 Our next speaker this afternoon will be Dr. James L. Bernat, the Lewis and Ruth Frank professor of neuroscience at the Dartmouth Medical School. Jim received his MD from Cornell University and then trained in internal medicine and in urology at Dartmouth. Jim, did you tell me this is your 40th year at Dartmouth? 40th, yes. Dr. Bernat is the director of the program in clinical ethics at the Dartmouth Hitchcock Medical Center. He served for 28 years on the American Academy of Neurologies Ethics Law and Humanities Committee. Ten of those 28 years, Jim was the chair of that committee. In 2011, he received the Presidential Award from the American Academy of Neurology, the Lifetime Service to American Neurology. Today, Jim will give a presentation on death determination in organ donors. Jim, Bernat. Mark, thanks very much for the introduction and especially for inviting me here today. It's a great honor. I have some few disclosures, which is now to reger at any kind of meeting, but I don't think that any of these are going to influence what I say perhaps other than the last one serving on a national panel that's looking at the question of circulatory death. My learning objectives today are to look at the question of death determination in critical care. Because this is a seminar on ethical issues in organ donation, the original title was death determination in organ donors, but what I have to say is going to pertain to non-donors as well and anybody dying today in the critical care situation. I want to start by reviewing some points about the legal definition of death, talk about death determination by brain tests and highlight a few of the controversies, and determination of death by circulatory tests and highlight a few of those controversies, and then talk a little bit about this panel that I've been working on and what we believe is appropriate for death determination and circulation. First of all, a few comments about ICU death determination. Clearly, the issues have been spurred by the availability of organ donation. Sociologists have studied the impact of organ donation in the development of brain death in the 1960s and 70s, and it clearly spurred this. In the last 20 years, the organ donation after the circulatory determination of death has spurred a similar attention to precision on identifying if possible what is the moment of death, and there's where a lot of the controversy occurs. We would look at the DBDD or brain death determination and DCDD, which used to be called non-heart beating organ donation and donation after cardiac death. Ironically, perhaps, although the brain death controversies have not been resolved and have not disappeared, there's less written and spoken about them now, and there's much more of an active controversy about some of the issues regarding death determination in the circulatory death donors. What we're going to do today is have a point counterpoint where I'm going to present an approach, and then after I speak, Bob Trug from Boston Children's is going to present his position. Those of you interested in seeing a similar point counterpoint in print can look at a chest, the journal Chest in 2010, and I'll show the reference of this soon, in which we conducted a similar debate that is in print. Let me start with the legal determination of death or legal definition of death, and there are lots of different ways to look at the question of the definition of death. There's a medical, there's a legal, there's what one might call an ontological or bio philosophical, there's religious ways of looking at this. So the way the law looks, and I think everyone in this room knows, the Uniform Determination of Death Act, which was proposed by the President's Commission in 1981, and to a greater or lesser extent has been incorporated into statutory law and the overwhelming majority of states, and it provides two different criteria, a brain criterion and a circulatory criteria. And the words that I think one might pay attention to here are irreversible and circulation, and I'll be coming back to those later. And finally, the last little comment of death, determination must be made in accordance with accepted medical standards. Now these two criteria are not independent, and reading carefully the text of Defining Death, the President's Commission report, which was the fundamental document defending the proposition of the UDDA, it's clear that the primary criterion is the brain criterion, and the circulatory respiratory criterion becomes valid only because when it exists, it leads to the brain criterion, and only really in the presence therefore of supported respiration does the brain criterion need to be tested directly. Now let me say a few words about brain death, the irreversible cessation of all of the brain's clinical functions as human death, and of course this is a misleading term, but it has been come standardized both in medical and in popular culture, and has been more or less accepted throughout society and biomedical practices, although a number of studies going back decades and still present show there's epidemic confusion about what this means, and there are probably fewer active controversies about this now. Looking worldwide, ilcovedics from the Mayo Clinic reported 10 years ago that at that time there were, in addition to all the states in the USA and all Canadian provinces, that was practiced in over 80 countries, and the critics, some of whom are in our audience and in our speakers panel here today, irrespective of the merits of some of the arguments which I believe have merits, these have not created the traction necessary to change anything, and when this has been looked at carefully by high level commissions such as the Institute of Medicine review that was done in Cleveland at Case Western in 1995, culminating in that book