Combined Intrathecal Fentanyl and Morphine for Postoperative Analgesia After Total Knee Arthroplasty: A Randomized Controlled Trial

Abstract (326 words)
Background: Total knee arthroplasty (TKA) is associated with significant postoperative pain. In patients receiving spinal anesthesia, intrathecal morphine is recommended when regional blocks are not feasible, and fentanyl is commonly added to improve the quality of spinal anesthesia. However, the analgesic efficacy of combined intrathecal morphine and fentanyl after TKA remains unclear. We evaluated whether combined intrathecal administration of morphine and fentanyl improves postoperative analgesia compared with either agent alone.
Methods: In this randomized controlled trial, 111 patients undergoing TKA under spinal anesthesia were assigned to receive intrathecal fentanyl 25 µg (F group), morphine 100 µg (M group), or fentanyl 25 µg plus morphine 100 µg (MF group). All patients received 0.5% hyperbaric bupivacaine 12.5 mg. The primary outcome was pain score at rest 6 hours postoperatively. Secondary outcomes included pain scores at rest and during motion at 12 and 24 hours, cumulative opioid consumption within 24 hours, opioid-related adverse effects, and intraoperative hemodynamic variables.
Results: Pain scores at rest at 6 hours were significantly lower in the MF group compared with the F and M groups (mean [SD], 1.5 [0.9] vs 4.2 [2.7] and 2.7 [2.0], respectively; P < 0.001). Pain scores at rest and during motion at 6, 12, and 24 hours were also lower in the MF group (P < 0.001). Cumulative 24-hour morphine consumption was reduced in the MF group (10 [7] mg) compared with the F (30 [16] mg) and M (15 [9] mg) groups (P < 0.001). Nausea and vomiting were more frequent in the M and MF groups than in the F group, with no difference between the M and MF groups. Hemodynamic variables were similar across groups.
Conclusion: Combined intrathecal administration of morphine and fentanyl significantly improved postoperative analgesia and reduced opioid consumption compared with either agent alone in patients undergoing TKA under spinal anesthesia, without increasing opioid-related adverse effects compared with intrathecal morphine alone. This strategy may represent a reasonable alternative when regional blocks are not feasible.