Benchmark 1

Innovations in CLINICAL NEUROSCIENCE [ V O L U M E 1 3 , N U M B E R 1 1 – 1 2 , N O V E M B E R – D E C E M B E R 2 0 1 6 ]12

ABSTRACT Managing individuals with chronic

disorders of consciousness raises

ethical questions about the

appropriateness of maintaining life-

sustaining treatments and end-of-life

decisions for those who are unable to

make decisions for themselves. For

many years, the positions fostering

the “sanctity” of human life (i.e., life

is inviolable in any case) have led to

maintaining life-sustaining

treatments (including artificial

nutrition and hydration) in patients

with disorders of consciousness,

allowing them to live for as long as

possible. Seldom have positions that

foster “dignity” of human life (i.e.,

everyone has the right to a worthy

death) allowed for the interruption

of life-sustaining treatments in some

patients with disorders of

consciousness. Indeed, most ethical

analyses conclude that the decision

to interrupt life-sustaining therapies,

including artificial nutrition and

hydration, should be guided by

reliable information about how the

patient wants or wanted to be

treated and/or whether the patient

wants or wanted to live in such a

condition. This would be in keeping

with the principles of patient-

centered medicine, and would

conciliate the duty of respecting both

the dignity and sanctity of life and

the right to a worthy death. This

“right to die” has been recognized in

some countries, which have legalized

euthanasia and/or physician-assisted

suicide, but some groups fear that

legalizing end-of-life decisions for

some patients may result in the

inappropriate use of euthanasia, both

voluntary and nonvoluntary forms

(slippery slope argument) in other

patients.

This review describes the current

opinions and ethical issues

concerning end-of-life decisions in

patients with disorders of

consciousness, with a focus on the

impact misdiagnoses of disorders of

consciousness may have on end-of-

life decisions, the concept of

“dignity” and “sanctity” of human life

in view of end-of-life decisions, and

the risk of the slippery slope

argument when dealing with

euthanasia and end-of-life decisions.

We argue that the patient’s diagnosis,

prognosis, and wishes should be

by ROCCO SALVATORE CALABRÒ, MD, PhD; ANTONINO NARO, MD, PhD; ROSARIA DE LUCA, MS, PhD; MARGHERITA RUSSO, MD, PhD; LORY CACCAMO, PhD; ALFREDO MANULI, MS; ALESSIA BRAMANTI; and PLACIDO BRAMANTI, MD

Drs. Calabró, Naro, de Luca, Russo, Manuli, A. Bramanti, and P. Bramanti are from the IRCCS

Centro Neurolesi “Bonino-Pulejo” in Messina, Italy; and Dr. Caccamo is from the Department

of Psychology, University of Padua, Padua, Italy.

Innov Clin Neurosci. 2016;13(11–12):12–24

FUNDING: No funding was received for the preparation of this article.

FINANCIAL DISCLOSURES: The authors have no conflicts of interest relevant to the content of this article.

ADDRESS CORRESPONDENCE TO: Rocco Salvatore Calabrò, MD, PhD; E-mail: salbro77@tiscali.it

KEY WORDS: Artificial nutrition and hydration; euthanasia; minimally conscious state; right to die; sanctity of life; vegetative state.

R E V I E W A N D C O M M E N T A R Y

The Right to Die in Chronic Disorders of Consciousness: Can We Avoid the Slippery Slope Argument?

Innovations in CLINICAL NEUROSCIENCE [ V O L U M E 1 3 , N U M B E R 1 1 – 1 2 , N O V E M B E R – D E C E M B E R 2 0 1 6 13

central to determining the most

appropriate therapeutic approach

and end-of-life decisions for that

individual. Each patient’s diagnosis,

prognosis, and wishes should also be

central to legislation that guarantees

the right to die and prevents the

slippery slope argument through the

establishment of evidence-based

criteria and protocol for managing

these patients with disorders of

consciousness.

