BACKGROUND: The efficacy of low-dose intravenous (IV) ketamine as an adjunct analgesic to spinal anesthesia in total knee arthroplasty (TKA) remains uncertain. This study aims to assess ketamine's impact on postoperative pain level and opioid consumption. METHODS: In a randomized, triple-blind, placebo-controlled trial conducted at Shariati Hospital, Tehran, Iran, 65 patients undergoing unilateral TKA were assigned to receive either 0.5 mg/kg IV ketamine or saline. The primary outcome was cumulative opioid consumption in the first 24 h. Secondary outcomes were visual analog scale (VAS) pain scores at 2, 6, 12, and 24 h and at 2 and 6 weeks, knee range of motion at discharge, operative time, length of stay, and adverse effects. RESULTS: Median 0- to 24-h opioid use was similar (ketamine 10 range 10-17.5 vs. placebo 10 range 10-15 morphine milligram equivalents MME; p = 1.00). VAS scores were numerically lower with ketamine at all time points, but no comparison remained significant after adjustment for multiple comparisons, and there was no time × treatment interaction. No significant differences were observed in other secondary outcomes, including knee flexion and extension, operative time, and length of stay. Side effects were minimal and comparable between groups. CONCLUSIONS: Low-dose IV ketamine shows no measurable analgesic benefits in the long term, and it does not significantly reduce pain or opioid use after TKA within a multimodal pain protocol. Further research is needed to explore various analgesia strategies and follow-up durations to optimize pain management. TRIAL REGISTRATION: Iranian Registry of Clinical Trials: IRCT20220315054298N1.
Sharafatvaziri et al. (2026) studied this question.