ABSTRACTS Assessment of Lungs for Transplant Recovered from Uncontrolled Donation after Circulatory Determination of Death Donors
or knowledge of death, could increase yield. Donor medical problems were higher than expected and may limit the effect of uDCDDs on the lung donor pool.
Thomas Egan1, John Blackwell1, Katherine Birchard1, Benjamin Haithcock1, Jason Long1, Stephen Gazda1, Nissa Casey2, and Caitlin Thys2
Clinical Trial Registration: NCT01615484.
1 University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and 2Carolina Donor Services, Durham, North Carolina
Rationale: To address the lung donor shortage, we obtained institutional review board and U.S. Food and Drug Administration approval to transplant lungs recovered from uncontrolled donation after circulatory determination of death donors (uDCDDs). Objectives: To compare outcomes of recipients of lungs recovered from uDCDDs versus brain-dead donors. Methods: After consent and screening, lungs recovered from uDCDDs were assessed by 4 hours ex vivo lung perfusion (EVLP) and computed tomography (CT) scan. Measurements and Main Results: Over the course of 29 months, 502 potential uDCDDs younger than 66 years were identified in a single county, with death declaration by emergency medical services and four emergency departments in this and two other counties. We determined reasons that lungs from these uDCDDs were not able to be transplanted: uDCDDs could not have lungs recovered (224), next-of-kin could not be found or refused to discuss (67), next-of-kin refused (48), medical examiner case (39), logistics/missed (35), and miscellaneous (35). There were 247 medical contraindications: 141 pulmonary and 106 nonpulmonary. Lungs were recovered from 31 uDCDDs. Thirteen lungs did not have EVLP: five injured lungs (one pulmonary embolism [PE] with perforated infarct, two motor vehicle crash with severe injuries, one adhesion, and one lightning strike), two large PE, two prolonged ischemic time, two obvious chronic obstructive pulmonary disease, one technical, and one consent withdrawn. Eighteen lungs had EVLP: 10 with immediate edema (three PE, three unknown down time, three long ischemic time, and one ruptured aneurysm into left pleural space, making long cardiopulmonary resuscitation ineffective), and one myocarditis, possible lung involvement. In three lungs, CT showed edema after EVLP: one poor flush and poor EVLP performance, one edema after myocardial infarction (MI) with 10-year history of chronic heart failure, and one edema with MI, resuscitated, arrested again. One concurrent pneumonia was diagnosed by bronchoscopy, CT, and cultures; one patient had chronic obstructive pulmonary disease with small subpleural blebs and poor collapse, confirmed by CT. Two uDCDDs with MIs were suitable but not transplanted: no consented recipient from one large blood type B uDCDD, and the senior surgeon was unavailable to transplant suitable lungs from a uDCDD and did not allow the transplant. Conclusions: The objective was not met: no lungs from uDCDDs were transplanted. uDCDDs can be a source of lungs for transplant. Resolving logistical challenges and better use of first-person authorization, allowing organ recovery without next-of-kin consent Abstracts
Author disclosures are available with the text of this article at www.atsjournals.org. (Received in original form September 12, 2016; accepted in final form November 2, 2016 ) Supported by the National Institutes of Health grant 1UM1HL113115-01A1. Correspondence and requests for reprints should be addressed to Thomas Egan, M.D., M.Sc., University of North Carolina at Chapel Hill, Division of Cardiothoracic Surgery, CB #7065, 3040 Burnett Womack Bldg., Chapel Hill, NC 27599-7065. E-mail: [email protected] Ann Am Thorac Soc Vol 14, Supplement 3, p S251, Sep 2017 Copyright © 2017 by the American Thoracic Society Internet address: www.atsjournals.org
Cell-Free Hemoglobin-mediated Increases in Vascular Permeability A Novel Mechanism of Primary Graft Dysfunction and a New Therapeutic Target Ciara M. Shaver1, Nancy Wickersham1, J. Brennan McNeil1, Hiromasa Nagata1,2, Gillian Sills1, Jamie L. Kuck1, David R. Janz3, Julie A. Bastarache1, and Lorraine B. Ware1,4 1
Department of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; 2 Department of Anesthesia, Keio University, Tokyo, Japan; 3Internal Medicine/Pulmonary and Critical Care Medicine, Louisiana State University School of Medicine, New Orleans, Louisiana; and 4Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee
Rationale: Cell-free hemoglobin (CFH) is a potent oxidant associated with poor clinical outcomes in a variety of clinical settings. Recent studies suggest that acetaminophen (APAP), a specific hemoprotein reductant, can abrogate CFH-mediated oxidative injury and organ dysfunction. Preoperative plasma CFH levels are independently associated with primary graft dysfunction (PGD) after lung transplant (1). Objectives: Our objectives were to determine whether CFH would increase lung vascular permeability in the isolated perfused human lung and whether APAP would limit these effects. Methods: Human lungs declined for transplant were inflated and perfused with Dulbecco’s modified Eagle medium/5% albumin at a pulmonary artery pressure of 8–12 mm Hg. After steady state was achieved, CFH (100 mg/dl) was added to the perfusate 6 APAP (15 mg/ml). Lung permeability was measured by continuous monitoring of lung weight gain and by extravasation of Evans blue dye–labeled albumin from the vasculature into bronchoalveolar lavage. To test the mechanism of increased permeability, human pulmonary microvascular endothelial cells were exposed to CFH (0.5 mg/ml) 6 APAP (160 mM) for 24 hours S251
or knowledge of death, could increase yield. Donor medical problems were higher than expected and may limit the effect of uDCDDs on the lung donor pool.
