In a recent study, a research team from the University of Toronto found that adding five medications to a pain control regimen after total knee arthroplasty (TKA) did NOT provide additional pain control or functional improvements.
TKA: Adding to Analgesic Regimen Does Nothing?
The research, “No Benefits of Adding Dexmedetomidine, Ketamine, Dexamethasone and Nerve Blocks to an Established Multimodal Analgesic Regimen after Total Knee Arthroplasty,” was published in the July 2022 edition of Anesthesiology.
The team, which cited in their paper the cascade effects of pain following TKA, designed a double-blind study with 78 patients, of which 39 were assigned to the TKA control group (spinal anesthesia with intrathecal morphine, periarticular local anesthesia infiltration, IV dexamethasone and a single injection adductor canal block) and an equal number, 39 patients, were assigned to the study group and received the same set of analgesic treatments as the control group but, in addition, local anesthetic infiltration between the popliteal artery and capsule of the posterior knee, intraoperative IV dexmedetomidine and ketamine, and postoperatively, one more IV dexamethasone bolus, and two more adductor canal block injections.
Vincent Chan, M.D., Professor Emeritus in the Department of Anesthesia and Pain Medicine at the University of Toronto in Canada and study co-author, explained the purpose and outcome of the study to OTW, “We looked at analgesic metrics—pain scores, time to first analgesics, opioid consumption (short and long term). In addition, we also looked at functional metrics—timed up and go, joint range of movement, rehab milestones. Lastly, we considered patient centered outcomes.”
Bottom line, the team found NO difference in the consumption of opioids between the two groups at 24 hours and all other postoperative time points. They found NO major differences in pain scores, quality of recovery, or time to reach rehabilitation milestones.
“The addition of five more recently described analgesic modalities to existing multimodal analgesia does not provide additional benefits,” Dr. Chan told OTW. “This means more interventions may not be necessary. In the clinical setting, always define the optimal Rx.”
When OTW asked if the researchers were surprised with their findings, Dr. Chan commented, “Yes. We generally think more interventions are better than a few. But in this case, when each intervention has been shown to be analgesic, the combination of five newer Rx was not able to further improve the analgesic/functional outcomes when compared to a popular multimodal analgesic regimen we use today.”
[Going forward] “we may vary the dose of IV dexmedetomidine, ketamine and dexamethasone but no immediate plan at this time.”

Discussion
This is a fascinating development. In my practice we've seen similar outcomes with the revised protocol. The key differentiator seems to be patient selection criteria. Has anyone else noticed the correlation with BMI thresholds?
Great point. I'd push back slightly on the conclusion, the sample size in the cited study is too small to draw population-level inferences. That said, the directional signal is compelling and worth a larger RCT.
We implemented a similar approach last year. Early results are promising but we're still gathering 12-month follow-up data. Happy to share our protocol if anyone is interested.
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