published by Stuart Younger at all, editing it in 1999, there was a belief that the way things are works well and should be left alone. The more recent analysis by the Presidential Council published in 2009 reached a similar conclusion that yes there were some defects in some of the conceptual parts of this, but as a public policy it is working well and should be left alone. Now the critiques, and I'll just summarize a few of them and you'll hear more than by the next speaker, are first in a, if you will, an ontology issue that it's not really what we mean when we say that someone has died. Alan Schumann from UCLA clearly made the point that the integration of subsystems rationale that I and my colleagues, for example, 30 years ago cited as one of the justifications, and I'll come back to that in a moment, was inadequate and the President's Council accepted that as true and came forward with an alternative justification, a rationale which Alan also felt was inadequate, but in any event that point has been made. Bob, in his writings, eloquently has said that it's in a way an unnecessary an agronism that the concept arose in an era when it needed to be respected in order to accomplish certain things that now could be accomplished through other ways, such as discontinuing life sustaining therapy that wasn't possible to do in the late 1960s and early 1970s, and this was a solution to that problem. And similarly, organ donation, and again Bob will be talking about his ideas about that, that it can be done by consent if the patient is beyond harm, dying beyond harm. Religious opposition a little, although in most settings it's not a common issue. Now, what I'd like to do is just very briefly, and I apologize for going through all this material so quickly, but I know we have an audience of sophisticated people who are familiar with a lot of the work that has been done on this. I want to talk a little bit about the biophilosophical analysis that my colleagues at Dartmouth and I proposed in 1981, and I've refined several times since then, that provides an approach to this problem. And I think it's fair to say that even most of those who disagree with some of the substantive points that we made and some of the assertions that we have made agree that this type of analysis itself is fruitful and is a reasonable approach. And we came up with four sequential steps. The first was the paradigm stating the preconditions that frame the analysis, then the definition making explicit the ordinary meaning when we use the term debt, the criterion of debt, a general measurable standard that can be incorporated into a debt statute, and the tests of debt, which are done by physicians to show that the criterion has been satisfied. So if one looks at the paradigm conditions, either the ones we came up with, and not everybody accepts these, but what they are is to clarify that the meaning of the consensual usage of the non-technical word, it's not a technical word, and not to contrive a new definition the way some attempts are, if you will, redefine debt, but rather the ordinary meaning has been made ambiguous by life-sustaining technology, and we can't rely on it anymore and we need to look a little more deeply. A second, that death fundamentally is a biological phenomenon. It's the cessation of life. Life is a biological phenomenon. It has social, anthropological, legal, religious, cultural, etc. aspects, but it is fundamentally a biological phenomenon. We restrict the analysis to higher vertebrates. We're not talking about deaths of cells or tissues or organs or unicellular organisms. Those are valid, but not the task here, that the term applies only directly to organisms and other uses are metaphorical, like death of a culture, and specifically death of a person, and we'll come back to that a little bit, that the organism resides in only one of two states, alive or dead. There aren't in between states. You're either one or you're the other, and therefore death is an event out of process, and in fact it's the event separating a process of dying, which is a process, from the process of disintegration of the body, which is a process, and it's that event. And even though it's an event, we may not know exactly when it is, we may know it only in retrospect, but theoretically it's an event, and of course it's irreversible. Then the definition that we chose is the irreversible cessation, a function of the organism as a whole, and I want to talk a little bit about that concept. The criterion is a brain, whole brain, criterion, irreversible cessation, a function of critical number of neurons in the whole brain, and the tests have been put forward by the American Academy of Neurology, the Canadian Medical Association Journal last year by the children's criteria by the multi-society task force. So the organism as a whole is important to understand, to understand this. It's not the whole organism, but it's that functioning that is greater than the sum of the parts of the organism, and it looks at the question of the unity and wholeness and integrity of the organism. And this concept was first discussed in the early part of the 20th century in a text by Jacques Leub, the Rockefeller now university biologist in a book entitled The Organisms of the Whole, published in 1916. Now, bio-philosophical analyses of this talk about emergent functions, these concepts that individual subunits when they're operating together from those emerge functions that cannot be reduced to any single component of those, but rather emerge spontaneously in the presence of these. And this is the concept of wholeness and unity that we're talking about, and that there's a difference between the life of a component of an organism and of the organism itself. And that's really essential to grasp here so that the definition is the universal