Acute Kidney Injury, Acute Type A Aortic Dissection, Nitrous Oxide
Conditions
Keywords
Acute Kidney Injury, Nitrous Oxide, Aortic Dissection, cardiopulmonary bypass
Brief summary
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.
Detailed description
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.
Interventions
DRUGNitric Oxide
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.
OTHERPlacebo
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.
Sponsors
Beijing Anzhen Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
Single-center prospective, randomized, placebo-controlled study
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Provide written informed consent; 2. Participants must be over 18 years of age; 3. Participants should meet the diagnostic and treatment guidelines for thoracic aortic diseases jointly issued by ACC/AHA in 2022, have received clinical and radiological diagnosis of acute type A aortic dissection, and undergone surgical thoracotomy within two weeks after symptom onset.
Exclusion criteria
1. Missing baseline value or missing postoperative serum creatinine value (Scr); 2. Preoperative eGFR less than 30ml/min/1.73m2 or receive renal replacement therapy; 3. History of kidney disease, including glomerular diseases: acute glomerulonephritis, rapidly progressive glomerulonephritis, chronic glomerulonephritis, nephrotic syndrome, etc., secondary nephropathy: lupus nephritis, diabetic nephropathy, interstitial nephritis, renal tubular disease, chronic renal failure, renal replacement therapy, etc.; 4. Previous renal tumor, kidney transplantation, and other related surgery; 5. Patients with single kidney; 6. History of malignant tumor or received radiotherapy and chemotherapy; 7. Severe skeletal muscle disease and autoimmune disease; 8. Preoperative dissection rupture or hemodynamic instability (systolic blood pressure \<90mmHg); 9. Life expectancy less than 90 days; 10. Pregnant and lactating women, patients with mental disorders; 11. With intravascular or extravascular hemolytic disease; 12. Have participated in other clinical trials.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acute kidney injury (AKI) | 48 hours | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AKI grade | 48 hours after surgery | 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. |
| Urine output | During CPB surgery, 12 and 24 hours after surgery | Urine output values (mL/kg/h) are assessed during CPB and 24 hours after surgery. |
| Vasoactive-inotropic score | immediate admission to ICU, 12 and 24 hours after surgery | 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). |
| Neutrophil gelatinase-associated lipocalin concentration | before surgery, immediate ICU admission, 12 and 24 hours after surgery | Neutrophil gelatinase-associated lipocalin concentrations will be measured in the two groups. |
| Multiple organ failure | 24 hours after surgery | 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. |
| Duration of mechanical ventilation (hours) | 90 days after surgery | Difference of duration of mechanical ventilation defined as number of hours. |
| Duration of non-invasive ventilation and High flow oxygen therapy | 90 days after surgery | Difference of duration of non-invasive ventilation and high flow oxygen therapy defined as number of hours. |
| ICU stay | 90 days after surgery | Difference between groups of intensive care unit length of stay defined as number of days. |
| Hospital stay | 90 days after surgery | Difference between groups of hospital length of stay defined as number of days. |
| Major Adverse Kidney Events | 90 days after surgery | 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). |
| Postoperative pleural and pericardial drainage | 24 hours after surgery | Difference values between groups of postoperative pleural and pericardial drainage. |
Countries
China
Outcome results
None listed