Thomas Egan1, John Blackwell1, Katherine Birchard1, Benjamin Haithcock1, Jason Long1, Stephen Gazda1, Nissa Casey2, and Caitlin Thys2
Clinical Trial Registration: NCT01615484.
1 University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and 2Carolina Donor Services, Durham, North Carolina
Rationale: To address the lung donor shortage, we obtained institutional review board and U.S. Food and Drug Administration approval to transplant lungs recovered from uncontrolled donation after circulatory determination of death donors (uDCDDs). Objectives: To compare outcomes of recipients of lungs recovered from uDCDDs versus brain-dead donors. Methods: After consent and screening, lungs recovered from uDCDDs were assessed by 4 hours ex vivo lung perfusion (EVLP) and computed tomography (CT) scan. Measurements and Main Results: Over the course of 29 months, 502 potential uDCDDs younger than 66 years were identified in a single county, with death declaration by emergency medical services and four emergency departments in this and two other counties. We determined reasons that lungs from these uDCDDs were not able to be transplanted: uDCDDs could not have lungs recovered (224), next-of-kin could not be found or refused to discuss (67), next-of-kin refused (48), medical examiner case (39), logistics/missed (35), and miscellaneous (35). There were 247 medical contraindications: 141 pulmonary and 106 nonpulmonary. Lungs were recovered from 31 uDCDDs. Thirteen lungs did not have EVLP: five injured lungs (one pulmonary embolism [PE] with perforated infarct, two motor vehicle crash with severe injuries, one adhesion, and one lightning strike), two large PE, two prolonged ischemic time, two obvious chronic obstructive pulmonary disease, one technical, and one consent withdrawn. Eighteen lungs had EVLP: 10 with immediate edema (three PE, three unknown down time, three long ischemic time, and one ruptured aneurysm into left pleural space, making long cardiopulmonary resuscitation ineffective), and one myocarditis, possible lung involvement. In three lungs, CT showed edema after EVLP: one poor flush and poor EVLP performance, one edema after myocardial infarction (MI) with 10-year history of chronic heart failure, and one edema with MI, resuscitated, arrested again. One concurrent pneumonia was diagnosed by bronchoscopy, CT, and cultures; one patient had chronic obstructive pulmonary disease with small subpleural blebs and poor collapse, confirmed by CT. Two uDCDDs with MIs were suitable but not transplanted: no consented recipient from one large blood type B uDCDD, and the senior surgeon was unavailable to transplant suitable lungs from a uDCDD and did not allow the transplant. Conclusions: The objective was not met: no lungs from uDCDDs were transplanted. uDCDDs can be a source of lungs for transplant. Resolving logistical challenges and better use of first-person authorization, allowing organ recovery without next-of-kin consent Abstracts
Author disclosures are available with the text of this article at www.atsjournals.org. (Received in original form September 12, 2016; accepted in final form November 2, 2016 ) Supported by the National Institutes of Health grant 1UM1HL113115-01A1. Correspondence and requests for reprints should be addressed to Thomas Egan, M.D., M.Sc., University of North Carolina at Chapel Hill, Division of Cardiothoracic Surgery, CB #7065, 3040 Burnett Womack Bldg., Chapel Hill, NC 27599-7065. E-mail: [email protected] Ann Am Thorac Soc Vol 14, Supplement 3, p S251, Sep 2017 Copyright © 2017 by the American Thoracic Society Internet address: www.atsjournals.org
Cell-Free Hemoglobin-mediated Increases in Vascular Permeability A Novel Mechanism of Primary Graft Dysfunction and a New Therapeutic Target Ciara M. Shaver1, Nancy Wickersham1, J. Brennan McNeil1, Hiromasa Nagata1,2, Gillian Sills1, Jamie L. Kuck1, David R. Janz3, Julie A. Bastarache1, and Lorraine B. Ware1,4 1
Department of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; 2 Department of Anesthesia, Keio University, Tokyo, Japan; 3Internal Medicine/Pulmonary and Critical Care Medicine, Louisiana State University School of Medicine, New Orleans, Louisiana; and 4Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee
Rationale: Cell-free hemoglobin (CFH) is a potent oxidant associated with poor clinical outcomes in a variety of clinical settings. Recent studies suggest that acetaminophen (APAP), a specific hemoprotein reductant, can abrogate CFH-mediated oxidative injury and organ dysfunction. Preoperative plasma CFH levels are independently associated with primary graft dysfunction (PGD) after lung transplant (1). Objectives: Our objectives were to determine whether CFH would increase lung vascular permeability in the isolated perfused human lung and whether APAP would limit these effects. Methods: Human lungs declined for transplant were inflated and perfused with Dulbecco’s modified Eagle medium/5% albumin at a pulmonary artery pressure of 8–12 mm Hg. After steady state was achieved, CFH (100 mg/dl) was added to the perfusate 6 APAP (15 mg/ml). Lung permeability was measured by continuous monitoring of lung weight gain and by extravasation of Evans blue dye–labeled albumin from the vasculature into bronchoalveolar lavage. To test the mechanism of increased permeability, human pulmonary microvascular endothelial cells were exposed to CFH (0.5 mg/ml) 6 APAP (160 mM) for 24 hours S251
