Acute Kidney Injury, Cardiomyopathies, Coronary Artery Disease, Heart Valve Diseases
Conditions
Keywords
Cardiopulmonary Bypass, Nitric Oxide, Kidney Function Tests, Renal Insufficiency, Protective Agents, Coronary Artery Bypass, Cardiac Surgery
Brief summary
This prospective randomized study evaluates the nephroprotective effects of exogenous nitric oxide delivered to the extracorporeal circulation circuit during cardiac surgery with cardiopulmonary bypass.
Detailed description
The aim of this work is to study nephroprotective effects of nitric oxide (NO) supplementation to the cardiopulmonary bypass (CPB) circuit during cardiac surgery with normothermic CPB in adult patients. The prospective randomized study is performed in the settings of Federal Cardiology Center. A total of 96 adult patients who underwent cardiac surgery with CPB are enrolled in the study. Patients are randomized to two groups: main group receive NO treatment; control group undergoes sham procedure. In the main group, NO is supplied to the CPB line in a dose of 40 ppm throughout the entire CPB period. The primary endpoint is the frequency of acute kidney injury (AKI). The secondary endpoints are urine output during CPB; uNGAL level 4 h after surgery; plasma concentration of free hemoglobin (Hb); concentrations of NO metabolites (nitrite (NO2-) and nitrate (NO3-)) and the total concentration of metabolites of NO (NOx, μM/mL) in blood plasma in the intraoperative period; concentration of proinflammatory (TNF-α, IL-1β, -6, and -8) and anti-inflammatory mediators (IL-1ra, IL-4) in blood plasma in the intraoperative period. Cumulative fluid balance, diuresis, and Lasix doses are assessed within the first 48 h of the postoperative period. The dynamics of serum creatinine is assessed during the first week following the intervention.
Interventions
DRUGNitric Oxide
40 ppm of exogenous gaseous nitric oxide is supplied directly to the oxygenator in the cardiopulmonary bypass circuit during cardiac surgery.
OTHERStandard CPB
Standard CPB protocol of delivery of air gas mixture to the cardiopulmonary bypass circuit during cardiac surgery.
Sponsors
Nikolay Kamenshchikov
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Masking description
Trial participants, data analysts, and report writers are blinded.
Intervention model description
Single-center prospective, randomized, placebo-controlled study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Age above 18 years; planned primary cardiac intervention with cardiopulmonary bypass including coronary artery bypass grafting, valve surgery, and surgical reconstructions of the left ventricle.
Exclusion criteria
Preoperative anemia; the intake of nephrotoxic drugs or the use of X-ray contrast within 72 h before surgery; active phase of endocarditis; emergency surgery; chronic kidney disease; hematologic diseases accompanied by hemolysis; complications of the surgery and the early postoperative period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acute kidney injury rate measure | 48 hours after surgery | The presence of acute kidney injury (AKI) is assessed during 48 hours after surgery. AKI is defined as follows: an increase in serum creatinine ≥ 0.3 mg/dL (≥ 26.5 μM/L) during 48 hours after surgery; an increase in serum creatinine by ≥ 1.5 times compared with the initial preoperative level for seven days after intervention; and urine output \< 0.5 mL/kg/h for 6 hours during the first 48 h after surgery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urine neutrophil gelatinase-associated lipocalin concentration measure (uNGAL) | 4 hours after surgery | The level of uNGAL (ng/mL) is assessed 4 hours after the surgery. |
| Free hemoglobin (Hb) concentration measure | 24 hours after surgery | Plasma concentrations of Hg (g/L) are assessed during intraoperative period: before sternotomy, 5 minutes after aortic clamping, 5 minutes after aortic declamping, at the end of surgery, and 24 hours after surgery. |
| Urine output measure | During cardiopulmonary bypass | Urine output values (mL/kg/h) are assessed during cardiopulmonary bypass (CPB). |
| Proinflammatory mediator concentration measure | 24 hours after surgery | Concentrations of proinflammatory (TNF-α, IL-1β, -6, and -8) (pg/mL) in blood plasma are assessed in the intraoperative period: before sternotomy, at the end of surgery, 6 hours after surgery, and 24 hours after surgery. |
| Anti-inflammatory mediator concentration measure | 24 hours after surgery | Concentrations of anti-inflammatory mediators (IL-1ra, IL-4) (pg/mL) in blood plasma are assessed in the intraoperative period: before sternotomy, at the end of surgery, 6 hours after surgery, and 24 hours after surgery. |
| Nitric oxide metabolite concentration measure | 24 hours after surgery | Concentrations of NO metabolites (nitrite (NO2-) and nitrate (NO3-)) (μM/mL) and the total concentration of metabolites of NO (NOx) (μM/mL) in blood plasma are assessed in the intraoperative period: before sternotomy, 5 minutes after aortic clamping, 5 minutes after aortic declamping, at the end of surgery, and 24 hours after surgery. |
Outcome results
None listed