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Archived Comments for: Clarifying the paradigm for the ethics of donation and transplantation: Was 'dead' really so clear before organ donation?

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  1. Autoresuscitation and organ donation after cardiac death: clarifying misunderstandings about the physiology of human circulation

    Mohamed Rady, Mayo Clinic Arizona

    18 September 2007

    Shemie dismisses autoresuscitation beyond 2 minutes of circulatory arrest in controlled donation after cardiac death [1]. The only evidence commonly cited for this dismissal is DeVita’s review of selected case reports on 108 patients who died without receiving cardiopulmonary resuscitation and were published between 1912 and 1970 [2]. DeVita continues to posit that there is no evidence that humans have recovered spontaneous circulation after 65 seconds of absent cardiac output. The same evidence is also the principal scientific basis for the expert opinion of the Committee on Non-Heart-Beating Transplantation of the Institute of Medicine to recommend the practice and protocols of donation after cardiac death in the US [3, 4].

    Shemie is rightfully skeptic about this limited and outdated evidence because of the lack of subsequent clinical studies for validation and reproducibility of DeVita’s claim. Since 1970, there have been major advances in medical practice in intensive care units. Donation after controlled cardiac death commonly occurs in patients in intensive care units. Shemie’s proposal to study autoresuscitation in 10,000 patients after controlled cardiac death in the intensive care unit should be most welcomed and embraced by the transplant community globally. But, this is doubtful!

    Certain principles of the physiology of human circulation were buried in the overzealous attempts to produce support for a questionable practice of donation after cardiac death. Pressure within blood vessels in a closed human circulatory system is determined by cardiac output (blood flow), resistance, and compliance of blood vessels (vascular resistance and capacitance). The cardiac output, vascular resistance and capacitance are independent physiological variables of the human circulation. Vascular resistance and capacitance are determined by the intrinsic contraction of smooth muscles around arteries and veins also called arterial and venous vasomotor tones, respectively. The cessation of cardiac output (circulatory arrest) leads to the disappearance of systolic arterial pressure and pulse pressure in a closed circulatory system. In circulatory arrest, arterial and venous vasomotor tones are maintained and can be measured as continuous mean pressures within a closed circulatory system (in diastole). In circulatory arrest (diastole), a pressure gradient between arterial (upstream) and venous (downstream) blood vessels (organ perfusion pressure) can be generated by differences between arterial and venous vasomotor tones. Coronary and cerebral perfusion pressures are generated when gradients between arterial and venous pressures develop across the coronary and cerebral circulation. Paradis et al reported a difference between arterial and venous pressures as small as 15 mmHg can lead to the return of spontaneous circulation in humans after circulatory arrest [5].

    The mechanism for autoresuscitation after cessation of cardiac output, within a closed circulatory system, is similar in controlled and uncontrolled circulatory arrest. The time to autoresuscitation after discontinuation of cardiopulmonary resuscitation is longer than 10 minutes after uncontrolled cardiac death. However, the time to autoresuscitation after discontinuation of mechanical lung ventilation and hemodynamic support has not been adequately studied in controlled cardiac death. In the absence of scientific proof from properly conducted clinical studies, Shemie’ s claim that the temporal characteristics of autoresuscitation after uncontrolled cardiac death are not applicable to controlled cardiac death is no more than a speculation. In both types of cardiac death, identical life support technologies are withdrawn: mechanical positive pressure ventilation, medications and other mechanical devices used for hemodynamic support are discontinued. It is pertinent to note that smooth muscles around blood vessels can maintain intrinsic contraction so that vasomotor tones can be sustained in both controlled and uncontrolled cardiac death. The temporal characteristics, determinants and threshold of arterial and venous pressure gradients for organ perfusion in controlled and uncontrolled cardiac arrest are unknown[6]. However, pressure gradient between arterial and venous blood vessels of vital organs are essential for spontaneous return of circulation and reperfusion of the brain after circulatory arrest.

    It should be noted that the Institute of Medicine proposed to replace the term “cardiac death” with “circulatory death” in the report published in 2006 to denote that the determination of circulatory death can be solely based on cardiac output (or blood flow) criteria [7]. The Institute of Medicine changed the nomenclature without scholarly scientific evidence or study of the in vivo temporal characteristics of circulatory arterial and venous smooth muscles activity and vasomotor tones after cessation of cardiac output in humans. What would William Harvey [8] say four centuries later when reputable institutions attempt to re-interpret the physiology of human circulation to serve the interest of a particular practice in medicine?

