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Do Opioids Cause Knee Replacement Complications?

Marc Darrow, MD.

One of the more frequent emails we receive is one from people with knee pain who may have had prolonged wait for a knee replacement and had a lot of pain issues. Because of the delay or wait in getting a knee replacement they have found themselves asking for and taking more medications to help them with their pain until they got the knee replacement. For some however, after the knee replacement, they have just as much pain as before. While knee replacement surgery enjoys great success, research is showing us that the use of painkillers to help people manage knee pain before knee replacement is putting these same people at a greater risk of knee replacement failure and greater needs for opioids post-surgery.

I would like to start with a study that supports this idea. From Stanford University research: “Patients taking opioids (narcotic painkillers) prior to surgery experience prolonged postoperative opioid use, worse clinical outcomes, increased pain, and more postoperative complications.”(1) From the same research comes concerning suggestions that patients presenting with preoperative opioid use have potentially an increased risk for opioid misuse after surgery. This should not come as a surprise to anyone. If you are taking more painkillers before surgery, the stronger likelihood is that you will be taking more painkillers after surgery. Let’s explore the research that debates this.

More than 10% of people over 65 getting total knee replacement become persistent opioid users after knee replacement

A study from January 2021 (2) found that 10.6% of patients, over the age of 65, became persistent high dose opioid users after total knee replacement. The people at higher risk were prior to surgery use of “opioids, benzodiazepines, anxiolytics, antidepressants and diagnosis or treatments for chronic painful conditions.” Older black men and women presented the largest secondary risk group.

Opioids cause hypersensitivity to pain

The prioir to surgery use of opioids prior to knee replacement has been the subject of years of research. In 2011, researchers in Canada wrote in the American Journal of Bone and Joint Surgery: (3)

  • “Chronic use of opioid medications may lead to dependence or hyperalgesia, (Opioid-induced hyperalgesia is an increased sensitivity to pain) both of which might adversely affect perioperative and postoperative pain management, rehabilitation, and clinical outcomes after total knee replacement.”

The purpose of this study was to evaluate patients who underwent total knee replacement 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 pre-operatively.

A significantly higher prevalence of complications was seen in the opioid group

  • of the 49 knees replaced in this group –
    • 5 needed arthroscopic evaluations and
    • 8 needed revision surgery 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 replacement 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.”

Although a moderate delay in surgical intervention may not produce a significant progression of osteoarthritis within the knee, it could lead to muscle wasting

This research from 2011 was brought up to date by the 2020 pandemic. (4) Because of hospitals pausing elective surgeries, many people found themselves on longer medication care than originally anticipated.

“Although a moderate delay in surgical intervention may not produce a significant progression of osteoarthritis within the knee, it could lead to muscle wasting due to immobility and exacerbate comorbidities, making rehabilitation more challenging. Importantly, it will have an impact on comorbidities driven by osteoarthritis severity, notably decreased quality of life and depression. These patients with unremitting pain become increasingly susceptible to substance use disorders including opioids, alcohol, as well as prescription and illegal drugs. Appreciation of this downstream crisis created by delayed surgical correction requires aggressive consideration of nonsurgical, non-opiate supported interventions to reduce the morbidity associated with these delays brought upon by the currently restricted access to joint repair.”

Alternatives to opioids not as popular as opioids

In a paper from leading French researchers published in the European pain journal, the doctors wrote:

  • Despite the development of multimodal analgesia (many different pain medications) for postoperative pain management, opioids are still required for effective pain relief after knee replacement.(5)

Doctors at Mount Sinai in New York wrote in The Journal of the American Academy of Orthopaedic Surgeons:

  • Total knee replacement is associated with substantial postoperative pain that may impair mobility, reduce the ability to participate in rehabilitation, lead to chronic pain, and reduce patient satisfaction. Traditional general anesthesia with postoperative epidural and patient-controlled opioid analgesia is associated with an undesirable adverse-effect profile, including postoperative nausea and vomiting, hypotension, urinary retention, respiratory depression, delirium, and an increased infection rate.”(6)

In another study doctors found that many patients undergoing hip or knee replacement are still taking prescription opioid pain medications up to six months after surgery. The study that appeared in the medical journal PAIN was led by  Jenna Goesling, PhD, of the University of Michigan, the study identifies several “red flags” for persistent opioid use–particularly previous use of high-dose opioids. The results also suggest that some patients continue to use these potentially addictive pain medications despite improvement in their hip or knee pain.(7)

Concerns about Persistent Opioid Use after Joint Replacement

Dr. Goesling and her team analyzed patterns of opioid use in 574 patients undergoing knee or hip replacement surgery. Patients were followed up at one, three, and six months after surgery to assess rates of and risk factors for long-term opioid use.

  • About 30 percent of the patients were taking opioids prior to their joint replacement surgery. Of this group, 53 percent of knee-replacement patients and 35 percent of hip replacement patients were still taking opioids at six months after surgery.

