Prevention of Renal Failure by Nitric Oxide in Prolonged Cardiopulmonary Bypass.
|Heart Valve Diseases Heart; Complications, Valve, Prosthesis Cardiac Valve Replacement Complication||Other: inhaled nitric oxide Other: inhaled Nitrogen||Phase 1 Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator
Primary Purpose: Prevention
|Official Title:||Prevention of Renal Failure by Nitric Oxide in Prolonged Cardiopulmonary Bypass: A Double Blind Randomized Controlled Trial.|
- acute renal failure [ Time Frame: within 28 days after the procedure ]Renal failure will be defined according to the RIFLE/ AKIN criteria .
- acute renal failure [ Time Frame: at 60 days, 90 days and 1 year ]
- Incidence of nonfatal stroke and nonfatal myocardial infarction. [ Time Frame: at 28 days, 60 days, 90 days and 1 year ]
Nonfatal stroke will be assessed by the NIH Stroke Scale at baseline before surgery and at 28 days, 60 days, 90 days and 1 year after surgery.
Nonfatal myocardial infarction is defined by the third universal definition of MI released in 2012 by the ESC/ACCF/AHA/WHF.
- Quality of life [ Time Frame: at 28 days, 60 days, 90 days and 1 year ]The quality of life will be evaluated by the Katz Index of In dependence in Activities of Daily living
- overall mortality [ Time Frame: at 28 days, 60 days, 90 days and 1 year ]
- In-hospital stay [ Time Frame: at 28 days ]It is the length of hospital stay
- ICU-stay [ Time Frame: at 28 days ]It is the length of stay in ICU
- Incidence of prolonged ventilation [ Time Frame: at 28 days ]Prolonged ventilation is defined as patients remaining on the ventilator for more than 48 hours
|Actual Study Start Date:||August 2013|
|Study Completion Date:||June 2016|
|Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
Placebo Comparator: inhaled nitrogen
Using an Inovent (Ikaria Inc, N.J., USA) or volumetrically-calibrated flowmeters, pure nitrogen (placebo) is mixed with pure O2 or air. During CPB the gas mixture is delivered through the extracorporeal oxygenator, after CPB the NO is delivered through the inspiratory limb of the anesthetic or ventilator circuit.
Other: inhaled Nitrogen
Standard gas including nitrogen (the vehicle of the Nitric oxide) administration will commence at the onset of CPB and last for 24 hours. At the end of 24 hours, inhaled gases will be weaned and discontinued while carefully monitoring hemodynamics for a period of 2-4 hours.
Experimental: inhaled nitric oxide
Using an Inovent (Ikaria Inc, N.J., USA) or volumetrically-calibrated flowmeters, 800 ppm NO gas is mixed with pure O2 or air to obtain a final concentration of 80 ppm NO. During CPB the gas mixture is delivered through the extracorporeal oxygenator, after CPB the gas is delivered through the inspiratory limb of the anesthetic or ventilator circuit. NO, NO2 and O2 and methemoglobin levels are monitored by an unblinded observer.
Other: inhaled nitric oxide
Nitric oxide administration will commence at the onset of CPB and last for 24 hours. At the end of 24 hours, inhaled NO will be weaned and discontinued while carefully monitoring hemodynamics for a period of 2-4 hours.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01802619
|Xi'an, Shaanxi, China, 710032|
|Study Chair:||lize Xiong, M.D.,Ph.D.||Xijing Hospital|