cessation of the critical functions of the organism as a whole, and the criterion is the whole brain criterion. And what is a brain that patient, but we say is dead, but subsystems of that patient clearly are a lot. There's quite a bit of that patient who remains alive, but not their organism as a whole. And the whole brain criterion, in addition to being coherent in that way, permits certain other attractive features from a medical perspective in terms of determination that are attractive to neurologists, neurosurgeons, and intensivists who are those who are called to the bedside to do these determinations. And that is once intracranial pressure exceeds min arterial blood pressure, there's no further intracranial forward blood flow, and then neurons that weren't killed by the original injury, whether it was traumatic brain injury, meningitis, hypoxic ischemic, neuronal injury, fallen cardiac arrest, stroke, or whatever it was, are killed secondarily and it allows confirmatory tests showing absence of intracranial blood flow. So these tests of death, the cardiopulmonary tests are sufficient when there's no cardiopulmonary resuscitation or mechanical tracheal positive pressure ventilation, and the brain death tests are used when this is used or planned, and the tests must have no false positives or negatives. The society has been very concerned about false positive death determination. This is a painting by the Belgian artist Antoine Viertz hanging in the Viertz Museum in Brussels occurring during a cholera epidemic when there was a false positive death determination, presumably someone who was hypovolemic shock with no blood pressure and no palpable pulse, but was still alive. And this type of painting, and of course the works of Edgar Allan Poe, similarly looking at premature burial, which is the English translation of the French title. And this type of device, many of you have seen this image before, sold quite a few units in the 19th century where people would be buried in these special caskets in case the doctor had made an error on death determination. And there were elaborate treatises written about the signs of death to prevent this sort of thing. And of course the examination of the brain death patient, which I'm not going to go through here, but all of you are well aware, and this is from Vedic's paper in neurology a couple of years ago, which is the brain death standards for adults from the American Academy of Neurology with the usual knowing of structural lesion excluding reversible causes and responsiveness, cranial nerve reflexia, proper athlete testing. So a quick review of some both bio-philosophical justification of the concept of brain death and some of the testing and so on that we have. I'd like to change gears now and to move to the second subject I wanted to cover today, which is the death determination in after circulatory determination of death. And again, I'll use as a paradigm the patients who are in the DCDD protocols, which I'm sure exist in the majority of medical centers of people here. But for those that don't have a lot of firsthand experience, let me just briefly summarize it saying that the usual situation is of a dying ICU patient who is ventilator dependent usually with severe brain damage, although they're not categorically limited to that group, but they're not brain dead. If they were brain dead, one wouldn't need to go through this exercise. They would simply be declared. But these people are not yet because of the magnitude of the damage and the poor prognosis neurologically families make a decision to withdraw life-sustaining treatment, which as you all know is exceedingly common and is a very common modus of death in ICUs throughout the country. However, in addition to that they would like the patient to serve as an organ donor. So the protocols essentially link in time the readiness of the surgical team to do the donation with the stopping life-sustaining therapy and death determination. And this has been well described in a number of papers. But the controversy of this has been present since the beginning. If you look back at the original work from the University of Pittsburgh Medical Center where this protocol really, it wasn't the only one, but it was the most well reported and highly publicized one of this type. There was significant question raised then and now on the same question, which is, is the donor really dead at the moment that they're declared dead and taken to the OR for organ procurement? And basically the argument went that I mean the way it's done of course is that in Pittsburgh they would after dialing down ventilator or excavating the patient however it was done the heart would stop beating and they would wait two minutes by the clock and after two minutes of assistively they would declare the patient dead with them to the OR. And the question was that two minutes after assistively are they really dead given the fact that we know that some of some patients could have their heart restarted and circulation regenerated therefore by cardiopulmonary resuscitation. Now we know that these people have DNR orders and they're not going to do that. But that doesn't matter because what if you weren't going to do that? This would be possible and if death is by definition irreversible then something's wrong here because you've just reversed something. And as it violates the death statute which says irreversible on the UDDA and the question that we'll be discussing later has to do with the death donor rule should that be suspended or abrogated or is that necessary anymore? Now each institution who have DCD protocols have their own standards for death determination and most I can't I haven't surveyed them all but there is a report that's looked at all of the protocols as of last year in the United States and Canada. The