• Ziying Wu, Xiaoxiao Li, Na Lu, Yilun Wang, and Xiang Ding.
• Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China.
• Eur J Pain. 2022 Jul 1; 26 (6): 1245-1255.

BackgroundTramadol is a widely used weak opioid; however, the evidence for its safety profile in respiratory system needs additional information. We aimed to examine whether tramadol use is associated with an increased risk of pneumonia in the general population.MethodsWe conducted five propensity-score (PS) matched cohort studies in The Health Improvement Network database. Participants aged ≥50-years initiated tramadol were compared with those initiated one of the following analgesics: codeine (n = 144,506), naproxen (n = 113,028), diclofenac (n = 74,297), celecoxib (n = 42,538), or etoricoxib (n = 27,232). The outcome was incident pneumonia.OutcomesDuring 6-month follow-up, 395 pneumonia (5.6/1000 person-years) occurred in the tramadol group and 414 pneumonia (5.9/1000 person-years) occurred in the PS matched codeine group. Compared with codeine group, the risk of pneumonia was lower in the tramadol group (hazard ratio [HR] = 0.63, 95% confidence interval [CI]: 0.49-0.82) during the first 30-day follow-up, but comparable between groups over the entire 6-month follow-up (HR = 0.95, 95%CI: 0.83-1.09). In addition, the risk of pneumonia was higher in the tramadol group than that in the PS matched naproxen (HR = 1.68, 95%CI: 1.37-2.06), diclofenac (HR = 1.63, 95%CI: 1.31-2.03), celecoxib (HR = 1.64, 95%CI: 1.20-2.24) or etoricoxib (HR = 1.61, 95%CI: 1.04-2.49) group.ConclusionsThe present study indicated that tramadol initiators had a lower risk of incident pneumonia than codeine initiators during the short-time follow-up, but had a comparable pneumonia risk compared with codeine initiators and had a higher risk of pneumonia compared with NSAIDs initiators over the entire 6-month follow-up duration. Confirmation of the present findings and determination of the underlying mechanism will require more studies.SignificanceTramadol might not be a safer alternative analgesic to codeine or NSAIDs. Both of health-care providers and patients may need to be on alert for its safety profile in respiratory system in future clinical practice.© 2022 European Pain Federation - EFIC®.

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