When Is Dead Really Dead? Results From the Largest International Study of Its Kind

Heart Beat

A new international study documents the physiology of the dying process.

The death prediction and physiology after removal of therapy study (DePPaRT study)

A new international study, led by Dr. Sonny Dhanani of the CHEO Research Institute, and published in the January 28, 2021, issue of the New England Journal of Medicine, documents the physiology of the dying process. Working closely with the Canadian Donation and Transplantation Research Program, the research team asked over 600 families to allow their loved ones in the ICU to have their vital signs monitored during the dying process. This is the largest international study of its kind.

Why is a study like this important?

For families to choose organ donation when a loved one has died, they must be able to trust that death has really happened and that it is irreversible. Trust allows people to decide to donate at a time of grief and allows the medical community to feel comfortable opening a dialogue about donation. For donation after circulatory-determined death to be medically possible, death must be declared within a window of time after life sustaining measures are withdrawn. Yet, stories persist about people “coming back to life” following a declaration of death, and there was little evidence to inform the medical understanding of dying.

“To do this, we had to go into ICUs and monitor people as they were dying. This is a very personal experience. And here we were collecting data, sending it to a server, downloading it and having people review the vital signs … how things stopped and if they restarted. People were worried. Some physicians didn’t want to do it. Some researchers felt uncomfortable. But we knew we should keep going when we met Heather.”

– Dr. Sonny Dhanani, MD
DePPaRT Study Lead
Investigator, CHEO Research Institute
Chief Critical Care, Children’s Hospital of Eastern Ontario
Associate Professor, University of Ottawa

What did the study find?

Dr. Dhanani and his team found that the classic “flatline” of death is not so straightforward. The study showed that cardiac activity often stops and re-starts several times during the dying process before it finally stops completely — but no one regained sustained circulation or consciousness. The study provides evidence to support the current standard to wait for 5 minutes after the heart stops before determining death and proceeding to organ donation.

How do you ask a family whose loved one is dying in the ICU to participate in a research study on organ donation? DePPaRT was empowered by the support and perspectives of a family partner, Ms. Heather Talbot, a woman whose son became a donor after dying in a car accident. The Canadian Donation and Transplantation Research Program’s Patient, Family, and Donor Partnership Platform connected Heather with the DePPaRT team in 2015, and she took on the emotional challenges of joining as a consultant. Heather provided feedback from a family’s perspective, contributing ideas on how to appropriately approach families of dying patients. Her ability to reflect on her experiences and apply them to the study was pivotal for the project’s success. Her contributions helped achieve a family consent rate of 93% and dampened the team’s fears of overstepping boundaries. Her son’s gift of organ donation saved at least four lives and her involvement in DePPaRT is multiplying those gifts.

“This is an outstanding example of the powerful impact that a national framework for collaborative team science can achieve. Through the Canadian Donation and Transplantation Research Program, we have brought together different research communities, patient, family and donor partners, stakeholder organizations, and health care professionals who take non-traditional paths to doing research. This has created new synergies and new knowledge that will help more Canadians become donors and more patients receive transplants.”

— Dr. Lori West, MD, DPhil
Canada Research Chair in Cardiac Transplantation, University of Alberta
Director, Canadian Donation and Transplantation Research Program
Officer of the Order of Canada (2020)

What is the take away for the public?

Families and health care teams can trust that when death is determined, it is safe to begin the organ donation process. DePPaRT study data can now be used to inform policy and guidelines for determining death for organ donation both nationally and internationally. Further work using the study data will allow donation and transplant teams to predict how long it will take patients to die after removing life-sustaining measures. Predicting a time of death would be immensely useful to coordinate a donation and improve how organs are allocated.

“On behalf of the Canadian Institutes of Health Research (CIHR), I would like to congratulate CDTRP and the DePPaRT team on the publication of this important study. CIHR is very pleased to be supporting a national network like CDTRP that has been able to bring together multiple stakeholders in the transplant area. This study is an example of the impactful work collaborations such as this one can achieve that will lead to improved outcomes for Canadians waiting for transplants.”

— Dr. Charu Kaushic, MSc, PhD
Scientific Director, CIHR Institute of Infection and Immunity

Reference: “Resumption of Cardiac Activity after Withdrawal of Life-Sustaining Measures” by Sonny Dhanani, M.D., Laura Hornby, M.Sc., Amanda van Beinum, M.Sc., Nathan B. Scales, Ph.D., Melanie Hogue, M.Sc., Andrew Baker, M.D., Stephen Beed, M.D., J. Gordon Boyd, M.D., Ph.D., Jennifer A. Chandler, L.L.B., L.L.M., Michaël Chassé, M.D., Ph.D., Frederick D’Aragon, M.D., Ph.D., Cameron Dezfulian, M.D., Christopher J. Doig, M.D., Frantisek Duska, M.D., Ph.D., Jan O. Friedrich, M.D., D.Phil., Dale Gardiner, M.D., Teneille Gofton, M.D., Dan Harvey, M.D., Christophe Herry, Ph.D., George Isac, M.D., Andreas H. Kramer, M.D., Demetrios J. Kutsogiannis, M.D., David M. Maslove, M.D., Maureen Meade, M.D., Sangeeta Mehta, M.D., Laveena Munshi, M.D., Loretta Norton, Ph.D., Giuseppe Pagliarello, M.D., Tim Ramsay, Ph.D., Katerina Rusinova, M.D., Ph.D., Damon Scales, M.D., Ph.D., Matous Schmidt, M.D., Andrew Seely, M.D., Ph.D., Jason Shahin, M.D., C.M., Marat Slessarev, M.D., Derek So, M.D., Heather Talbot, B.Ed., Walther N.K.A. van Mook, M.D., Ph.D., Petr Waldauf, M.D., Matthew Weiss, M.D., Jentina T. Wind, R.N., Ph.D. and Sam D. Shemie, M.D. for the Canadian Critical Care Trials Group and the Canadian Donation and Transplantation Research Program, 27 January 2021, New England Journal of Medicine.
DOI: 10.1056/NEJMoa2022713

This research was supported by the Canadian Institutes of Health Research as part of the Canadian Donation and Transplantation Research Program, the CHEO Research Institute, and Karel Pavlík Foundation.

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