Tourniquet Study: A Clinical Trial Into the Effect of Tourniquet Use on the Coagulation System

NCT02567903 | Completed

• 1 other identifier: NL49117.058.14
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

Knee arthroscopy is the most commonly performed orthopaedic procedure worldwide, with, according to the American Society for Sports Medicine, over 4 million procedures performed each year. The risk of venous thrombosis following this procedure is considerable with rates of symptomatic events varying between 0.9% and 4.6%. It is currently unknown how this high risk comes about considering its short duration and minimal tissue damage caused by the procedure. A factor that may play a role is the use of a tourniquet. A large majority of orthopaedic surgeons prefer to operate within a 'dry field', which is obtained by the use of a tourniquet. Tourniquet applied surgery is not without risks. Although its use during orthopedic surgery is widely accepted and a standard procedure, tourniquet use can lead to loss of muscle functional strength and contractile speed, vessel wall damage and nerve injury, next to the possibly increased risk of venous thrombosis. In the proposed study the investigators will investigate the effect of a tourniquet on local and systemic markers of hypoxia, inflammation, involvement of endothelium, and coagulation activation. A finding of more prominent activation of the coagulation system with tourniquet use than with non-use will create an important opportunity to prevent thromboembolic events in these patients, as it has been shown that knee arthroscopy can be performed adequately without the use of a tourniquet. Furthermore, it will increase the understanding of the pathophysiology of thrombosis.

Conditions

Venous Thrombosis

Outcome Measures

Primary Outcomes (16)

• Change in parameters that reflect a hypoxic state assessed by pH

  Change in pH between timepoints

  Change in parameters between timepoints; Before surgery (blood drawn approximately 1 hour before surgery), directly after surgery (blood drawn within 5 minutes), 1 hour after surgery.

• Change in parameters that reflect a hypoxic state assessed by pO2

  Change in pO2 between timepoints

  Change in parameters between timepoints; Before surgery (blood drawn approximately 1 hour before surgery), directly after surgery (blood drawn within 5 minutes), 1 hour after surgery.

• Change in parameters that reflect a hypoxic state assessed by pCO2

  Change in pCO2 between timepoints

  Change in parameters between timepoints; Before surgery (blood drawn approximately 1 hour before surgery), directly after surgery (blood drawn within 5 minutes), 1 hour after surgery.

• Change in parameters that reflect a hypoxic state assessed by Lactate

  Change in Lactate between timepoints

  Change in parameters between timepoints; Before surgery (blood drawn approximately 1 hour before surgery), directly after surgery (blood drawn within 5 minutes), 1 hour after surgery.

• Change in parameters that reflect an inflammatory reaction assessed by WBCC

  Change in White Blood Cell Count (WBCC) between timepoints

  Change in parameters between timepoints; Before surgery (blood drawn approximately 1 hour before surgery), directly after surgery (blood drawn within 5 minutes), 1 hour after surgery.

• Change in parameters that reflect an inflammatory reaction and/or endothelium involvement assessed by E-selectin

  Change in E-selectin between timepoints

  Change in parameters between timepoints; Before surgery (blood drawn approximately 1 hour before surgery), directly after surgery (blood drawn within 5 minutes), 1 hour after surgery.

• Change in parameters that reflect an inflammatory reaction assessed by NETs

  Change in Neutrophil Extracellular traps (NETs) between timepoints

  Change in parameters between timepoints; Before surgery (blood drawn approximately 1 hour before surgery), directly after surgery (blood drawn within 5 minutes), 1 hour after surgery.

• Outcome parameters that reflect involvement of the endothelium assessed by vWF

  Change in Von Willebrand Factor (vWF) between timepoints

  Change in parameters between timepoints; Before surgery (blood drawn approximately 1 hour before surgery), directly after surgery (blood drawn within 5 minutes), 1 hour after surgery.

• Outcome parameters that reflect involvement of the endothelium assessed by thrombomodulin.

