Variation in risk of opioid therapy and association with mortality following hip or knee arthroplasty: an analysis based on 14 different definitions
DOI:
https://doi.org/10.2340/17453674.2025.44572Keywords:
Hip, Knee, Mortality, Opioids, OsteoarthrosisAbstract
Background and purpose: Long-term opioid therapy (LTOT) has frequently been reported in patients undergoing total hip or knee arthroplasty (THA or KA). However, there is no clear recommendation on the definition. We aimed to evaluate the sensitivity of the estimated risk of LTOT and association with mortality after THA and KA to the selection among 14 different candidate LTOT definitions.
Methods: Using data from the nationwide Danish registries, we included patients with osteoarthritis undergoing primary THA during 2016–2019 (n = 28,957) or KA during 2014–2020 (n = 51,239). We obtained individual-level information on opioid prescriptions from any pharmacy 1 year before and 1 year after surgery. 14 common LTOT definitions were selected from the literature. The primary outcome was the variation in the 1-year crude risk of LTOT corresponding to variation in LTOT definition. Analysis was done overall and stratified by sex, age, prior opioid use, and year of surgery. The secondary outcome was the 4-year mortality among patients meeting each LTOT definition.
Results: The 1-year risk of LTOT varied from 1.2% (95% confidence interval [CI] 1.1–1.3) to 20.1% (CI 19.6–20.5) for THA and 0.2% (CI 0.1–0.2) to 29.6% (CI 29.2–30.0) for KA patients depending on definition. For THA or KA, women had a higher risk of LTOT than men for all definitions, thus, LTOT varies from 0.2% (CI 0.1–0.2) to 32.9% (CI 32.3–33.4) for women and from 0.1% (CI 0.1–0.2) to 24.9% (24.4–25.5) for men. With increasing age risks of LTOT were steady or slightly decreasing. There was a decrease in the risk of LTOT from 2016 to 2019 for all definitions. 4-year mortality in patients meeting LTOT definitions varied from 9.8% (CI 8.9–10.7) to 16.3% (CI 13.2–20.1) for THA and 6.9% (CI 6.4–7.4) to 10.5% (CI 8.5–12.9) for KA patients.
Conclusion: The estimation of the risk of LTOT after THA or KA and association with mortality is strongly dependent on the definition of LTOT used by researchers. This highlights the limitation on the comparability of opioid studies assessing risk and prognosis in these patients.
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Kleno A N, Sorensen H T, Pedersen A B. Time trends in use of non-steroidal anti-inflammatory drugs and opioids one year after total hip arthroplasty due to osteoarthritis during 1996–2018: a population-based cohort study of 103,209 patients. Osteoarthritis Cartilage 2022; 30(10): 1376-84. doi: 10.1016/j.joca.2022.07.006. DOI: https://doi.org/10.1016/j.joca.2022.07.006
Kleno A N, Stisen M B, Edwards N M, Mechlenburg I, Pedersen A B. Socioeconomic status and use of analgesic drugs before and after primary hip arthroplasty: a population-based cohort study of 103,209 patients during 1996–2018. Acta Orthop 2022; 93: 171-8. doi: 10.2340/17453674.2021.955. DOI: https://doi.org/10.2340/17453674.2021.955
Kleno A S, Mechlenburg I, Gademan M G J, Sorensen H T, Pedersen A B. Do sex, age, and comorbidities modify the association of socioeconomic status and opioid use after total hip arthroplasty?: a population-based study from the Danish Hip Arthroplasty Register. Acta Orthop 2024; 95: 233-42. doi: 10.2340/17453674.2024.40708. DOI: https://doi.org/10.2340/17453674.2024.40708
Kornvig S, Kehlet H, Jorgensen C C, Fink-Jensen A, Videbech P, Pedersen A B, et al. Association of preoperative psychopharmacological treatment and the risk of new chronic opioid use after hip and knee arthroplasty: a Danish registry-based cohort study of 73,033 procedures. Acta Orthop 2025; 96: 492-8. doi: 10.2340/17453674.2025.44228. DOI: https://doi.org/10.2340/17453674.2025.44228
Jorgensen C C, Petersen M, Kehlet H, Aasvang E K. Analgesic consumption trajectories in 8975 patients 1 year after fast-track total hip or knee arthroplasty. Eur J Pain 2018 doi: 10.1002/ejp.1232. DOI: https://doi.org/10.1002/ejp.1232
Florence C S, Zhou C, Luo F, Xu L. The economic burden of prescription opioid overdose, abuse, and dependence in the United States, 2013. Med Care 2016; 54(10): 901-6. doi: 10.1097/mlr.0000000000000625. DOI: https://doi.org/10.1097/MLR.0000000000000625
Alho H, Dematteis M, Lembo D, Maremmani I, Roncero C, Somaini L. Opioid-related deaths in Europe: strategies for a comprehensive approach to address a major public health concern. Int J Drug Policy 2020; 76:102616. doi: 10.1016/j.drugpo.2019.102616. DOI: https://doi.org/10.1016/j.drugpo.2019.102616
