Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Bispebjerg Hospital | OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This study evaluates the pathophysiological effects of a single dose methylprednisolone administered prior to total knee-arthroplasty surgery (TKA). The investigators examine the effect on the endothelial glycocalyx shedding due to surgical trauma.
Half of participants will receive intravenous Solu-Medrol 125 mg, while the other half will receive placebo.
The investigators hypothesize that the group receiving methylprednisolone will experience reduction in glycocalyx degradation compared to the placebo-group, early after TKA.
The anti-inflammatory effects of glucocorticoids are well known. The beneficial effects on postoperative pain, postoperative nausea and vomiting are well-documented.
Postoperatively, activation and / or dysregulation of the inflammatory system influence on the endothelial glycocalyx. Damage of the vascular endothelia increases the risk of cardiovascular and thromboembolic complications.
In animal studies glucocorticoids have been found to preserve the endothelial glycocalyx and the vascular barrier.
The effect of glucocorticoids on human endothelial glycocalyx after surgery is unknown and calls for further investigation.
This study is embedded in a primary study registrated as: NCT02319343
For further details please view the EudraCT registration:
EudraCT nr.: 2014-003395-23
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Methylprednisolone | Active Comparator | Preoperative single high dose of Solu-Medrol 125 mg iv. |
|
| Isotonic Sodium Chloride | Placebo Comparator | Preoperative single dose of isotonic Sodium Chloride |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Methylprednisolone | Drug | Comparison of preoperative single high dose of Methylprednisolone 125 mg iv. and isotonic Sodium Chloride |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in plasma Syndecan-1 from baseline (before surgery) to 24 hours after surgery | baseline to 24 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Change in plasma soluble Thrombomodulin from baseline (before surgery) to 24 hours after surgery | baseline to 24 hours | |
| Change in plasma SE-Selectin from baseline (before surgery) to 24 hours after surgery | One day after surgery |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Viktoria Lindberg-Larsen, MD | Section for Surgical Pathophysiology, Rigshospitalet | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Bispebjerg Hospital | Copenhagen NV | 2400 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23205862 | Background | Husted H. Fast-track hip and knee arthroplasty: clinical and organizational aspects. Acta Orthop Suppl. 2012 Oct;83(346):1-39. doi: 10.3109/17453674.2012.700593. | |
| 23663938 | Background | Kehlet H. Fast-track hip and knee arthroplasty. Lancet. 2013 May 11;381(9878):1600-2. doi: 10.1016/S0140-6736(13)61003-X. No abstract available. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D010003 | Osteoarthritis |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D008775 | Methylprednisolone |
| D008776 | Methylprednisolone Hemisuccinate |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D011239 | Prednisolone |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Isotonic Sodium Chloride | Drug | Placebo |
|
| Change in plasma VE-Cadherin from baseline (before surgery) to 24 hours after surgery | baseline to 24 hours |
| 24359028 | Background | Khan SK, Malviya A, Muller SD, Carluke I, Partington PF, Emmerson KP, Reed MR. Reduced short-term complications and mortality following Enhanced Recovery primary hip and knee arthroplasty: results from 6,000 consecutive procedures. Acta Orthop. 2014 Feb;85(1):26-31. doi: 10.3109/17453674.2013.874925. Epub 2013 Dec 20. |
| 21895500 | Background | Malviya A, Martin K, Harper I, Muller SD, Emmerson KP, Partington PF, Reed MR. Enhanced recovery program for hip and knee replacement reduces death rate. Acta Orthop. 2011 Oct;82(5):577-81. doi: 10.3109/17453674.2011.618911. Epub 2011 Sep 6. |
| 22743373 | Background | Ostrowski SR, Johansson PI. Endothelial glycocalyx degradation induces endogenous heparinization in patients with severe injury and early traumatic coagulopathy. J Trauma Acute Care Surg. 2012 Jul;73(1):60-6. doi: 10.1097/TA.0b013e31825b5c10. |
| 21772125 | Background | Johansson PI, Stensballe J, Rasmussen LS, Ostrowski SR. A high admission syndecan-1 level, a marker of endothelial glycocalyx degradation, is associated with inflammation, protein C depletion, fibrinolysis, and increased mortality in trauma patients. Ann Surg. 2011 Aug;254(2):194-200. doi: 10.1097/SLA.0b013e318226113d. |
| 17923576 | Background | Rehm M, Bruegger D, Christ F, Conzen P, Thiel M, Jacob M, Chappell D, Stoeckelhuber M, Welsch U, Reichart B, Peter K, Becker BF. Shedding of the endothelial glycocalyx in patients undergoing major vascular surgery with global and regional ischemia. Circulation. 2007 Oct 23;116(17):1896-906. doi: 10.1161/CIRCULATIONAHA.106.684852. Epub 2007 Oct 8. |
| 22290457 | Background | Woodcock TE, Woodcock TM. Revised Starling equation and the glycocalyx model of transvascular fluid exchange: an improved paradigm for prescribing intravenous fluid therapy. Br J Anaesth. 2012 Mar;108(3):384-94. doi: 10.1093/bja/aer515. Epub 2012 Jan 29. |
| 18073553 | Background | Chappell D, Jacob M, Hofmann-Kiefer K, Bruegger D, Rehm M, Conzen P, Welsch U, Becker BF. Hydrocortisone preserves the vascular barrier by protecting the endothelial glycocalyx. Anesthesiology. 2007 Nov;107(5):776-84. doi: 10.1097/01.anes.0000286984.39328.96. |
| 18836678 | Background | Chappell D, Hofmann-Kiefer K, Jacob M, Rehm M, Briegel J, Welsch U, Conzen P, Becker BF. TNF-alpha induced shedding of the endothelial glycocalyx is prevented by hydrocortisone and antithrombin. Basic Res Cardiol. 2009 Jan;104(1):78-89. doi: 10.1007/s00395-008-0749-5. Epub 2008 Oct 3. |
| D013256 |
| Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |