Ethical issues in cardiac arrest and acute cardiac care: a European perspective
Summary
Cardiac arrest constitutes a situation that focuses major ethical challenges in both the in-hospital and out-of-hospital settings. Although this situation is characterized by the necessity of immediate action and by the lack of reliable tools to predict outcome, the key ethical principles (autonomy, beneficence, nonmaleficence, justice) have to be considered, mainly in the context of withholding or withdrawing cardiopulmonary resuscitation (CPR). Advance directives may translate the ethical principles into practice; however, their application is often restricted by the need for timely interventions, especially in an out-of-hospital setting, and their legal power varies considerably throughout Europe. Important related ethical issues are euthanasia and organ donation.
Leading international resuscitation organizations such as the European Resuscitation Council (ERC) and the American Heart Association (AHA) have provided guidelines and recommendations on when to start or not to start CPR, and when to stop it. These guidelines are updated regularly and are easily accessible, but their implementation and application vary substantially, with local practice, culture, religion, society, and legislation being the main influencing factors.
The health care provider should understand the ethical principles and the context of individual, cultural, legal, social, and economic factors before being involved in a real situation where resuscitation decisions must be made. Therefore, this chapter deals with the key ethical principles and the factors that influence their implementation; the decision to start, withhold, or stop CPR; and the perspective of organ donation.
Ethics is dealing with how humans should act or behave. It is also about what is morally right or wrong, good or bad, which depends on time, place, culture, and other factors that are related to the patient and the caregiver and to external circumstances. This chapter will consider ethical aspects of emergency cardiac care when dealing with the acute situation of adult cardiac arrest and in situations where resuscitation efforts appear inappropriate or unsuccessful.
Sudden death, cardiac arrest, and the process of dying
Sudden cardiac death or cardiac arrest is the cessation of cardiac mechanical activity as confirmed by the absence of signs of circulation [1]. The nature, the mechanism, and the context of the potentially reversible sudden death syndrome should not be confused with the expected cessation of circulation and respiration at the end of a chronic condition.
Sudden death is a catastrophic unexpected event that may happen outside or inside the hospital. Outside the hospital, cardiac arrest is frequently initiated by ventricular fibrillation and has the potential to be successfully resuscitated, but the conditions are usually unfavourable: the arrest may or may not be witnessed by a partner or family member with some knowledge of cardiopulmonary resuscitation (CPR); the efficiency of the telephone call to the emergency number is variable; sometimes there is an automatic external defibrillator (AED) around; and after a more or less short time professional help will arrive with the EMS (emergency medical services) ambulance. Inside the hospital there is frequently comorbidity, but the external conditions are more favourable: expert health care professionals and resuscitation equipment are readily available within a short time, and the intensive care unit (ICU) is a short distance away.
Although the two settings are very different, the decision to start CPR or not, and to continue it or not, need to be made by the first health care provider. This is an individual responsibility to ensure the best chance of survival for those patients who may benefit but also to avoid prolonged suffering and waste of resources in cases where CPR is not indicated. These decisions are made in the perspective of scientific evidence, legislation, religion, culture, medical context, preferences and skills and beliefs of the rescuer, and preferences of the patient and the societal environment.
Nonmedical health care providers usually apply precise rules (standing orders), but medically qualified rescuers are expected to use their expert knowledge and judgement. It is their responsibility to use their judgement, not as an excuse for inconsequential behaviour or ad hoc decisions inspired by convenience or other nonmedical arguments, but with knowledge of current scientific evidence and according to the principles of ethical practice. These decisions should be guided by general ethical principles and modulated according to influencing factors.
Many national and international organizations have issued recommendations, but implementation of these recommendations among individual health care professionals, EMS systems, emergency departments (EDs), and hospitals is variable. Differences in national legislation and medical practice and social changes are obstacles to the production of uniform rules or flowcharts for starting or not starting CPR, continuing or not continuing it. This should not, however, serve as an excuse for not adhering to a consequentially implemented policy.
In Europe each year, between 4 and 10 per 10 000 inhabitants per year suffer out-of-hospital cardiac arrest (OoHCA): this represents between 350 000 and 700 000 people. Overall survival is low, with an average of less than 10%. The majority of these events occur at home, mostly in the presence of a witness. Cardiac arrest victims who are found in ventricular fibrillation have higher chances for survival: restoration of spontaneous circulation (ROSC) may be achieved in up to 50% of cases and eventual survival to hospital discharge may be up to 20% and even 30%, depending on the process of prehospital and in-hospital care [2, 3]. But the chance of survival decreases rapidly as time to defibrillation becomes longer.
