Dexamethasone Effective as an Analgesic Adjuvant in Total Knee Replacement

NEW YORK (Reuters Health) – Two doses of dexamethasone given in the perioperative period reduced morphine consumption during 48 hours after total knee arthroplasty (TKA) and reduced postoperative pain in the randomized, placebo-controlled DEX-2-TKA trial.

“Dexamethasone is one of the most well-known and -tested glucocorticoids (GCC) that we use daily in the OR for nausea. If we could show benefit of not just one but two larger doses of dexamethasone, then we would have a new and better treatment for one of the most frequently performed planned orthopedic procedures,” Dr. Ole Mathiesen with the Department of Anesthesiology, Zealand University Hospital, in Koege, Denmark, explained in an email to Reuters Health.

“I believe that our trial makes a good case for using two doses of 24 mg dexamethasone as adjunct treatment to paracetamol, ibuprofen, and local infiltration analgesia following total knee arthroplasty,” he said. “Even though this was a fourth member of this multimodal analgesic treatment, we found patient-relevant reductions of morphine (20% down), pain, and adverse effects of nausea, dizziness and sedation for 48 hours after surgery. We found no indication of harm.”

The trial included 485 adults undergoing TKA at five Danish hospitals. They were randomly allocated to one of three groups: DX1 (one dose of 24 mg dexamethasone plus placebo); DX2 (two doses of 24 mg dexamethasone) or placebo (placebo plus placebo).

The first dose of dexamethasone (or placebo) was given after onset of spinal or general anesthesia and the second dose 24 hours after the end of surgery. All participants received paracetamol, ibuprofen, and local infiltration analgesia.

As reported in The BMJ, the median morphine consumption up to 48 hours postoperatively was 37.9 mg in the DX1 group and 35.0 mg in the DX2 group versus 43.0 mg in the placebo group.

Median differences between groups were 2.7 mg between DX1 and DX2 (P=0.30); 7.8 mg between DX1 and placebo (P=0.008); and 10.7 mg between DX2 and placebo (P<0.001).

The effect size of two dexamethasone doses reached the predefined minimal important difference in intravenous morphine consumption of 10 mg. “This choice of minimal important difference of opioid reductions is in line with other postoperative pain trials,” the researchers say.

“The reduction in morphine consumption of patients found in this trial corresponds to almost 25%, even with dexamethasone as an adjuvant to three non-opioid analgesic interventions,” they note.

Postoperative pain was reduced at 24 hours with one 24 mg dose of dexamethasone and at 48 hours with two doses.

“This DEX-2-TKA low risk of bias trial shows a statistically and patient important adjuvant analgesic effect of two doses of high dose dexamethasone, and with follow-up at 90 days,” the researchers write.

The study had no commercial funding.

SOURCE: BMJ, online January 4, 2022.

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