INTRODUCTION

Consciousness is the condition of

normal wakefulness (opening and

closing eyes, preserved sleep-wake

cycle) and awareness (of the self and

environment) in which an individual

is fully responsive to thoughts and

perceptions, as suggested by his or

her behaviors and speech. 1,2

A

disorder of consciousness (DOC)

results when awareness and/or

wakefulness are compromised

because of severe brain damage. 3

In recent years, the advances in

diagnostic procedures and intensive

care have increased the number of

patients who survive severe brain

injury and enter a vegetative state

(VS) (also recently named

unresponsive wakefulness

syndrome)4,5 or a minimally

conscious state (MCS). These

entities represent the two main

forms of chronic DOCs. 6–9

In

particular, patients suffering from VS

are unaware of the self and the

environment and cannot show

voluntary, purposeful behaviors

because of severe cortico-thalamo-

cortical connectivity breakdown 10,11

that globally impairs sensory-motor

processing and cognition. On the

other hand, patients with MCS show

fluctuant but reproducible signs of

awareness and have a limited

repertoire of purposeful behaviors.

The best management of patients

in VS and MCS requires a correct

diagnosis, an evidence-based

prognosis, and the full consideration

of the medical, ethical, and legal

elements concerning DOC. 12

In

particular, patients with DOC need

artificial nutrition and hydration

(ANH) and, often, intensive

treatments. These issues evoke a

thorny ethical problem concerning

the therapeutic decision-making of

such patients (including the

continuation of life-sustaining

therapies) in view of the

uncertainties about their state of

consciousness, prognosis, and

personal wishes, with particular

regard to the end-of-life decisions

(ELD). 13

In fact, it is worth

remembering that the

implementation of any life-sustaining

treatment, including ANH, should

not be automatic when considering

that every individual should make his

or her own decisions regarding any

kind of therapy, according to the

ethical principles of autonomy and

the right of self-determination and

freedom. If an individual is unable to

make a decision, as in the case of

patients with DOC, a surrogate

should be empowered to ensure the

patient’s best interest and personal

wishes concerning ELDs. Therefore,

the right to lose health, become ill,

refuse treatment, live the end of life

according to one’s personal view of

life, and die should be guaranteed,

which is in keeping with human

dignity and the duty to protect

physical and mental health. 14

The right to die is further

supported by the following

arguments. 14–19

1. The right to (a worthy) life

implies the right to (a worthy)

death.

2. There is no reason to have a

“dedicated” right to die, given that

dying is a very natural

phenomenon, as is life.

3. Death is a private matter, and

other people have no right to

interfere if there is no harm to

others or the community (a

libertarian argument.

4. It is possible to regulate

euthanasia by proper laws, and

thus avoid the slippery slope

argument (SSA).

3. Euthanasia may avoid illegal acts,

given that euthanasia may happen

anyway (a utilitarian or

consequentialist argument) and

save the extreme despair of

suicide or homicide.

6. Death is not necessarily a bad

thing, owing to the naturalness of

the phenomenon, regardless of

whether it is induced.

7. Euthanasia may satisfy the

criterion that moral rules must be

universalizable, but

universalizability is a necessary

but not a sufficient condition for a

rule to be morally good.

8. Medical resources can be better

managed, and though this is not a

primary reason for the right to

die, it is a useful consequence.

On the other hand, an opposite

view states that life is a unique and

incorruptible gift that, in keeping

with the concept of the sanctity of

human life, must always be

preserved. Hence, each individual

has the moral duty to attend to all

the treatment necessary to preserve

life, with the exception of those

burdensome and/or disproportionate

to the hoped for or expected result

(i.e., life preservation), and to avoid

behaviors that can deliberately

hasten or cause death. 13,19–24

A possible middle ground is

represented by the concept that the

sanctity and the dignity of life are

somehow coincident; consequently,

there is no reason why accepting

euthanasia makes some individuals

worth less than others. Since it is

possible to regulate euthanasia by

proper laws, there is no risk of the

following: 13,19–24

1. Starting an SSA that leads to

involuntary euthanasia, thus

killing people who are thought

undesirable

2. Less than optimal care for

terminally ill patients (for

economic reasons)

3. Giving too much power to medical

staff in limiting the access to

palliative and optimal care for the

dying, pain relief, saving lives,

using euthanasia as a cost-

effective way to treat the

terminally ill, and limiting the

research for new cures and

treatments for the terminally ill

Innovations in CLINICAL NEUROSCIENCE [ V O L U M E 1 3 , N U M B E R 1 1 – 1 2 , N O V E M B E R – D E C E M B E R 2 0 1 6 ]14

3. Exposing vulnerable people to

pressure to end their lives (duty

to die) by selfish families or by

medical staff to free up medical

resources or when patients are

abandoned by their families.