Less accurate data are available about cardiac arrest inside the hospital. The incidence of cardiac arrest is estimated 0.175 per bed per year, or 1–5 per 1000 admissions per year. Although the underlying disease is different from OoHCA (comorbidity, endstage respiratory, neurologic, and metabolic disease), long-term survival from in-hospital cardiac arrest is similar to that for out-of-hospital cardiac arrest (average 20%).
More than 20% of hospital deaths follow admission to an ICU [4–7]. Frequently, patients unlikely to benefit from intensive care are admitted, leading to needless prolongation of the dying process, suffering for the patient and family, and unnecessary waste of resources.
In the in-hospital context more information is available about the medical condition, the prognosis, and the personal preferences, allowing a balanced decision to start or continue CPR.
Ethical principles are universal
Decisions on CPR and end of life are based on universally accepted ethical principles, but the implementation of these principles is influenced by the context and by individual, cultural, legal, social, and economic factors.
Health care providers should understand these ethical principles before being involved in a real situation where resuscitation decisions must be made. The key ethical principles of autonomy, justice, beneficence, and nonmaleficence [9] are the basis of the declarations of human rights [10, 11] (
Box 13.1) and reflect the principles of our
individual behaviour in medical practice as expressed in the Hippocratic Oath [8].
Universal ethical principles
♦ Autonomy implies that a patient has the right to take informed decisions on future treatment. This implies also that the patient is adequately informed, competent, and free of pressure.
♦ Justice implies that the access to essential health care, including resuscitation, must be distributed equally within the society according to the available resources.
♦ Beneficence implies that health care must provide benefit to the individual or to society, taking into account the balance between benefit and risk.
♦ Nonmaleficence implies that no harm must be done. Resuscitation should not be applied if it is futile or if it is against the patient’s wishes.
Definitions relating to end-of-life decisions
♦ Withholding a treatment is defined as a decision not to start a life-sustaining intervention, such as CPR.
♦ Withdrawing a treatment is defined as stopping a life-sustaining intervention that is currently provided.
♦ Shortening of the dying process is defined as an act with the specific intention to actively shorten the dying process.
♦ Futility is defined as an intervention that cannot establish any increase in length or quality of life. If the purpose of a treatment cannot be achieved, the treatment is futile.
Definitions relating to advance directives and do-not-(attempt)-resuscitation orders
Advance directives, sometimes known as living wills, and do-not-(attempt)-resuscitation (DN(A)R) declarations, are a direct translation of these key principles and conventions into practice. But although all European countries and religions support the principle that resuscitation should not be attempted in case of endstage disease or injury, only a minority of countries have adopted a formal DN(A)R policy, and advance directives are more an exception than a rule.
Although the principles of advance directives and DNR orders are identical for the out-of-hospital and the in-hospital situation, the application in clinical practice will be fundamentally different according to this context:
♦ In out-of-hospital cardiac arrest the timely administration of CPR, defibrillation, and advanced resuscitation interventions is critical. Decisions need to be made in seconds, and delay of intervention is sanctioned by decreased outcome. CPR should be initiated unless there are evident contraindications of futility or refusal.
♦ Inside the hospital, there has been time to reflect and to ascertain the patient’s well-informed preferences about end-of life decisions. In the critical care unit the medical history and the preferences of the individual patient are even better known and there has been time to place the treatment strategies in the appropriate legal, religious, individual, and medical perspective [12, 13].
There is considerable international variation in the medical attitude to written advance directives. In some countries they are considered legally binding; in other countries they are ignored if the doctor does not agree with the contents. However, in recent years there has been a growing tendency towards compliance with patient autonomy and a reduction in patronizing attitudes by the medical profession.
Predicting outcome
The objective of the key ethical principle of ‘justice’ implies giving the best care to the patients who are likely to benefit, and to avoid useless and costly interventions that prolong suffering in hopeless situations (‘futility’).
Many investigators have tried to develop a reliable algorithm for identifying those cardiac arrest patients who have a high potential and those who have only a dismal chance, or none, of survival. This might allow the health care provider to decide on starting or not starting, continuing or not continuing CPR. However, most methods seem to have good sensitivity but low specificity.
