Coronary Artery Disease, Edema
Conditions
Keywords
Organ dysfunction, Hypertonic solution, Extravascular water, Cardiopulmonary Bypass
Brief summary
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.
Interventions
DRUG7.2% NaCl plus 6% hydroxyethyl starch 200/0.5
DRUG0.9% NaCl
Sponsors
Meshalkin Research Institute of Pathology of Circulation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
30 Years to 70 Years
Healthy volunteers
No
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%.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Extravascular Lung Water Index | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Oxygen Delivery | 24 hours | Oxygen delivery index (DO2I) will be used to assess this outcome measure. |
| Cardiac Index | 24 hours | — |
| Fluid Balance | 24 hours | 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. |
| Inflammation Response | 24 hours | Serum levels of Interleukin 6 (IL-6) and Interleukin 10 (IL-10) will be used to assess this outcome measure. |
| Endothelial Integrity | 24 hours | Serum levels of intercellular adhesion molecule-1 (ICAM-1), E-selectin will be used to assess this outcome measure. |
| Plasma Na | 24 hours | — |
| Plasma Osmolarity | 24 hours | — |
| Pulmonary Oxygenation | 24 hours | Index of arterial oxygenation efficiency (PaO2/FiO2), alveolar-arterial oxygen tension difference (AaDO2) will be used to assess this outcome measure. |
| Rate of Hyperchloremic Metabolic Acidosis | 24 hours | blood pH, base excess (BE), plasma level of Cl will be used to assess this outcome measure. |
| Stroke Volume Index | 24 hours | — |
| Rate of Neurological Complications | 24 hours | Delirium, clinically diagnosed stroke, and encephalopathy. |
| Blood Loss | 24 hours | Bleeding from chest tubes |
| Duration of Mechanical Ventilation | 24 hours | — |
| Chloride Loading | 24 h | The amount of chloride ions (mmol per patient) which will be infused during the surgery and ICU stay |
| Rate of Acute Kidney Injury | 48 hours | serum creatinine, serum cystatin C, urine neutrophil gelatinase-associated lipocalin (uNGAL) will be used to asses this outcome measure. |
Countries
Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 7.2% NaCl /Hydroxyethyl Starch 200/0.5 (Study Group) 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)
7.2% NaCl plus 6% hydroxyethyl starch 200/0.5 | 20 |
| 0.9% NaCl (Control Group) 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)
0.9% NaCl | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | 0.9% NaCl (Control Group) | 7.2% NaCl /Hydroxyethyl Starch 200/0.5 (Study Group) | Total |
|---|---|---|---|
| Age, Continuous | 57 years | 59 years | 58 years |
| Region of Enrollment Russian Federation | 20 participants | 20 participants | 40 participants |
| Sex: Female, Male Female | 1 Participants | 5 Participants | 6 Participants |
| Sex: Female, Male Male | 19 Participants | 15 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
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.
Time frame: 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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 7.2% NaCl /Hydroxyethyl Starch 200/0.5 (Study Group) | Extravascular Lung Water Index | baseline | 9 mL/kg |
| 7.2% NaCl /Hydroxyethyl Starch 200/0.5 (Study Group) | Extravascular Lung Water Index | 5 min after infusion | 9 mL/kg |
| 7.2% NaCl /Hydroxyethyl Starch 200/0.5 (Study Group) | Extravascular Lung Water Index | 5 min after CPB | 9 mL/kg |
| 7.2% NaCl /Hydroxyethyl Starch 200/0.5 (Study Group) | Extravascular Lung Water Index | 30 min after CPB | 9 mL/kg |
| 7.2% NaCl /Hydroxyethyl Starch 200/0.5 (Study Group) | Extravascular Lung Water Index | end of surgery | 8 mL/kg |
| 7.2% NaCl /Hydroxyethyl Starch 200/0.5 (Study Group) | Extravascular Lung Water Index | 2 h after CPB | 8 mL/kg |
| 7.2% NaCl /Hydroxyethyl Starch 200/0.5 (Study Group) | Extravascular Lung Water Index | 4 h after CPB | 7 mL/kg |
| 7.2% NaCl /Hydroxyethyl Starch 200/0.5 (Study Group) | Extravascular Lung Water Index | 6 h after CPB | 7 mL/kg |
| 7.2% NaCl /Hydroxyethyl Starch 200/0.5 (Study Group) | Extravascular Lung Water Index | 12 h after CPB | 7 mL/kg |
| 7.2% NaCl /Hydroxyethyl Starch 200/0.5 (Study Group) | Extravascular Lung Water Index | POD 1 | 7 mL/kg |
| 0.9% NaCl (Control Group) | Extravascular Lung Water Index | 6 h after CPB | 9 mL/kg |
| 0.9% NaCl (Control Group) | Extravascular Lung Water Index | baseline | 8 mL/kg |
| 0.9% NaCl (Control Group) | Extravascular Lung Water Index | 2 h after CPB | 9 mL/kg |
| 0.9% NaCl (Control Group) | Extravascular Lung Water Index | 5 min after infusion | 8 mL/kg |
| 0.9% NaCl (Control Group) | Extravascular Lung Water Index | POD 1 | 9 mL/kg |
| 0.9% NaCl (Control Group) | Extravascular Lung Water Index | 5 min after CPB | 10 mL/kg |
| 0.9% NaCl (Control Group) | Extravascular Lung Water Index | 4 h after CPB | 9 mL/kg |
| 0.9% NaCl (Control Group) | Extravascular Lung Water Index | 30 min after CPB | 9 mL/kg |
| 0.9% NaCl (Control Group) | Extravascular Lung Water Index | 12 h after CPB | 9 mL/kg |
| 0.9% NaCl (Control Group) | Extravascular Lung Water Index | end of surgery | 9 mL/kg |
Secondary
Blood Loss
Bleeding from chest tubes
Time frame: 24 hours
Secondary
Cardiac Index
Time frame: 24 hours
Secondary
Chloride Loading
The amount of chloride ions (mmol per patient) which will be infused during the surgery and ICU stay
Time frame: 24 h
Secondary
Duration of Mechanical Ventilation
Time frame: 24 hours
Secondary
Endothelial Integrity
Serum levels of intercellular adhesion molecule-1 (ICAM-1), E-selectin will be used to assess this outcome measure.
Time frame: 24 hours
Secondary
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.
Time frame: 24 hours
Secondary
Inflammation Response
Serum levels of Interleukin 6 (IL-6) and Interleukin 10 (IL-10) will be used to assess this outcome measure.
Time frame: 24 hours
Secondary
Oxygen Delivery
Oxygen delivery index (DO2I) will be used to assess this outcome measure.
Time frame: 24 hours
Secondary
Plasma Na
Time frame: 24 hours
Secondary
Plasma Osmolarity
Time frame: 24 hours
Secondary
Pulmonary Oxygenation
Index of arterial oxygenation efficiency (PaO2/FiO2), alveolar-arterial oxygen tension difference (AaDO2) will be used to assess this outcome measure.
Time frame: 24 hours
Secondary
Rate of Acute Kidney Injury
serum creatinine, serum cystatin C, urine neutrophil gelatinase-associated lipocalin (uNGAL) will be used to asses this outcome measure.
Time frame: 48 hours
Secondary
Rate of Hyperchloremic Metabolic Acidosis
blood pH, base excess (BE), plasma level of Cl will be used to assess this outcome measure.
Time frame: 24 hours
Secondary
Rate of Neurological Complications
Delirium, clinically diagnosed stroke, and encephalopathy.
Time frame: 24 hours
Secondary
Stroke Volume Index
Time frame: 24 hours