Subcutaneous versus intravenous tramadol for extremity injury with moderate pain in the emergency department: a randomised controlled noninferiority trial

Abstract

Background and importance Musculoskeletal trauma is a common presentation in the emergency department (ED). Tramadol as an analgesic has been recommended by pain management guidelines for musculoskeletal pain. Parenteral tramadol in the ED is commonly administered intravenously. Subcutaneously administered tramadol may have other advantages such as easier and faster preparation, avoids the need for intravenous (i.v.) access, and reduces the incidence of respiratory and gastrointestinal effects. However, studies comparing subcutaneous (s.c.) and i.v. tramadol for the management of acute moderate pain in patients with extremity injury are lacking. Objective The objective of this study was to compare the clinical efficacy of s.c. tramadol vs. i.v. tramadol in patients with moderate pain due to extremity injury in the ED. Design, settings, and participants This non-inferiority randomized controlled trial included adult patients presented to an academic, tertiary hospital ED with moderate pain (pain score of 4–6 on the visual analog scale) due to extremity injury. Intervention patients stratified to pain score were randomized to receive 50 mg of i.v. or s.c. tramadol. Outcomes measure and analysis Primary outcome measure was the difference in the pain score reduction at 30 min after tramadol administration between the two groups. The noninferiority null hypothesis was that the therapeutic difference in terms of pain score reduction of more than 0.8 exists between the two treatment groups at the endpoint. Main results In total 232 patients were randomized to i.v. (n = 115) or s.c. (n = 117). Although 225 were analyzed in the per-protocol population (i.v. = 113; s.c. = 112). The baseline median pain score was 6 (IQR, 5–6). Median pain score reduction at 30 min after administration was 2 (IQR, 1–3) in the IV group vs. 2 (IQR, 1–2) in the s.c. group with a median difference of 0 (IQR, 0–0), which was below the prespecified noninferiority margin of 0.8. Adverse events in the i.v. group were higher compared to the s.c. group (33.6% vs. 8.9%, P ≤ 0.001). Conclusions The s.c. tramadol is noninferior to i.v. tramadol in the treatment of moderate pain from extremity injuries.