The Effect of Nebulized Albuterol on Donor Oxygenation

Phase 2

Completed

Conditions: Brain Death
Organ Donor
Pulmonary Edema

Interventions: Drug: Albuterol
Drug: Saline

Registration Number: NCT00310401

Lead Sponsor: Vanderbilt University Medical Center

Brief Summary: The purpose of this study is to test the effectiveness of albuterol versus placebo with the following specific aims: a) Treatment of brain dead organ donors with albuterol will reduce pulmonary edema, improve donor oxygenation, and increase the number of lungs available for transplantation, b) Developing a blood test to predict the development of primary graft dysfunction in lung transplant recipients, and c) treating brain dead organ donors with albuterol will decrease markers of primary graft dysfunction and lead to improved lung transplant recipient outcomes and to higher rates of lungs suitable for transplantation.

Detailed Description: The donor lung utilization rate in the United States remains less than 15%, and the demand for donor lungs far exceeds the available supply. The most common reasons for failure to utilize donor lungs are donor hypoxemia and/or pulmonary infiltrates. Since pulmonary edema is a common, reversible cause of hypoxemia and infiltrates in patients with brain injury, strategies to treat pulmonary edema in organ donors should lead to improved donor oxygenation and higher rates of donor lung utilization. Inhaled beta-2 agonists increase the rate of alveolar fluid clearance and reduce pulmonary edema in both animal and human lungs. In addition, our group has recently reported that the majority of human donor lungs that are rejected for transplantation have measurable pulmonary edema and respond to beta-2 agonists with increased rates of alveolar fluid clearance. Based on this compelling scientific evidence, we propose to test the efficacy of an inhaled beta-2 agonist to increase the rate of alveolar fluid clearance and reduce pulmonary edema in brain dead organ donors with the following specific aims:

Specific Aim 1: To test the effect of aerosolized albuterol on donor oxygenation in a multicenter, randomized, double-blinded, placebo-controlled trial in 500 brain dead organ donors managed over a 2 year period by the California Transplant Donor Network (CTDN).

Hypothesis 1a: Treatment of brain dead organ donors with aerosolized albuterol will improve donor oxygenation and increase the donor lung utilization rate compared to treatment with placebo.

Hypothesis 1b: Treatment of brain dead organ donors with aerosolized albuterol will reduce the severity of pulmonary edema in procured lungs compared to treatment with placebo.

Specific Aim 2: To develop and validate a panel of biological markers that can predict and diagnose acute lung injury due to primary graft dysfunction in lung transplant recipients.

Hypothesis 2a: A panel of plasma biological markers measured in brain dead organ donors that includes markers of inflammation, coagulation, endothelial injury and lung epithelial injury will predict the development of primary graft dysfunction in the lung recipient.

Hypothesis 2b: Treatment of brain dead organ donors with inhaled beta-2 agonists will lead to reductions in levels of a panel of biological markers of inflammation, coagulation, endothelial injury, and lung epithelial injury that will be associated with increased donor lung utilization and improved recipient outcomes.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 506

Inclusion Criteria

Brain death
Consent for lung donation and donor research
Release from coroner or medical examiner

Exclusion Criteria

Age less than 14 years

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Saline	Saline	Saline administered every 4 hours by nebulization
Albuterol	Albuterol	Albuterol sulfate 5 mg dissolved in normal saline administered every 4 hours by nebulization
Saline	Albuterol	Saline administered every 4 hours by nebulization

Primary Outcome Measures

Name	Time	Method
Donor Oxygenation	Change from enrollment to organ procurement (about ~40h after enrollment)	The primary outcome was the change in oxygenation as measured by change in the PaO2/FiO2 ratio from study enrollment to organ procurement

Secondary Outcome Measures

Name	Time	Method
Lung Compliance	baseline and at organ procurement (about ~40h after enrollment)	Static compliance of the respiratory system using plateau pressure (Pplat) measured at end-inspiration and calculated using the equation static compliance = tidal volume/(Pplat - PEEP)
Pulmonary Vascular Resistance	72 hours
Number of Donor Lungs Used for Transplantation	72 hours	Number of lungs procured and used for transplantation
Chest X-ray Findings	change from enrollment to organ procurement (about ~40h after enrollment)	Chest radiographs were scored using a radiographic score that scored each quadrant for extent of radiographic infiltrates on a scale of 0 to 4, then summed each quadrant for a total score from 0 (no infiltrates) to 16 (extensive infiltrates in all 4 radiographic quadrants).