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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.

OriginalsprogEngelsk
TidsskriftAnaesthesia
Vol/bind72
Udgave nummer10
Sider (fra-til)1217-1224
ISSN0003-2409
DOI
StatusUdgivet - okt. 2017
Udgivet eksterntJa

Fingeraftryk

Knee Replacement Arthroplasties
Placebos
Thrombomodulin
Vascular Endothelial Growth Factor A
Glycocalyx
Control Groups
Outcome Assessment (Health Care)

Bibliografisk note

© 2017 The Association of Anaesthetists of Great Britain and Ireland.

Citer dette

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title = "The effect of pre-operative methylprednisolone on early endothelial damage after total knee arthroplasty: a randomised, double-blind, placebo-controlled trial",
abstract = "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.",
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The effect of pre-operative methylprednisolone on early endothelial damage after total knee arthroplasty : a randomised, double-blind, placebo-controlled trial. / Lindberg-Larsen, V; Ostrowski, S R; Lindberg-Larsen, M; Rovsing, M L; Johansson, P I; Kehlet, H.

I: Anaesthesia, Bind 72, Nr. 10, 10.2017, s. 1217-1224.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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 - Aged

KW - Anesthesia, Spinal/methods

KW - Anti-Inflammatory Agents/administration & dosage

KW - Arthroplasty, Replacement, Knee/adverse effects

KW - Biomarkers/blood

KW - C-Reactive Protein/metabolism

KW - Double-Blind Method

KW - Drug Administration Schedule

KW - Endothelium, Vascular/drug effects

KW - Female

KW - Glucocorticoids/administration & dosage

KW - Humans

KW - Male

KW - Methylprednisolone/administration & dosage

KW - Middle Aged

KW - Postoperative Complications/prevention & control

KW - Premedication/methods

KW - Systemic Inflammatory Response Syndrome/etiology

U2 - 10.1111/anae.13983

DO - 10.1111/anae.13983

M3 - Journal article

C2 - 28744857

VL - 72

SP - 1217

EP - 1224

JO - Anaesthesia

JF - Anaesthesia

SN - 0003-2409

IS - 10

ER -