Effect of dexamethasone as an analgesic adjuvant to multimodal pain treatment after total knee arthroplasty: randomised clinical trial
Kasper Smidt Gasbjerg, doctoral student1, Daniel Hägi-Pedersen, clinical associate professor2 3 4, Troels Haxholdt Lunn, clinical associate professor2 5, Christina Cleveland Laursen, junior doctor5 6, Majken Holmqvist, junior doctor7, Louise Ørts Vinstrup, junior doctor5 6, Mette Ammitzboell, junior doctor8, Karina Jakobsen, research nurse1, Mette Skov Jensen, research nurse1, Marie Jøhnk Pallesen, nurse8, Jens Bagger, senior consultant8, Peter Lindholm, senior consultant9, Niels Anker Pedersen, senior consultant10, Henrik Morville Schrøder, clinical associate professor11, Martin Lindberg-Larsen, clinical associate professor12 16, Anders Kehlet Nørskov, consultant13 14, Kasper Højgaard Thybo, junior doctor7, Stig Brorson, professor2 15, Søren Overgaard, professor2 8 12 16, Janus Christian Jakobsen, professor3 14, Ole Mathiesen, professor2 7Knee
Objective To investigate the effects of one and two doses of intravenous dexamethasone in patients after total knee arthroplasty.
Design Randomised, blinded, placebo controlled trial with follow-up at 90 days.
Setting Five Danish hospitals, September 2018 to March 2020.
Participants 485 adult participants undergoing total knee arthroplasty.
Intervention A computer generated randomised sequence stratified for site was used to allocate participants to one of three groups: DX1 (dexamethasone (24 mg)+placebo); DX2 (dexamethasone (24 mg)+dexamethasone (24 mg)); or placebo (placebo+placebo). The intervention was given preoperatively and after 24 hours. Participants, investigators, and outcome assessors were blinded. All participants received paracetamol, ibuprofen, and local infiltration analgesia.
Main outcome measures The primary outcome was total intravenous morphine consumption 0 to 48 hours postoperatively. Multiplicity adjusted threshold for statistical significance was P<0.017 and minimal important difference was 10 mg morphine. Secondary outcomes included postoperative pain.
Results 485 participants were randomised: 161 to DX1, 162 to DX2, and 162 to placebo. Data from 472 participants (97.3%) were included in the primary outcome analysis. The median (interquartile range) morphine consumptions at 0-48 hours were: DX1 37.9 mg (20.7 to 56.7); DX2 35.0 mg (20.6 to 52.0); and placebo 43.0 mg (28.7 to 64.0). Hodges-Lehmann median differences between groups were: −2.7 mg (98.3% confidence interval −9.3 to 3.7), P=0.30 between DX1 and DX2; 7.8 mg (0.7 to 14.7), P=0.008 between DX1 and placebo; and 10.7 mg (4.0 to 17.3), P<0.001 between DX2 and placebo. Postoperative pain was reduced at 24 hours with one dose, and at 48 hours with two doses, of dexamethasone.
Conclusion Two doses of dexamethasone reduced morphine consumption during 48 hours after total knee arthroplasty and reduced postoperative pain.
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