The OPALS study [14], for example, looked into the predictive value of termination of resuscitation (TOR) guidelines for identifying ‘futility’ in out-of-hospital cardiac arrest, defining ‘futile’ as an intervention with less than 1% chance of benefit. The following elements had a high predictive potential:
♦ Event not witnessed by EMS personnel.
♦ No AED or manual defibrillation applied in the out-of-hospital setting.
♦ No ROSC in the out-of-hospital setting.
♦ Arrest not witnessed by a bystander.
♦ No bystander-administered CPR.
The sensitivity of these guidelines for predicting futility was high (99%), but specificity was low (ranging between 10 and 53%); these findings where confirmed in other studies [15–20]. These data were generated in North America and extrapolation to other regions and EMS systems should be made with care, because of major differences in systems, organization, qualification, and legislation.
As a result, there are no validated reliable tools that allow us to predict early the outcome from cardiac arrest with an acceptable accuracy in an individual case.
Guidelines and recommendations
In the 2005 guidelines for CPR and emergency cardiovascular care, both the European Resuscitation Council (ERC) and the American Heart Association (AHA) provide recommendations for the care provider about starting, not starting, and stopping CPR. The guidelines are currently being updated and the 2010 CPR guidelines can be downloaded from the websites of the ERC (https://www.erc.edu/index.php/mainpage/en/) and AHA.
European Resuscitation Council guidelines
In its CPR guidelines [21], the ERC emphasizes that a well-informed, competent patient has the right to refuse treatment, but this does not imply that a patient has the right to demand any treatment in all circumstances.
ERC recommendations for withholding CPR and DN(A)R orders
♦ A physician is expected to provide treatment that is likely to benefit the patient and not to provide treatment that would be futile. Futility exists if resuscitation will be of no benefit in terms of prolonging life of acceptable quality. However, no validated tools for predicting nonsurvival after attempted resuscitation are available.
♦ Therefore, judgements will have to be made, and there will be grey areas where subjective opinions are required in patients with end stage disease, asphyxia or major trauma. The age of the patient is a weak predictor of outcome, but age is frequently associated with comorbidity.
ERC recommendation for stopping a CPR attempt
The ERC recommends to consider stopping a CPR attempt
♦ if it is evident that CPR is futile (not likely to be beneficial)
♦ if there is an advance directive
♦ if asystole persists after at least 20 min of full advanced life support.
This implies that in OoHCA CPR should be initiated while collecting information.
The decision to abandon the resuscitation attempt is made by the team leader, after consultation with the other team members. Many cases of out-of-hospital cardiac arrest are dealt with by emergency medical technicians or paramedics, who face dilemmas of when to determine if resuscitation is futile and when it should be abandoned. Clearly resuscitation is futile in cases of cardiac arrest with a mortal condition such as decapitation, incineration, rigor mortis, dependent lividity, and fetal maceration. In such cases the nonphysician is making a diagnosis of death but is not certifying death (which can only be done by a physician in most countries).
When considering abandoning the resuscitation attempt, the possibility of prolonging CPR and other resuscitative measures to allow organ donation to take place should be taken into account. The issue of initiating life-prolonging treatment with the sole purpose of harvesting organs is debated by ethicists and no consensus exists.
Also, it should be noted that the introduction of therapeutic hypothermia after cardiac arrest may have changed the predictive algorithms, and caution should be taken until new predictive values have been established for these patients.
In 2010 the ERC updated the CPR guidelines, after a systematic review by the International Liaison Committee on Resuscitation (ILCOR) of the scientific developments that have taken place since 2005. This science review is published as the ILCOR Consensus on Science and Treatment Recommendations (COSTR) document and provides ILCOR members with the common science on which to base their updated 2010 CPR guidelines. These documents are available on the ERC website (http://www.erc.edu).
American Heart Association guidelines
In the AHA guidelines for CPR and emergency cardiovascular care[22], guidance is provided to health care providers for making the decision to provide or withhold emergency cardiovascular care. This guidance is based on the goals of emergency cardiovascular care: to preserve life, restore health, relieve suffering, limit disability, and reverse clinical death.
The AHA emphasizes that truly informed decisions require that patients receive and understand accurate information about their condition and prognosis, the nature of the interventions, and the risks and benefits. When patients’ preferences are uncertain, emergency conditions should be treated until those preferences can be clarified.
