Effect of dexamethasone as an analgesic adjuvant to multimodal pain treatment after total knee arthroplasty: randomised clinical trial

Kasper Smidt Gasbjerg, Daniel Hägi-Pedersen, Troels Haxholdt Lunn, Christina Cleveland Laursen, Majken Holmqvist, Louise Ørts Vinstrup, Mette Ammitzboell, Karina Jakobsen, Mette Skov Jensen, Marie Jøhnk Pallesen, Jens Bagger, Peter Lindholm, Niels Anker Pedersen, Henrik Morville Schrøder, Martin Lindberg-Larsen, Anders Kehlet Nørskov, Kasper Højgaard Thybo, Stig Brorson, Søren Overgaard, Janus Christian Jakobsen, Ole Mathiesen, Kasper Smidt Gasbjerg, Daniel Hägi-Pedersen, Troels Haxholdt Lunn, Christina Cleveland Laursen, Majken Holmqvist, Louise Ørts Vinstrup, Mette Ammitzboell, Karina Jakobsen, Mette Skov Jensen, Marie Jøhnk Pallesen, Jens Bagger, Peter Lindholm, Niels Anker Pedersen, Henrik Morville Schrøder, Martin Lindberg-Larsen, Anders Kehlet Nørskov, Kasper Højgaard Thybo, Stig Brorson, Søren Overgaard, Janus Christian Jakobsen, Ole Mathiesen

Abstract

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.

Trial registration: Clinicaltrials.gov NCT03506789.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from Næstved, Slagelse, and Ringsted Hospitals’ Research Fund and the Department of Anaesthesiology at Næstved, Slagelse and Ringsted Hospitals for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Fig 1
Fig 1
Screening, randomisation, and primary outcome population
Fig 2
Fig 2
Distribution of morphine consumption according to group 0-48 hours postoperatively. Vertical dashed yellow lines indicate median level of morphine consumption. DX1=dexamethasone (24 mg)+placebo; DX2=dexamethasone (24 mg)+dexamethasone (24 mg); placebo=placebo+placebo

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