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

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.

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Edema
• Intervention / Treatment: Drug: 0.9% NaCl; Drug: 7.2% NaCl plus 6% hydroxyethyl starch 200/0.5

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russian Federation
  • Novosibirsk territory
    • Novosibirsk, Novosibirsk territory, Russian Federation, 630055
      • Novosibirsk Research Institute of Pathology of Circulation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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%.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 7.2% NaCl /hydroxyethyl starch 200/0.5; 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; Other Names: HyperHAES
Placebo Comparator: 0.9% NaCl; 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; Other Names: Saline

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Meshalkin Research Institute of Pathology of Circulation
• Investigators: Principal Investigator: Vladimir V Lomivorotov, MD, PhD, Novosibirsk Research Institute of Pathology of Circulation

Publications and helpful links

General Publications

• Lomivorotov VV, Fominskiy EV, Efremov SM, Nepomniashchikh VA, Lomivorotov VN, Chernyavskiy AM, Shilova AN, Karaskov AM. Infusion of 7.2% NaCl/6% hydroxyethyl starch 200/0.5 in on-pump coronary artery bypass surgery patients: a randomized, single-blind pilot study. Shock. 2014 Mar;41(3):193-9. doi: 10.1097/SHK.0000000000000087.

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: August 5, 2012
• First Submitted That Met QC Criteria: August 27, 2012
• First Posted (Estimate): August 30, 2012

Study Record Updates

• Last Update Posted (Estimate): May 27, 2016
• Last Update Submitted That Met QC Criteria: April 29, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Cardiopulmonary Bypass; Organ dysfunction; Hypertonic solution; Extravascular water
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease
• Other Study ID Numbers: ESHHS