the Effect of Tracleer on Tourniquet-associated Hypertension

Study Overview
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Brief Summary
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Tourniquet is widely used in orthopedic surgery. However, prolonged tourniquet inflation may cause a gradual rise in blood pressure, which named as tourniquet-associated hypertension. Thus, to effectively prevent the tourniquet related hemodynamic responses is important for patients receiving limb surgery. Tracleer is an endothelin receptor antagonist indicated for the treatment of pulmonary arterial hypertension. Tracleer can also be used to treat retistant hypertension. At present trial, the investigators are going to investigate the effect of Tracleer on tourniquet-associated hypertension during total knee arthroplasty.

Detailed Description
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At present study, the investigators will use endothelin receptor antagonist, Tracleer (Bosentan), to investigate the effect of Tracleer on tourniquet-associated hypertension during unilateral total knee arthroplasty, and evaluate its safety and effectivity. The purpose of this study is to find a new therapy to prevent and treat tourniquet-associated hypertension.

Official Title
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Effect of Endothelin Receptor Blocker Tracleer on Toruniquet-associated Hypertension During Total Knee Arthroplasty

Conditions
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Tourniquets, Hypertension, Bosentan

Intervention / Treatment
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* Drug: Tracleer 125Mg Tablet
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients underwent selected total knee arthroplasty under general anesthesia ASA II-III 18 65 years old Signed informed consent voluntarily Exclusion Criteria: Do not apply tourniquet during the surgery Patients underwent emergency surgery Having applied tourniquet in last three months Patients underwent bilateral total knee arthroplasty Dysfunction of liver or kidney Anemia (Hb <90 g/L) Serious myocardial disease (eg. coronary heart disease, heart failure, severe arrhythmia) Coagulation disorder Diabetic Leukocyte higher than normal value Pneumonia, asthma, chronic obstructive pulmonary disease Hypotension before surgery (systolic pressure < 90 mmHg) Pregnant woman or puerpera Having being enrolled in other clinical trial in last 3 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tracleer (or Bosentan)<br>Tracleer (Tracleer 125Mg Tablet) was administered orally at two hours before surgery and six hours after surgery | Drug: Tracleer 125Mg Tablet<br>* Tracleer was administered orally at two hours before surgery and six hours after surgery.<br>* Other names: endothelin receptor antagonist;|
| Placebo Comparator: Placebo<br>Placebo was administered orally at two hours before surgery and six hours after surgery | Drug: Placebo<br>* Placebo was administered orally at two hour before surgery and six hours after surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum rate of change in systolic blood pressure (MR) | During the observation, MR=(the highest value of systolic blood pressure - the baseline of systolic pressure ) / the baseline of systolic pressure | 24 hours after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the concentration of endothelin-1, 5-hydroxytrypatamine, and norepinephrine | test the concentration of endothelin-1, 5-hydroxytrypatamine, and norepinephrine in plasma at different time point | baseline and intraoperative | 
| visual analog scale | assess the efficacy of analgesia using visual analog scale (VAS) | 24 hrs after surgery |