Inhaled nitrogen will be administered via the cardiopulmonary bypass (CPB) machine and after CPB via the inspiratory limb of the anesthetic or ventilator circuit, and thereafter via the mechanical ventilator in the Intensive Care Unit (ICU). Once patients are extubated they will breathe test gas via a facemask or nasal cannula. Test gas administration will commence at the onset of CPB and last for 24 hours.

Inhaled nitric oxide (iNO) will be administered via the CPB machine and after CPB via the inspiratory limb of the anesthetic or ventilator circuit, and thereafter via the mechanical ventilator in the ICU. Once patients are extubated they will breathe test gas via a facemask or nasal cannula. Test gas administration will commence at the onset of CPB and last for 24 hours. At the end of 24 hours, iNO will be weaned and discontinued while carefully monitoring hemodynamics for a period of 2-4 hours.

Acute Kidney Injury

Inhaled nitric oxide will be administered in a final concentration of 80 ppm. The treatment will begin at the onset of the cardiopulmonary bypass until to 24h after Intensive Care Unit (ICU) admission, including 2-4 hours of weaning from nitric oxide and careful hemodynamics monitoring.

Nitric Oxide

This is the placebo group. Nitrogen will be added instead of nitric oxide.

Placebo

This is the clinical trial that we previously performed in collaboration with Xijing Hospital.

The first preliminary data analysis of the NCT01802619 has been presented at the section "Late Breaking Trial" of the American Heart Association in Orlando,Florida,November 2015.

Massachusetts General Hospital

Effect of Nitric Oxide in Cardiac Surgery Patients With Endothelial Dysfunction.

Prevention of Acute Kidney Injury by Nitric Oxide in Prolonged Cardiopulmonary Bypass. A Double Blind Controlled Randomized Trial in Cardiac Surgical Patients With Endothelial Dysfunction.

Incidence of Acute Kidney injury according to KDIGO criteria.

Difference in AKI severity between the two groups using following KDIGO stages.

To study the incidence of acute renal failure requiring RRT

Difference between groups of MAKE at 6 weeks 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).

Assessment of organ dysfunction through the evaluation of SOFA score

Difference between groups of prolonged cardiovascular support defined as need for vasopressors, inotropic agents, balloon pump, or ventricular-assist device for more than 48 hours after cardiac surgery.

Difference between groups of maximum daily VIS and duration of vasopressors and or inotropic agents support. VIS is calculated as Dopamine dose (mcg/kg/min) + Dobutamine dose (mcg/kg/min) + 100 x Epinephrine dose (mcg/kg/min) + 10 x Milrinone dose (mcg/kg/min) + 10,000 x Vasopressin dose (units/kg/min) + 100 x Norepinephrine dose (mcg/kg/min) + 10 x Phenilephrine dose (mcg/kg/min).

Difference of duration of mechanical ventilation

Difference between groups of ICU-LOS defined as number of days spent in an ICU bed.

Difference between groups of hospital LOS defined as number of days spent in a hospital bed.

Renal biomarkers to evaluate renal tubular injury.

Incidence and severity of AKI related to presence of CKD at baseline, duration of CPB, duration of aortic cross clamp, levels of free Hb, levels of NO consumption, pulmonary pressure at baseline, cardiovascular risks associated with endothelial dysfunction, scheduled procedure and EuroSCORE II.

Difference between groups of Incidence of Delirium will be assessed daily in the first 7 days after surgery by using the confusion assessment method for intensive care unit (CAM-ICU).

Analysis of the quality of life up to 1 year after surgery by the Activity of Daily Living evaluation (by Katz Index) and PROMIS global health.

Evaluation of the overall intrahospital mortality and at 28 6 weeks 90 days and 1 year after surgery

Blood methemoglobin levels will be measured to evaluate the oxidation of oxyhemoglobin in the two groups until 48h after surgery.

Difference between groups of incidence of non fatal stroke will be assessed by at 6 weeks after cardiac surgery.

Incidence of Perioperative and non-perioperative nonfatal myocardial infarction as defined by the third universal definition of MI released in 2012 by the ESC/ACCF/AHA/WHF.

Incidence of postoperative bleeding calculated as the sum of blood loss through thoracic drains from the moment of closure of the chest over a period of 24 hours.

Differences between the two groups of transfusions with plasma and stored or autologous red blood cells (RBCs) recovered using intraoperative cell salvage devices.

Post-operative infections (e.g., pneumonia, wound infection, endocarditis, central line infection, urinary tract infection, sepsis).

Cardiac arrhythmias and other non-cardiac post-operative complications (e.g., hepatobiliary disorders, pneumothorax, pleural effusion, vascular disorders).

Lorenzo Berra, MD

Lorenzo Berra, MD, Assistant Professor, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School

Ichinose, Fumito, M.D., Ph.D., Massachusetts General Hospital

Kenneth, Shelton, M.D., Massachusetts General Hospital

Kacmarek, Robert M., Ph.D., Massachusetts General Hospital

Sundt, Thoralf M., M.D., Massachusetts General Hospital

Villavicencio-Theoduloz, Mauricio A., M.D., Massachusetts General Hospital

Thompson, Boyd Taylor, M.D., Massachusetts General Hospital

Bonventre, Joseph V., M.D., Brigham Women Hospital

Shann, Kenneth G., Massachusetts General Hospital

Zapol, Warren M., M.D.

Marrazzo, Francesco, M.D., Massachusetts General Hospital

Spina, Stefano, M.D., Massachusetts General Hospital

Zadek, Francesco, M.D., Massachusetts General Hospital

Rezoagli, Emanuele, M.D., Massachusetts General Hospital

National Heart, Lung, and Blood Institute (NHLBI)

Kidney Transplantation

Anemia

darbopoeitin

Effects of Anemia Correction on Vascular and Monocyte Function in Renal Transplant Recipients

Effects of Anemia Correction on Vascular Function, Endothelial Cell Markers and Monocyte Apoptosis in Renal Transplant Recipients

University Hospital Muenster

Amgen

30,000 units of erythropoietin beta in one vial; 3 vials as one set per patient

Aneurysmal Subarachnoid Hemorrhage

30,000 units in 6 mL of 0.9% saline IV for 15 minutes every other day for 3 doses within 72 hours after aneurysmal subarachnoid hemorrhage

erythropoietin beta

Department of Neurosurgery, Addenbrooke's Hospital

Erythropoietin Therapy for Subarachnoid Hemorrhage

Effects of Systemic Erythropoietin Therapy on Cerebral Autoregulation and Incidence of Delayed Ischemic Deficits in Patients With Aneurysmal Subarachnoid Hemorrhage

vasculitis/hipoksiya

Effect of Nitric Oxide in Cardiac Surgery Patients With Endothelial Dysfunction.

Effects of Anemia Correction on Vascular and Monocyte Function in Renal Transplant Recipients

Erythropoietin Therapy for Subarachnoid Hemorrhage

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