infusion of local anesthetic into an epidural catheter, or intermittent intravenous analgesia. Postoperatively, patients were transitioned to oral analgesia in preparation for discharge. Results Patients with a history of preoperative opioid medication use had a significantly longer duration of postoperative hospitalization compared with those who did not use preoperative opioids. The opioid group was discharged from the hospital at a mean of 4.3 days following the arthroplasty, compared with 3.4 days for the non-opioid group. A significantly higher number of patients in the opioid group required additional surgical procedures over the course of the study period for unexplained knee stiffness or pain. There were - 5 arthroscopic evaluations and debridements for unexplained knee pain and/or stiffness resistant to nonoperative treatment in the opioid group. - 8 arthroplasties in the opioid group revised for unexplained knee stiffness and/or pain despite being aseptic and with all components well fixed, - 1 arthroplasty in one patient who had previously undergone an arthroscopic evaluation but remained symptomatic and - 1 arthroplasty in a patient who originally underwent bilateral total knee arthroplasties and had both knees revised. All patients who underwent revision for persistent stiffness had previously undergone manipulations under anesthesia without lasting benefit. A total of 17 manipulations were performed in the opioid group, and 9 in the non-opioid group. On the basis of the numbers, no significant difference in preoperative range of motion was identified between the patients in the study group who did and did not undergo manipulation under anesthesia. In contrast, no patients in the non-opioid group underwent these procedures for aseptic reasons. A significantly greater number of patients in the opioid group were referred for specialized management of intractable pain of unknown cause compared with the non-opioid group, with ten referrals in the former group and one in the latter. Clinical outcomes as measured with use of the Knee Society objective knee score were significantly worse in the opioid group. At the time of final follow-up, the mean Knee Society objective score was 79 points in the opioid group, compared with a mean score of 92 points in the non-opioid group. A moderately significant correlation was identified in the study group between higher preoperative Knee Society scores and a shorter postoperative length of stay. The mean knee range of motion at the time of final follow-up was similar between the two groups, with 107° in the opioid group and 111° in the non-opioid group. Discussion Recently, there has been increasing trend of oral opioid analgesics are being prescribed by primary-care physicians despite reported associations between the use of opioid analgesia and poorer outcomes following the treatment of musculoskeletal conditions. One report reviewed 6,364 primary total knee arthroplasties that had been performed over a 5 year period and found that preoperative opioid users had lower mean Knee Society scores at a follow-up time of one year, and were significantly more likely to be dissatisfied with the results of the procedure. In contrast, 74 patients from a total of 1024 patients had been identified who had a total knee arthroplasty performed at a single center and who had knee pain or stiffness one year following the arthroplasty, and those authors found that preoperative opioid medication use was not associated with an outcome of stiffness or pain. In conclusion, the use of chronic oral opioid analgesia prior to total knee arthroplasty was associated with an increased rate of complications requiring return to the operating room and poorer clinical outcomes. It may be beneficial to investigate and define limits of preoperative opioid dosage and duration to improve the postoperative outcomes of patients with degenerative disease of the knee who cannot or prefer not to be immediately treated surgically. However, larger and more rigorous studies should be conducted to better elucidate the relationship between opioid use and the outcomes of total knee arthroplasty.