    The United Network for Organ Sharing (UNOS) introduced the Attachment III to Appendix B of the UNOS Bylaws (Model Elements for Controlled DCD Recovery Protocols) in March 2007 and became effective from July 2007 [9]. The UNOS Bylaws permit life sustaining technologies such as extracorporeal membrane oxygenation (ECMO) and artificial airways with lung inflation for bronchoscopy as donation related procedures after controlled cardiac death (i.e. 2 to 5 minutes of circulatory arrest) for the sole purpose of organ preservation. We commend Shemie for affirming that extracorporeal oxygenated circulation (or ECMO) applied after death for the purposes of organ preservation is a true violation of the dead donor rule, as death cannot be ensured if brain function recommences [1]. Currently, the UNOS Bylaws permit (after obtaining surrogate consent!) the resuscitation of organ donors after cardiac death for procurement and, effectively, the violation of the dead donor rule in the US.

    Mohamed Y. Rady MD PhD

    Mayo Clinic Arizona,

    Phoenix, Arizona

    Joseph L. Verheijde, PhD, MBA, PT

    Mayo Clinic Arizona,

    Phoenix, Arizona

    Joan L. McGregor, Ph.D.

    Arizona State University

    Tempe, Arizona

    Reference:

    1. Shemie SD: Clarifying the paradigm for the ethics of donation and transplantation: Was 'dead' really so clear before organ donation? Available at http://www.peh-med.com/content/2/1/18 (doi:10.1186/1747-5341-2-18) Philos Ethics Humanit Med 2007, 2:18.

    2. DeVita MA: The death watch: certifying death using cardiac criteria. Prog Transplant 2001 11:58-66.

    3. Institute of Medicine: Non-heart-beating organ transplantation medical and ethical issues in procurement. Washington, DC: National Academy Press; 1997.

    4. Committee on Non-Heart-Beating Transplantation II-The Scientific and Ethical Basis for Practice and Protocols Division of Health Care Services Institute of Medicine: Non-Heart-Beating Organ Transplantation: Practice and Protocols. Washington, DC: National Academy Press; 2000.

    5. Paradis NA, Martin GB, Rivers EP, Goetting MG, Appleton TJ, Feingold M, Nowak RM: Coronary perfusion pressure and the return of spontaneous circulation in human cardiopulmonary resuscitation. JAMA 1990, 263:1106-1113.

    6. Rady MY, Verheijde JL, McGregor J: Non-heart beating or cardiac death organ donation: Why we should care. J Hosp Med 2007, doi 10.1002/jhm.204

    7. Committee on Increasing Rates of Organ Donation-Board on Health Sciences Policy-Institute of Medicine: Organ Donation: Opportunities for Action. . Washington, D.C.: The National Academies Press; 2006.

    8. William Harvey (April 1, 1578 – June 3, 1657) . [http://en.wikipedia.org/wiki/William_Harvey]

    9. Bylaws Appendix B Attachment III - DCD Recovery Protocol Model Elements. http://www.unos.org/policiesandbylaws/bylaws.asp?resources=true

    and

    http://www.unos.org/PoliciesandBylaws2/byLaws/pdfs/bylaw_145.pdf

    Competing interests

    none

  2. Was 'dead' really so clear before organ donation?

    David Wainwright Evans, Queens' College, University of Cambridge (UK)

    25 September 2007

    The difference between someone who was unequivocally dead and someone who was manifestly alive was just as clear before the advent of organ transplantation as it is today. There is nothing ambiguous about use of the term 'complete and irreversible' to describe the former state. To suggest that there is serves merely to divert the argument from its essential focus in the context of organ procurement practice under the 'dead donor rule'. Neither is it helpful to describe death as 'a biological transition'. That is the process of dying.

    In the context of organ procurement from donors who have agreed to the removal of their organs after their death, discussion necessarily centres upon the time at which death can reasonably (and legally) be declared and certified for that purpose. That is what's new in death certification practice - and what has spawned attempts to conceptualize death in novel ways which permit its definition and diagnosis before the wanted organs deteriorate beyond use.

    As Shemie says - at least where permanent loss of brain function is an element of any concept of human death - "it is the arrest of brain blood flow that occurs after cardiac arrest that is of vital importance" (or, perhaps, lethal importance). He goes on to say that "the duration of circulatory arrest that precludes recovery of any residual amount of brain function is unknown but is lengthening" and refers(1) to the "ability to grow human brain cells 8 hours after death". The survival of human brain neurons in brain tissue taken up to 8 hours after (circulatory) death had earlier been reported by Dai,Swaab & Buijs(2) who found that so-called 'dead' neurons, if suitably treated, recovered oxidative metabolism, energy production and axonal transport.

    These findings serve to emphasize the impossibility of defining a 'moment of death' on the basis of current scientific knowledge (of brain function in particular).

    Any such 'moment', or period of time after final circulatory arrest after which death can be safely pronounced, must be seen as arbitrary and purely notional. Even as a concept, the 'moment of death' can exist only in some such context as the departure of the soul from the dying body.

    References

    1. Verwer RWH et al. Cells in adult human postmortem brain slices remain alive for several weeks in culture. FASEB J 2002;16:54-60

    2. Dai J, Swaab DF, Buijs RM. Recovery of axonal transport in "dead neurons". The Lancet 1998;351:499-500

    Competing interests

    None

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