TY - JOUR
T1 - The effect of pre-operative methylprednisolone on early endothelial damage after total knee arthroplasty
T2 - a randomised, double-blind, placebo-controlled trial
AU - Lindberg-Larsen, V
AU - Ostrowski, S R
AU - Lindberg-Larsen, M
AU - Rovsing, M L
AU - Johansson, P I
AU - Kehlet, H
N1 - © 2017 The Association of Anaesthetists of Great Britain and Ireland.
PY - 2017/10
Y1 - 2017/10
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1111/anae.13983
DO - 10.1111/anae.13983
M3 - Journal article
C2 - 28744857
SN - 0003-2409
VL - 72
SP - 1217
EP - 1224
JO - Anaesthesia
JF - Anaesthesia
IS - 10
ER -