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

Summary 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) ng.ml −1 vs. 13.4 (1.1) ng.ml −1 p = 0.046; soluble thrombomodulin: 5.1 (0.1) ng.ml −1 vs. 5.7 (0.2) ng.ml −1 , p = 0.009; sE ‐Selectin: 64.8 (1.8) ng.ml −1 vs. 75.7 (1.9) ng.ml −1 , p = 0.001, and vascular endothelial growth factor: 35.3 (2.7) ng.ml −1 vs. 58.5 (2.8) ng.ml −1 , 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.