At first glance, the problem of

ELDs in patients with DOC may

seem easy to solve. The supporters

of the dignity of human life claim

that since patients with DOC are

unconscious and therefore cannot

fully benefit from their rights, ELDs

should assumed by a third party

(e.g., those with whom the patient is

familiar, medical staff, ethics

committees, or courts).25 These

parties would make the ELDs, taking

into account the best interests of the

patient, his or her wishes, the right

to freedom, and the respect of

human dignity. On the contrary,

those who advocate the sanctity of

life deny any possibility to hasten (by

interrupting life-sustaining

treatments) or cause death (by using

euthanasia and physician-assisted

suicide) (PAS), because they believe

that life preservation is a social and

ethical duty. Moreover, patients with

DOC are in a very frail and

vulnerable condition in which they

cannot express their thoughts on

these issues.13,19–24

Judgements in the Schiavo and

Englaro cases highlight this

controversy. In the Schiavo case,26

the argument was over whether Terri

Schiavo was in a persistent VS,

which had already lasted 15 years. It

began with her collapse in 1990, due

to cardiac arrest, and then her

husband’s initial court attempt to

have her feeding tubes removed in

1998. That was followed by court

battles between the husband and

Schiavo’s parents, who opposed the

removal the feeding tube. Her

feeding tube was removed several

times and then reinserted after more

court orders. It was removed for the

last time in March 2005 after the last

successful court petition by the

husband. Schiavo died 13 days later.

Likewise, Eluana Englaro27

entered a persistent VS in 1992

following a car accident, and

subsequently became the focus of a

court battle between supporters and

opponents of euthanasia. Shortly

after her accident, medical staff

began feeding Englaro with a feeding

tube, but her father “fought to have

her feeding tube removed, saying it

would be a dignified end to his

daughter’s life.” According to

reports, Englaro’s father said that

before the car accident, his daughter

visited a friend who was in a coma

and afterward told him, “If something

like that ever happened to me, you

have to do something. If I can’t be

what I am now, I’d prefer to be left to

die. I don’t want to be resuscitated

and left in a condition like that.” The

authorities refused father’s request,

but the decision was finally reversed

in 2009, after she had spent 17 years

in a persistent VS.

Of note, the United States

Supreme Court has stated that the

irreversibility of a DOC condition and

the clearly defined patient’s wish to

not live under such conditions should

both be clearly demonstrated in

order to withdraw the sustaining

therapies, including ANH.28,29 These

decisions are fully in keeping with

the right of freedom and self-

determination and with the

supporters of the right to life.

However, these are fiercely criticized

and hindered by the sanctity of life

supporters.13,19–24

Therefore, we consider whether it

is more ethical to respect human

dignity than to protect the sanctity

of human life at all costs. A correct

approach to this thorny ethical

dilemma requires taking into account

that there is a tangible uncertainty of

DOC diagnosis and prognosis,

consequently making it more difficult

to respect a patient’s rights properly

when making ELDs. Moreover, it is

still debated whether ANH should be

considered a fundamental (i.e.,

always due) or an aggressive therapy

(i.e., useless and bearer of further

suffering).22,24,30–34 Finally, the

motivation sustaining the right to live

with dignity and in respect of human

life sanctity must be analyzed

carefully, given that the access to the

right to die is a SSA. In fact, both the

withdrawal and the maintenance of

ANH may lead to a chain of related

events that may culminate in some

significant and potentially negative

effects on patients with DOC (e.g.,

death or unnecessary and prolonged

suffering). Liberalizing euthanasia

may lead to unnecessary application

in some cases. The strength of each

argument in favor or against ELDs

depends on whether one can

demonstrate a process that leads to a

significant effect. SSAs can be used

as a form of fear mongering in an

attempt to scare the audience, thus

ignoring the possibility of a middle

ground between the dignity and the

sanctity of human life. In this article,

we will review the key concepts of

the positions supporting the dignity

and the sanctity of human life in an

attempt to find a conciliating view to

solve the SSA.