majority follow the IOM recommendation of five minutes but some still do what Pittsburgh does at two minutes and I'm sure all of you read the paper in the New England Journal in the fall of 2008 from Denver Children's Hospital where they did three successful neonatal heart transplants from DCDD neonatal donors and in those in the second two they started out with two minutes but then they asked the Ethics Committee if it would be okay if they reduce the required interval of asystole from 120 to 75 seconds which they approved and that was done in the following two. So there's this odd-hook part of this whole thing that's not very satisfying and we're going to be talking and this was the paper the butchett paper that was in the New England Journal and all of the protocols except for experimental ones being done in this country now are the so-called control like the paradigm I gave where they're in the unit the decisions made to solve their life's the same treatment it's stopped they're watched everything is under control the so-called uncontrolled once of course would be the people in or more likely out of hospital who just dropped it of primary cardiac arrest usually a primary fib or a systolic arrest and then if they can't be resuscitated then they would be an organ that's the so-called uncontrolled I'm not going to be talking too much about that but I'll mention well what happened was I had when they did this they asked several of us to write little papers and Bob wrote one and I wrote one and Bob Beach wrote one also that was these little perspective articles in the New England Journal that a company of paper that they anticipate is going to have a controversy and it did and there was quite a bit of controversy about this and some of the controversy focused on whether the person whether these babies were in fact dead at the moment that their hearts were taken out part of it was about the shorting of the interval and all that sort of thing and part of my commentary had to do with gee you know it's not right that there that every protocol will have a different depth of termination there needs to be some uniformity and the uniformity should be based on a reasoned data driven and to some extent consensus driven approach to this that has some kind of uniformity so the HRSA that had funded that funds these experimental organ donation protocols did put a panel together and we worked on this in the control setting right from right after that until 2010 and published this paper and I'm going to be talking a little bit about some of the findings in this paper so some of the issues regarding the legal definition of death that our group tackled had to do with the fact that the UDDA and the President's Commission chose the term irreversible but didn't define what they meant by irreversible in fact when you read through the document defining death they use the term permanent and irreversible interchangeably but there's an important distinction between those that I think and our group thinks is important to understand and these despite the fact that they've been used synonymously there's an important distinction there by the Oxford English Dictionary irreversible means cannot be undone irrevocable and it's an absolute and univocal thing it's essentially impossible at least with current technology whereas permanent means continually without change or enduring and that's an equivocal in a contingent condition that it's contingent on certain conditions without those without which they it doesn't exist so those are some points and so irreversible means cannot reverse using current technology permanent means will not be restored spontaneously or through intervention and if you look at the set of permanently lost functions they encompass those that are lost irreversibly and those that are lost permanently rapidly progress to those that are lost irreversibly and the question is which of these do we mean when we're saying for the determination of debt and we made the claim and not everybody goes along with this you'll hear exceptions that that the permanence was the accepted medical standard of the application of the circulatory criterion of death in the non donation circumstance terminally ill patient a hospital expected to die getting palliative care as a dnr order they stop breathing their heart stops beating they're immediately declared dead one doesn't require the doctor to prove that it's irreversible by either observing them for 30 or 40 minutes or however long it would take to make it transparent that it was irreversible or to try to resuscitate them and show that that's unsuccessful and thereby prove it's irreversible that is not necessary as long as it's permanent that's sufficient so one of the points about this was that it's already the standard in non donation circumstances one could say yeah but this is different here it's consequential and I agree it is very consequential in this situation and it was perhaps inconsequential in the previous one the non donation circumstance but let's move on to some of the other points about this in a conference in a Philadelphia in 2005 of a group of people involved in this from a variety of areas that included ICU people who were involved in death determination as well as transplant surgeons there was a consensus that when we talk about a Sicily we're not talking about electrical a system we're talking about mechanically a Sicily or so-called pulseless electrical activity because the issue in death is circulation not cardiac function and part of the confusion was that a former term of this was donation after cardiac death and I use it myself all of us did but that isn't really the issue and you look at the udda or any death statute or the meaning of death it all talks about circulation it doesn't talk about cardiac function now