Organ donation from intensive care units in England.

OBJECTIVE--To audit all deaths in intensive care units (excepting coronary care only and neonatal intensive care units) in England to assess potential for organ procurement. DESIGN--An audit in which 14 regional health authorities and London special health authorities each designated a regional liaison officer to identify intensive care units and liaise with Department of Health and the Medical Research Council''s biostatistics unit in distribution, return, and checking of audit forms. Audit took place from 1 January to 31 March 1989 and will continue to 31 December 1990. SETTING--278 Intensive care units in England. PARTICIPANTS--Colleagues in intensive care units (doctors, nurses, coordinators, and others), who completed serially numbered audit forms for all patients who died in intensive care. RESULTS--The estimated number of deaths in intensive care units was 3085, and validated audit forms were received for 2853 deaths (92%). Brain stem death was a possible diagnosis in only 407 (14%) patients (about 1700 cases a year) and was confirmed in 282 (10%) patients (an estimated 1200 cases a year). Half the patients (95% confidence interval 45% to 57%) in whom brain stem death was confirmed became actual donors of solid organs. Tests for brain stem death were not performed in 106 (26%) of 407 patients with brain stem death as a possible diagnosis, and general medical contraindication to organ donation was recorded for 48 (17%) of 282 patients who fulfilled brain stem death criteria before cessation of heart beat. The criteria were fulfilled before cessation of heart beat and in the absence of any general medical contraindication to organ donation in 234 patients, 8% of those dying in intensive care (an estimated 1000 cases a year). Consent for organ donation was given in 152 (70%) of 218 cases (64% to 76%) when the possibility of organ donation was suggested to relatives. In only 14 out of 232 families (6%; 3% to 9%) was there no discussion of organ donation with relatives. Corneal suitability was recorded as "not known" in a high proportion (1271; 45%) of all deaths and intensive care units reported only 123 corneal donors (4% of all audited deaths). CONCLUSION--When brain stem death is a possible diagnosis tests should always be carried out for confirmation. Early referral to the transplant team or coordinator should occur in all cases of brain stem death to check contraindications to organ donation. There should be increased use of asystolic kidney donation, and patients should be routinely assessed for suitability for corneal donation. Finally, more publicity and education are necessary to promote consent.     

ETHICAL DEBATE OVER ORGAN DONATION IN THE CONTEXT OF BRAIN DEATH

This study investigated what information about brain death was available from Google searches for five major religions. A substantial body of supporting research examining online behaviors shows that information seekers use Google as their preferred search engine and usually limit their search to entries on the first page. For each of the five religions in this study, Google listings reveal ethical controversy about organ donation in the context of brain death. These results suggest that family members who go online to find information about organ donation in the context of brain death would find information about ethical controversy in the first page of Google listings. Organ procurement agencies claim that all major world religions approve of organ donation and do not address the ethical controversy about organ donation in the context of brain death that is readily available online.     

Potential availability of cadaver organs for transplantation.

OBJECTIVE--To determine the potential number of cadaver kidney donors by applying defined donor criteria to people dying in hospital. DESIGN--Prospective study of all deaths occurring in 21 hospitals from 1 September 1988 to 31 August 1989. Questionnaires were administered to medical and nursing staff and families of potential donors aged 1-69. SETTING--Acute care hospitals in Gwent, South Glamorgan, Mid Glamorgan, West Glamorgan, Pembrokeshire, and East Dyfed health authorities, serving a population of 2.2 million. MAIN OUTCOME MEASURES--Cause of death, age, ventilation at time of death, diagnosis of brain death, and consideration of consent. RESULTS--Adequate data were available for 9840 of 10,095 hospital deaths (97.5% coverage). 188 patients aged 0-69 were identified as potential organ donors (widest definition), and of these 108 died without being ventilated at the time of death. Tests of brain stem death were formally completed in 57 cases, and organ donation was considered by the families of 47 of these potential donors. 26 patients became organ donors. Patients aged 50-69 with stroke were less likely to be ventilated than those aged less than or equal to 49 (21/96 v 24/34). Families of potential donors aged 20-39 were least likely to give permission. CONCLUSIONS--The supply of donor organs (specifically kidneys) could be increased by altering the management of patients aged 50-69 dying of severe cerebrovascular disease in general medical wards, in particular by increasing the proportion ventilated. The ethics of elective ventilation for the purposes of organ donation require discussion.     

Non-heart-beating organ donors as a source of kidneys for transplantation: a chart review

BACKGROUND: Organ transplantation is the treatment of choice for patients with end-stage organ failure, but the supply of organs has not increased to meet demand. This study was undertaken to determine the potential for kidney donation from patients with irremediable brain injuries who do not meet the criteria for brain death and who experience cardiopulmonary arrest after withdrawal of ventilatory support (controlled non-heart-beating organ donors). METHODS: The charts of 209 patients who died during 1995 in the Emergency Department and the intensive care unit at the Foothills Hospital in Calgary were reviewed. The records of patients who met the criteria for controlled non-heart-beating organ donation were studied in detail. The main outcome measure was the time from discontinuation of ventilation until cardiopulmonary arrest. RESULTS: Seventeen potential controlled non-heart-beating organ donors were identified. Their mean age was 62 (standard deviation 19) years. Twelve of the patients (71%) had had a cerebrovascular accident, and more than half (10 [59%]) did not meet the criteria for brain death because one or more brain stem reflexes were present. At the time of withdrawal of ventilatory support, the mean serum creatinine level was 71 (29) mumol/L, mean urine output was 214 (178) mL/h, and 9 (53%) patients were receiving inotropic agents. The mean time from withdrawal of ventilatory support to cardiac arrest was 2.3 (5.0) hours; 13 of the 17 patients died within 1 hour, and all but one died within 6 hours. For the year for which charts were reviewed, 33 potential conventional donors (people whose hearts were beating) were identified, of whom 21 (64%) became donors. On the assumption that 40% of the potential controlled non-heart-beating donors would not in fact have been donors (25% because of family refusal and 15% because of nonviability of the organs), there might have been 10 additional donors, which would have increased the supply of cadaveric kidneys for transplantation by 48%. INTERPRETATION: A significant number of viable kidneys could be retrieved and transplanted if eligibility for kidney donation was extended to include controlled non-heart-beating organ donors.     

Public awareness of organ donation.

A telephone survey of public attitudes toward organ donation and transplantation was conducted in a community in southwestern Ontario. The subjects were selected at random; the response rate was 57%. Of the 50 respondents 62% stated that they had signed the organ donor card accompanying their driver''s licence. These respondents were more likely than those who did not sign it to have discussed organ donation with their families. At least 80% of the respondents said they would agree to donate their organs and those of their next-of-kin, and 80% said that the organ donor card should be considered a legal document. Organ transplantation was regarded by all but one respondent as an acceptable medical procedure. Also discussed were concerns about organ donation and possible strategies to improve the availability of organs for transplantation.     

Brain stem death and organ donation.

Organs for donation are in short supply in the United Kingdom, resulting in allegations that relatives of potential donors are not being asked for consent. Legislation on "required request" has been proposed to overcome this. The incidence, causes, complications, and patterns of organ donation in brain stem dead patients in one referral centre were studied over 12 months. Data were collected on all patients fulfilling criteria for brain stem death or considered suitable for donating organs after circulatory arrest. Forty two patients fulfilled the criteria for brain stem death, and in 10 further patients circulatory arrest occurred before formal testing was finished. The major causes of brain stem death were head injury (28) and intracranial haemorrhage (17). Consent to organ donation was obtained for 24 potential donors, and organs were donated by 23 of them. Twenty nine patients did not donate organs. The commonest reasons for failure to donate were medical unsuitability (13) and the coroner not releasing the body (eight). Consent was not sought in three cases, and the relatives refused consent in the remaining five. This study suggests that required request will not considerably increase the supply of donor organs.     

Brain death and the anencephalic newborn

We will set the stage for our analysis by reviewing selected medical aspects of anencephaly, outlining the history of the use of anencephalics as organ sources, and summarising the results of an important study recently completed at Loma Linda University. We will then employ some of the arguments and justifications underlying the Uniform Determination of Death Act (UDDA) to claim that anencephaly is morally equivalent to brain death, i.e., the reasons for considering brain-dead patients to be dead also apply to anencephalics. Finally, we will critique our proposal and discuss its implications.     

Brain death in Britain as reflected in renal donors.

The diagnostic mix of 1228 brain-dead renal donors in Britain was similar to that of 479 cases of brain death recently reported from three neurosurgical units. About half the donors came from non-teaching hospitals without a neurosurgical unit, many of them small and distant from the centre. The different circumstances that preceded brain deaths were examined--namely, diagnosis and whether the fatal ictus of brain damage occurred when the patient was already in hospital--to explain why donors spend varying times on the ventilator. Head injuries accounted for half the donors, and intracranial haemorrhage for almost a third. While many potential donors are not made available, the size of the pool has been overestimated, particularly in regard to head injury. Reduction in organ donation since "Panorama" has been very uneven, with some places increasing their yield; this suggests reluctance of doctors to initiate donation rather than relatives withholding permission.     

