Good afternoon. I would first like to thank the Society of Critical Care Medicine for the opportunity to share this perspective, these perspectives, on clinical management of the organ donor. I will grant I have the easy part. To get us started, I have no disclosures to make. Now, when we speak about protocol directive management of the organ donor, or in general an organized approach to care, we also have to think most organ donation cases occur within the context of death by neurologic criteria. Of that general subset, probably greater than, say, 85% to 90% or thereabouts that occur, they occur often as a result of ICP elevation with sudden brainstem herniation or sudden terminal brainstem dysfunction. And typically, the cardiovascular response, this is, think of it like an early, I like to think of it in my practice as an early warning of terminal brainstem dysfunction in that with the initial stages of brainstem herniation, typically, it is accompanied by a catecholamine rush. All catecholamine stores are unceremoniously dumped into the circulating blood volume, producing the characteristic spike in blood pressure, spike in heart rate. The numbers cited in this graphic are from a patient in my practice. And yes, the heart rate did get to nearly 250 beats per minute. Now, the initial spike that is characterized in the journals as phase one, that has a whole host of risks associated with it, not the least of which is a massive increase in SVR, massive increase in myocardial O2 demand, and massive vasoconstriction that increase myocardial work can cause a significant bump in troponin. And with massive vasoconstriction peripherally, typically, that shunts blood from the periphery to the central circulation and floods the alveoli characterized by neurogenic pulmonary edema. Those are part of the physiology of brain death that makes heart procurement and lung procurement so very, very challenging in this population. In a time-sensitive manner, typically, this is measured in hours rather than days. As the catecholamine stores are used up, then it becomes the hypotensive or hypodynamic phase where there is drop in heart rate, drop in blood pressure. And the risks associated in this stage are organ hypoperfusion and organ ischemia, acute tubular necrosis, as well as ischemic hepatopathy. Now, as if that's not complicated enough, in the brain-dead organ donor, we also have a pronounced pro-inflammatory state that most typically begins at the moment of the terminal event. And I'm separating moment of terminal event as separate from pronouncement of death by neurologic criteria. Now, I want to ask just a quick show of hands. In anyone's practice, how often is there, do people notice that there's an interval or a delay between clinically evident brainstem herniation and completion of formal brain death testing, including ancillary testing as appropriate? Yes. Now, it's also worthwhile pointing out this has dramatic implications for what happens at the other end. Think of this as a very, very complicated ballet. There's a set of, there's a team at the potential donor center. There is also a team at the potential recipient center. And so there's a great deal of what we do that can and does make a huge difference in recipient outcomes. And it's for that reason, I'm really, I'm going to be hitting this hard, recognizing and eliminating those intervals, eliminating delays in formal brain death testing. I'm choosing those terms very, very carefully. I don't want to say expedite brain death testing because that can be taken out of context, but it's recognizing delays in a care process and then simply applying the lens of quality management as a result. Now, we've seen, we've heard numbers like this before. This was updated as of December, yes, December 31st of 2023. And yes, there's always the graphics, very, very similar, very, very dramatic mismatch between organ, between people waiting for organ transplants, between donors, and between available transplants. Now, whenever I get the opportunity, I often prefer to use case exemplars from my practice to illustrate clinical points. This first patient, protocol-directed care, 50 years old, status post head trauma, fell down 15 steps. He obviously didn't do well. Pretty significant subdural hematoma, big midline shift, a lot of edema, and a lot of soft tissue swelling. On admission to the emergency department, GCS was 4 over 15, had a very rapid decline, became unresponsive, agonal respirations, right out of the gate. What does a care protocol tell us to do? We have to secure the airway ASAP. Airway was secured very, very rapidly and safely, and he then began to progress to less and less pronounced brainstem reflexes. Next, from the emergency department, in a case like this, the goal, if it is judged as somebody who is, for lack of a better term, potentially recoverable, then the care process would go emergency department, CAT scan, and then directly to the OR, bypassing the ICU. And that was his care process. In the OR holding area, he was experiencing further decline in his neurologic status. He had a hit of mannitol hyperventilation in the short term. He became