No Benefits of Adding Dexmedetomidine, Ketamine, Dexamethasone, and Nerve Blocks to an Established Multimodal Analgesic Regimen after Total Knee Arthroplasty

Anesthesiology. 2022 Oct 1;137(4):459-470. doi: 10.1097/ALN.0000000000004326.


Background: An optimal opioid-sparing multimodal analgesic regimen to treat severe pain can enhance recovery after total knee arthroplasty. The hypothesis was that adding five recently described intravenous and regional interventions to multimodal analgesic regimen can further reduce opioid consumption.

Methods: In a double-blinded fashion, 78 patients undergoing elective total knee arthroplasty were randomized to either (1) a control group (n = 39) that received spinal anesthesia with intrathecal morphine, periarticular local anesthesia infiltration, intravenous dexamethasone, and a single injection adductor canal block or (2) a study group (n = 39) that received the same set of analgesic treatments plus five additional interventions: local anesthetic infiltration between the popliteal artery and capsule of the posterior knee, intraoperative intravenous dexmedetomidine and ketamine, and postoperatively, one additional intravenous dexamethasone bolus and two additional adductor canal block injections. The primary outcome measure was 24-h cumulative opioid consumption after surgery and secondary outcomes were other analgesics, patient recovery, functional outcomes, and adverse events.

Results: Opioid consumption was not different between groups at 24 h (oral morphine equivalents, mean ± SD; study: 23.7 ± 18.0 mg vs. control: 29.3 ± 18.7 mg; mean difference [95% CI], -5.6 mg [-2.7 to 13.9]; P = 0.189) and all other time points after surgery. There were no major differences in pain scores, quality of recovery, or time to reach rehabilitation milestones. Hypotensive episodes occurred more frequently in the study group (25 of 39 [64.1%] vs. 13 of 39 [33.3%]; P = 0.010).

Conclusions: In the presence of periarticular local anesthesia infiltration, intrathecal morphine, single-shot adductor canal block and dexamethasone, the addition of five analgesic interventions-local anesthetic infiltration between the popliteal artery and capsule of the posterior knee, intravenous dexmedetomidine, intravenous ketamine, an additional intravenous dexamethasone dose, and repeated adductor canal block injections-failed to further reduce opioid consumption or pain scores or to improve functional outcomes after total knee arthroplasty.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / therapeutic use
  • Analgesics, Opioid
  • Anesthetics, Local
  • Arthroplasty, Replacement, Knee* / adverse effects
  • Dexamethasone / therapeutic use
  • Dexmedetomidine* / therapeutic use
  • Humans
  • Ketamine* / therapeutic use
  • Morphine
  • Nerve Block* / adverse effects
  • Pain, Postoperative / chemically induced
  • Pain, Postoperative / drug therapy
  • Pain, Postoperative / prevention & control


  • Analgesics
  • Analgesics, Opioid
  • Anesthetics, Local
  • Dexmedetomidine
  • Ketamine
  • Morphine
  • Dexamethasone