The Patient Self-determination Act of 1991 implies that health care institutions should inquire whether the patient has advance directives and that they facilitate the completion of these directives.
American College of Critical Care Medicine recommendations
The American College of Critical Care Medicine and the Society of Critical Care Medicine have published recommendations for end-of-life care in the ICU [23]. It is emphasized that ICU clinicians should be competent in all aspects of end-of-life care, including the practical and ethical aspects of withdrawing different modalities of life-sustaining treatment, and the use of sedatives, analgesics, and nonpharmacological approaches to easing the suffering of the dying person.
The key ethical principles for this care include the distinction between withholding and withdrawing treatment, between actions of actively terminating life and allowing to die, and between consequences that are intended versus those that are merely foreseen (the doctrine of double effect).
Implementation of universal principles in different European countries
Many investigators have studied the implementation of these principles, guidelines and recommendations in clinical practice. The plethora of reports underlines the wide divergence in the interpretation and application [12, 24–29].
Most European countries have signed the Oviedo Convention and the Declaration of Helsinki for the protection of human rights and dignity [10, 11]. However, so far, many countries have not introduced specific legislation to implement these recommendations. Some have rather progressive legislation, such as the Netherlands and Belgium, whereas others have more conservative legislation. As a result, it is still difficult in many countries to provide physicians with legal guidance on decisions about end-of-life caring, regarding limiting or withholding support in critically ill patients.
Baskett and Lim [24] reviewed the attitudes of experienced emergency health care providers about ethical issues in resuscitation in 20 European countries. They observed a widespread divergence of views on ethical aspects of resuscitation that are not always in line with the conventionally perceived national characteristics. Only a minority of countries had a formal DNAR policy, although virtually all reported not attempting resuscitation in patients with an endstage disease or injury. Advance directives were in use in only a minority of countries, and there is a considerable amount of individual variation. The majority felt that it is probably not possible in these critical situations to ensure really informed consent, and that doctors, nurses, patients, and relatives may have different perceptions of the situation. Active euthanasia was legal in three countries, but many responders reported on a liberal use of analgesia and sedation in patients with endstage disease or injury. In deciding to stop resuscitation attempts, almost all respondents abandoned resuscitation after 20 min of asystole in the absence of reversible causes; but the majority were also reluctant to leave the application of this rule to the responsibility of ambulance personnel who are not medically qualified.
Surveys in European ICUs by the European Society for Intensive Care Medicine (ESICM) documented that decisions to withdraw or withhold treatment vary substantially, depending on local practice, cultural and religious backgrounds, legal frameworks, organization of ICUs, national and societal guidelines, and even family or peer pressure [27, 30, 31]. The ETHICUS study [12] investigated patients admitted to ICUs in European countries. Of the admitted patients, 13.5% died and 10% had limitations of treatment. Substantial differences between countries were found in the limitation of therapy and in the manner of dying. Age, diagnosis, region, religion, and length of stay were most significantly associated with limitation of therapy versus continuation of life-sustaining treatment.
Specific information on end-of-life practice and law in European countries is also available in a series of articles in the journal of the ESICM and in national recommendations [32–37].
In recent studies a high involvement of intensive care nurses in the end-of-life (EOL) decision-making process in Europe has been reported. The opinions about practical modalities for EOL were consistent for many aspects such as oxygen treatment and presence of family, but were divergent for sedation and nutritional support. This is an encouraging evolution after the rather sobering findings in an earlier study, where the process of EOL decision-making was perceived as satisfactory by 73% of physicians but by only 33% of nurses [38, 39].
Others have investigated the wide variability in the acceptance of euthanasia by the general public. Religious beliefs, socio-demographic factors, and moral values (i.e. the belief in the right to self-determination) could largely explain the differences between countries, but national traditions and history were also major contributors. These variables might amount to the global ‘culture’ of a given population [25].
In most surveys, religion appears as a constant factor with a significant impact on the attitudes of patients and care providers. In 2005, the Lancet published a series of articles devoted to the position of religions on EOL care [40]. These positions were recently updated [41]: today, many religions have spread worldwide and with increasing mobility and globalization, health care providers should understand the religious beliefs of their patients well when dealing with EOL decisions. Religious authorities have expressed their opinions about decisions to withhold or to withdraw vital treatment, the principle of futility, the notion of brain death, the dual effect of analgesia and sedation, DNAR orders, advance directives, and euthanasia ( Table 13.1). The purpose of medicine is to ensure ‘a good life and a good death’. Religious doctrines and beliefs should therefore be considered as an important element in our medico-scientific approach to EOL care.
