Association of Preoperative Opioid Use With Mortality and Short-term Safety Outcomes After Total Knee Replacement

JAMA Netw Open. 2019 Jul 3;2(7):e198061. doi: 10.1001/jamanetworkopen.2019.8061.


Importance: Prescription opioid use is common among patients with moderate to severe knee osteoarthritis before undergoing total knee replacement (TKR). Preoperative opioid use may be associated with worse clinical and safety outcomes after TKR.

Objective: To determine the association of preoperative opioid use among patients 65 years and older with mortality and other complications at 30 days post-TKR.

Design, setting, and participants: This cohort study used claims data from January 1, 2010, to December 31, 2014, from a random sample of US Medicare enrollees 65 years and older who underwent TKR. Based on opioid dispensing in 360 days prior to TKR, patients were classified as continuous (≥1 opioid dispensing in each of the past 12 months) or intermittent (any dispensing of opioids in the past 12 months but not continuous use) opioid users or as opioid-naive patients (no opioids dispensed in the past 12 months). Data analyses were conducted from October 3, 2017, to November 8, 2018.

Main outcomes and measures: Primary outcomes included in-hospital mortality and 30-day post-TKR mortality, hospital readmission, and revision operation. Secondary safety outcomes at 30 days post-TKR included opioid overdose and vertebral and nonvertebral fracture. Multivariable Cox proportional hazards models estimated hazard ratios (HRs) and 95% CIs.

Results: Of 316 593 patients (mean [SD] age, 73.9 [5.8] years; 214 677 [67.8%] women) who underwent TKR, 22 895 (7.2%) were continuous opioid users, 161 511 (51.0%) were intermittent opioid users, and 132 187 (41.7%) were opioid naive. In-hospital mortality occurred in 276 patients (0.09%). At 30 days post-TKR, 828 patients (0.26%) died, 16 786 patients (5.30%) had hospital readmission, and 921 patients (0.29%) had a revision operation. All primary and secondary outcomes occurred more frequently among continuous opioid users compared with opioid-naive patients. Compared with opioid-naive patients and after adjusting for demographic characteristics, combined comorbidity score, number of different prescription medications, and frailty, continuous opioid users had greater risk of revision operations (HR, 1.63; 95% CI, 1.15-2.32), vertebral fractures (HR, 2.37; 95% CI, 1.37-4.09), and opioid overdose (HR, 4.82; 95% CI, 1.36-17.07) at 30 days post-TKR. However, after adjusting covariates, there were no statistically significant differences in in-hospital (HR, 1.18; 95% CI, 0.73-1.90) or 30-day (HR, 1.05; 95% CI, 0.73-1.51) mortality between continuous opioid users and opioid-naive patients.

Conclusions and relevance: After adjusting for baseline risk profiles, including comorbidities and frailty, continuous opioid users had a higher risk of revision operations, vertebral fractures, and opioid overdose at 30 days post-TKR but not of in-hospital or 30-day mortality, compared with opioid-naive patients. These results highlight the need for better understanding of patient characteristics associated with chronic opioid use to optimize preoperative assessment of overall risk after TKR.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Analgesics, Opioid / adverse effects*
  • Arthroplasty, Replacement, Knee / mortality*
  • Female
  • Humans
  • Male
  • Medicare
  • Osteoarthritis, Knee / drug therapy
  • Osteoarthritis, Knee / mortality*
  • Osteoarthritis, Knee / surgery
  • Patient Readmission / statistics & numerical data
  • Postoperative Complications / chemically induced
  • Postoperative Complications / mortality*
  • Preoperative Period
  • Proportional Hazards Models
  • Retrospective Studies
  • United States


  • Analgesics, Opioid