title: Relating Clinical and Electrophysiological Parameters in Death Determination in a Laboratory Model of Progressive Hypoxemia.
abstract: Death after withdrawal of mechanical ventilation frequently follows the sequence of progressive hypoxemia and hypotension leading to cardiac arrest. Accurate timing of the determination of death is fundamental to trust in controlled donation after circulatory death (cDCD) programs and is generally based on cessation of circulation (pulselessness), brain function (apnea), and the passage of time. If death is understood to be the unresuscitatable loss of brain function, the clinical determination that death following apnea and pulselessness has occurred is largely inferential. We sought to elucidate the relationship between the available clinical variables and the loss of brain function and its inability to be resuscitated.
  
  
  
  We developed a rat model of progressive hypoxia resulting in apnea and circulatory failure. We monitored clinical physiological variables including heart rate, respiration, and arterial pulse pressure. In addition, we simultaneously monitored spontaneous and evoked brain activity within the hippocampus through microelectrode field potential recordings. We also examined neurological function following restoration of pulmonary and circulatory function.
  
  
  
  Our data provide evidence that in a model of progressive hypoxemia, loss of spontaneous and evoked brain activity preceded the loss of circulation. Importantly, the data suggest that the loss of brain function, in the presence of restored cardiopulmonary indices, occurred at a time point after apnea but before the loss of detectable arterial pulse pressure.
  
  
  
  These are important data that act as a conceptual reference point when clinicians undertake the inferential activity of identifying the time prior to which a patient has died following progressive hypoxemia and while observing apnea and pulselessness.
authors.affiliation: Keenan Research Centre for Biomedical Science in the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
authors.forename: Eugene
authors.initials: E
authors.lastname: Park
authors.affiliation: Keenan Research Centre for Biomedical Science in the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
authors.forename: Elaine
authors.initials: E
authors.lastname: Liu
authors.affiliation: Division of Critical Care Medicine, Montreal Children's Hospital, Montreal, QC, Canada.|McGill University Health Centre and Research Institute, Montreal, QC, Canada.
authors.forename: Sam D
authors.initials: SD
authors.lastname: Shemie
authors.affiliation: Keenan Research Centre for Biomedical Science in the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada. bakera@smh.ca.|Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada. bakera@smh.ca.|Departments of Anesthesia and Surgery, Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada. bakera@smh.ca.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Baker
mesh_terms: D000818:Animals; D001926:Brain Death / Q000503:physiopathology*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004562:Electrocardiography; D004569:Electroencephalography; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000379:methods*
keywords: Animal model; Brain death; Controlled donation after circulatory death; Death; Electrophysiology; Hypoxia; Resuscitation; cDCD