DOC DIAGNOSES AND

PROGNOSES

When family members are faced

with an irreversible and hopeless

case of unconsciousness, leaving

their loved one in such a condition

may be unbearable for both the

patient and his or her family

members. The relatives of patients

with DOC live a paradoxical reality.

In fact, they live with a family

member who is both present

(inasmuch as he or she is awake)

and absent (unaware) and alive

(inasmuch as he can open and close

his or her eyes, breathe

independently, and make some

movements) and dead (given that he

or she cannot interact with the

family members or the

environment).35–37 These issues can

foster denial or misunderstanding in

the family members of their current

situation. For example, they may

deny that their loved one is in a VS

because they interpret spastic or

reflexive movements as signs of

improvement,6 thus imagining

chances of recovery that are not

supported by evidence-based

medicine. Given that the family

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members may witness important

responses by the patient that have

not been observed by the clinicians,

the medical staff should attempt to

observe the patient with the family

members and involve them in the

patient evaluation. Assisting family

members in better understanding the

patient’s behaviors and level of

awareness is important and may

strengthen the family members’

relationship with the medical staff.38

Hence, the correct communication

of a proper diagnosis and a reliable

prognosis is essential for the best

management of a patient with DOC.

In fact, inaccurate diagnoses and

prognoses and disclosure of false

diagnostic information to families

may have serious ethical, medical,

and legal consequences regarding

the medical management of the

patient, the well-being of patient’s

family members, and ELDs.39,40 In

fact, an incorrect diagnosis and

prognosis may result in a false

expectancy for recovery by the

family members, the unnecessary

and potentially harmful life-support

prolongation of the patient, financial

and emotional resources being

withheld or withdrawn, resource

misuse and misallocation, and an

inappropriate rehabilitation or long-

term care facility enrollment.13

Nonetheless, identifying residual

awareness in unconscious patients

(thus differentiating VS from MCS)

and establishing a correct prognosis

are extremely challenging, owing to

the inadequate sensitivity of the

clinical and paraclinical approaches

currently available for DOC diagnosis

and prognosis.41–47 Even though the

rate of consciousness recovery varies

from eight percent to 72 percent

(but decreases to 20–30% in patients

persisting in comas longer than 24

hours),47 a severe brain injury may

result persistent unconsciousness for

many years. There have been cases

of emergence from DOC, even after

many years.48 Generally, recovery

from a metabolic or toxic coma is far

more likely than from an anoxic one

where the traumatic brain injury

(TBI) occupies an intermediate

prognostic position. A post-anoxic

coma is a state of unconsciousness

caused by global anoxia of the brain,

most commonly due to cardiac

arrest. The outcome after a post-

anoxic coma lasting more than

several hours is generally, but not

invariably, poor.47

About 40 percent of patients with

VS may be clinically misdiagnosed in

that they may be conscious but are

unable to manifest any signs of

consciousness.49–51 Such a condition

has been recently labeled functional

locked-in syndrome (FLIS),

whereby, using neurophysiological

and functional neuroimaging

approaches, clinicians are able to

record residual brain network

connectivity that is sustaining a

covert awareness.52 A patient with

FLIS is clinically similar to one with

VS, with the exception that the

former is aware of the self and the

environment but is unable to

demonstrate awareness or

communicate.6–9 This may due to the

deterioration of sensory-motor

processes, which support motor

function, rather than the breakdown

of cerebral connectivity.6–12,53,60

The low rate of correct diagnoses

and prognoses may depend on the

variations in scale application,

awareness fluctuation, and subjective

interpretation of clinical findings.

