The effect of pre-operative methylprednisolone on early endothelial damage after total knee arthroplasty: a randomised, double-blind, placebo-controlled trial

V Lindberg-Larsen, S R Ostrowski, M Lindberg-Larsen, M L Rovsing, P I Johansson, H Kehlet

Research output: Contribution to journalJournal articleResearchpeer-review


We wished to evaluate whether inhibition of the systemic inflammatory response by a single pre-operative dose of methylprednisolone reduced markers of early endothelial damage after fast-track total knee arthroplasty. We randomly allocated 70 patients undergoing elective unilateral total knee arthroplasty (1:1) to receive either pre-operative intravenous methylprednisolone 125 mg (methylprednisolone group) or isotonic saline (control group). All procedures were performed under spinal anaesthesia without a tourniquet, using a standardised multimodal analgesic regime. The outcomes included changes in Syndecan-1 concentrations, a marker of glycocalyx degradation, markers of endothelial cell damage and activation (plasma soluble thrombomodulin and sE-Selectin), and permeability by vascular endothelial growth factor, as well as C-reactive protein concentrations. Blood samples were collected at baseline and 2 h, 6 h and 24 h after surgery, with complete sampling from 63 patients for analyses. Methylprednisolone significantly reduced markers of endothelial damage at 24 h following surgery compared with saline (methylprednisolone group vs. control group, adjusted means (SEM)) expressed by circulating Syndecan-1: 11.6 (1.0) vs. 13.4 (1.1) p = 0.046; soluble thrombomodulin: 5.1 (0.1) vs. 5.7 (0.2) , p = 0.009; sE-Selectin: 64.8 (1.8) vs. 75.7 (1.9) , p = 0.001, and vascular endothelial growth factor: 35.3 (2.7) vs. 58.5 (2.8) , p < 0.001. The effect of the intervention increased with time for soluble thrombomodulin, sE-Selectin and vascular endothelial growth factor, and was more pronounced in patients with high baseline values. Finally, methylprednisolone reduced the C-reactive protein response 24 h postoperatively; 31.1 (1.1) mg.l-1 vs. 68.4 (1.1) mg.l-1 , p < 0.001. Pre-operative administration of methylprednisolone 125 mg reduced circulating markers of endothelial activation and damage, as well as the systemic inflammatory response (C-reactive protein) early after fast-track total knee arthroplasty. These findings may have a positive effect on surgical outcome, but require studies in major surgery.

Original languageEnglish
Issue number10
Pages (from-to)1217-1224
Publication statusPublished - Oct 2017
Externally publishedYes


  • Aged
  • Anesthesia, Spinal/methods
  • Anti-Inflammatory Agents/administration & dosage
  • Arthroplasty, Replacement, Knee/adverse effects
  • Biomarkers/blood
  • C-Reactive Protein/metabolism
  • Double-Blind Method
  • Drug Administration Schedule
  • Endothelium, Vascular/drug effects
  • Female
  • Glucocorticoids/administration & dosage
  • Humans
  • Male
  • Methylprednisolone/administration & dosage
  • Middle Aged
  • Postoperative Complications/prevention & control
  • Premedication/methods
  • Systemic Inflammatory Response Syndrome/etiology
  • glycocalyx
  • inflammation
  • glucocorticoids
  • endothelial damage


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