The optimal hormonal replacement modality selection for multiple organ procurement from brain-dead organ donors

Abstract

Zhibao Mi,1 Dimitri Novitzky,2 Joseph F Collins,1 David KC Cooper3 1Cooperative Studies Program Coordinating Center, VA Maryland Health Care Systems, Perry Point, MD, USA; 2Department of Cardiothoracic Surgery, University of South Florida, Tampa, FL, USA; 3Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA Abstract: The management of brain-dead organ donors is complex. The use of inotropic agents and replacement of depleted hormones (hormonal replacement therapy) is crucial for successful multiple organ procurement, yet the optimal hormonal replacement has not been identified, and the statistical adjustment to determine the best selection is not trivial. Traditional pair-wise comparisons between every pair of treatments, and multiple comparisons to all (MCA), are statistically conservative. Hsu’s multiple comparisons with the best (MCB) – adapted from the Dunnett’s multiple comparisons with control (MCC) – has been used for selecting the best treatment based on continuous variables. We selected the best hormonal replacement modality for successful multiple organ procurement using a two-step approach. First, we estimated the predicted margins by constructing generalized linear models (GLM) or generalized linear mixed models (GLMM), and then we applied the multiple comparison methods to identify the best hormonal replacement modality given that the testing of hormonal replacement modalities is independent. Based on 10-year data from the United Network for Organ Sharing (UNOS), among 16 hormonal replacement modalities, and using the 95% simultaneous confidence intervals, we found that the combination of thyroid hormone, a corticosteroid, antidiuretic hormone, and insulin was the best modality for multiple organ procurement for transplantation. Keywords: best treatment selection, brain-dead organ donors, hormonal replacement, multiple binary endpoints, organ procurement, multiple comparisons