Tourniquet Study: A Clinical Trial Into the Effect of Tourniquet Use on the Coagulation System
- Conditions
- Venous Thrombosis
- Interventions
- Device: Thigh TourniquetProcedure: Knee arthroscopy
- Registration Number
- NCT02567903
- Lead Sponsor
- Groene Hart Ziekenhuis
- 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.
- Detailed Description
Background
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. 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.
Objective
To investigate the effect of tourniquet application on the coagulation system in patients undergoing a knee arthroscopy. 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.
Study Design
In a randomized, controlled clinical study the investigators will compare local and systemic coagulation and inflammation markers before and after knee arthroscopy between two groups: 25 patients will be randomized to arthroscopy with tourniquet (Group I) and 25 patients to arthroscopy without tourniquet (Group II).
Inclusion and exclusion criteria
The patients will be recruited from one hospital in Gouda over a 6 months inclusion period. All patients over 18 years, scheduled for a meniscectomy, diagnostic arthroscopy or removal of corpora libera will be eligible for inclusion. Patients will be excluded when they suffer from any kind of coagulation disorder, use of hormonal anticonception, in case of pregnancy or puerperium, when they have a history of venous thrombosis, had major surgery or cast-immobilisation of the lower extremity in the past two months, have a neoplasm or inflammatory disease, have a BMI\>30, or when they use anticoagulant therapy. Patients will generally receive spinal anaesthesia. Patients who are nevertheless exposed to any other type of anaesthesia will be excluded as well, to keep the effect of anaesthesia equal for all participants.
Intervention
Patients will be randomized to knee arthroscopy without tourniquet use and to knee arthroscopy with tourniquet use. In patients randomized to arthroscopy with tourniquet use, exsanguination in the leg in which the knee arthroscopy will be performed will be accomplished by raising the leg vertically for one minute. The tourniquet will be inflated to 100-150 mmHg above systolic blood pressure.
Data on duration of surgery and duration of tourniquet use will be collected. Blood collected from the cubital vein and the great saphenous vein during arthroscopy of the knee will be analyzed on outcome parameters that reflect a hypoxic state, an inflammatory reaction, involvement of the endothelium, a procoagulant state and thrombin formation.
Main study endpoints (primary)
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 will be analyzed.
Different patterns will be analyzed to explore the effect of tourniquet application on the coagulation system by possible biological mechanism. A change (increase or decrease) of markers within one pattern, compared to baseline measurements (before surgery), is considered as a relevant shift of that pattern, thereby suggesting the involvement of that specific pathway.
Outcome parameters that reflect a hypoxic state:
* pH
* pO2
* pCO2
* Lactate
Outcome parameters that reflect an inflammatory reaction:
* White Blood Cell Count (WBCC)
* E-selectin
* Neutrophil Extracellular traps (NETs)
Outcome parameters that reflect involvement of the endothelium:
* Von Willebrand Factor (vWF)
* Thrombomodulin
* E-selectin
Outcome parameters that reflect a procoagulant state and thrombin formation:
* Prothrombin fragments 1+2
* D-dimer
* Plasmin Activator Inhibitor 1 (PAI 1)
* Tissue plasminogen activator (tPA)
* Factor VIII
* Thrombin and Antithrombin complexes (TAT)
* Plasmin and antiplasmin complexes (PAP)
Secondary study paramaters
• Visibility during arthroscopy and technical difficulty score.
Time Schedule
Month 1-3: Completion of study protocol, procedure for approval by METC. Set up of database and randomisation procedure. Instruction of participating clinicians and surgery/anaesthesia staff.
Month 4-6: Inclusion of patients, data collection. Month 7-8: Laboratory tests. Month 9-12: Data analysis, writing and submission of manuscript.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 55
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tourniquet Knee arthroscopy Knee arthroscopy with the use of a thigh tourniquet. No Tourniquet Knee arthroscopy Knee arthroscopy without the use of a thigh tourniquet. Tourniquet Thigh Tourniquet Knee arthroscopy with the use of a thigh tourniquet.
- Primary Outcome Measures
Name Time Method Outcome parameters that reflect involvement of the endothelium assessed by thrombomodulin. 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 Thrombomodulin between timepoints
Outcome parameters that reflect involvement of the endothelium assessed by f 1+2 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 Prothrombin fragments 1+2 (f 1+2) between timepoints
Change in parameters that reflect an inflammatory reaction assessed by WBCC 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 White Blood Cell Count (WBCC) between timepoints
Change in parameters that reflect an inflammatory reaction and/or endothelium involvement assessed by E-selectin 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 E-selectin between timepoints
Outcome parameters that reflect a procoagulant state and thrombin formation assessed by D-dimer 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 D-dimer between timepoints
Outcome parameters that reflect a procoagulant state and thrombin formation assessed by factor VIII 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 Factor VIII between timepoints
Outcome parameters that reflect a procoagulant state and thrombin formation assessed by TAT 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 Thrombin and Antithrombin complexes (TAT) between timepoints
Change in parameters that reflect a hypoxic state assessed by pO2 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 pO2 between timepoints
Change in parameters that reflect a hypoxic state assessed by pCO2 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 pCO2 between timepoints
Change in parameters that reflect an inflammatory reaction assessed by NETs 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 Neutrophil Extracellular traps (NETs) between timepoints
Outcome parameters that reflect involvement of the endothelium assessed by vWF 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 Von Willebrand Factor (vWF) between timepoints
Change in parameters that reflect a hypoxic state assessed by pH 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 pH between timepoints
Change in parameters that reflect a hypoxic state assessed by Lactate 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 Lactate between timepoints
Outcome parameters that reflect a procoagulant state and thrombin formation assessed by PAI 1 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 Plasmin Activator Inhibitor 1 (PAI 1) between timepoints
Outcome parameters that reflect a procoagulant state and thrombin formation assessed by tPA 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 Tissue plasminogen activator (tPA) between timepoints
Outcome parameters that reflect a procoagulant state and thrombin formation assessed by PAP 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 Plasmin and antiplasmin complexes (PAP) between timepoints
- Secondary Outcome Measures
Name Time Method Per-operative visibility Per-operative Visibility during surgery, measured on a Visual Analogue Scale scale (0-10)
Duration of surgery intraoperative, duration in minutes between first incision until closure The total duration of surgery in minutes
Duration of tourniquet use intraoperative, duration in minutes between tourniquet inflation and deflation The total duration of tourniquet inflation in minutes
Trial Locations
- Locations (1)
Groene Hart Ziekenhuis
🇳🇱Gouda, Zuid Holland, Netherlands