Dexamethasone Reduces Morphine Intake Following Total Knee Arthroplasty

Kasper Smidt Gasbjerg

Dexamethasone can reduce the need for morphine after a total knee arthroplasty. A team of investigators found that during the 48 hours after the surgery, 2 doses of the treatment reduced morphine consumption and postoperative pain.

Kasper Smidt Gasbjerg, Department of Anaesthesiology, Naestved, Slagelse and Ringsted Hospitals, led the investigation on the effects of intravenous dexamethasone by examining the impact of 1 or 2 doses compared with placebo.

“Our hypothesis was that 24 mg intravenous dexamethasone as an adjuvant to multimodal pain treatment would reduce postoperative opioid consumption and pain, and that two doses would be better than one,” investigators wrote.

Motivation

More than 1 million total knee arthroplasty procedures are performed worldwide each year. As this number is expected to grow, investigators aimed to find a method to manage postoperative pain in patients that didn’t rely solely on opioids.

Total knee arthroplasty is associated with moderate to severe postoperative pain and multimodal analgesic treatment is recommended–usually including dexamethasone.

However, the evidence for the adjuvant analgesic effects of this treatment was uncertain. Much of the literature consisted of smaller trials, leaving the risk of bias and random errors, according to investigators.

Glucocorticoids potential for pain relief come from their anti-inflammatory properties including suppression of proinflammatory cytokines and induction of anti-inflammatory cytokines, reduction of prostaglandin synthesis, and with possible lowering of the excitability of nerve cells.

Investigators noted that this trial was supported by a review that called for large trials with higher doses of dexamethasone than what’s generally used for the treatment of nausea and vomiting, as it might improve the treatment of pain.

The Study

The randomized, blinded, placebo-controlled trial occurred from September 2018-March 2020 with 485 adult participants who had a total knee arthroplasty.

The patients were randomized into 3 groups: DX1 received 24 mg of dexamethasone and placebo; DX2 received 2 doses of 24 mg dexamethasone; placebo received only placebo doses. All patients received paracetamol, ibuprofen, and local infiltration analgesia.

Patients received the intervention preoperatively and after 24 hours. Total intravenous morphine consumption 0-48 hours postoperatively was measured for the primary outcome. Secondary outcomes included postoperative pain.

The Results

Of the 485 randomized patients, 97.3% of the data was included in the primary outcome analysis.

The placebo group had a median morphine consumption of 43 mg. DX1 had a median morphine consumption of 37.9 mg and DX2 had a median morphine consumption of 35 mg. Investigators found that postoperative pain was reduced at 24 hours with 1 dose of dexamethasone, and at 48 hours with 2 doses.

Median difference between DX1 and DX2 was -2.7 mg (98.3% confidence interval -9.3 to 3.7), P=0.30. The difference between DX1 and placebo was 7.8 mg (0.7 to 14.7), P=0.008, and between DX2 and placebo was 10.7 mg (4.0 to 17.3), P<0.001.

“The Hodges-Lehmann median difference reduction of morphine consumption in DX1 compared with placebo was below the predefined minimal important difference,” investigators wrote, “but for reduction of morphine consumption in DX2 compared with placebo was above the predefined minimal important difference.”

The study, "Effect of dexamethasone as an analgesic adjuvant to multimodal pain treatment after total knee arthroplasty: randomised clinical trial" was published in The BMJ.