Comparative Efficacy of Two Multimodal Analgesia Protocols for Postoperative Pain Management Following Total Knee Arthroplasty: A Double-Blind, Randomized Clinical Trial

Abstract Background: Total knee arthroplasty (TKA) is associated with significant postoperative pain (POP), which can hinder rehabilitation and recovery. Multimodal analgesia strategies are increasingly used to optimize pain relief and minimize opioid consumption. This study compared the effectiveness and safety of two multimodal analgesia regimens in patients undergoing TKA. Materials and Methods: In this double-blind, randomized clinical trial, 84 patients scheduled for elective TKA under spinal anesthesia were allocated to receive either dexmedetomidine–dexamethasone–ketamine (DDK) group or granisetron–midazolam–ketorolac group as 24 h postoperative infusions. The pain was assessed using a visual analog scale at 0, 2, 4, 8, 12, and 24 h postoperatively. Pethidine requirements and adverse effects (e.g., dizziness and drowsiness) were recorded. Data were analyzed using repeated measures analysis of variance and the chi-square tests. Results: Baseline characteristics were similar between groups. Pain scores did not differ significantly at most time points, except at 8 h postoperatively, where the DDK group reported significantly lower pain scores (2.23 ± 0.48 vs. 2.80 ± 0.30; P < 0.001). Pethidine use and side effect incidence were comparable between groups. Mean arterial pressure trends were stable and not significantly different over time. Conclusion: Both multimodal analgesia protocols were effective and safe for early POP management after TKA. The DDK protocol offered a transient advantage at 8 h postoperatively but showed no overall superiority in opioid use or adverse events. Either regimen may be appropriate based on clinical context. Further studies should evaluate long-term outcomes and cost-effectiveness.