admittedly the heart is responsible for the circulation and the majority of the time except in special technical circumstances nevertheless it the distinction between those two becomes relevant here because what we need to show is the permanent cessation of circulation so pulseless electrical activity that does not lead to circulation counts as a Sicily commonly seen in cardiac arrest our group said that pulse palpation as a means to determine cessation of circulation was not sensitive enough you really needed to have either an indwelling arterial line or echocardiography looking for open and closing of the aortic valve or a Doppler looking for something in the organ donation to be sure that you didn't end up with the patient like the veered space not that we would do that in our units but it's pretty important to be sure and that the question of a Sicily was empirical I said that the permanent you can say that it's permanent when you can show that there will not spontaneously reverse and we will not reverse it so what about spontaneous reversing this is so-called auto resuscitation and some of the early work in this by Mike DeVita from Pittsburgh and other people show that there were these cases of so-called auto resuscitation where the heart would start again after 65 seconds would Mike didn't do and the early work didn't do was distinguish those who restored to PEA from those that restored the circulation and that was done later and this just lists the different lengths that were required for different protocols to try to eliminate auto resuscitation well the Hornby group at Montreal did a very important study published in critical care medicine in 2010 where they comprehensively viewed all published cases of auto resuscitation and they showed an important distinction and that is in plan withdrawal of life sustaining therapy such as that occurs in controlled DCDD there wasn't a single reported case of auto resuscitation to restored circulation yes there were cases to restored PEA but not circulation however in failed CPR where somebody had a primary cardiac rex drop dead resuscitated after 25 minutes the team says this is hopeless we're stopping they stop there have been innumerable cases reported of re starting of the heart to the point of circulation some of it is from the auto peep phenomenon some from other causes but that is a well-recognizing including one case of well documented up to seven minutes after failed CPR so what you can say in the controlled circumstances that after five minutes or some brief time even less than that of of assistly that respiratory and circulatory functions that are lost permanently we know that there will be no CPR and auto resuscitation will not occur and therefore it satisfies the criteria for permanent cessation of circulation in order to prove that we want to do some technique that sensitively measures the presence or absence of blood flow and wait at least two minutes probably even though argue arguably that's a long time because the database on which these data are generated is very small and therefore the confidence limits aren't too hot some comments about the dead donor rule and I don't want to take much more time but I think I have about two more minutes that of course it says the multi organ donor first must be dead in the corollary that is you cannot kill the donor to procure organs and some scholars and Bob and some of his colleagues have written very convincingly about that that if the patient consents for donation and the dying patients be on harm my position and maybe we can debate this a little bit in the Q&A period is that that it I worry about it as public policy because even though in highly motivated and intelligent donors I think it would work well for a general public policy I'm concerned about public confidence in the system so our panel recommended that the C in DC DD be circulatory and not cardiac it's always hard to retroactively change an accepted thing but we I think defended why this should be the issue of circulation and not cardiac function that we can continue to rely on permanence in the organ donation as we do in non donation circumstances that if we do that that correctly applied it respects the dead donor rule we need to use these blood flow measurements we should choose a conservative interval I'd say sisterly until such time that our database of cases exceed extends to such a point that the confidence intervals get sharp enough that we can reduce that it's just a matter of prudence to do that that we had talked about it come we didn't have time to get into that so I don't want to get into some of these other points I don't want to overstay my time here but what I tried to do was to first talk a little bit about the legal definition of death and parse some of the words of the udda particularly their term irreversible and make the point that the physicians involved meant permanent and if you look at the appendix f of defining death it's clear that they were talking about permanent which I think is the medical standard and that it's worth noting that the medical standard may not always be completely congruent with what you might call the ontological approach to this but it's consistent with the medical standard to use permanence that most of the brain death controversies have been mitigated to the point that groups that have studied this including recently feel that it continues to represent a coherent and framework with good public policy that now more of the controversies are in circulation and that these hearsay panel in our paper in critical care medicine a couple of years ago talked about the controlled situation where our group is now meeting and talking about the uncontrolled determining death of the uncontrolled donor which is frankly a much more challenging question thank you very much