Patients who were not taking opioids prior to surgery were less likely to report persistent opioid use: About 8 percent in the knee-replacement group and 4 percent in the hip-replacement group continued to take opioids at the six-month follow up. Although these are relatively small percentages, this suggests that a portion of patients who were “opioid naïve” prior to surgery will become new chronic opioid users following arthroplasty.

  • The strongest predictor of long-term opioid use was taking high-dose opioids before joint replacement surgery. For patients in the highest preoperative dose group (equivalent to more than 60 milligrams of oral morphine per day), the predicted probability of persistent opioid use at six months was 80 percent.
  • Among patients not previously taking opioids, those with higher pain scores the day of surgery–both in the affected joint and overall body pain–were more likely to report persistent opioid use at six months.
  • Opioid use was also more likely for patients who scored higher on a measure of pain catastrophizing–exaggerated responses and worries about pain–than those with depressive symptoms.

Improvement in knee or hip pain after joint replacement did not reduce the likelihood of long-term opioid use

For all patients, reductions in overall body pain were associated with decreased odds of being on opioids at six months. However, improvement in knee or hip pain after joint replacement did not reduce the likelihood of long-term opioid use.

Persistent opioid use after knee or hip replacement surgery may be more common than previously reported, the results suggest. Importantly, continued opioid use is not necessarily related to pain in the affected joint. “We hypothesize that the reasons patients continue to use opioids may be due to pain in other areas, self-medicating affective distress, and therapeutic opioid dependence,” the researchers wrote.

Duloxetine after knee replacement

In an effort to find options to opioids following knee replacement, a June 2022 study (8) suggested duloxetine, a serotonin-norepinephrine dual reuptake inhibitor, may improve pain relief.

  • A total of 160 patients received 60 mg duloxetine or placebo daily, starting from the day of surgery and continuing 14 days postoperatively.
  • Patients received neuraxial anesthesia, peripheral nerve blocks, acetaminophen, nonsteroidal anti-inflammatory drugs, and oral opioids as needed.
  • The dual primary outcomes were Numeric Rating Scale (NRS – pain scale) scores with movement on postoperative days 1, 2, and 14, and cumulative opioid consumption surgery through postoperative day 14.

Duloxetine was superior to placebo for both primary outcomes and was superior to placebo for reducing opioid consumption. Duloxetine reduced pain with walking, normal work, and sleep.

Overall, there was a 29% reduction in opioid use which corresponds to 17 fewer pills of oxycodone, 5 mg, and was achieved without increasing pain scores. The researchers write: “Considering the ongoing opioid epidemic, duloxetine can be used to reduce opioid usage after knee arthroplasty in selected patients that can be appropriately monitored for potential side effects of the medication.”

Opioids before knee replacement seen as a “placebo” and non-effective as rescue painkiller

A study from January 2023 (9) suggested that opioids given just before knee replacement were of no help in preventing pain after the knee replacement surgery. In this paper the authors discuss “Preemptive multimodal analgesia” as a commonly used technique to control pain following total knee replacement. Their study, according to the authors, was aimed to evaluate the effectiveness of the pre-emptive opioids technique for pain management in patients who underwent total knee replacement.

  • Two hours before surgery, 100 patients were divided into two groups.
    • An oxycodone group or control group.
  • At 2 hours before surgery, patients in the oxycodone group received 400 mg celecoxib, 150 mg pregabalin, and 10 mg extended-release oxycodone hydrochloride. Patients in the control group received 400 mg celecoxib, 150 mg pregabalin, and placebo.
  • The primary outcome was postoperative consumption of morphine hydrochloride as rescue analgesia. (Typically the patient tells the doctors they are having significant pain and need “something more.”
  • Secondary outcomes were time to need of the first rescue analgesia, postoperative pain assessed by the visual analogue scale, functional recovery assessed by range of knee motion and ambulation distance, time until hospital discharge, indicators of liver function, and complication rates.

The study authors found: “The 2 groups were similar in average postoperative 0 to 24 hour morphine consumption and average total morphine consumption.” In this study, “preemptive opioid administration did not provide clinical benefits over placebo. Orthopaedic surgeons should consider not using pre-operative opioids in patients undergoing total knee replacement.”

In May 2022, (10) other researchers suggested a modest benefit in offering pre-operative opioids. In this paper a preemptive three-drug regimen (acetaminophen, celecoxib, and gabapentin) were examined for pain relief and to assess if it would help reduce post-operative opioid consumption following a joint replacement surgery. In a test of 1416 knee replacement and hip replacement patients, statistically significant reductions in oral morphine equivalents were shown on post-operative day zero (day of surgery) and two within the knee replacement cohort, and non-significant reductions were demonstrated in other intervals for both procedure types.  . . “The receipt of preemptive acetaminophen, celecoxib, and gabapentin 30-60 min prior to total joint arthroplasty demonstrated modest reductions in opioid requirements post-operatively.” Patients also reported lower pain scores throughout nearly every time interval during their admission after surgery.”