  Change in Thrombomodulin between timepoints

  Change in parameters between timepoints; Before surgery (blood drawn approximately 1 hour before surgery), directly after surgery (blood drawn within 5 minutes), 1 hour after surgery.

• Outcome parameters that reflect involvement of the endothelium assessed by f 1+2

  Change in Prothrombin fragments 1+2 (f 1+2) between timepoints

  Change in parameters between timepoints; Before surgery (blood drawn approximately 1 hour before surgery), directly after surgery (blood drawn within 5 minutes), 1 hour after surgery.

• Outcome parameters that reflect a procoagulant state and thrombin formation assessed by D-dimer

  Change in D-dimer between timepoints

  Change in parameters between timepoints; Before surgery (blood drawn approximately 1 hour before surgery), directly after surgery (blood drawn within 5 minutes), 1 hour after surgery.

• Outcome parameters that reflect a procoagulant state and thrombin formation assessed by PAI 1

  Change in Plasmin Activator Inhibitor 1 (PAI 1) between timepoints

  Change in parameters between timepoints; Before surgery (blood drawn approximately 1 hour before surgery), directly after surgery (blood drawn within 5 minutes), 1 hour after surgery.

• Outcome parameters that reflect a procoagulant state and thrombin formation assessed by tPA

  Change in Tissue plasminogen activator (tPA) between timepoints

  Change in parameters between timepoints; Before surgery (blood drawn approximately 1 hour before surgery), directly after surgery (blood drawn within 5 minutes), 1 hour after surgery.

• Outcome parameters that reflect a procoagulant state and thrombin formation assessed by factor VIII

  Change in Factor VIII between timepoints

  Change in parameters between timepoints; Before surgery (blood drawn approximately 1 hour before surgery), directly after surgery (blood drawn within 5 minutes), 1 hour after surgery.

• Outcome parameters that reflect a procoagulant state and thrombin formation assessed by TAT

  Change in Thrombin and Antithrombin complexes (TAT) between timepoints

  Change in parameters between timepoints; Before surgery (blood drawn approximately 1 hour before surgery), directly after surgery (blood drawn within 5 minutes), 1 hour after surgery.

• Outcome parameters that reflect a procoagulant state and thrombin formation assessed by PAP

  Change in Plasmin and antiplasmin complexes (PAP) between timepoints

  Change in parameters between timepoints; Before surgery (blood drawn approximately 1 hour before surgery), directly after surgery (blood drawn within 5 minutes), 1 hour after surgery.

Secondary Outcomes (3)

• Duration of surgery

  intraoperative, duration in minutes between first incision until closure

• Duration of tourniquet use

  intraoperative, duration in minutes between tourniquet inflation and deflation

• Per-operative visibility

  Per-operative

Study Arms (2)

No Tourniquet

ACTIVE COMPARATOR

Knee arthroscopy without the use of a thigh tourniquet.

Procedure: Knee arthroscopy

Tourniquet

EXPERIMENTAL

Knee arthroscopy with the use of a thigh tourniquet.

Device: Thigh Tourniquet; Procedure: Knee arthroscopy

Interventions

Thigh Tourniquet DEVICE

Knee arthroscopy with the use of a thigh tourniquet that is inflated to 100-150 mmHg above systolic blood pressure.

