The goal of this clinical trial is to determine the effectiveness of exogenous nitric oxide therapy in reducing the occurrence of acute kidney injury in patients with acute type A aortic dissection. Additionally, it aims to assess the safety of exogenous nitric oxide therapy.
The incidence of acute kidney injury following acute type A aortic dissection is significantly high, thereby exerting a substantial impact on patient prognosis. Nitric oxide, an endogenous gaseous molecule with potential therapeutic effects, has been investigated in clinical studies as a treatment for acute kidney injury following cardiac surgery. However, there is currently no clinical study exploring the application of nitric oxide in patients with acute type A aortic dissection. Therefore, this study aims to investigate whether exogenous nitric oxide therapy has renal protective effects and its mechanism. This prospective randomized study is conducted at Beijing Anzhen Hospital in Beijing, China. A total of 106 adult patients with acute type A aortic dissection are enrolled in this study. The patients are randomly divided into two groups: the experimental group received NO combined with conventional treatment, and the control group is only given conventional treatment. In the experimental group, 60 ppm NO is administered during intraoperative CPB and continued until within 12 hours after surgery. The primary endpoint is the incidence of acute kidney injury (AKI) within 48 hours after surgery. The secondary endpoints include AKI grade (KDIGO); urine volume during CPB, within 12 and 24 hours after surgery; blood flow grade, resistance index, and pulsatility index in renal ultrasound at ICU admission, 12 and 24 hours after surgery; SOFA score at 24 hours after surgery; VIS score at ICU admission, 12 and 24 hours after surgery; duration of mechanical ventilation, non-invasive ventilation, and high-flow oxygen therapy; length of ICU stay and hospital stay; renal adverse events within 90 days; volume of drainage from the pleural and pericardial cavities after surgery. Additionally, dosage of diuretics and recombinant human brain natriuretic peptide during surgery and within 48 hours after surgery; oxygenation index and near-renal infrared oxygen saturation; levels of free hemoglobin, methemoglobin, nitrite (NO2-) and the total of NO metabolites (NOt); neutrophil gelatinase-associated lipocalin concentration; levels of the neutrophils lymphocytes ratio (NLR), the platelet lymphocyte ratio (PLR), systemic inflammatory response index (SIRI), and systemic immune response index (SII) ; CVP and PEEP, the volume of transfusions with plasma and stored or autologous RBCs will also be measured in both groups.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
106
Exogenous nitric oxide is directly administered to the oxygenator in the cardiopulmonary bypass circuit at a concentration of 60 ppm. Nitric oxide is also directly administered to the ventilator at a concentration of 60 ppm for 12 hours post-operation.
This is the placebo group. The standard CPB protocol involves delivering an air-gas mixture to the cardiopulmonary bypass circuit during cardiac surgery and avoiding the use of nitric oxide within 12 hours after surgery.
Beijing Anzhen Hospital
Beijing, Beijing Municipality, China
Acute kidney injury (AKI)
Incidence of Acute Kidney injury. 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; or an increase in serum creatinine by ≥ 1.5 times compared with the initial preoperative level for seven days after intervention; or urine output \< 0.5 mL/kg/h for 6 hours during the first 48 h after surgery.
Time frame: 48 hours
AKI grade
Grade I: an increase in serum creatinine ≥ 0.3 mg/dL (≥ 26.5 μM/L) during 48 hours after surgery; or an increase in serum creatinine by ≥ 1.5 times compared with the initial preoperative level for seven days after the intervention; or urine output \< 0.5 mL/kg/h for 6 hours during the first 48 h after surgery. Grade II: an increase in serum creatinine by 2-2.9 times compared with the initial preoperative level for seven days after the intervention. Grade III: an increase in serum creatinine by ≥ 3 times compared with the initial preoperative level for seven days after the intervention; or an increase in serum creatinine ≥ 4.0 mg/dL (≥ 353.6 μM/L) during 48 hours after surgery; or start RRT.
Time frame: 48 hours after surgery
Urine output
Urine output values (mL/kg/h) are assessed during CPB and 24 hours after surgery.
Time frame: During CPB surgery, 12 and 24 hours after surgery
Vasoactive-inotropic score
Difference between groups of vasoactive-inotropic score. VIS is calculated as Dopamine dose (mg/kg/min) + Dobutamine dose (mg/kg/min) + 100 x Epinephrine dose (mg/kg/min) + 100 x Norepinephrine dose (mg/kg/min) + 10 x Milrinone dose (mg/kg/min) + 10,000 x Vasopressin dose (units/kg/min).
Time frame: immediate admission to ICU, 12 and 24 hours after surgery
Neutrophil gelatinase-associated lipocalin concentration
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Neutrophil gelatinase-associated lipocalin concentrations will be measured in the two groups.
Time frame: before surgery, immediate ICU admission, 12 and 24 hours after surgery
Multiple organ failure
Assessment of multiple organ failure through the Sequential organ failure score. The scoring system is mainly divided into 6 parts, namely respiratory function, coagulation function, liver, cardiovascular system, central nervous system, and renal function. The scores range from 0 to 4, with a score of 0 indicating normal function in all organs. The higher the score, the worse the prognosis.
Time frame: 24 hours after surgery
Duration of mechanical ventilation (hours)
Difference of duration of mechanical ventilation defined as number of hours.
Time frame: 90 days after surgery
Duration of non-invasive ventilation and High flow oxygen therapy
Difference of duration of non-invasive ventilation and high flow oxygen therapy defined as number of hours.
Time frame: 90 days after surgery
ICU stay
Difference between groups of intensive care unit length of stay defined as number of days.
Time frame: 90 days after surgery
Hospital stay
Difference between groups of hospital length of stay defined as number of days.
Time frame: 90 days after surgery
Major Adverse Kidney Events
Difference between groups of major adverse kidney events at 90 days after surgery. MAKE is a composite outcome of death, new dialysis and worsened renal function (defined as a 25% or greater decline in eGFR compared to the baseline).
Time frame: 90 days after surgery
Postoperative pleural and pericardial drainage
Difference values between groups of postoperative pleural and pericardial drainage.
Time frame: 24 hours after surgery