Hello, my name is Marie Carmel-Elly. I'm the chair and professor of the Department of Emergency Medicine at the University of Alabama at Birmingham in Birmingham, Alabama. Today I'll be talking to you about the donation process in brain dead and cardiac death donors. For the next 20 minutes, we will review traditional organ donation. Transplantation following cardiac death will characterize donor types, recipient types, and also discuss some transplantation outcomes. The age at which a donor is eligible for and suitable for organ donation varies by organization and by organ procurement agency. However, in general, patients that are 70 years of age and under are typically suitable for evaluation for kidney and liver. Under 50, suitable for evaluation for heart and lungs, and under 30, suitable for evaluation for pancreas. Exclusions include HIV, active cancer, severe infection, and in heart, coronary artery disease. Especially in lungs, tobacco history, generally over 10 years. The Maastricht system classifies the types of death into these four categories, the first of which are patients that are found dead either out of the hospital or in the hospital. The second category is those that have had witness cardiac arrest. The third, in patients that are withdrawn from life-sustaining therapy. And then the fourth, in patients that have had circulatory arrest after a neurologic determination of death. In general, patients that are eligible for potential donation are patients that would be considered in the controlled category. And those controlled categories would include category three, where patients would be withdrawn from life-sustaining therapy, meaning that there was a planned withdrawal of therapy. And in category four, which could be uncontrolled or controlled, but a circulatory arrest following neurological determination of death would be the controlled version of how to proceed with donation. So donation after cardiac death. So this process begins with the patient assessment and determination of brain death. Many centers have protocols that allow for the assessment of brain death. And so you'd have to refer to your state as well as your local institutional guidelines. Once the patient has been determined to bring brain dead, the family is informed and a referral is made to OPO. OPO then approaches the family and obtains consent in order for organ procurement or for research. Sometimes the engagement of or the referral process to OPO actually occurs before the brain death determination has occurred, depending on the protocols at the institution. If a consent is provided, then the donor undergoes extensive evaluation. An assessment, management, and optimization is performed in order to see whether or not the patient is actually suitable for organ donation. And this evaluation includes laboratory work, invasive hemodynamic monitoring, imaging, and additional studies, which could include biopsies, to determine whether or not the patient is eligible and suitable. And if the patient is deemed to be suitable, the patient is taken to the operating room where organ procurement occurs. And OPO will then engage family in counseling and in bereavement. If at any point the family decides to withdraw consent or the donor is found unsuitable for procurement, the process is halted. So the brain death patient can actually pose physiologic challenges in the patient's management in the ICU, largely because of the disruption of sympathomimetic and adrenergic regulation. Specifically there's a loss of hypothalamic, pituitary, adrenocortical regulation, causing all sorts of neurohumoral changes. Very commonly, these patients will develop a variety of symptoms and manifestations of their brain death. Their rising intracranial pressures specifically result in a massive release of pro-inflammatory and anti-inflammatory mediators and catecholamines. And this leads to cytokine storm and capillary leak, which consequently causes alterations in hemodynamics, hormone imbalance, changes in body temperature, and changes in lung function. Hypothermia as an example is the most common manifestation, and this should be addressed with anticipatory temperature management. The patients also tend to experience hypotension, which can occur in as many as 80% of patients that are brain dead. These insipidus is common as well, followed by arrhythmias, pulmonary edema, and cardiac arrest. So the pillars of optimization in these patients include cardiovascular resuscitation. These are criteria that have been adopted by several organizations, including UNOS. There are also ventilation guidelines with tidal volumes, which have traditionally been thought to be, should be between 10 and 15 cc's per kilo. However, recent studies have suggested that tidal volume should be lower at 6 to 8 cc's per kilo with lung protective strategies. Leaky airway pressure should be kept below 30, and there should be a mild respiratory alkalosis. Now the study that looked at lung protective strategy published in 2010 demonstrated that in 118 patients that had the conventional and protective lung strategies, after a period of observation, they noted that patients that had lung protective strategies were actually had an increased propensity for eligibility, and ultimately a larger portion of that group was harvested, had lungs harvested, that