Repeat-dose dexamethasone to prevent pain relapse after total knee arthroplasty in high-pain-response patients: A randomised, double-blind, placebo-controlled superiority trial

BACKGROUND: Peri-operative glucocorticoids reduce pain after total knee arthroplasty, with evidence suggesting potential benefits of increased dosing in specific patient groups. However, the impact of repeat-dose glucocorticoids has not been studied in high-pain-response patients receiving pre-operative high-dose glucocorticoids.

OBJECTIVE: To investigate the effect on pain of an oral dose of dexamethasone after total knee arthroplasty in selected high-pain-response patients who had received a pre-operative high dose of intravenous dexamethasone (1 mg kg -1 ).

DESIGN: Randomised, double-blind, placebo-controlled superiority study.

SETTING: A multicentre study conducted at two major arthroplasty centres in Denmark from November 2021 to March 2024.

PATIENTS: One hundred and ten patients undergoing total knee arthroplasty who had received multimodal analgesia including pre-operative intravenous dexamethasone 1 mg kg -1 . Selection criteria included a Pain Catastrophising Scale score greater than 20 and moderate-to-severe pain (VAS >30) during walking 24 h postoperatively.

INTERVENTION: Patients were randomised to either oral dexamethasone 24 mg or placebo on postoperative day 1.

MAIN OUTCOME MEASURES: The primary outcome was the proportion of patients experiencing moderate-to-severe pain during walking at 48 h postoperatively. Secondary outcomes included pain scores at various time points within 1 week postoperatively, rescue analgesics, quality of sleep, length of hospital stay and morbidity with follow-up at 30 days.

RESULTS: At 48 h postoperatively, 65% of patients in the dexamethasone group and 79% in the placebo group reported moderate-to-severe pain during walking: odds ratio 0.48 [95% confidence interval (CI), 0.20 to 1.16]; P  = 0.100. The mean ± SD Visual Analogue Scale (VAS) at 48 h during walking was 43 ± 21 in the dexamethasone group and 51 ± 22 in the placebo group ( P  = 0.051). There were no differences between the groups regarding secondary pain outcomes or the use of rescue analgesics.

CONCLUSION: The administration of a high oral dose of dexamethasone following an initial pre-operative dose of 1 mg kg -1 intravenously in selected high-pain-response patients had no effect on postoperative pain following total knee arthroplasty.

TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05563155.