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. 2024 Apr 5;24(1):319.
doi: 10.1186/s12877-024-04933-2.

Comparative safety of tramadol and other opioids following total hip and knee arthroplasty

Elliott Bosco  1   2 , Melissa R Riester  3   4   5 , Francesca L Beaudoin  1   6   7 , Andrew J Schoenfeld  8 , Stefan Gravenstein  1   2   9   10 , Vincent Mor  1   2   9 , Andrew R Zullo  1   2   6   9
Affiliations

Comparative safety of tramadol and other opioids following total hip and knee arthroplasty

Elliott Bosco et al. BMC Geriatr. .

Abstract

Background: Tramadol is increasingly used to treat acute postoperative pain among older adults following total hip and knee arthroplasty (THA/TKA). However, tramadol has a complex pharmacology and may be no safer than full opioid agonists. We compared the safety of tramadol, oxycodone, and hydrocodone among opioid-naïve older adults following elective THA/TKA.

Methods: This retrospective cohort included Medicare Fee-for-Service beneficiaries ≥ 65 years with elective THA/TKA between January 1, 2010 and September 30, 2015, 12 months of continuous Parts A and B enrollment, 6 months of continuous Part D enrollment, and no opioid use in the 6 months prior to THA/TKA. Participants initiated single-opioid therapy with tramadol, oxycodone, or hydrocodone within 7 days of discharge from THA/TKA hospitalization, regardless of concurrently administered nonopioid analgesics. Outcomes of interest included all-cause hospitalizations or emergency department visits (serious adverse events (SAEs)) and a composite of 10 surgical- and opioid-related SAEs within 90-days of THA/TKA. The intention-to-treat (ITT) and per-protocol (PP) hazard ratios (HRs) for tramadol versus other opioids were estimated using inverse-probability-of-treatment-weighted pooled logistic regression models.

Results: The study population included 2,697 tramadol, 11,407 oxycodone, and 14,665 hydrocodone initiators. Compared to oxycodone, tramadol increased the rate of all-cause SAEs in ITT analyses only (ITT HR 1.19, 95%CLs, 1.02, 1.41; PP HR 1.05, 95%CLs, 0.86, 1.29). Rates of composite SAEs were not significant across comparisons. Compared to hydrocodone, tramadol increased the rate of all-cause SAEs in the ITT and PP analyses (ITT HR 1.40, 95%CLs, 1.10, 1.76; PP HR 1.34, 95%CLs, 1.03, 1.75), but rates of composite SAEs were not significant across comparisons.

Conclusions: Postoperative tramadol was associated with increased rates of all-cause SAEs, but not composite SAEs, compared to oxycodone and hydrocodone. Tramadol does not appear to have a superior safety profile and should not be preferentially prescribed to opioid-naïve older adults following THA/TKA.

Keywords: Arthroplasty; Geriatrics; Hydrocodone; Oxycodone; Tramadol.

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Conflict of interest statement

E.B. reports prior grants from Sanofi Pasteur paid directly to Brown University for research on the epidemiology of infections and vaccinations in older nursing home residents. F.B. works as a Senior Medical Advisor for the Institute for Clinical and Economic Review with funds paid directly to Brown University. A.J.S. reports royalties from Wolters-Kluwer and Springer-Nature. S.G. reports grants from Seqirus, Sanofi; and consulting or speaker fees from Sanofi, Seqirus, Merck, and the Gerontological Society of America related to vaccines or nursing home care quality. V.M. is a paid consultant and Scientific Advisory Board chair to NaviHealth, Inc. which offers post-acute care management and services to health plans and health systems. A.R.Z. reports prior grants from Sanofi Pasteur paid directly to Brown University for research on the epidemiology of infections and vaccinations in older nursing home residents as well as respiratory syncytial virus in infants. Some authors are VA employees [S.G., V.M., A.R.Z.]. The content and views expressed in this article are those of the authors and do not necessarily reflect the position or official policies of the United States Government or the US Department of Veterans Affairs.

Figures

Fig. 1
Fig. 1
Crude and adjusted hazard ratios comparing postoperative tramadol versus oxycodone use for 90-day outcomes. Abbreviations: SAEs, Serious Adverse Events, SAEs; CI, Confidence Interval. Note: Outcome definitions for SAEs are listed in Additional Table 4. The unadjusted estimate is the intention-to-treat (ITT) estimand without covariate adjustment. Both the ITT and per-protocol estimates are covariate-adjusted
Fig. 2
Fig. 2
Crude and adjusted hazard ratios comparing postoperative tramadol versus hydrocodone use for 90-day outcomes. Abbreviations: SAEs, Serious Adverse Events, SAEs; CI, Confidence Interval. Note: Outcome definitions for SAEs are listed in Additional Table 4. The unadjusted estimate is the intention-to-treat (ITT) estimand without covariate adjustment. Both the ITT and per-protocol estimates are covariate-adjusted
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