The use of paraclinical tests to

detect residual and covert signs of

awareness may help in better

managing patients with DOC and

consequently supporting their right

to ELDs. Nevertheless, different

paraclinical tests would be necessary

to confirm awareness since single

tests may suffer from the same

methodological bias that clinical

approaches do.39,40,54

ELDs AND THE DIGNITY OF

HUMAN LIFE

The thought of interrupting life-

sustaining treatments, including

ANH, may arise in family members

and caregivers when their loved one

suffers from a long-lasting and

potentially irreversible DOC

condition.34 The idea of hastening

one’s own death may occur when

one’s quality of life is poor or

unbearable (e.g., in the case of

physical pain and/or mental anguish)

and life is considered without dignity

(e.g., feeling there is no chance of

recovery, finding nothing that makes

life worth living, and perceiving life

as a burden to others).55–58 One might

consider that respecting the dignity

of life means respecting the dignity

of death and thus avoiding

unbearable and/or unnecessary

suffering or living in what one might

considered a handicapped and

hopeless condition. As stated by

Marc Augé,59 “To die without dignity

is to die alone, abandoned, in an

inhospitable and anonymous place, in

a non-place. To die without dignity

means to die, suffering needlessly or

to die tied up to a technical gadget

that becomes the sovereign of my

last days. To die without dignity also

means to die in isolation, surrounded

by insensitive people, soulless

specialists, and bureaucrats who

carry out their professional tasks

mechanically.”

Many authors22,24,30–34,60–62 criticize

using the interruption of ANH as a

way to hasten death because ANH

suspension inevitably leads to a

lengthy death with the potential for

suffering, and suffering would be

considered an unworthy way to die.

This reasoning suggests that ANH

should be continued in order to avoid

suffering by the patient, even when

that patient is unconscious.61,62

Others argue that ANH is a

standard part of treatment for

patients with DOC, and suggest that

the discontinuation of ANH along

with any other standard treatment

should be permitted when explicitly

requested and that this is in keeping

with the principles of beneficence

and non-maleficence and the

“patient’s best interests” rationale.63–65

However, the rights to freely live

(with obvious due respect for others)

and to make any decision concerning

one’s own personal health are well

established as respecting the

principles of free will and the

personal understanding of the quality

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of life and human dignity.66 This

suggests that a human being has an

innate right to be valued and

respected and to receive ethical

treatment. In 1964, the Declaration

of Helsinki56 stated, “It is the duty of

physicians who participate in medical

research to protect the life, health,

dignity, integrity, right to self-

determination, privacy, and

confidentiality of personal

information of research subjects.”

Such issue was further corroborated

by the Council of Europe in 1997 in

the Convention for the Protection

of Human Rights and Dignity of

the Human Being with regard to

the Application of Biology and

Medicine57 and by the United

Nations Educational, Scientific, and

Cultural Organization’s Declaration

on the Human Genome and

Human Rights58 in 1998. Both of

these councils stated that there is an

absolute need for respecting the

human being both as an individual

and as a member of the human

species, for recognizing the

importance of ensuring the dignity of

the human being, and for

safeguarding human dignity and the

fundamental rights and freedoms of

the individual with regard to the

application of biology and medicine.

In keeping with the duties and

rights set forth in the

aforementioned declarations, a

competent individual or an

individual’s surrogate should be free

to make ELDs. We might consider

that ANH contributes to the physical

well-being of the patient and permits

a continuation of life and, possibly,

improvement in the quality of life.

And in cases of long-lasting VS

where the chances of recovery are

slim at best, we might consider that

withholding ANH might cause

physical and/or emotional pain. One

might also consider, however, that

when the burden of life on the

patient outweighs the benefits (e.g.,

in the case of a patient with DOC

who has no chance of amelioration),

the administration of ANH might be

futile treatment. Even the most

conservative positions on life

maintenance, e.g., the Catholic

church, admit that treatments are

not obligatory when considered

harmful.67 Hence, a form of passive

euthanasia might be acceptable when

1) aggressive or unnecessary

therapies in cases of terminal or

hopeless illness only prolong a

painful and suffering life, 2) an

informed request is made by a

sentient patient or, conscientiously,

by that patient’s surrogate(s); and 3)

death is an unintended, although

foreseeable, consequence of therapy

interruption. In this regard, the

unique scope of therapy interruption

must be to avoid the suffering of the

patient and not to provide or hasten

death. Thus, the most conservative

positions will deny any form of

euthanasia but will provide palliative

care, even if this shortens the

patient’s life, thus producing the

unwanted and undesired side effect

of death (passive euthanasia).

