E x p a n d i n g t h e Do n o r Po o l Donation After Cardiac Death Haytham Elgharably, MDa, Alexis E. Shafii, MDb, David P. Mason, MDb,* KEYWORDS  Lung transplantation  Donation after cardiac death  Ex vivo lung perfusion  Outcomes

KEY POINTS Donor shortage remains a limiting factor for expanding lung transplantation rates. Donation after cardiac death (DCD) has become a valuable approach to increase the donor pool. Outcomes of controlled DCD are promising and comparable to conventional lung transplantation. Ex vivo lung perfusion can be used to assess and improve the quality of injured grafts in uncontrolled DCD.

INTRODUCTION

DONATION AFTER CARDIAC DEATH

Lung transplantation (LTx) represents a life-saving therapy for patients with end-stage lung disease. Since the first successful LTx, 50 years ago,1 the number of patients listed for transplant has been steadily increasing. However, that increase has been constantly challenged by a donor shortage. Of the available organ donors, only 20% are typically acceptable for lung donation. Although the selection process may vary between institutions, there are common criteria for ideal donors, including age less than 55 years, history of smoking less than 20 years, less than 48 hours mechanical ventilation, PO2 to FiO2 greater than 300, and no evidence of infection or pulmonary edema.2,3 Over the last three decades, donation after brain death (DBD) constituted the primary source for LTx. Multiple approaches have been developed to overcome the supply-demand mismatch in LTx, such as living lobar donation, use of extended criteria donors, ex vivo lung perfusion (EVLP), and donation after cardiac death (DCD).4–7 This article reviews DCD LTx and its value in increasing the LTx donor pool.

The first human lung transplant was performed by Dr James Hardy at the University of Mississippi in 1963 using a DCD donor. Formal criteria for brain death had not yet been established. This patient survived briefly although several decades passed before successful outcomes were reported using DCD lung donors. In 1995, D’Alessandro and colleagues8 reported the first successful LTx from a DCD donor. Planned withdrawal of life support was performed in the operating room using controlled conditions. The recipient was on extracorporeal membrane oxygenation for severe rejection following a recent LTx for end-stage chronic obstructive pulmonary disease. Four days after retransplantation, the patient was successfully weaned and extubated. Although the posttransplant course was complicated by rejection 81 days later, and the patient ultimately expired 3 months after retransplantation, this was generally considered to be a success in DCD LTx. In 2001, Steen and colleagues9 also reported successful transplantation of lungs retrieved from

The authors have nothing to disclose. a Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA; b Department of Thoracic Surgery and Lung Transplantation, Baylor University Medical Center, 3409 Worth Street, Suite 640, Dallas, TX 75246, USA * Corresponding author. E-mail address: [email protected] Thorac Surg Clin 25 (2015) 35–46 http://dx.doi.org/10.1016/j.thorsurg.2014.09.011 1547-4127/15/$ – see front matter Ó 2015 Elsevier Inc. All rights reserved.

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Elgharably et al a donor who suffered from an acute myocardial infarction and died after failed resuscitation efforts. Intrapleural cooling was applied 65 minutes after death to preserve the lungs, and, 3 hours later, the right lung was transplanted into a 54-year-old woman with end-stage chronic obstructive pulmonary disease. Follow-up at 5 months posttransplant demonstrated good graft function.9 These initial cases set the stage for increased use of DCD lungs for transplantation. The use of DCD lungs has grown internationally with DCD lungs accounting for 2% of lung transplants in the United States, 5% in Canada, 4.4% in Europe, 13.3% in the United Kingdom, and 22.5% in Australia.10

defined as the warm ischemia (WI) time. The duration of WI can directly affect graft function after transplantation. Accordingly, reliable assessment of organ function is necessary before procurement.9 Considering the limitations of uDCD donors, Maastricht category III has been considered by LTx centers as the DCD donor of choice for expansion of the donor pool.10,12–14 In some countries more recently, donation after euthanasia (medically assisted death) has become and accepted practice and is considered as cDCD analogous to Maastricht category III. Proper DCD classification is essential to compare outcomes after LTx.

Maastricht Classification

Eligibility for Donation After Cardiac Death

With the intent of expanding DCD use, the first international workshop for DCD was held in Maastricht in the Netherlands in 1995 to further characterize potential donors after cardiac death.11 Four categories of donors were identified (Table 1). Category I (dead on arrival) and II (unsuccessful resuscitation) were considered to be uncontrolled donors, whereas category III (awaiting cardiac arrest) and IV (cardiac arrest in a brain-dead donor) were considered to be controlled donors. The controlled DCD (cDCD) scenario entails withdrawal of life-support measures in the intensive care unit (ICU) or operating room. Benefits of DCD donation include the ability to allocate the organ in advance, relative ability to predict cardiac arrest, and opportunity to evaluate graft function. Furthermore, it permits time for family discussion and to obtain consent. Potential donors of uncontrolled DCD (uDCD) typically suffer from unexpected cardiac arrest and/or unsuccessful cardiopulmonary resuscitation. In these scenarios, evaluation of graft function a priori is not feasible. Additionally, it is often difficult to precisely identify the time interval between cessation of circulation and the start of organ preservation measures,

Potential donors for cDCD are typically patients with irreversible cerebral injury, high spinal cord injury, or end-stage musculoskeletal disorders who are expected to die within 60 minutes following withdrawal of life-support.15 An algorithm has been developed by The University of Wisconsin to predict the expiration of potential DCD donors based on the patient’s cardiopulmonary status, age, body mass index, and need for vasopressors.16 Similarly, The United Network for Organ Sharing has proposed cardiopulmonary criteria that have been found useful in identifying potential DCD donors. DeVita and colleagues17 validated these predictive models in 505 patients who died in the ICU at variable time points after withdrawal of life support. They suggested that additional criteria be added to the predictive model for the likelihood of donor expiration including Glasgow Coma Scale, PaO2/FiO2 ratio, and peak inspiratory pressure. Other models have been developed with the inclusion of neurologic criteria and hemodynamic parameters at the time of withdrawal of life support.18 Use of these predictive tools has further improved the ability to define eligibility for lung donation in the DCD setting.

Table 1 Maastricht classification of DCD donors Category I Dead on arrival Category II Unsuccessful resuscitation Category III Awaiting cardiac arrest After planned withdrawal of life support Category IV Cardiac arrest in a brain dead donor

Uncontrolled Uncontrolled Controlled

Controlled

DONATION AFTER CARDIAC DEATH LUNG PROCUREMENT Warm Ischemia An important difference between the brain dead donor and the non-beating-heart donor is the additional WI interval. As defined by the American Society of Transplant Surgeons, total WI time is “the period between withdrawal of life-support and initiation of organ perfusion,” and true WI time is “the time between significant organ hypoperfusion (mean arterial pressure

Expanding the donor pool: donation after cardiac death.

Lung transplantation (LTx) is the definitive treatment of patients with end-stage lung disease. Availability of donor lungs remains the primary limita...
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