Selection of reference genes for normalisation of real-time RT-PCR in brain-stem death injury in Ovis aries

Background  

Heart and lung transplantation is frequently the only therapeutic option for patients with end stage cardio respiratory disease. Organ donation post brain stem death (BSD) is a pre-requisite, yet BSD itself causes such severe damage that many organs offered for donation are unusable, with lung being the organ most affected by BSD. In Australia and New Zealand, less than 50% of lungs offered for donation post BSD are suitable for transplantation, as compared with over 90% of kidneys, resulting in patients dying for lack of suitable lungs. Our group has developed a novel 24 h sheep BSD model to mimic the physiological milieu of the typical human organ donor. Characterisation of the gene expression changes associated with BSD is critical and will assist in determining the aetiology of lung damage post BSD. Real-time PCR is a highly sensitive method involving multiple steps from extraction to processing RNA so the choice of housekeeping genes is important in obtaining reliable results. Little information however, is available on the expression stability of reference genes in the sheep pulmonary artery and lung. We aimed to establish a set of stably expressed reference genes for use as a standard for analysis of gene expression changes in BSD.     

Religious and secular death: a parting of the ways

Most organized religions have indicated a level of support for organ donation including the diagnosis of death by the brain criterion. Organ donation is seen as a gift of love and fits within a communitarian ethos that most religions embrace. The acceptance of the determination of death by the brain criterion, where it has been explained, is reconciled with religious views of soul and body by using a notion of integration. Because the soul may be seen as that which integrates the human body, in the absence of any other signs of human functioning, loss of integration is considered to be an indication that soul and body have separated. To some extent this view would seem to be informed by an Aristotelian notion of the soul, but it fits well enough with religious notions of the person continuing after death. There have been several developments internationally that indicate that the acceptance of so-called 'brain death' by organized religions has been challenged by new developments including the acceptance of a lesser standard than loss of all brain function and a rejection by the US President's Council on Bioethics of the notion of loss of integration as an explanation of death by the brain criterion.     

Collaborative systematic review of the randomised trials of organised inpatient (stroke unit) care after stroke. Stroke Unit Trialists' Collaboration.

OBJECTIVES: To define the characteristics and determine the effectiveness of organised inpatient (stroke unit) care compared with conventional care in reducing death, dependency, and the requirement for long term institutional care after stroke. DESIGN: Systematic review of all randomised trials which compared organised inpatient stroke care with the contemporary conventional care. Specialist stroke unit interventions were defined as either a ward or team exclusively managing stroke (dedicated stroke unit) or a ward or team specialising in the management of disabling illnesses, which include stroke (mixed assessment/rehabilitation unit). Conventional care was usually provided in a general medical ward. SETTING: 19 trials (of which three had two treatment arms). 12 trials randomised a total of 2060 patients to a dedicated stroke unit or a general medical ward, six trials (647 patients) compared a mixed assessment/rehabilitation unit with a general medical ward, and four trials (542 patients) compared a dedicated stroke unit with a mixed assessment/rehabilitation unit. MAIN OUTCOME MEASURES: Death, institutionalisation, and dependency. RESULTS: Organised inpatient (stroke unit) care, when compared with conventional care, was best characterised by coordinated multidisciplinary rehabilitation, programmes of education and training in stroke, and specialisation of medical and nursing staff. The stroke unit care was usually housed in a geographically discrete ward. Stroke unit care was associated with a long term (median one year follow up) reduction of death (odds ratio 0.83, 95% confidence interval 0.69 to 0.98; P < 0.05) and of the combined poor outcomes of death or dependency (0.69, 0.59 to 0.82; P < 0.0001) and death or institutionalisation (0.75, 0.65 to 0.87; P < 0.0001). Beneficial effects were independent of patients'' age, sex, or stroke severity and of variations in stroke unit organisation. Length of stay in a hospital or institution was reduced by 8% (95% confidence interval 3% to 13%) compared with conventional care but there was considerable heterogeneity of results. CONCLUSIONS: Organised stroke unit care resulted in long term reductions in death, dependency, and the need for institutional care. The observed benefits were not restricted to any particular subgroup of patients or model of stroke unit care. No systematic increase in the use of resources (in terms of length of stay) was apparent.     

