Prevention of Renal Failure by Nitric Oxide in Prolonged Cardiopulmonary Bypass.

Air Force Military Medical University of People's Liberation Army

Status and phase: Completed; Phase 2; Phase 1

Conditions: Heart Valve Diseases; Cardiac Valve Replacement Complication; Heart; Complications, Valve, Prosthesis

Treatments: Other: inhaled Nitrogen; Other: inhaled nitric oxide

Study type: Interventional

Funder types: Other

Identifiers

NCT01802619

20121025-8

81000232 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full description

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:

1. Nitric oxide reduces ischemia-reperfusion injury (such as in acute myocardial infarction, stroke, and acute tubular necrosis).
2. 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.
3. 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.

Enrollment: 217 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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217 participants in 2 patient groups, including a placebo group

inhaled nitrogen

Placebo Comparator group

Description:

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.

Treatment:

Other: inhaled Nitrogen

inhaled nitric oxide

Experimental group

Description:

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.

Treatment:

Other: inhaled nitric oxide