ELDs IN VIEW OF THE SANCTITY

OF HUMAN LIFE

The right to die is strongly

criticized by those who claim the

sanctity of human life and argue that

the willingness to die should be

considered unacceptable for moral,

religious, logical, and philosophical

reasons.13,20–24 In fact, it might be

argued that euthanasia and PAS can

be similarly compared to suicide and

homicide, respectively, even when

performed at the explicit request of

the patient or surrogate, given that

they cause death with established

methods and times. As argued by the

most conservatory positions

(including the Catholic Church),13,20–24

this issue is considered by some as

unacceptable because life is an

inviolable gift (by God or nature)

that cannot be removed by self of by

others. The expression sanctity of

life refers to the idea that human life

is sacred and holy, given that A) all

human beings are to be valued,

irrespective of age, sex, race,

religion, social status, or their

potential for achievement; B) human

life is a basic good as opposed to an

instrumental good—a good in itself

rather than a means to an end; and

C) human life is sacred because it is

a gift from God. Therefore, the

deliberate taking of human life

should be prohibited except in self-

defense or the legitimate defense of

others.

In religion and ethics, the

inviolability or sanctity of life is a

principle of implied protection

regarding the aspects of sentient life,

which are said to be holy, sacred, or

otherwise of such a value that they

are not to be violated.13,20–24 Hence, by

merely existing, every human being

lives his or her own life with dignity,

which includes living correctly,

according to moral and ethical

principles. This suggests that one

must die in a natural way, given that

death is a natural phenomenon.

Death might be considered the ‘last

page’ of life, and life must be

experienced with dignity. One’s

death has been decided by the

superior Being, and thus one should

adopt options of preservation,

including the administration of

analgesics and the provision of

adequate human, psychological, and

spiritual support, which may relieve

the sense of solitude and allow

relatives to grieve and be given the

opportunity to humanize death. On

the other hand, the voluntary refusal

of treatment may lengthen the

patient’s period of suffering but will

still result in death as a result of the

disease itself, not by any action or

omission of life-sustaining therapy. In

such cases, death would be natural

and expected.

Some secular positions criticize

the right to euthanasia and PAS from

a logical point of view.28,29 They claim

that it is unreasonable for one person

to determine the death of another

person as there could be a

reasonable chance of healing,

survival, or alternative care. In

addition, they argue that such a

determination should not be made

due to the inherent uncertainty of

the chances for recovery and real

level of awareness in patients with

DOC (e.g., a patient may be in a

state of FLIS, thus unable to

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communicate with those around him

or her but is still aware). Hence,

using this line of thinking, we might

conclude that patients with DOC

should always have the right to live

and to die peacefully and naturally

later rather than have their lives

prematurely ended by removing a

feeding tube, which would lead to

forced starvation.

MAKING CHOICES

We might consider in what way

the worthiness of life is defined,

since “worthy” is the pivotal element

of the right to death argument. An

important component of ELDs is

each individual’s perception of what

makes life important, worthy, and

valuable. For example, one individual

might perceive that living with a

disability makes his or her life

unworthy, whereas another

individual with the same disability

may consider his or her life

important and worth living.

Therefore, one might argue that the

dignity of one’s life has to be

determined by oneself, as long as

such determination does not harm

others, including family members.

From this point of view, dignity and

sanctity of life are not conflicting,

and ELDs for patients with DOC

could be based on sufficient evidence

that their condition is irreversible

and hopeless and any ELDs are in

keeping with their wishes. It could be

argued that putting an end to

unnecessary suffering is not an

affront to but rather a strengthening

of the sanctity and dignity of life,

provided this end is freely and

consciously wanted by the either the

patient or his or her surrogate on

behalf of the patient.