Preservation of Alpha-3 Neuronal Nicotinic Acetylcholine Receptor Expression in Sympathetic Ganglia After Brain Death

The goal of this study was to evaluate if the immunohistochemical expression of alpha-3 neuronal nicotinic acetylcholine receptor subunit in sympathetic ganglia remains stable after brain death, determining the possible use of sympathetic thoracic ganglia from subjects after brain death as study group. The third left sympathetic ganglion was resected from patients divided in two groups: BD—organ donors after brain death and CON—patients submitted to sympathectomy for hyperhidrosis (control group). Immunohistochemical staining for alpha-3 neuronal nicotinic acetylcholine receptor subunit was performed; strong and weak expression areas were quantified in both groups. The BD group showed strong alpha-3 neuronal nicotinic acetylcholine receptor expression in 6.55% of the total area, whereas the CON group showed strong expression in 5.91% (p = 0.78). Weak expression was found in 6.47% of brain-dead subjects and in 7.23% of control subjects (p = 0.31). Brain death did not affect the results of the immunohistochemical analysis of sympathetic ganglia, and its use as study group is feasible.     

Brain death and organ donation in a neurosurgical unit: audit of recent practice.

OBJECTIVE--To assess the potential for increasing the yield of donors by comparing the current pattern of brain death and organ donation in a neurosurgical unit with that reported in 1981 and with a recent national audit. DESIGN--Retrospective review of all deaths for 1986, 1987, and 1988 and prospective data for 1989. SETTING--A regional neurosurgical unit serving 2.7 million population. RESULTS--Of 553 deaths, 35% (191) patients died while on a ventilator and 17% (92) after discontinuation of ventilation. Medical contraindications to donation were found in 23% (32) of 141 patients tested for brain death, in 38% (19) of 50 patients who died while being ventilated who were not tested, and in 12% (11) of 92 patients no longer being ventilated. Consent for donation was sought in 88% (96) of 109 medically suitable brain dead patients and granted in 70% (67) of these. Half those with permission for multiorgan donation had only the kidneys removed. CONCLUSIONS--More organs may be lost owing to transplant team logistics than by failure to seek consent from relatives of brain dead patients. The estimated size of the pool of potential donors depends on what types of patients might be considered. Ensuring that all who die while being ventilated are tested for brain death and considering the potential for donation before withdrawing ventilation could yield more donors. Ventilating more patients who are hopelessly brain damaged to secure more donors raises ethical and economic issues.     

Organ Donation After Acute Brain Death: Addressing Limitations of Time and Resources in the Emergency Department

It is not unusual for emergency physicians to quickly identify whether a patient would have wanted to be resuscitated or intubated in a cardiac arrest situation, but patients’ other preferences for end-of-life care or organ donation are less commonly ascertained in the emergency department. Typically, the decision process regarding such goals at end of life may be “deferred” to the intensive care unit. We present a case illustrative of the complexity of discussing organ donation in the emergency department and suggest that patients who die in the emergency department should be afforded the respect and consideration provided in other parts of the hospital, including facilitation of organ transplantation. As circulatory determination of death becomes a more common antecedent to organ transplantation, specific questions may arise in the emergency department setting. When in the emergency department, how should organ donation be addressed and by whom? Should temporary organ preservation be initiated in the setting of uncertainty regarding a patient’s wishes? To better facilitate discussions about organ donation when they arise in emergency settings, we propose increased coordination between organ procurement organizations and emergency physicians to improve awareness of organ transplantation.     

Liver transplantation in adults

Liver transplantation allows to treat patients with end-stage cirrhosis as well as some liver malignancies (small size hepatocellular carcinoma) with a life expectancy exceeding 70 and 60 % at 5 years, respectively. Current immunosuppressive agents make it possible to prevent chronic rejection in more than 90 % of the patients and to preserve an excellent quality of life in most cases. The principal limiting factor for liver transplantation is represented by the scarcity of brain-dead donors. Indeed, despite the selection of those candidates who have the best chance of surviving after transplantation, several months are usually necessary for obtaining a graft and the mortality on the waiting list may reach 10 to 15 %. Organ shortage incited to develop alternatives to conventional transplantation, the most important of which are living donor transplantation and split liver transplantation. Living donor transplantation can be applied to about 20 to 30 % of candidates. Thought initially smaller, the partial graft regenerates and its volume is restored within a few weeks. The results of living donor transplantation in terms of survival are comparable to those of cadaveric transplantation. The risk for the donor has to be lower than 1 % which makes that selection must be especially cautious. Donors must be direct relatives or spouses. Split liver transplantation technique, based on the separation of a cadaveric graft into two functional parts transplanted in two distinct recipients, although attractive, is applicable to less than 25 % of the donors. Education for organ donation in the general population still remains a priority.     