markedly cardiovascular unstable, very hypertensive, very tachycardic. What is the most probable event occurring here? He's beginning to experience terminal brainstem herniation, as evidenced by we've got a radiographically documented injury. We have the spike in the heart rate and the blood pressure. Next, we absolutely cannot, absolutely cannot separate the family from this process. Now one can almost argue that with the patient being unconscious, they in some ways are spared the anxiety and the mortal fear of what's happening to them. The family is not. And so what also has to be hardwired into any care protocol is a family update, use any and every opportunity to develop trust between that family and between the health care team. And of that, using individualized language for describing injury severity, answering any questions. And one of my favorite things to do as far as my clinical recommendations is I have our chaplaincy on speed dial. And so communication of the initial prognosis and allowing trust to develop and nurturing that relationship between the family and the care team. Next, clinical decisions have to be made based on any and all clinical evidence at the time at a documented radiographic evidence of a severe injury. And his neurologic status began to progress from minimal brainstem reflexes to no brainstem reflexes within a period of a couple of minutes. And so flaccid abreflexic exam, pupil's fix dilated in at midpoint, documented lesion, he became bradycardic, and had refractory hypotension. What are the options? In a particular case like this where he's already lost his brainstem reflexes with a documented severe traumatic injury, then would it be appropriate to continue ineffective care? Probably not. And so next would be reasonable to eliminate any confounders, but then consider going forward with a full brain death protocol and looking for opportunities to eliminate delays in that particular care process. And so if he's very unstable, can we do a valid set of brain death testing exams, in particular an apnea test? The answer is no. So given the diagnosis of a presumptive brainstem herniation, yes, you'll notice I love using pictures and graphics whenever I get the opportunity. This is one, this is a general template. Not every care process or every care protocol from assessment through management and disposition has to follow this pattern. But generally, we have a pattern of there's the onset of the injury. There's however many hours it takes to progress that injury to the point where loss of brain and brainstem function occurs. When there's a potential delay between loss of brain and brainstem function, it has to be recognized. It then has to be communicated to the care provider. They have to push the panic button and as clinically appropriate, initiate and move forward with formal brainstem testing. Now what is ongoing and should be ongoing is nurturing that relationship between the family and the care team, speaking to the family members at their level of understanding, and then as clinically appropriate, involving the OPL. Next, in many instances, mechanism-based clinical donor management protocols such as early and aggressive use of volume resuscitation and hormonal replacement therapy, that is at times not done until much later in the process. Now this is simply a template, but if you had loss of brain and brainstem function here and say 20 hours between that terminal event and start of, say, clinically appropriate hormonal resuscitation, you've got 20 some odd hours where there is not the best, not the optimal clinical management and clinical support for cardiovascular stability. That in turn we know has implications for recipient outcomes. And so for that patient in this exemplar, this is his particular protocol timeline. And so his ED admission here went from there to the OR holding area, his probable terminal event occurred approximately here. Now in the lavender is the mean arterial pressure. It got up to around a map of around 140, volume resuscitation throughout. And so what happens with phase two, there is a significant increase in vessel capacitance. The tank gets bigger. We have to fill the tank up. And most effective, what I call cocktails, is a combination of lactated ringers and a colloid. My favorite combination is FFP, acrid blood cells, and crystalloid as a result. And so volume resuscitation needs to go throughout. And so probable terminal event here in the OR holding area, presser number one, presser number two is becoming bradycardic, and then now presser number three. And so looking at this, the clinical team had recognized, yes, what we're dealing with is highly probable brain stem herniation, and the patient is having those cardiovascular, those pulmonary consequences of the terminal event. We then initiated, as a team, the hormonal resuscitation protocol. We had two grams of methylpred, vasopressin was started at one unit per hour, and he had T4. There's a number of ways to do this that may differ a little bit between hospital A and hospital B. However, in our protocol, it was 50 mics of ivibolus followed by an infusion, a titratable infusion at 20 