A clear and conscious decision to

request the discontinuation of one’s

own life-sustaining therapy, including

ANH, may serve as sufficient legal

justification for such a decision in

most United States courts as long as

the patient is an adult who is capable

of making decisions. But what about

in cases of DOC, in which the

patients lack the capacity to make

decisions, and thus the burden of

decision falls on the patient’s

surrogate or guardian? In the United

States, the Quinlan and Cruzan

cases highlight two important

considerations regarding the ethical

admissibility of ELDs made by a

patient’s guardian or surrogate when

the irreversibility of unconsciousness

has been established: 1) making a

presumptive decision for the patient

in the absence of a living will and 2)

making a decision for the patient

with a living will.68–70 Based on the

principle of substituted judgment, in

some states in the United States, a

surrogate is allowed to refuse life-

sustaining treatment on behalf of the

patient, with or without a living will,

if the patient lacks the capacity to

decide for him- or herself and the

treatment is considered burdensome

and/or unnecessary (i.e., the patient

will never recover, even with

treatment). In these cases,

withholding or interrupting life-

sustaining therapy would be

considered to be in the best interest

of the patient. In other states,

however, a surrogate must provide

evidence of a living will that

satisfactorily communicates the

patient’s desire to have life support

discontinued in the event of

irreversible DOC—before the

surrogate can make such a

request.68–70

The ethical admissibility of ELDs

made by a patient’s guardian or

surrogate becomes thornier when

dealing with cases of MCS, because

these patients may have residual

decision-making capacity and

cognitive ability. There are several

cases in the United States where

ANH was withheld in patients with

MCS (e.g., Conroy, Edna, Martin,

and Wendland cases).71–73 Because

MCS individuals are partially

conscious and are not typically

terminally ill, their legal status is

complex. While consciousness itself

might be a good reason to continue

life-sustaining aids, it may not always

be in the patient’s best interest to

continue living a severely

handicapped life.74,75 Determining

when existence is no longer

subjectively valuable for an individual

with a severely limited capacity to

communicate is a vexing situation.

Assuming that all persons have the

same right to die, MCS surrogates

should remain empowered to act on

behalf of these vulnerable

individuals,76 but also should take

into account the potential that their

loved one with MCS might still have

some cognitive ability.

Altogether, the ethical issues

surrounding ELDs made by someone

other than the patient highlight the

importance of establishing living

wills, which are written, legal

instructions regarding a patient’s

preferences for medical care

(doctors and caregivers) if he or she

is unable to make decisions for him-

or herself because of a terminal

illness, severe brain injury, coma, the

late stages of dementia, or the near-

end of life. By careful planning,

unnecessary suffering of the patient

and burdening the caregiver with

difficult ELDs might be avoided

during times of crisis or grief.

Through the power of attorney, a

person (healthcare agent, proxy,

surrogate, representative, attorney-

in-fact, or patient advocate) is

empowered to make decisions for the

individual who is unable to do so.

Living wills are allowed or legalized

in the United States (e.g., California

Natural Death Act77 and United

States Patient Self Determination

Act78), Germany, France, Canada,

Australia, Denmark, and England,

whereas they are still debated in

Italy.79–81 However, a living will may

present some critical problems. For

example, a patient’s wishes may not

be respected due to the lack of clear

legislation concerning the warranty

of the patient’s right to die. The

medical staff’s rights and duties also

may not be clearly defined, causing

further push back on respecting an

individual’s living wills by raising the

concern about potential criminal

consequences of an omission or

fulfillment of patient’s will.82

Furthermore, the disproportionality

of therapies has not been clearly

defined.83 Some may argue that a

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dying patient has the right to refuse

burdensome medical treatments that

A) have no chance of curing or

improving the patient’s medical

condition(s) and/or B) are

disproportionately painful, intrusive,

risky, or costly when compared to

the expected therapeutic outcome. It

can be argued that every individual

should be free to decide whether to

live in such a condition. But

regarding the living wills of patients

with DOC, it is important to consider

not the value of the life of the person

but rather the value of the treatment

to that person.

