The demand for organ donors and transplants dwarfs the supply. There were 7,000 organ transplants and 3,500 donors from January-March 2009 yet at this moment (summer 2009) there are 101,000 people on the waiting list. In recent years the most rapid increase in the rate of organ recovery from deceased persons has occurred in the category of donation after “cardiac death” (DCD) – that is, death declared on the basis of cardiopulmonary criteria (irreversible cessation of circulatory and respiratory function) rather than the neurological criteria used to declare “brain death” (irreversible loss of all functions of the entire brain, including brain stem). Obtaining organs from donors after “cardiac death” was the approach that was generally followed in the 1960s and earlier. An example is the first heart transplantation in 1967. However, since 1968 when an ad hoc committee of Harvard Medical School proposed a brain-based definition of death that became widely accepted, organs for transplantation have been removed primarily from hospitalized patients who have been pronounced dead on the basis of neurological criteria, while they are still on ventilators and their hearts continue to function. The continued circulation of blood helps to prevent the organs from deteriorating.

Over the past 15 years DCD has made a comeback. Programs permitting such donations satisfy two needs. They provide organs in addition to those procured after brain death and thus narrow the wide gap between supply and demand for organs. And they fulfill the wish of family members that relatives with severe brain injuries serve as organ donors after cessation of life-sustaining therapy and subsequent cardiac death. Although DCD has great potential to narrow the supply-demand gap in organs available for transplant, it presents ethical, legal and medical difficulties. This commentary focuses on the medical dimension and more particularly on the vital importance of timing to insure the viability of donated organs in the case of DCD.

It is common knowledge how important it is to get immediate medical treatment for a heart attack. The longer a coronary artery is blocked by clot, the longer the heart muscle it supplies is deprived of its blood supply. The process of heart muscle ischemia begins immediately after the blockage, but it may be reversed if the blockage is relieved expeditiously. However, if the coronary artery remains blocked for four hours, the affected heart muscle which was once ischemic tissue becomes dead tissue. Thus it is vital to shorten the time of ischemia to avoid a heart attack (myocardial infarction). Clot-busters, angioplasty and coronary stents are often successful in reversing this deadly process.

Likewise, timing is of paramount importance to the success of DCD. The window of opportunity for successful transplantation is very short. Organs become ischemic from the moment the heart stops beating. The first phase of ischemia is called warm ischemia since the internal body temperature is warm (normally 98.6). Warm ischemia time should not exceed 30 minutes for successful liver transplantation and 60 minutes for kidney and pancreas transplantations. If organs are not transplanted within this narrow time interval, ischemic tissue will become dead tissue and thus unsuitable for transplantation. It takes time to discuss and obtain the approval of family members to perform a transplant. And it takes time to mobilize a surgical team and prepare the recipient in the operating room. Surely it would take longer than 30 or 60 minutes. Without additional measures to shorten the time of warm ischemia, DCD would be impossible.

Cold storage can delay the deadly effect of prolonged ischemia and give the surgical team the time it needs to perform successful organ transplantation. Once death is pronounced, cold organ-preserving solution is perfused into donor’s veins, thus putting the organs in cold storage. This organ-preserving cold storage interval is called cold ischemia time (CIT). It extends from the initiation of cold preservation of donor organs to restoration of warm circulation in the organ recipient. For kidney transplantation, the CIT should be < 24 hours; for pancreas transplantation, < 18 hours; and for liver transplantation, < 8 hours. Even with the benefit of cold storage, the window of opportunity for successful organ transplantation remains short, but with the efficiencies of transportation and modern transplant teams, it is feasible.

The issue of timing is pertinent to our case study. Let’s analyze the length of time Michael Horton’s organs remain in warm ischemia. Moment of his collapse to arrival of medics, 8 minutes;  transport to ER, 10 minutes;  failed cardiovascular resuscitation in ER, 20 minutes;  total treatment time, 38 minutes. Already it’s too late to transplant Michael’s liver (maximum allowable warm ischemia time for viability, 30 minutes). Once Michael is pronounced dead after failed cardiopulmonary resuscitation, the treating team calls the transplant team which arrives on scene within 10 minutes. The transplant team reviews the patient record to assess suitability for organ transplantation, 5 minutes, and then makes attempts to reach next-of-kin, 5 more minutes. Already 58 minutes have passed. Two minutes of warm ischemia time remain before Michael’s kidney and pancreas also lose their viability for transplantation. The transplant team has 2 minutes to make its decision. Either it immediately initiates cold storage of Michael’s organs by instilling cold organ-preserving solution into his veins, or it gives up its quest for transplantable organs from Michael Horton.

It is rare indeed that persons who die after failed cardiovascular resuscitation - like Michael Horton – would ever be suitable organ donors. There is not enough time to save the organs from damage due to prolonged warm ischemia time.  Rather, donations after “cardiac death” (DCD) typically involve patients who are on a ventilator as a result of devastating and irreversible brain injuries, such as those caused by trauma or intracranial bleeding. Although such patients may be so near death that further treatment is futile, they are not dead. Of course, the dead donor rule requires that a person is truly dead (“brain death” or “cardiac death) before organ transplantation.

 If the decision is made to remove life-support and the patient is a suitable candidate and consent is given to perform organ transplantation, then life-sustaining measures are withdrawn under controlled circumstances in the intensive care unit or operating room. When the potential donor meets the criteria for cardiac death, a doctor pronounces the patient dead. The time from the onset of asystole – the absence of sufficient cardiac activity to generate a pulse or blood pressure (not necessarily the absence of all electrocardiographic activity) – to declaration of death is generally about 5 minutes, but it may be as short as 2 minutes. Once death is pronounced, cold organ-preserving solution is perfused through the donor’s body. The organs – most commonly the kidneys and liver but also the pancreas, lungs, and in rare cases, the heart – are then recovered. To avoid conflicts of interest, neither the surgeon who recovers the organs nor any other personnel involved in transplantation can participate in end-of-life care or the declaration of death.

Organ donors may be patients who are dead on arrival to the ER (category 1), patients like Michael Horton who do not respond to cardiopulmonary resuscitation (category 2), patients as just described from whom life support has been withdrawn (category 3), or patients who are brain dead (category 4). The likelihood for successful organ transplantation increases with each category. It would be rare indeed that transplantation of organs from category 1 or category 2 donors would be successful. There is not enough time. The time interval of warm ischemia would be too long for the organs to retain viability. The time of warm ischemia is shorter for category 3 donors (also DCD) unless the process of dying after removal from life-support takes longer than expected. There may be a prolonged period of low blood pressure until finally the heart stops beating and the patient is pronounced dead. In such circumstances category 3 donors would no longer be suitable candidates for organ transplant due to prolonged warm ischemia time. Category 4 brain-dead donors are the best candidates for organ transplantation. Up until the moment of harvesting, their organs receive full circulation of blood. And since cold organ-preserving solution is perfused before their organs are removed, the time of warm ischemia is zero.

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