Use of Inhaled Nitric Oxide to Prevent Pulmonary Hypertension Associated to Stored Blood Transfusion

Study Overview
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Brief Summary
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The objective of this study is to assess if prolonged storage time of a packed red blood cell unit may cause pulmonary vasoconstriction after transfusion, in a susceptible population such as cardiac surgery patients. The investigators will also evaluate the potential reversal effect of Inhaled Nitric Oxide on pulmonary vasoconstriction induced by stored blood transfusions.

Detailed Description
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Patients will be randomized into one of the three groups: I. Blood transfusion stored for less than 10 days II. Blood transfusion stored for more than 30 days III. Blood transfusion stored for more than 30 days days plus inhalation of Nitric Oxide at 80 part per million for an hour during blood transfusion.

Official Title
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Pulmonary Hemodynamic Effects of Stored Red Blood Cell Transfusion in Post-Operative Cardiac Surgical Patients: Influence of Breathing Nitric Oxide. A Randomized Controlled Trial in the Cardiac-Intensive Care Unit.

Conditions
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Hypertension, Pulmonary, Hemolysis

Intervention / Treatment
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* Drug: Nitric Oxide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide written informed consent Elective cardiac or aortic surgery One or more blood transfusions scheduled for clinical reasons Presence of an arterial catheter and pulmonary arterial catheter Exclusion Criteria: Emergent cardiac surgery. Patients requiring irradiated or washed blood transfusions.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Young blood transfusion<br>The first group of patients (n=30) will be randomized to receive leukoreduced blood transfusion stored for less than 10 days | |
| No Intervention: Old blood transfusion<br>This randomized group of patients (n=30) will receive leukoreduced blood transfusion stored for more than 30 days | |
| Active Comparator: Old blood transfusion and Nitric Oxide<br>This randomized group of patients (n=30) will receive leukoreduced blood transfusion stored for more than 30 days while breathing nitric oxide (80 part per million) and oxygen | Drug: Nitric Oxide<br>* Nitric oxide at 80 part per million will be administrated by inhalation for approximately 1 hour during the blood transfusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary vascular resistance index | Parameters to calculate pulmonary vascular resistance index will be measured during and after blood transfusion for about 6 hours. The following parameters will be recorded: height, weight, systemic pressure, pulmonary pressure, wedge pressure, central venous pressure, cardiac output) of each subjects will be recorded. | During and after blood transfusion- average time of observation 6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemolysis | Hemolytic markers will be measured such as: haptoglobin, plasma free hemoglobin, hemopexin, and iron metabolites. | During and after blood transfusion- average time of observation 6 hours | 
| Nitric oxide metabolites | Plasma nitric oxide consumption, plasma and red blood cell levels of circulating nitrate, nitrite, nitric will be measured | During and after blood transfusion- average time of observation 6 hours | 
| Inflammation | Inflammation will be assessed by changes of the plasma concentration of cytokines, such as IL-6, IL-8, IL-10, IL-12, TNF, IFN-γ | During and after blood transfusion- average time of observation 6 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Catheterization, Swan-Ganz, Cardiac Surgical Procedures, Blood Transfusion, Nitric Oxide