Cardiac Valve Replacement Complication, Heart; Complications, Valve, Prosthesis, Heart Valve Diseases
Conditions
Brief summary
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.
Detailed 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.
Interventions
OTHERinhaled 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.
OTHERinhaled 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.
Sponsors
Xijing Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| acute kidney injury | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major adverse kidney events (MAKE) | at 30 days, 90 days, and 1 year following ICU admission | a composite outcome of loss of 25% of eGFR from baseline, end stage renal disease requiring a continuous renal replacement therapy and mortality. |
| Incidence of nonfatal stroke and nonfatal myocardial infarction. | at 30 days, 90 days, and 1 year following ICU admission | 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 | at 30 days, 90 days, and 1 year following ICU admission | The quality of life will be evaluated by the Katz Index of In dependence in Activities of Daily living |
| overall mortality | at 30 days, 90 days, and 1 year following ICU admission | all cause mortality |
| Chronic kidney disease | at 30 days, 90 days, and 1 year following ICU admission | defined as eGFR\<60 mL/min/1.73m2 |
| Loss of 25% of eGFR compared to baseline | at 30 days, 90 days, and 1 year following ICU admission | Loss of 25% of eGFR compared to baseline |
| Renal Replacement Therapy | at 30 days, 90 days, and 1 year following ICU admission | the incidence of need for Renal Replacement Therapy |
Other
| Measure | Time frame | Description |
|---|---|---|
| Incidence of prolonged ventilation | During hospital stay, normally within 30 days | Prolonged ventilation is defined as patients remaining on the ventilator for more than 48 hours |
| In-hospital stay | Normally within 30 days, when patients was discharged from ICU | It is the length of hospital stay |
| ICU-stay | Normally within 30 days, when patients was discharged from ICU | It is the length of stay in ICU |
Countries
China
Outcome results
None listed