The Efficacy and Safety of Hypertonic Saline in Cardiac Surgery Patients.

Study Overview
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Brief Summary
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The organ dysfunction following cardiopulmonary bypass (CPB) occurs frequently in cardiac surgery patients. Systemic inflammatory response initiated by CPB through releasing of several mediators lead to altered endothelial integrity and in consequence the leakage of proteins and fluids from the intravascular to the interstitial compartment is occurred. Increased capillary permeability and decreased colloid osmotic pressure were shown to play a key role for fluid shift and increasing of extravascular water. Further tissue edema can result in injury to many organs, including the heart, lungs, brain, kidneys and can lead to adverse outcomes. Hypertonic solution creates an osmotic gradient across the cellular membrane, causing a fluid shift from the intracellular and the interstitial spaces of tissue into the intravascular compartment. The purpose of this study is to investigate the efficacy and safety of 7.2% NaCl plus 6% hydroxyethyl starch 200/0.5 in patients scheduled for first-time coronary artery bypass grafting with cardiopulmonary bypass.

Official Title
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The Efficacy and Safety of 7.2% NaCl Plus 6% Hydroxyethyl 200/0.5 in Patients Scheduled for First-time Coronary Artery Bypass Grafting With Cardiopulmonary Bypass.

Conditions
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Edema, Coronary Artery Disease

Intervention / Treatment
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* Drug: 7.2% NaCl plus 6% hydroxyethyl starch 200/0.5
* Drug: 0.9% NaCl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients scheduled for first-time coronary artery bypass grafting with cardiopulmonary bypass Exclusion Criteria: age >70 years body mass index <18 and >35 kg/m2 left ventricular ejection fraction <40% myocardial infarction <6 months before surgery stroke or transient ischemic attack <12 months before surgery diabetes mellitus glomerular filtration rate <90 mL/min emergency surgery hematocrit <30%.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 7.2% NaCl /hydroxyethyl starch 200/0.5<br>On-pump CABG. 7.2% NaCl plus 6% hydroxyethyl starch 200/0.5 solution (HyperHAES) 4 mL/kg for 30 min, IV (in the vein), once, starting after the first hemodynamic measurement is obtained (before the beginning of CPB) | Drug: 7.2% NaCl plus 6% hydroxyethyl starch 200/0.5<br> <br> * Other names: HyperHAES;|
| Placebo Comparator: 0.9% NaCl<br>On-pump CABG. 0.9% NaCl (isotonic saline) 4 mL/kg for 30 min, IV (in the vein), once, starting after the first hemodynamic measurement is obtained (before the beginning of CPB) | Drug: 0.9% NaCl<br> <br> * Other names: Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extravascular Lung Water Index | Extravascular lung water index (ELWI; mL/kg) will be used to assess this outcome measure. ELWI was monitored by transcardiopulmonary thermodilution technique with the PiCCO plus system. Extravascular lung water represents the extravascular fluid of the lung tissue. It includes intra-cellular, interstitial and intra-alveolar water (not pleural effusion). It is indexed to Predicted Body Weight. | baseline; 5 min after infusion; 5 min after CPB; 30 min after CPB; end of surgery; 2 h, 4 h, 6 h, 12 h after CPB; Postoperative day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary Oxygenation | Index of arterial oxygenation efficiency (PaO2/FiO2), alveolar-arterial oxygen tension difference (AaDO2) will be used to assess this outcome measure. | 24 hours | 
| Oxygen Delivery | Oxygen delivery index (DO2I) will be used to assess this outcome measure. | 24 hours | 
| Cardiac Index |  | 24 hours | 
| Fluid Balance | Net fluid balance at the end of surgery equals the sum of all infusions minus the urine output. Net fluid balance at postoperative day 1 equals the sum of all infusions minus the urine output and blood loss. | 24 hours | 
| Inflammation Response | Serum levels of Interleukin 6 (IL-6) and Interleukin 10 (IL-10) will be used to assess this outcome measure. | 24 hours | 
| Endothelial Integrity | Serum levels of intercellular adhesion molecule-1 (ICAM-1), E-selectin will be used to assess this outcome measure. | 24 hours | 
| Plasma Na |  | 24 hours | 
| Plasma Osmolarity |  | 24 hours | 
| Rate of Acute Kidney Injury | serum creatinine, serum cystatin C, urine neutrophil gelatinase-associated lipocalin (uNGAL) will be used to asses this outcome measure. | 48 hours | 
| Rate of Hyperchloremic Metabolic Acidosis | blood pH, base excess (BE), plasma level of Cl will be used to assess this outcome measure. | 24 hours | 
| Stroke Volume Index |  | 24 hours | 
| Rate of Neurological Complications | Delirium, clinically diagnosed stroke, and encephalopathy. | 24 hours | 
| Blood Loss | Bleeding from chest tubes | 24 hours | 
| Duration of Mechanical Ventilation |  | 24 hours | 
| Chloride Loading | The amount of chloride ions (mmol per patient) which will be infused during the surgery and ICU stay | 24 h | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Organ dysfunction, Hypertonic solution, Extravascular water, Cardiopulmonary Bypass