ultimately went on to recipients. And when looking at six months for survival in the recipients, the rates did not differ. What we also know that we have to do in these patients is we have to be careful with volume resuscitation. In patients in whom lungs may be considered suitable for transplantation, CVP targets are even lower than what would be considered appropriate for patients that are having abdominal organs procured. Longer than administration of crystalloid, we'll opt to administer patients albumin, fresh frozen plasma, or packed red blood cells. In patients that have normal coagulation values, albumin is preferred, but in those who have elevated PT or PTT, fresh frozen plasma may be used. Hemoglobin targets are 10 or higher, and all of these patients tend to have advanced hemodynamic monitoring placed with a optimization of wedge pressure at 8 to 12 millimeters per mercury. So earlier I mentioned that these patients develop dysregulation of their hypothalamic and adrenal cortical cortex. These patients tend to have what they consider to be psyche thyroid syndrome and may benefit from thyroid replacement. While it hasn't been demonstrated to improve cardiac output in all donors, the administration of thyroid hormone has been associated with an increase in the number of organs retrieved and improvement in left ventricular dysfunction in some donors. Diabetes insipidus is common and can be treated with vasopressin and desmopressin. We know that many of these patients could develop a relative or an actual adrenal suppression and knowing the benefits of the administration of methylprednisolone and its ability to enhance vascular tone, methylprednisolone is recommended. In addition, it may have the added benefit of attenuating the inflammatory response, which we understand occurs as a result of brain death. Finally, we want to avoid hyperglycemia with the administration of insulin. Another very important feature of optimization guidelines includes electrolyte management in these patients so that their sodium should be kept below 150, maintaining potassium before, and acid doses should be corrected with sodium bicarb, as well as with mild to moderate hyperventilation, as mentioned earlier. In some cases and in certain centers, CRT may also be utilized in order to manage a patient's electrolytes while the patient is being assessed for suitability for procurement. So donation after cardiac death. This is the intentional withdrawal of life support measures with the goal of a controlled circulatory death. So these candidates tend to be candidates that are not necessarily brain dead, but may have devastating neurologic injuries or other organ failures that require mechanical ventilator or circulatory support. The family or the clinical provider team have to initiate a conversation about withdrawal of support in order for discussions around donation after circulatory death to occur. So clinical scenarios for a death following circulatory arrest include patients that are dependent on artificial support. So these could be patients that are ventilator dependent for respiratory insufficiency or dependent on mechanical circulatory support, including an LVAD, RVAD, or VA ECMO. These may be patients that have a disruption in oxygenation, such as in your ARDS patient or patients that are on VV ECMO, or dependent on pharmacologic and vasoactive agents on multiple pressors, or who have an intra-aortic balloon plump in place. What's important is that as you're assessing these patients, there has to be a likelihood that the patient's going to experience a circulatory arrest within one hour. So how does a DCD process look? So first, the process is pretty similar to what the death after brain death determination has been made. The difference is that the clinical team at this point would have spoken to the family, and the family would have made a decision to withdraw support. Once a decision to withdraw support has occurred, the organ procurement organization would approach this patient for consent. And that would be followed by an assessment. That assessment and management would be, if there was a determination that the patient was suitable for procurement, would be followed by withdrawal of support. In this case, the withdrawal of support would typically occur in the operating room, unlike a withdrawal of support in your typical palliative care or comfort measures patient. And this would be done so that the clinical team could make the assessment of a cardiac death in the operating room. If the clinical team makes an assessment of cardiac death in the operating room, there is a period of standoff which is observed. And this could be 5 to 10 minutes based on law or based on the organization, at which point the death could be officially declared, and the procurement could begin. Now, if circulatory death does not occur, then the patient would be returned to the intensive care unit and to their family where palliative care measures would be initiated. Once again, if at any point during this process the family withdraws consent or the donor is found unsuitable for procurement, the process would be halted. So who are these donors that proceed with donors after cardiac death versus donation after brain death? What we know is that the donors secondary to cardiac death tend to be older compared