Paper of the Week: Dose-Dependent Early Postoperative Opioid Use Is Associated with Periprosthetic Joint Infection and Other Complications in Primary TJA

Paper of the Week: Dose-Dependent Early Postoperative Opioid Use Is Associated with Periprosthetic Joint Infection and Other Complications in Primary TJA

ICM Philly July 20, 2021

Brian C. Chung, BS, Gabriel J. Bouz, MD, Cory K. Mayfield, MD, Haley Nakata, MD, Alexander B. Christ, MD, Daniel A. Oakes, MD, Jay R. Lieberman, MD, and Nathanael D. Heckmann, MD

The Journal of Bone and Joint Surgery, May 27, 2021
doi: 10.2106/JBJS.21.00045

Summary by Justin A. Magnuson, BA

Preoperative opioid use has been associated with increased rates of surgical site infection, prosthetic joint infection (PJI), and need for revision surgery in patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA) [1-3]. It has been postulated that these findings, along with less improvement in pain and function following arthroplasty in opioid users, may be due in part to immunosuppressive and hyperalgesic effects of opioids [4]. Despite the established risks of preoperative opioid use, there is little published on the effects of postoperative opioid use on complications following total joint arthroplasty.

Chung et al. investigated whether postoperative opioid use was associated with increased rates of PJI and pulmonary complications following total joint arthroplasty. They looked at 1,525,985 patients aged 18 or older undergoing primary elective TKA and THA from 2004-2014 using a large retrospective database (Premier Healthcare Database). Primary outcomes included PJI, deep venous thrombosis (DVT), and pulmonary embolism (PE). Secondary outcomes were wound infection, dehiscence, infected seroma, sepsis, myocardial infarction (MI), stroke, acute kidney injury (AKI), and readmission. All outcomes were evaluated for the first 90 days after surgery. Opioid use from the day of surgery to postoperative day 2 was divided into five quintiles based on morphine milligram equivalent (MME) exposure (<54, 54-82, 83-116, 117-172, and >172). Logistic regression modeling was used to examine dose-dependent associations of postoperative opioid use while adjusting for comorbidities, obesity, tobacco use, alcohol, use, and preoperative opioid use.

The study found that increasing MME exposure was associated with increased rates of PJI (p<0.001), DVT (p<0.001), and PE (p<0.001) when adjusted for confounders. A dose-dependent association was observed, which was most prominent in patients receiving >172 MMEs. Compared to the reference group of patients using <54 MMEs, patients with the highest opioid use were more likely to develop PJI (aOR 1.37, 95% CI 1.33-1.42), DVT, (aOR 1.34, 95% CI 1.30-1.38), and PE (aOR 1.29, 95% CI 1.25-1.34). Dose-dependent associations with opioid use were also observed for wound infection, wound dehiscence, AKI, total pulmonary complications, 30-day readmissions, and 90-day readmissions.

The authors concluded that postoperative opioid use has a dose-dependent association with multiple types of clinically significant and potentially catastrophic complications, and that multimodal pain management strategies should be emphasized to decrease opioid use. The primary limitations of the study were its retrospective nature and reliance on ICD-9 codes and patient-specific billing information. Thus, it was unable to establish true causality, but provided insight into the relationship between postoperative opioid use and complications for patients undergoing total joint arthroplasty.


  1. Bell KL, Shohat N, Goswami K, Tan TL, Kalbian I, Parvizi J. Preoperative Opioids Increase the Risk of Periprosthetic Joint Infection After Total Joint Arthroplasty. The Journal of arthroplasty 33(10): 3246, 2018
  2. Sodhi N, Anis HK, Acuña AJ, Vakharia RM, Gold PA, Garbarino LJ, Mahmood BM, Ehiorobo JO, Grossman EL, Higuera CA, Roche MW, Mont MA. Opioid Use Disorder Is Associated with an Increased Risk of Infection after Total Joint Arthroplasty: A Large Database Study. Clinical Orthopaedics and Related Research® 478(8): 1752, 2020
  3. Malahias M-A, Loucas R, Loucas M, Denti M, Sculco PK, Greenberg A. Preoperative Opioid Use Is Associated With Higher Revision Rates in Total Joint Arthroplasty: A Systematic Review. The Journal of arthroplasty, 2021
  4. Shadbolt C, Schilling C, Inacio MC, Abbott JH, Pryymachenko Y, Wilson R, Choong PF, Dowsey MM. Opioid use and total joint replacement. Current Rheumatology Reports 22(10): 1, 2020
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