Safety and Efficacy Study of Nitric Oxide in Patients Going Through Lung Transplantation

• Pilot, single-center, prospective, randomized, parallel-group, controlled, open-label trial.
• Sixty lung donors will be analyzed, making a comparative study between donors receiving NO for 3 hours prior to removal of the organ versus a control group to which NO will not be administered.
• A Swan-Ganz catheter will be placed to determine PVR, PAP, MV, and PCP; and blood gases will be done after arterial cannulation to determine FiO2/PaO2 hourly. Also, standard blood chemistry, hematology, coagulation parameters, and arterial blood gas.
• Prior to NO administration and before procurement, a BAL (bronchoalveolar lavage) will be done to determine the presence of leukocytes, predominantly neutrophils, IL-1, IL-6, IL-8, IL-10, TNF, and proteins as well as obtaining secretions for culture.
• The dosage of NO will be 10ppm, with NO2 and methemoglobinemia being monitored exhaustively.
• In the operating room and prior to lung removal, a new BAL will be done and the anti-inflammatory agents described above will be determined.
• Organ removal and the preservation fluid used will be standard, according to the established surgical protocol.
• Anesthesia: methylprednisolone 1 g will be administered before organ extraction; hemodynamic determinations of mAP, PAP, CVP, MV, and hourly urinary output and arterial blood gas.
• Hemodynamic and respiratory determinations will be made in the lung receptors: mAP, mPAP, PVR, MV, PCP, DO2, Qs/Qt, and CVP as well as gas determinations every 30 minutes, blood chemistry, hematology, and coagulation immediately after reperfusion. A BAL will also be done after anesthesia induction.
• Incidents during surgery will be recorded, especially the need for extracorporeal circulation as well as transfusion requirements and ischemia times.
• After surgery, another BAL will be done both 24 hours and 48 hours after return to the Recovery Unit. Hemodynamic and respiratory parameters will be monitored every 4 hours for the first 48 hours after surgery, as well as arterial blood gases.
• Blood chemistry will be done every 12 hours along with coagulation and hematology tests.
• Chest x-ray on admission and daily to determine the degree of the patient's edema over the first 48 hours.
• Drug administration: the NO will be administered in the respirator intake at a dose of 10ppm for 48 hours. A monitor will be used showing the gas dosage continuously, as well as NO2 and methemoglobinemia.
• The inflammatory agents (TNF, IL-1, IL-2, IL-6, IL-8, and IL-10) will be determined with the ELISA technique.

Inclusion criteria

• Have a lung graft scheduled
• Males and females aged 18 to 65
• Signed informed consent approved by the IRB/EC

Exclusion criteria

• Uncontrolled bacterial infection
• Creatinine clearance <50 ml/min
• Severe extrapulmonary organic dysfunction
• Continuing smoking habit
• Neoplastic disease (2-5 years free of tumor, depending on type)
• Pregnancy or nursing
• Severe osteoporosis
• Active peptic ulcer
• Progressive neuromuscular disease
• Active limiting systemic disease. Complicated diabetes.
• Any contraindication based on the judgement of the investigator