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.
Results: This review discusses the current status of mesenchymal stem cell (MSC) therapy for SCI, criteria to considering for the application of MSC therapy and novel biological therapies that can be applied together with MSCs to enhance its efficacy. Bone marrow-derived MSCs (BMSCs), umbilical cord-derived MSCs (UC-MSCs) and adipose tissue-derived MSCs (ADSCs) have been trialed for the treatment of SCI. Application of MSCs may minimize secondary injury to the spinal cord and protect the neural elements that survived the initial mechanical insult by suppressing the inflammation. Additionally, MSCs have been shown to differentiate into neuron-like cells and stimulate neural stem cell proliferation to rebuild the damaged nerve tissue.
Conclusion: These characteristics are crucial for the restoration of spinal cord function upon SCI as damaged cord has limited regenerative capacity and it is also something that cannot be achieved by pharmacological and physiotherapy interventions. New biological therapies including stem cell secretome therapy, immunotherapy and scaffolds can be combined with MSC therapy to enhance its therapeutic effects.