Prevention of Renal Failure by Nitric Oxide in Prolonged Cardiopulmonary Bypass: A Double Blind Randomized Controlled Trial.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 217
- 试验地点
- 1
- 主要终点
- acute kidney injury
研究概览
简要总结
Prolonged periods of cardiopulmonary bypass (CPB) cause high levels of plasma free haemoglobin(Hb) and are associated with increased morbidity. We hypothesized that repletion of nitric oxide (NO) during and after the surgical procedure on CPB may protect against endothelium dysfunction and organ failure caused by plasma-Hb induced NO scavenging.
详细描述
Prolonged periods of cardiopulmonary bypass (CPB) cause high levels of plasma free haemoglobin(Hb) and are associated with increased morbidity. We hypothesized that repletion of nitric oxide (NO) during and after the surgical procedure on CPB may protect against endothelium dysfunction and organ failure caused by plasma-Hb induced NO scavenging. There are three possible beneficial mechanisms of delivering NO:
- Nitric oxide reduces ischemia-reperfusion injury (such as in acute myocardial infarction, stroke, and acute tubular necrosis).
- Nitric oxide has anti-inflammatory properties. As antioxidants, exogenous NO may reduce injury by counteracting the cytotoxic effects of reactive oxygen species, modulating leukocyte recruitment, edema formation and tissue disruption.
- Exogenous nitric oxide prevents noxious effects of hemolysis-associated NO dysregulation. During hemolysis, nitric oxide gas oxidized of plasma oxyhemoglobin to methemoglobin, thereby inhibiting endogenous endothelium NO scavenging by cell-free Hb.
NO depletion during hemolysis and its sequelae. The release of plasma free Hb (with Fe2+ iron) by hemolysis avidly scavenges nitric oxide (NO) by the dioxygenation reaction. Elevated plasma ferrous Hb levels can induce a "NO deficiency" state. Reduced vascular nitric oxide levels can contribute to vasoconstriction, inflammation, and thrombosis, potentially contributing to systemic endothelial dysfunction after cardiac surgery with CPB.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provide written informed consent
- •Are > 18 years of age
- •Elective cardiac or aortic surgery with CPB, when the surgeon plans double valve replacement.
- •Stable pre-operative renal function, without dialysis.
排除标准
- •Emergent cardiac surgery
- •Life expectancy < 1 year
- •Hemodynamic instability as defined by a systolic blood pressure <90 mmHg
- •Administration of ≥1 Packed Red Blood Cell transfusion in the week before surgery
- •X-ray contrast infusion less than 1 week before surgery
- •Anticipate administration of nephrotoxic agents, such as hydroxyethyl starch
- •Evidence of intravascular or extravascular hemolysis
结局指标
主要结局
acute kidney injury
时间窗: an increase of serum creatinine by 50% within 7 days after surgery, or an increase of serum creatinine by 0.3 mg/dl within 2 days after surgery
acute kidney injury was defined by the KDIGO criteria
次要结局
- Chronic kidney disease(at 30 days, 90 days, and 1 year following ICU admission)
- Incidence of nonfatal stroke and nonfatal myocardial infarction.(at 30 days, 90 days, and 1 year following ICU admission)
- Major adverse kidney events (MAKE)(at 30 days, 90 days, and 1 year following ICU admission)
- Renal Replacement Therapy(at 30 days, 90 days, and 1 year following ICU admission)
- Loss of 25% of eGFR compared to baseline(at 30 days, 90 days, and 1 year following ICU admission)
- Quality of life(at 30 days, 90 days, and 1 year following ICU admission)
- overall mortality(at 30 days, 90 days, and 1 year following ICU admission)
研究者
chonglei
M.D.& Ph.D.
Xijing Hospital