Table 13.1 Religious attitudes to end-of-life decisions
Withhold | Withdraw | Organ donation | Dual effect | Euthanasia | |
|---|---|---|---|---|---|
Catholic | Y | Y | N | Y | N |
Protestant | Y | Y | Y | Y | Y |
Orthodox | N | N | Y | N | N |
Muslim | Y | Y | Y | Y | N |
Jew | Y | N | Y | Y | N |
Buddhist | Y | Y | N | Y | N |
Hindu | Y | Y | Variable | Y | N |
Y, yes, accepted; N, no, not accepted.
Adapted from End-of-Life series, Lancet 2005;366: August–October, and Bülow H, et al. The world’s major religions’ points of view on end-of-life decisions in the intensive care unit. Intensive Care Med 2008;34:423–430.
Save the patient, save the organs
Death and brain death
Diagnosis of death is essential if organ removal for transplantation is considered. This concept is also known as the ‘dead donor’ rule [42]. According to cardiorespiratory criteria, death is clinically defined as the irreversible loss of all cardiorespiratory activity. In the absence of external conditions (hypothermia, drugs) or in conditions indicating reversibility, cessation of oxygen delivery to the brain will lead within minutes to brain death. According to the Harvard neurologic criteria, brain death is defined as the irreversible and complete loss of all activity of the brain [43]. Diagnosis of brain death implies the following steps:
♦ Establish the aetiology of the underlying disease.
♦ Exclude potentially reversible conditions, such as hypothermia, metabolic disturbances or drugs that can lead to potentially reversible coma.
♦ Clinical diagnosis of coma, brainstem areflexia and apnoea.
♦ Confirmation procedure (repetition, multiple physicians, technical procedures such as EEG, evoked potentials, angiography, Doppler sonography, scintigraphy).
This step-by-step approach and the principles for diagnosis of brain death are widely accepted in Europe. However, the application of these diagnostic steps in clinical and hospital practice is variable in individual European countries: there are variations in the repetition of the diagnostic tests, the methods for testing apnoea, the need of a confirmatory technical test, and the qualifications of the physician responsible for brain death diagnosis [44–46]. The responsible health care professional should have good knowledge of the diagnostic procedures in the country where he/she is professionally active.
Heart-beating organ donation
Accurate diagnosis of brain death has provided the possibility of harvesting of organs for transplantation in heart-beating conditions. In intensive care patients suffering disastrous brain damage (hypoxic or traumatic) with irreversible loss of brain function and with no hope for any meaningful recovery, the transport of oxygen to organs may be continued by artificial ventilation, intravenous feeding, and other intensive care treatment. After diagnosis of brain death according to the accurately defined procedures, this allows many patients with organ failure to benefit from the possibilities that are offered by transplant surgery.
The principles of organ donation and transplantation are also widely accepted throughout Europe. However, there is variability in the related legislation as to how an individuals can express their preferences about organ donation: in some countries (such as the United Kingdom, Ireland, Denmark, Netherlands, Germany) the individual may actively consent with organ donation (‘opting in’); in other countries (such as Austria, Portugal, Belgium, Spain, Italy, France, Greece, Switzerland, the Scandinavian and most central European countries) the individual is assumed to agree with organ donation unless active disagreement (‘opting out’).
Non-heart-beating organ donation
Non-heart-beating organ donation (NHBOD) may be considered, in the absence of brain death, after the decision is made to stop the resuscitation efforts because of futility. If an injury is not compatible with life or if there is no response to CPR as defined by the current CPR guidelines for, organ harvesting may be considered after irreversible cardiorespiratory arrest has led to the death of the individual. In these situations, after stopping CPR and after an observation period of several minutes (variable from country to country), the initiation of intravascular preservation methods with a view to organ harvesting and transplantation may be considered.
There is wide variation within Europe about the acceptance of NHBOD, about the selection of potential candidates, and about the procedures and protocols. Therefore, no general recommendation can be made.
Many reports have documented the good clinical results of this approach, mainly in kidney transplantation [47].