Higher body mass index may cause knee replacement complications and the need for more opioid use

An August 2022 study (11) found a higher body mass index may cause knee replacement complications and the need for more opioid use. In this research the authors summarize: Persistent pain following knee replacement occurs in up to 20% of patients and may require ongoing analgesia, including extended opioid administration. A comprehensive secondary analysis was performed from results of a study that considered persistent postoperative pain in 242 patients who underwent unilateral knee arthroplasty. Opioid prescribing for 12 months before and 12 months after surgery was evaluated. Forty-nine percent of patients had at least one opioid prescription in the 12 months before surgery. Opioid prescriptions were filled in 93% of patients from discharge to 3 months and in 27% of patients more than 6 months after surgery. “Pre-operatively, patients with a higher body mass index, more comorbid pain sites and those who had filled an opioid prescription in the last 12 months, were at increased risk of persistent opioid use and a higher oral morphine equivalent daily dose more than 6 months after surgery.”


As a 2020 study in the journal BMC musculoskeletal disorders points out: (9) : “people who take daily opioids pre-surgery have significantly greater odds for greater opioid consumption acutely and ongoing use post-surgery. ”


1 Hah JM, Sharifzadeh Y, Wang BM, Gillespie MJ, Goodman SB, Mackey SC, Carroll IR. Factors associated with opioid use in a cohort of patients presenting for surgery. Pain research and treatment. 2015;2015.
2 Gopalakrishnan C, Desai RJ, Franklin JM, Jin Y, Lii J, Solomon DH, Katz JN, Lee YC, Franklin PD, Kim SC. Development of a Medicare Claims–Based Model to Predict Persistent High‐Dose Opioid Use After Total Knee Replacement. Arthritis care & research. 2022 Aug;74(8):1342-8.
3 Zywiel MG, Stroh DA, Lee SY, Bonutti PM, Mont MA. Chronic opioid use prior to total knee arthroplasty. J Bone JointSurg Am. 2011 Nov 2;93(21):1988-93. doi: 10.2106/JBJS.J.01473.
4 Cisternas AF, Ramachandran R, Yaksh TL, Nahama A. Unintended consequences of COVID-19 safety measures on patients with chronic knee pain forced to defer joint replacement surgery. Pain Reports. 2020 Nov;5(6).
5 Thomazeau J, Rouquette A, Martinez V, Rabuel C, Prince N, Laplanche JL, Nizard R, Bergmann JF, Perrot S, Lloret-Linares C. Acute pain Factors predictive of post-operative pain and opioid requirement in multimodal analgesia following knee replacement. Eur J Pain. 2015 Oct 30. doi: 10.1002/ejp.808.
6 Moucha CS, Weiser MC, Levin EJ. Current Strategies in Anesthesia and Analgesia for Total Knee Arthroplasty.  J Am Acad Orthop Surg. 2016 Feb;24(2):60-73. doi: 10.5435/JAAOS-D-14-00259.
7 Goesling J, Moser SE, Zaidi B, Hassett AL, Hilliard P, Hallstrom B, Clauw DJ, Brummett CM. Trends and predictors of opioid use following total knee and total hip arthroplasty. Pain. 2016 Jun;157(6):1259.
8 YaDeau JT, Mayman DJ, Jules-Elysee KM, Lin Y, Padgett DE, DeMeo DA, Gbaje EC, Goytizolo EA, Kim DH, Sculco TP, Kahn RL. Effect of Duloxetine on Opioid Use and Pain After Total Knee Arthroplasty: A Triple-Blinded Randomized Controlled Trial. The Journal of Arthroplasty. 2022 Jun 1;37(6):S147-54.
9 Wang Q, Zhang W, Xiao T, Wang L, Ma T, Kang P. Efficacy of Opioids in Preemptive Multimodal Analgesia for Total Knee Arthroplasty: A Prospective, Double-Blind, Placebo-Controlled, Randomized Trial. The Journal of Arthroplasty. 2023 Jan 1;38(1):65-71.
10 Passias BJ, Johnson DB, Schuette HB, Secic M, Heilbronner B, Hyland SJ, Sager A. Preemptive multimodal analgesia and post-operative pain outcomes in total hip and total knee arthroplasty. Archives of Orthopaedic and Trauma Surgery. 2022 May 2:1-7.
11 Kluger MT, Rice DA, Borotkanics R, Lewis GN, Somogyi AA, Barratt DT, Walker M, McNair PJ. Factors associated with persistent opioid use 6–12 months after primary total knee arthroplasty. Anaesthesia. 2022 Jun 27.

10 Naylor JM, Pavlovic N, Farrugia M, Ogul S, Hackett D, Wan A, Adie S, Brady B, Gray L, Wright R, Nazar M. Associations between pre-surgical daily opioid use and short-term outcomes following knee or hip arthroplasty: a prospective, exploratory cohort study. BMC musculoskeletal disorders. 2020 Dec;21(1):1-0.



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