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Nitric Oxide in Cardiopulmonary Bypass for Renal Protection in Cardiac Surgery

Phase 1
Completed
Conditions
Coronary Artery Disease
Heart Valve Diseases
Cardiomyopathies
Acute Kidney Injury
Interventions
Other: Standard CPB
Registration Number
NCT03527381
Lead Sponsor
Nikolay Kamenshchikov
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
96
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Standard CPBStandard CPBPatients of this group receive sham-treatment without supplying nitric oxide to the cardiopulmonary bypass circuit (Standard CPB) during cardiac surgery. Considering dilution of nitric oxide at a high ratio of 1 to 25,000 in the gas mixture of the cardiopulmonary bypass circuit (CPB), no addition of any inert gas to the CPB circuit is required in sham-treatment group.
Nitric OxideNitric OxidePatients of this group receive treatment with exogenous gaseous nitric oxide supplied directly to the oxygenator in the cardiopulmonary bypass circuit during cardiac surgery.
Primary Outcome Measures
NameTimeMethod
Acute kidney injury rate measure48 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 Outcome Measures
NameTimeMethod
Free hemoglobin (Hb) concentration measure24 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.

Nitric oxide metabolite concentration measure24 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.

Urine output measureDuring cardiopulmonary bypass

Urine output values (mL/kg/h) are assessed during cardiopulmonary bypass (CPB).

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.

Proinflammatory mediator concentration measure24 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 measure24 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.

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