Conclusions
Although the general ethical principles are universal, their implementation and translation into practice throughout Europe is far from being uniform. A variety of factors are influential, including social, legal, religious, cultural and economic facts and conditions, most of which are rather stable and resistant to the short-term exercise of influence. Besides this, medical characteristics, especially in the context of cardiac arrest, make it difficult to always act clearly according to ethical rules. However, the core ethical principles are valid across borders and should be followed in any situation, and cardiac arrest and acute cardiac care, despite their very special conditions, are not ethics-free areas.
To act in an ethically competent way in a stressful and time-critical emergency situation such as cardiac arrest requires that the caregiver has reflected and thought about ethics in advance. If ethical considerations arise in such a situation for the first time they will be of no use. Thus, this subject should be included in any (continuing) education for personnel who will be confronted with such situations. Case conferences, debriefings, discussions with colleagues, etc. may further strengthen ethical competence.
Stating that implementation of ethical principles depends on many external factors and accepting those variables without criticism would fail to recognize that ethics is not stable, but a process subject to change. This implies that anyone involved should take any opportunity to actively participate in the debate, be it in the work environment, in scientific discussions, or at a political level. Ethics is not an end in itself but also serves the general purpose of applying the best possible care to our patients, their families, and their environment.
Personal perspective
This overview of ethical issues in cardiac arrest and acute cardiac care has revealed issues that may determine the discussion in the near future. Advance directives are of value for expressing wishes and preferences about EOL decisions; however, reliable mechanisms and tools are needed to facilitate their application especially in the out-of-hospital setting. Furthermore, international and intercultural approaches could identify strategies to promote their general acceptance and implementation.
Recent studies have shown that the involvement of nurses in EOL decisions has increased. This positive development might be further pursued and strengthened by ethical team discussions and by continuing interdisciplinary education, to improve integration of nurses into the decision-making process and thus to minimize team conflicts. Assuming that nurses’ contact with patients and relatives is deeper and more frequent, they could play an important role in addressing ethical subjects, in the hospital as well as in society.
On a European level the debate on euthanasia is far from being harmonized, as a result of strongly differing historical, socio-cultural, and legal national backgrounds. It is hardly possible to predict whether there will be ever a rapprochement when we look at countries having enacted laws on euthanasia on the one hand, and on the other at countries where euthanasia meets with widespread societal disapproval, mainly based on religious convictions. Nevertheless, or perhaps just because of the divergence, the ethical dispute on this subject will continue.
The lack of validated reliable tools allowing us to predict the individual outcome from cardiac arrest is a major disadvantage in the field. Besides further studies on this issue that might reveal new insights and improve the specificity of TOR criteria, an open ethical debate could be helpful to identify within a given society what level of specificity could be acceptable for such TOR decisions.
Further reading
American Heart Association. 2005 Guidelines for cardio-pulmonary resuscitation and emergency cardiovascular care. Circulation 2005;112:1–211.
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Azoulay E, Metnitz B, Sprung C, et al. End-of-life practices in 282 intensive care units: data from the SAPS 3 database. Intens Care Med 2009;35:623–630.
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Baskett P, Lim A. The varying ethical attitudes towards resuscitation in Europe. Resuscitation 2004;62:267–73.
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Beauchamp T, Childress J. Principles of biomedical ethics, 5th edition. Oxford University Press, Oxford. 2001.
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Bülow H, Sprung C, Reinhart K, et al. The world’s major religions points of view on end-of-life decisions in the intensive care unit. Intens Care Med 2008;34:423–430.
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Carlet J, Thijs L, Antonelli M, et al. Challenges of end-of-life care in the ICU. Intens Care Med 2004;30:770–784.
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European Resuscitation Council. ERC Guidelines for resuscitation 2005. Resuscitation 2005;67:S1–189.
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Siegel M. End-of-life decision making in the ICU. Clin Chest Med 2009;30:181–194.
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Sprung C, Cohen S, Sjokvist P, et al. End-of-life practices in European Intensive Care Units. The Ethicus study. JAMA 2003;290:790–797.
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Truog P, Campbell M, Curtis J, et al. Recommendations for end-of-life care in the intensive care unit: a consensus statement by the American College of Critical Care Medicine. Crit Care Med 2008;36:953–963.
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Wijdicks E, Rabinstein A, Manno E, et al. Pronouncing brain death: contemporary practice and safety of the apnea test. Neurology 2008;71:1240–1244.
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