The importance of knowledge and trust in the definition of death

Denmark is the only Western European country that has not changed the criterion of death from one based on the cessation of cardiac function to one based on the irreversible loss of all brain function. The Danish Council of Ethics, at the behest of the political establishment, launched an educational campaign to promote public debate on brain death before proceeding to legislation. National surveys conducted before and during the campaign and the debate to measure public knowledge of death criteria revealed that knowledge had increased but that there was still much misunderstanding of the current criterion of death, of brain death, of the persistent vegetative state, and of criteria for organ harvesting. Rix concludes that increased education targeted at specific groups is worthwhile to increase trust in the definition of death and in organ donation.     

Organ transplantation in Nepal: Ethical,legal, and practical issues

In Nepal, live donor organ transplantation is only 14 years old with the first successful kidney transplant made in 2008 and a successful liver and bone marrow transplant made in 2016. However, transplantation of cadaveric cornea dates back to 1998. There are still no cases of animal-to-human organ transplantation in Nepal. There are stringent laws to regulate human body organ transplantation in Nepal which are amended from time to time. However, there is a racket of human traffickers who lure rural people from this low-income country into the illegal organ trade. Furthermore, there is a substantial lack of awareness of organ donation among the general public. This article focuses on the stipulations of ethical, legal, and practical issues of obtaining organs procured from living and brain-dead donors that support the process of transplantation in Nepal. In addition, the article also explores the legal and practical issues of organ trafficking and organ donation awareness in Nepal on the basis of factual data and findings from other studies.     

Ensembled neural networks for brain death prediction for patients with severe head injury

The concept of organ donation has gradually been accepted by people in recent years so the judicial brain death determination process becomes very important. Clinically, patients with irreversible apnoeic coma (IAC) will be considered legally as brain death based on a judicial process, but this process can only be applied to people who had already signed the letter of consent to organ donation. The main idea behind the proposed model is to find out an easier way to diagnose the prognosis of patients with severe head injury, and offer the medical staffs more information to determine brain death. Therefore, the technique of ensembled neural networks (ENN) based on multi-layer perceptron (MLP) network has been applied to construct the prediction model of brain death index (BDI). Ten different signals were chosen to be the input data. Using these ten parameters, medical doctors depend on their experience to score the BDI hourly values. The BDI values from medical doctors become the training target of the ANN training process and the standard index of testing process. Moreover, in order to compare the differences between doctors’ and the network's rankings for the input data, the ranking of order of precedence of each input signal is analyzed via sensitivity analysis. The results show that the 4 layers network with validation has better performance than 3 layers. For sensitivity analysis, most of the input variables’ ranking from trained model were similar to the ranking of the medical doctors except RR/RR(Set) this parameter and 4 other parameters (PS-R, PR-R, PS-L, and PR-L) are difficult to rank, even medical doctors cannot decide the ranking accurately. Using the best topology structure of MLP 10-10-5-1, the ensemble neural network could effectively predict the BDI with small errors (i.e. training error = 0.219087; validation error = 0.370485; testing error = 0.280515). In conclusion, this model can provide medical staffs a reference index to evaluate the status of IAC and brain death patients. However, more clinical data are still needed, perhaps to refine the weights of EANN, and certainly to see how widely the model is applicable.     

From the editors

Kuhse and Singer, the editors of this special issue of Bioethics, introduce seven articles on conflicting concepts, public policies, and standards for the determination of cardiorespiratory and brain death and the relationship of brain death to the beginning of "brain life" and to organ donation, especially from anencephalic infants. The articles are "Consciousness, the brain and what matters," by Grant Gillett; "Brain death and the anencephalic newborn," by Robert D. Truog and John C. Fletcher; "Brain death and brain life: rethinking the connection," by Jocelyn Downie; "A plea for the heart," by Martyn Evans; "The importance of knowledge and trust in the definition of death," by Bo Andreassen Rix; "Death, democracy and public ethical choice," by Reid Cushman and Soren Holm; and "Misunderstanding death on a respirator," by Tom Tomlinson.