Tourniquet

Knee arthroscopy PROCEDURE

Knee arthroscopy

No Tourniquet; Tourniquet

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Meniscectomy
• Diagnostic arthroscopy
• Removal of corpora libera

You may not qualify if:

• Any kind of coagulation disorder
• pregnant or within 3 months of childbirth
• Use of hormonal anticonception
• A history of venous thrombosis
• Had major surgery in the past two months
• A history of cast-immobilization of the lower extremity the past two months
• A neoplasm or inflammatory disease
• A BMI\>30
• using anticoagulant therapy
• Any other anaesthesia technique than spinal anaesthesia

Sponsors & Collaborators

• Groene Hart Ziekenhuis: lead
• Leiden University Medical Center: collaborator

Study Sites (1)

Groene Hart Ziekenhuis

Gouda, South Holland, 2803HH, Netherlands

Location

Related Publications (20)

• American Academy of Orthopaedic Surgeons. Knee Arthroscopy. 2013. http://orthoinfo.aaos.org/topic.cfm?topic=a00299. Accessed April 15, 2014

  BACKGROUND

• Geerts WH, Bergqvist D, Pineo GF, Heit JA, Samama CM, Lassen MR, Colwell CW. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133(6 Suppl):381S-453S. doi: 10.1378/chest.08-0656.

  PMID: 18574271 BACKGROUND

• Hoppener MR, Ettema HB, Kraaijenhagen RA, Verheyen CC, Henny PC. Day-care or short-stay surgery and venous thromboembolism. J Thromb Haemost. 2003 Apr;1(4):863-5. doi: 10.1046/j.1538-7836.2003.t01-9-00115.x. No abstract available.

  PMID: 12871434 BACKGROUND

• Hoppener MR, Ettema HB, Henny CP, Verheyen CC, Buller HB. Symptomatic deep vein thrombosis and immobilization after day-care arthroscopy of the knee. J Thromb Haemost. 2005 Jan;3(1):185-7. doi: 10.1111/j.1538-7836.2004.01091.x. No abstract available.

  PMID: 15634289 BACKGROUND

• Hoppener MR, Ettema HB, Henny CP, Verheyen CC, Buller HR. Low incidence of deep vein thrombosis after knee arthroscopy without thromboprophylaxis: a prospective cohort study of 335 patients. Acta Orthop. 2006 Oct;77(5):767-71. doi: 10.1080/17453670610012962.

  PMID: 17068708 BACKGROUND

• Camporese G, Bernardi E, Prandoni P, Noventa F, Verlato F, Simioni P, Ntita K, Salmistraro G, Frangos C, Rossi F, Cordova R, Franz F, Zucchetta P, Kontothanassis D, Andreozzi GM; KANT (Knee Arthroscopy Nadroparin Thromboprophylaxis) Study Group. Low-molecular-weight heparin versus compression stockings for thromboprophylaxis after knee arthroscopy: a randomized trial. Ann Intern Med. 2008 Jul 15;149(2):73-82. doi: 10.7326/0003-4819-149-2-200807150-00003.

  PMID: 18626046 BACKGROUND

• Ilahi OA, Reddy J, Ahmad I. Deep venous thrombosis after knee arthroscopy: a meta-analysis. Arthroscopy. 2005 Jun;21(6):727-30. doi: 10.1016/j.arthro.2005.03.007.

  PMID: 15944631 BACKGROUND

• Ramos J, Perrotta C, Badariotti G, Berenstein G. Interventions for preventing venous thromboembolism in adults undergoing knee arthroscopy. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD005259. doi: 10.1002/14651858.CD005259.pub3.

  PMID: 18843687 BACKGROUND

• Bovill EG, van der Vliet A. Venous valvular stasis-associated hypoxia and thrombosis: what is the link? Annu Rev Physiol. 2011;73:527-45. doi: 10.1146/annurev-physiol-012110-142305.

  PMID: 21034220 BACKGROUND

• Aglietti P, Baldini A, Vena LM, Abbate R, Fedi S, Falciani M. Effect of tourniquet use on activation of coagulation in total knee replacement. Clin Orthop Relat Res. 2000 Feb;(371):169-77. doi: 10.1097/00003086-200002000-00021.

