The Effect of Nebulized Albuterol on Donor Oxygenation

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.

Inclusion Criteria:

- Brain death

- Consent for lung donation and donor research

- Release from coroner or medical examiner

Exclusion Criteria

- Age less than 14 years