Clinical trial NCT02567903: Tourniquet Study: A Clinical Trial Into the Effect of Tourniquet Use on the Coagulation System
Official title: Tourniquet Study: Is the High Thrombosis Risk After Knee Arthroscopy Caused by Limb-tourniquet Application? A Randomized Clinical Trial Into the Effect of Tourniquet Use on the Coagulation System
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Venous Thrombosis
Lead sponsor: Groene Hart Ziekenhuis
Sponsor class: OTHER
Collaborators: name: Leiden University Medical Center
First posted: 2015-10-05
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: Inclusion criteria

* Meniscectomy
* Diagnostic arthroscopy
* Removal of corpora libera

Exclusion Criteria

* 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

Primary outcomes:
measure: Change in parameters that reflect a hypoxic state assessed by pH
timeFrame: 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.
measure: Change in parameters that reflect a hypoxic state assessed by pO2
timeFrame: 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.
measure: Change in parameters that reflect a hypoxic state assessed by pCO2
timeFrame: 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.
measure: Change in parameters that reflect a hypoxic state assessed by Lactate
timeFrame: 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.
measure: Change in parameters that reflect an inflammatory reaction assessed by WBCC
timeFrame: 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.
measure: Change in parameters that reflect an inflammatory reaction and/or endothelium involvement assessed by E-selectin
timeFrame: 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.
measure: Change in parameters that reflect an inflammatory reaction assessed by NETs
timeFrame: 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.
measure: Outcome parameters that reflect involvement of the endothelium assessed by vWF
timeFrame: 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.
measure: Outcome parameters that reflect involvement of the endothelium assessed by thrombomodulin.
timeFrame: 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.
measure: Outcome parameters that reflect involvement of the endothelium assessed by f 1+2
timeFrame: 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.
measure: Outcome parameters that reflect a procoagulant state and thrombin formation assessed by D-dimer
timeFrame: 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.
measure: Outcome parameters that reflect a procoagulant state and thrombin formation assessed by PAI 1
timeFrame: 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.
measure: Outcome parameters that reflect a procoagulant state and thrombin formation assessed by tPA
timeFrame: 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.
measure: Outcome parameters that reflect a procoagulant state and thrombin formation assessed by factor VIII
timeFrame: 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.
measure: Outcome parameters that reflect a procoagulant state and thrombin formation assessed by TAT
timeFrame: 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.
measure: Outcome parameters that reflect a procoagulant state and thrombin formation assessed by PAP
timeFrame: 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:
measure: Duration of surgery
timeFrame: intraoperative, duration in minutes between first incision until closure
measure: Duration of tourniquet use
timeFrame: intraoperative, duration in minutes between tourniquet inflation and deflation
measure: Per-operative visibility
timeFrame: Per-operative
Other outcomes:
Locations:
city: Gouda
country: Netherlands
facility: Groene Hart Ziekenhuis
state: Zuid Holland
Study officials:
affiliation: Leiden University Medical Center
name: Suzanne C Cannegieter, MD, PhD
role: STUDY_CHAIR
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