to the donors after brain death. Not only are these patients older, but they tend to have experience in an anoxic brain injury. And they have lungs that are procured bilaterally versus unilaterally in the donation after brain death patients. The brain death donors tend to be younger and also tend to be trauma patients. Recipients of brain death candidates are statistically older without any significant differences based on the ideology of their lung transplantation. And these studies were performed in patients that ultimately received lung transplants. In the population of lung transplants, when looking at the outcomes between DBD versus DCD donors, what they found was that there was no difference in primary graft dysfunction, no difference in bronchiolitis obliterans syndrome. And survival is actually pretty similar at one, three, and five years post-transplantation. So what are the challenges with donation after circulatory death? Well, the first is that sometimes in the operating room, upon withdrawal, there's failure to progress to a circulatory death. And the progression could actually be prolonged for up to two hours. Now most institutions don't typically wait for two hours. Some institutions wait as long as 30 minutes and will discontinue the procedure. And this could actually take up a lot of resources at the institution, depending on where this is being conducted. The other consideration is that the longer you wait for there to be a circulatory arrest, the more likely that the organs that are procured are not going to be in the same ideal condition or suitable condition for transplantation. And so at this point, if you are procuring organs in a DCD patient that had a prolonged progression to circulatory death, it'll be important to match the donor with a recipient. So a young patient that had a progressed time to death would be most appropriately placed in a- that organ would be most appropriately placed in a young patient who may have much more reserve and could accept that organ. The other challenge with death following circulatory arrest is that cardiac procurement thus far has been poor. And expedited procurement period- and there could be an expedited procurement period post-arrest such that there's not a limited amount of time to procure all of the organs once the heart has stopped. So the donation following circulatory- circulatory arrest has actually not been done in the United States. In fact, it's rare. About four- in 2019, 441,000 adult heart transplants in the United States were from DCD donors. But in actuality, these donations have been done since the 1960s before the establishment of the brain death guidelines. And this was described by Barnard. In fact, now there are programs for DCD heart transplants in several countries, including UK, Belgium, and Australia. And there's at least one study that projects that if we were to perform more DCD donors, we could increase the heart donor pool by 20%. So there is- there are a couple of centers in the country that are looking at the opportunity to perform a normothermic regional perfusion, a procedure that would allow for heart transplantation and decrease the ischemia time that would be experienced traditionally with our DCD donor patients. Now this- performing these- this procedure could be associated with an ethical dilemmas. And so currently, this procedure is only being done with IRB approval. However, you can see that compared to using traditional methods of transport or other methods that would require animated products that cost well over $20,000 to $40,000, using ECMO cardiopulmonary bypass at your institution would cost no more than $2,000. The normothermic regional perfusion would require IRB protocol and an OPO medical advisory board approval. This would also require engagement by local transplant community and protocols at- and there would have to be protocols set up at your transplant center. In essence, following circulatory arrest, there would be a ligation of bilateral vertebral and carotid arteries. This would allow for or ensure a natural cessation of brain function following cardiac arrest. Subsequent to the ligation, patients would immediately be placed on ECMO. And this would allow for prolongation of warm ischemia time, extended assessment time, and increased organ procurement. Thus far, there has been two- there have been several DCD heart donors that have been done in at least two institutions in the country that have been experimenting with this particular approach. And patients have been able to arrest within 30 minutes. Again, the UNOS allocation policies would have to be followed in all of these cases. So in conclusion, the physiologic optimization is a hallmark of management of brain death donors. Donation after circulatory death isn't- it continues to be an opportunity for the increased pool of organs in our hospitals, including hearts, and thus far has comparable outcomes to donation after brain death and may increase the donor pool. There are future opportunities for investigation of best practice for optimization of organs and research models, including normothermic regional perfusion. Thank you all very much for your time.

brain dead donors

cardiac death donors

organ donation candidates

physiological challenges

donations after cardiac death

DCD heart transplants