Effect of Epidural Ketamine on Pain after Total Knee Arthroplasty: A Randomized Double- Blind Placebo Controlled Clinical Trial

Background and Aims: Managing the intense pain after a Total Knee Arthroplasty (TKA) is essential for early mobilization and physiotherapy which plays a crucial role for better clinical outcomes. Epidural infusion of local anesthetic and opioids provides good pain relief but can lead to side effects such as hypotension, motor weakness and respiratory depression. The objective of this study was to evaluate if epidurally administered ketamine could provide postoperative analgesia and therefore reduce the dose of the epidural infusion.  Methods: Thirty patients undergoing TKA under epidural anesthesia were randomized to receive 0.5% bupivacaine (Group I) or 0.5% bupivacaine + ketamine (0.5mg/kg) (Group II) as their primary anesthetic. At the end of the surgery, an infusion of 0.1% bupivacaine + fentanyl (1μg/ml) was started through the epidural catheter at 5ml/h. The rate was adjusted every 2 hours, depending on the pain experienced by the patient. If despite rate adjustment, the patient graded the pain as 5 or more, morphine 5mg intramuscularly could be administered as the rescue analgesic. Results: The demographic characteristics of the two groups were comparable. The dose of epidural infusion in the postoperative period was also comparable. Rescue analgesia was needed in 5 (35%) Group I and 8 (53%) Group II patients, which was not statistically significant. However, an analysis of the subset of patients who needed rescue analgesia using the Kaplan-Meier curves, showed that most of the patients from Group I needed the rescue dose at the 6th hour and although few of the Group II patients also needed rescue analgesia at the 6th hour, their rate of needing rescue analgesic was gradual, lasting up to 18 hours. Conclusion: Although, this study failed to show that the addition of a single dose of ketamine (0.5mg/kg) improved postoperative analgesia after TKA, it may have some benefit in a select subset of patients. It would need a larger sample size to identify those patients.