Research in imminently dying patients: an essential research direction?
How do we know that someone has died? It turns out death is a lot more complicated to identify than we might expect. In the movies, we might see the dying character on a hospital bed in the intensive care unit (ICU). They are fully lucid and speaking their prophetic last words to the teary-eyed audience. Seconds later, they peacefully turn their heads to the side and close their eyes—we hear the stereotypical flatline of the cardiac signal on the bedside monitor—scene.
In real life, there are a number of factors to consider. Patients tend to be critically ill and heavily sedated, so talking is often off the table. Without obvious behaviours that show the patient is still aware, doctors have to look at several parts of a patient's physiology: Is the heart pumping any blood? Is this blood adequately reaching the brain? Is it sufficient to produce meaningful function? Is the brain already too damaged to produce meaningful function? All these considerations have to be weighed prior to declaring that a patient is dead.
The situation is even more complicated in the context of organ donation, where death is declared by "circulatory criteria". At this point, the heart has not yet "flatlined" (see Figure 1) but is proposed to become so weak that brain activity and, therefore, awareness, pain and personhood are no longer possible. You won't necessarily wait for the "flatline" because that would mean that the organs are no longer receiving oxygenated blood from the heart and may quickly become unviable – perhaps even preventing another life from being saved by the donated organs. At the same time, you need to wait long enough that there is absolutely no risk of the patient experiencing any pain or having any experience during the organ donation process. While there are very strong theoretical and medical support that no experience is possible, it has yet to be experimentally determined. The catch is that the only way to get at this question is to work directly with imminently dying patients.
Example arterial blood pressure tracing. The top plot shows an example of cardiac arrest (“flatline”) and below indicating a gradual decrease in arterial blood pressure, which can occur in the context of withdrawal of life-sustaining measures.
So before science can start answering this question, it is essential to create an ethical framework to guide research in this vulnerable patient group. A recent study by researchers at Western University outlined several necessary considerations when conducting research in imminently dying patients. They describe their ethical approach within the context of their current study, called NeuPART (which stands for Neurologic Physiology after Removal of Therapy). In so doing, they hope to provide a roadmap for empirically measuring physiological changes during withdrawal of life-sustaining measures in an ethically but scientifically rigorous way. The goal of this work is to convince the broader research community, care settings, and potential patients and their families that this research can be conducted ethically.
Clearly, this is about as difficult a situation as it gets to unpack ethically. The researchers start at the foundational principles that guide research ethics. Specifically, they must be guided by three things: justice, respect for persons, and beneficence. Justice requires that the potential benefits, risks, and burdens of research participation apply fairly to each group. Next, respect for persons means that research must recognize the intrinsic value of people and allow them to make informed consent about participation. Last, beneficence means that participants must be protected from harm and get as much as possible from the research.
In addition, they laid out a set of eight questions that future research can use as a roadmap when working with this vulnerable patient group. Those questions can largely be summarized as follows: Is this patient group required? Are the potential risks justified, minimized, and worth the benefits? How is consent obtained from supplementary decision-makers, and how are their feelings best protected? How will unexpected findings be handled? How will clinical staff and researchers be protected?
This study carefully laid out how NeuPART addresses each of these questions. Ultimately, only imminently dying patients can allow us to understand physiological changes as we die – so there are no substitutes. The researchers argue that the patient will not be unfairly burdened or harmed by the testing procedure. For example, the standard of care for these patients (e.g., the administration of sedation) will not change. Additionally, the equipment used to measure physiological changes will not cause additional harm to the patient (although it may add to the time spent before starting the withdrawal process). Moreover, there is a potentially large social benefit of the study by ensuring that organ donation patients are not undergoing any harm. One key consideration is care in how researchers obtain consent from supplementary decision-makers, as they are likely experiencing a large range of emotions that may cloud their ability to understand the study and make a decision in the best interest of their loved one.
Importantly, the researchers lay out a plan that makes it likely that their research programme will be successful. With the NeuPART protocol, they can measure how essential physiological components change during the dying process. Specifically, they have separate techniques to simultaneously measure changes in pulse, electrical activity of the heart, blood flow to the brain, and electrical activity in the brain. By combining these different measurement tools, they can objectively measure dynamic changes in how the heart and circulation affects the brain during the dying process. This information is invaluable for inferring the presence of awareness under different physiological conditions.
Despite how ethically fraught and emotionally charged these clinical questions may be, it is hard to deny the importance of having a more complete understanding of death and death declaration. The ethical roadmap provided by this study justifies further exploration of research projects in this understudied patient group, while ensuring that the risks and benefits of research for all stakeholders are appropriately considered. While still preliminary, this roadmap enables projects such as NeuPART, which hope to increase our confidence in the organ donation process, better understand what happens to our loved ones as they pass, and ensure that those who bravely go through one of the greatest sacrifices of their lives do not experience undue harm.
Original Article: Murphy, N., Weijer, C., Debicki, D., Laforge, G., Norton, L., Gofton, T., & Slessarev, M. (2023). Ethics of non-therapeutic research on imminently dying patients in the intensive care unit. Journal of Medical Ethics, 49(5), 311–318. https://doi.org/10.1136/medethics-2021-107953 [Neurology]