mics per hour. We also had insulin and dextrose. And we can about set our watch by it. We saw a dramatic increase in his main arterial pressure. He became more stable to the point where vasoactive and inotropic agents were able to be weaned off, and he became stable enough to go to tolerate the full brain death clinical exam protocol, the apnea test, and it was, and if somebody is on three pressers, how many people here feel really comfortable about taking that patient two blocks away and down to the basement to get a flow study? That's right, I don't either. And so it became much, much safer for the patient, and I think with him being much more stable with early and clinically appropriate use of hormonal resuscitation, along with other resuscitative measures, that ended up producing a very, very good outcome. And so clinical outcomes, oxygenation and hemodynamic profile improved, lowered auto PEEP, regional perfusion improved, and we had one issue with movements following his terminal event. How many people have seen complex spinal reflexes that can really get the family squirrely? Yes. How many people have seen auto-triggering of a mechanical ventilator that can get the family very squirrely? And so in this particular case, he didn't have complex spinal reflexes, but he was over-breathing the ventilator at one point, as he was well into phase two. What's characteristic with phase two, vasoplegia, significant decrease in systemic vascular resistance, big increase in stroke volume, and with compliant lung tissue, there can be cyclical compression versus relaxation of the lung tissue, producing this. And so this is a screenshot from a servo eye ventilator. And so we can see these fairly uniform additional oscillations in the flow waveform. What's significant is ventilator set rate is 12, measured rate is 18. Remember, this patient had no cough, no gag, no corneal reflex, had all the clinical findings of terminal herniation. What's also important, flow trigger at two liters per minute, flow trigger characteristically is more sensitive. And so what we ended up doing as a team, how many people here are respiratory therapists? Well, I'll still get on my soapbox. Respiratory therapy is your best friend. Respiratory therapy, we were shoulder to shoulder throughout this, evaluated the patient, and changed his trigger mode and sensitivity from flow to pressure trigger at minus two, and lo and behold, his set rate is 12, measured rate is 12, and what was marching through, those cardiac oscillations, each of which was a perfect match with pulse volume, with turning up the dumb QRS volume on the bedside monitor, as well as having another team member staring at the pericordium, noting the chest wall movements. Outcomes OPO is involved clinically, as appropriate. Donation outcomes, all of these measures preserve the option of donation for the family, liver was recovered and transplanted, kidneys were recovered and transplanted, family considerations. What also was key, rightly, we had a big benefit from early involvement with chaplaincy, with other team members, nurturing that relationship between the family and the care team, and they began to share, patient was a very giving individual. It turned out, I can't say it was a completely positive experience, but they got some solace, they got some support and could see some good coming out of what was a tragedy for them. This next one, case exemplar number two, this is, yes, I love this picture, he lost a fight with his girlfriend, she stabbed him in the eye with an umbrella. That's true, I was there. Fragmented left orbit, significant intraventricular hemorrhage, a lot of extravasation of contrast, aggressive care, and despite a aggressive hemicraniectomy, he continued to decline. And so we're seeing here, what do we see characteristic with an aggressive and an effective management protocol for the potential donor, aggressive volume resuscitation as appropriate. And so terminal event appears to be around here, and then with a characteristic with maximizing dose of phenylephrine, and the mean arterial pressure is in the blue. And so as the case proceeds, she was ultimately requiring very, very high doses of phenylephrine, looked at the clinical picture, and found dramatic cardiovascular instability in the setting of strong presumptive diagnosis of brain stem herniation. And so prior to formal brain death testing, we ended up initiating standard donor management protocol, methylpred 2 grams, vasopressin, and T4. It became significant, we could about, as before, set our watch by it, pneumatic decrease rapidly in pressure requirements, and that enabled very safe and very stable situation where formal brain death testing could be completed. And so again, we had the best outcome that was possible in this setting. The appropriate conversation was had between the OPO coordinator and the patient's family, and they agreed to donation. Next, my contact information is available. If anyone has any questions, I believe we're available. Thank you so much for the opportunity. Thank you.

organ donation

neurological criteria

clinical management

donor protocols

family communication