Breaking New Ground: Unraveling the Physiology of Circulatory Death During Withdrawal of Life Support with Dr. Mypinder Sekhon
What if, based on the comment of a grieving father, you left work that day, also grieving, and realized that you had potentially stumbled into a groundbreaking idea that could transform what we know about the brain and death?
That’s what happened to Dr. Mypinder Sekhon, lead investigator and critical care physician at Vancouver General Hospital Intensive Care Unit, last February. A young man in his 20s had undergone a post-cardiac arrest, which refers to the period after the heart has stopped beating and has been successfully restarted. This is a critical period where the brain and other organs are at risk of irreversible damage. There was nothing further that could be done to save his life and his family wanted to donate their son’s organs.
“In order to be considered for organ donation, through death determination by circulatory criteria (DCC), a patient must be determined to have severe, irreversible brain injury with no hope of survival. DCC is only considered after a decision has been made to withdraw life-sustaining treatments.
But his heart continued to beat beyond the time allowance. When I told his parents, David and Lora, that we wouldn’t be able to use Michael’s organs, they were devastated that their son was not able to provide the gift of life. And David said to me, “You don’t understand; Michael is gone. I looked in his eyes; he’s gone.”
That night, Dr. Sekhon reflected on what David had said.
“I wondered if maybe he was onto something,” says Dr Sekhon. “Eyes are the only clinical, physical way to look inside the brain. What if what David was saying is that the brain dies before the heart does?”
And this encounter, this father’s observation, was the catalyst for Dr. Sekhon’s prospective feasibility study, which was the recipient of a 2023 Organ Donation and Transplant Research Foundation of British Columbia (ODTRF) Venture Grant: Characterizing the cerebrovascular physiology of circulatory death during withdrawal of life sustaining therapies in humans. Read more about this study.
Profound Implications
Fast forward 18 months and Dr. Sekhon has achieved a 71% enrollment rate in his groundbreaking pilot study, added additional researchers to his team, gained another grant, and submitted a manuscript for publication in a top-tier medical journal.
Determining the precise moment that brain function is absent stands to revolutionize practice. Ultimately, it will increase the number of organs available for transplant (currently a third of people eligible to be considered for organ donation aren’t able to donate because their heart continues beating longer than the cut-off time). The implications of this work are profound,” says Dr. Sekhon. “This body of work transcends fields of medicine and aspires to understand a universal process that is common to every single person and patient.”
Initial Findings
“We have determined that during dying, the brain is not able to draw oxygen out of the blood as well as other organs so it ceases function before other organs.,” says Dr. Sekhon. “We’re seeing that brain blood flow stops before the heart.”
He is careful to note that there is variation with this, and that individualization is important. But overall understanding of how the brain ceases function brings a heightened level of understanding to a range of neuro-related conditions, such as stroke, trauma and dementia.
“By understanding of how the brain dies, we can understand how to keep it alive,” explains Dr. Sekhon. In addition, Dr. Sekhon has been able to identify a blood test for the brain that can help families to know when their loved one in palliative care will pass.
“This is an important, empowering piece of information for families to know about their loved one – when they are likely to die. We now have a quantifiable, reproducible way of determining this, versus the current practice where a physician tries to predict a timeline based on signs that they’re observing.”
Research is Care
“When we think about the brain, it’s the most complex and important organ we have – but it’s also the least understood,” says Dr. Sekhon. “The dying process, in some ways, is a model of the most intense stimulus that the brain will ever get: low-flow, low oxygen, and high carbon dioxide tension, which all do different things to the brain. We monitor this process in multiple ways, complete with blood tests at the bedside to identify novel functions, and a full brain and heart autopsy to correlate what we saw in the monitoring and blood test with what actually happened in the tissue. The truth is always in the tissue.”
Dr. Sekhon confirms that new information has been revealed by the autopsies conducted as part of this research. The families of patients who have been enrolled in the study receive the autopsy results; Dr. Sekhon meets with and stays in touch with families to walk them through the results, give updates and help them understand medical jargon. Through this element of the study, the real-life implications continue to impact families.
What Unites Us All
“Initially we got feedback that this study was not realistic, and no one would consent to be part of it, but we have seen that it is very empowering for families. Many people want to make more out of a loved one’s dying process,” reflects Dr. Sekhon, sharing that his team enrolled 25 patients into their study in six months. “What is a terrible time is made slightly less terrible when families know that others will benefit from their loved one’s involvement in research.”
Dr. Sekhon states that the people who have agreed to have their loved one be part of this study are from all walks of life.
“I remember a case where I was in a patient’s room, literally getting blood samples from their central line while 20 people were gathered around the bedside, all singing religious hymns,” recalls Dr. Sekhon. “People from different cultures, different beliefs, different socio-economic backgrounds have all consented. I have been in the room during a smudging ceremony, Reiki being conducted – the participants are diverse and representative of our population.”
And while there isn’t much commonality across those who enlist to participate, there is a common denominator that unites everyone involved.
“Death is universal,” says Dr. Sekhon. “It’s a process that every single person has ever undergone and will undergo and yet, we don’t know much about it. This study is helping to change that.”
Next Steps
The initial outcomes of this work are already paving the way for further exploration. Dr. Sekhon and his team just enrolled their first Medical Assistance in Dying patient in their study so they can study patients with healthy brains. This project is co-funded by the ODTRF and Vancouver Coastal Health Research Institute.
This past November, Dr. Sekhon presented preliminary findings from his initial study at the Canadian Critical Care Forum in Toronto. Michael’s parents David and Lora, active patient partners in the project, were at his side for the presentation.
“This idea came from a patient’s family, and the findings that we are seeing are directly applicable to patients and families,” says Dr. Sekhon. “It has made this work feel different, than say, being a researcher just trying to come up with an idea to explore. It is far and away the most meaningful research I have undertaken.”
Planting the Seed
“In academia it’s very hard to get pilot data with a novel idea,” says Dr. Sekhon. “In 2023, with the ODTRF awarding us the Venture Grant, they took a real risk on us. By funding this out-of-the-box, unconventional idea, the ODTRF seed money allowed us to take this leap, and we have been able to prove what’s possible.”
Determining the precise moment that brain function is absent will forever change the landscape of donation and transplant medicine, enabling more people to donate and ensuring a better quality of organ for transplant. And it has far-reaching implications when it comes to revolutionizing practice.
Likening this project to that of a garden, Dr. Sekhon sees the initial grant by the ODTRF as what enabled the planting of the seed.
“I think that the best way to honour the donor funds we have been granted is to plant this first seed and then grow our findings into as many other areas as we can to find continued ways to expand this work and ensure that the ODTRF’s initial investment continues to flourish and benefit patients and their families.”