Comparison of chest radiograph scoring to lung weight as a quantitative index of pulmonary edema in organ donors.

Quantification of the degree of pulmonary edema in organ donors is useful for assessing the clinical severity of pulmonary edema, determining response to therapy, and as an endpoint for therapeutic trials. Currently, there is no accurate non-invasive method for assessing the degree of pulmonary edema. We tested the performance of a four-quadrant chest radiographic scoring system compared to quantification of pulmonary edema by excised lung weight in 84 donors whose lungs were not used for transplantation. Chest radiographs were taken 3.6 ± 3.0 h prior to organ procurement and were scored by two of the authors. Lungs were excised without perfusion and individually weighed. The chest radiographic scoring system had good performance: correlation between total radiographic score and total lung weight of 0.61, p < 0.001. Performance of the scoring system was improved when chest radiographs with atelectasis were excluded (r = 0.79, p < 0.001). The area under the receiver operator characteristic curve for the detection of moderate pulmonary edema (total lung weight >1000 g) was 0.80. This chest radiographic scoring system may potentially be used to assess the clinical severity of pulmonary edema and may be useful as part of the evaluation of donors for suitability for lung transplantation.

Advancing donor management research: design and implementation of a large, randomized, placebo-controlled trial.

BACKGROUND: Given the persistent shortage of organs for transplantation, new donor management strategies to improve both organ utilization and quality of procured organs are needed. Current management protocols for the care of the deceased donor before organ procurement are based on physiological rationale, experiential reasoning, and retrospective studies without rigorous testing. Although many factors contribute to the lack of controlled clinical trials in donor management, a major factor is the unique challenges posed by research in the brain-dead organ donor. METHODS AND RESULTS: This article describes the study design and the challenges faced during implementation of the Beta-agonists for Oxygenation in Lung Donors (BOLD) study, a randomized, placebo-controlled clinical trial of nebulized albuterol vs. placebo in 500 organ donors. The study design and implementation are described with emphasis on aspects of the study that are unique to research in brain-dead organ donors. CONCLUSIONS: Experience gained during the design and implementation of the BOLD study should be useful for investigators planning future clinical trials in the brain-dead donor population and for intensivists who are involved in the care of the brain-dead organ donor.

Single-nucleotide polymorphisms in the ß-adrenergic receptor genes are associated with lung allograft utilization.

BACKGROUND: Pulmonary edema and associated impaired oxygenation are a major reason for rejection of donor lung allografts offered for transplantation. Clearance of pulmonary edema can be upregulated by stimulation of ß-adrenergic receptors (ßARs). Single-nucleotide polymorphisms (SNPs) in ßAR genes have functional effects in vitro and in vivo. We hypothesized that SNPs in ßAR genes would be associated with rates of utilization of donor lung allografts offered for transplantation. METHODS: Nine hundred fifty-one organ donors were genotyped for 4 amino-acid-coding SNPs in the ßAR genes. Lung allograft utilization was compared among donors stratified by genotypes. RESULTS: Utilization of donor lung allografts was 55% vs 35% (p = 0.02) among donors with GG vs AA/AG genotypes of the Ser49Gly SNP, 39% vs 32% (p = 0.04) with GG vs AA/AG genotype of Gly16Arg SNP and 37% vs 32% (p = 0.1) with CC vs GC/GG genotype of the Arg389Gly SNP. In the combined analysis, donors carrying 0 or 1 associated genotype had a utilization rate of 33%, whereas donors carrying 2 or 3 associated genotypes had utilization rates of 44% and 58%, respectively (p = 0.008). There was a stepwise decrease in chest radiograph infiltrates and an increase in partial pressure of oxygen/fraction of inspired oxygen (PaO(2)/FIO(2)) with an increasing number of these associated genotypes. CONCLUSION: Genetic variants in the ßAR genes among organ donors are associated with higher rates of lung allograft utilization. The increased utilization may be related to increased clearance of pulmonary edema and improved oxygenation in donors with favorable genotypes and suggests that ßAR agonists may have a role in donor management.