  PMID: 10693564 BACKGROUND

• Katsumata S, Nagashima M, Kato K, Tachihara A, Wauke K, Saito S, Jin E, Kawanami O, Ogawa R, Yoshino S. Changes in coagulation-fibrinolysis marker and neutrophil elastase following the use of tourniquet during total knee arthroplasty and the influence of neutrophil elastase on thromboembolism. Acta Anaesthesiol Scand. 2005 Apr;49(4):510-6. doi: 10.1111/j.1399-6576.2005.00621.x.

  PMID: 15777299 BACKGROUND

• Kageyama K, Nakajima Y, Shibasaki M, Hashimoto S, Mizobe T. Increased platelet, leukocyte, and endothelial cell activity are associated with increased coagulability in patients after total knee arthroplasty. J Thromb Haemost. 2007 Apr;5(4):738-45. doi: 10.1111/j.1538-7836.2007.02443.x.

  PMID: 17408407 BACKGROUND

• Reikeras O, Clementsen T. Time course of thrombosis and fibrinolysis in total knee arthroplasty with tourniquet application. Local versus systemic activations. J Thromb Thrombolysis. 2009 Nov;28(4):425-8. doi: 10.1007/s11239-008-0299-6. Epub 2008 Dec 6.

  PMID: 19067121 BACKGROUND

• Sharrock NE, Go G, Sculco TP, Ranawat CS, Maynard MJ, Harpel PC. Changes in circulatory indices of thrombosis and fibrinolysis during total knee arthroplasty performed under tourniquet. J Arthroplasty. 1995 Aug;10(4):523-8. doi: 10.1016/s0883-5403(05)80155-x.

  PMID: 8523013 BACKGROUND

• Estebe JP, Davies JM, Richebe P. The pneumatic tourniquet: mechanical, ischaemia-reperfusion and systemic effects. Eur J Anaesthesiol. 2011 Jun;28(6):404-11. doi: 10.1097/EJA.0b013e328346d5a9.

  PMID: 21502865 BACKGROUND

• Johnson DS, Stewart H, Hirst P, Harper NJ. Is tourniquet use necessary for knee arthroscopy? Arthroscopy. 2000 Sep;16(6):648-51. doi: 10.1053/jars.2000.4826.

  PMID: 10976127 BACKGROUND

• Kam PC, Kavanagh R, Yoong FF. The arterial tourniquet: pathophysiological consequences and anaesthetic implications. Anaesthesia. 2001 Jun;56(6):534-45. doi: 10.1046/j.1365-2044.2001.01982.x.

  PMID: 11412159 BACKGROUND

• Alcelik I, Pollock RD, Sukeik M, Bettany-Saltikov J, Armstrong PM, Fismer P. A comparison of outcomes with and without a tourniquet in total knee arthroplasty: a systematic review and meta-analysis of randomized controlled trials. J Arthroplasty. 2012 Mar;27(3):331-40. doi: 10.1016/j.arth.2011.04.046. Epub 2011 Sep 22.

  PMID: 21944371 BACKGROUND

• Hoogeslag RA, Brouwer RW, van Raay JJ. The value of tourniquet use for visibility during arthroscopy of the knee: a double-blind, randomized controlled trial. Arthroscopy. 2010 Sep;26(9 Suppl):S67-72. doi: 10.1016/j.arthro.2009.12.008. Epub 2010 May 13.

  PMID: 20810094 BACKGROUND

• Schreijer AJ, Cannegieter SC, Meijers JC, Middeldorp S, Buller HR, Rosendaal FR. Activation of coagulation system during air travel: a crossover study. Lancet. 2006 Mar 11;367(9513):832-8. doi: 10.1016/S0140-6736(06)68339-6.

  PMID: 16530577 BACKGROUND

MeSH Terms

Conditions

Venous Thrombosis

Condition Hierarchy (Ancestors)

Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Suzanne C Cannegieter, MD, PhD

  Leiden University Medical Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: September 21, 2015
• First Posted: October 5, 2015
• Study Start: September 1, 2015
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2019
• Last Updated: February 5, 2020

Record last verified: 2020-02

Locations

NL (1)