Jivraj N K, Raghavji F, Bethell J, Wijeysundera D N, Ladha K S, Bateman B T, et al. Persistent postoperative opioid use: a systematic literature search of definitions and population-based cohort study. Anesthesiology 2020; 132(6): 1528-39. doi: 10.1097/ALN.0000000000003265. DOI: https://doi.org/10.1097/ALN.0000000000003265
Karmali R N, Bush C, Raman S R, Campbell C I, Skinner A C, Roberts A W. Long-term opioid therapy definitions and predictors: a systematic review. Pharmacoepidemiol Drug Saf 2020; 29(3): 252-69. doi: 10.1002/pds.4929. DOI: https://doi.org/10.1002/pds.4929
Schmidt M, Schmidt S A J, Adelborg K, Sundboll J, Laugesen K, Ehrenstein V, et al. The Danish health care system and epidemiological research: from health care contacts to database records. Clin Epidemiol 2019; 11: 563-91. doi: 10.2147/CLEP.S179083. DOI: https://doi.org/10.2147/CLEP.S179083
Schmidt M, Pedersen L, Sorensen H T. The Danish Civil Registration System as a tool in epidemiology. Eur J Epidemiol 2014; 29(8): 541-9. doi: 10.1007/s10654-014-9930-3. DOI: https://doi.org/10.1007/s10654-014-9930-3
Gundtoft P H, Varnum C, Pedersen A B, Overgaard S. The Danish Hip Arthroplasty Register. Clin Epidemiol 2016; 8: 509-14. doi: 10.2147/CLEP.S99498. DOI: https://doi.org/10.2147/CLEP.S99498
Pedersen A B, Mehnert F, Odgaard A, Schroder H M. Existing data sources for clinical epidemiology: the Danish Knee Arthroplasty Register. Clin Epidemiol 2012; 4:125-35. doi: 10.2147/CLEP.S30050. DOI: https://doi.org/10.2147/CLEP.S30050
Dansk Knæalloplastik Register (DKR), National Årsrapport 2022, Regionernes Kliniske Kvalitetsudviklingsprogram. 2023. Available from: https://sundk.dk/media/etrodind/429331bd55fd4176a75ccdb6be73e5b6.pdf
Dansk Hoftealloplastik Register (DHR), National Årsrapport 2022, Regionernes Kliniske Kvalitetsudviklingsprogram. 2023. Available from: https://www.sundk.dk/media/tiv15qj2/4b688570ad274f248625dadc671cad6e.pdf
Lübbeke A, Hoogervorst L A, Marang-van de Mheen P J, Prentice H A, Rolfson O, Nelissen R, et al. Arthroplasty registries at a glance: an initiative of the International Society of Arthroplasty Registries (ISAR) to facilitate access, understanding, and reporting of registry data from an international perspective. Acta Orthop 2025; 96: 116-26. doi: 10.2340/17453674.2024.42706. DOI: https://doi.org/10.2340/17453674.2024.42706
Pottegard A, Schmidt S A J, Wallach-Kildemoes H, Sorensen H T, Hallas J, Schmidt M. Data resource profile: the Danish National Prescription Registry. Int J Epidemiol 2017; 46(3): 798-98f. doi: 10.1093/ije/dyw213. DOI: https://doi.org/10.1093/ije/dyw213
Nielsen S, Degenhardt L, Hoban B, Gisev N. A synthesis of oral morphine equivalents (OME) for opioid utilisation studies. Pharmacoepidemiol Drug Saf 2016; 25(6): 733-7. doi: 10.1002/pds.3945. DOI: https://doi.org/10.1002/pds.3945
Charlson M E, Pompei P, Ales K L, MacKenzie C R. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40(5): 373-83. DOI: https://doi.org/10.1016/0021-9681(87)90171-8
Lind A N R, Jakobsen S K M, Kleno A S, Pedersen A B. Sex and age differences in the use of analgesic drugs before and after primary total hip arthroplasty in 105,520 Danish patients. Surgeon 2023; 21(6): 381-89. doi: 10.1016/j.surge.2023.07.007. DOI: https://doi.org/10.1016/j.surge.2023.07.007
Prentice H A, Inacio M C S, Singh A, Namba R S, Paxton E W. Preoperative risk factors for opioid utilization after total hip arthroplasty. J Bone Joint Surg Am 2019; 101(18): 1670-78. doi: 10.2106/JBJS.18.01005. DOI: https://doi.org/10.2106/JBJS.18.01005
Rajamaki T J, Puolakka P A, Hietaharju A, Moilanen T, Jamsen E. Use of prescription analgesic drugs before and after hip or knee replacement in patients with osteoarthritis. BMC Musculoskelet Disord 2019; 20(1): 427. doi: 10.1186/s12891-019-2809-4. DOI: https://doi.org/10.1186/s12891-019-2809-4
Holtzman J, Saleh K, Kane R. Gender differences in functional status and pain in a Medicare population undergoing elective total hip arthroplasty. Med Care 2002; 40(6): 461-70. doi: 10.1097/00005650-200206000-00003. DOI: https://doi.org/10.1097/00005650-200206000-00003
Bartley E J, Fillingim R B. Sex differences in pain: a brief review of clinical and experimental findings. Br J Anaesth 2013; 111(1): 52-8. doi: 10.1093/bja/aet127. DOI: https://doi.org/10.1093/bja/aet127
Kehlet H. Enhanced postoperative recovery: good from afar, but far from good? Anaesthesia 2020; 75 Suppl 1:e54-e61. doi: 10.1111/anae.14860. DOI: https://doi.org/10.1111/anae.14860
Ravi B, Pincus D, Croxford R, Leroux T, Paterson J M, Hawker G, et al. Patterns of pre-operative opioid use affect the risk for complications after total joint replacement. Sci Rep 2021; 11(1): 22124. doi: 10.1038/s41598-021-01179-5. DOI: https://doi.org/10.1038/s41598-021-01179-5
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