To avoid potential problems

regarding the authenticity of living

wills, they should be officially

certified by means of a notary or an

audio-video testimony overseen by a

lawyer or a solicitor. Moreover, a

living will should be checked and

updated continuously to confirm the

desires of its author in terms of ELDs

in general and ELDs specific to DOC,

should this occur. And finally, the

possibility of revising the will of an

incapacitated patient regarding

withdrawal of ANH and other life-

supporting care may need to be

considered, with the help of family

members and friends. Living wills

prepared in such a way will reduce

the chances of misinterpretation of

the document by judges, ethics

committees, and public health

committees.

THE SLIPPERY SLOPE ARGUMENT (SSA) OF THE “RIGHT TO DIE”

After considering the ethical

dilemma of maintaining a patient’s

dignity while respecting his or her

sanctity of life, the issue of how to

regulate the right to a worthy death

remains. In fact, the lack of a clear

position by those governments that

have not established ad hoc laws on

ELDs has led to the growth of the

phenomenon of indirect euthanasia,

in which pain medication is

administered to the patient to reduce

pain, with the side effect of

quickening the dying process.84 One

might consider that the primary

intention of such treatment is not to

kill the patient but to make the

patient more comfortable, which

might be viewed as morally

acceptable. This type of indirect

euthanasia might be justified using

the “Doctrine of Double Effect,”

which states that if doing something

morally good has a morally bad side

effect, it is ethically correct only

when the bad side effect is not

intended, even if the bad effect was

foreseeable.85 That is to say the good

result must be achieved

independently of the bad one, the

action must be proportional to the

cause, and the patient must be in a

terminal condition.

Without clear euthanasia

legislation, arbitrary nonvoluntary

and even involuntary euthanasia

could potentially occur.85 Euthanasia

must be voluntary to be ethical, but it

is nonvoluntary when it is used in

unconscious individuals or in persons

who are unable to make a meaningful

choice between living and dying and

an appropriate person (a surrogate or

a legal guardian) makes the decision

on their behalf. On the other hand,

nonvoluntary euthanasia can also be

when the person who dies had

chosen life but instead underwent

euthanasia at the request of someone

else (i.e., murder). A conservative

view is that this SSA could lead to an

out of control acceptance of

euthanasia or PAS, even if it is

deemed unacceptable.13,20–24 From a

logical point of view, if the

acceptance of an initial act logically

entails the acceptance of another

(but undesirable) act, it might be

argued that there is no relevant

conceptual difference between the

two acts. And on the other hand, if

the acceptance of an initial act will

lead to a series of similar acts that

are all acceptable, the eventual last

(and unacceptable) event is not

relevant. From an empirical or

psychological point of view, one

could argue that there is instead no

need for a logical connection between

two events; the acceptance of an

event will, in time and through a

process of moral change, lead to the

acceptance of another one.

To avoid an out of control

application of ELD, and to both grant

and regulate the right to die,

governments in the United Kingdom,

Canada, and some states in the

United States have outlined different

protocols for ELDs and euthanasia. A

clear law that limits ambiguity

regarding the representation of

patients with DOCs is still missing in

many countries, including Italy. The

media has brought attention to some

cases that have forced the courts to

decide whether to suspend ANH, but

no clear, consistent legislation with

documented protocol has been

established when considering

euthanasia for patients with

DOC.27,69,86–91

Active euthanasia, in which a

person (physician or not) directly

and deliberately causes the patient’s

death following that patient’s explicit

request (or that of the patient’s

surrogate) through the use of drugs

is legal in a few countries. As of June

2016, euthanasia of this nature is

legal in the Netherlands, Belgium,

Colombia, and Luxembourg.92 PAS

(which refers to cases wherein the

person, who is terminally ill, needs

and asks for the help of medical

professionals in ending his or her

life) is legal in Switzerland, Germany,

Japan, and Canada; it is also legal in

the states of Washington, Oregon,

Vermont, Montana, New Mexico, and

California in the United States.92

The Netherlands has legalized

both euthanasia and PAS but only

after the patient had received every

available type of palliative care. In

2004, the Groningen Protocol93 was

developed establishing the required

criteria each case must meet before

legal child euthanasia may be carried

out, which protects the liability of

the physician. It is worthy to note

that Belgium also allows child

euthanasia when the young patient is

conscious of his or her decision,

understands the meaning of

euthanasia, and suffers from a

terminal illness that causes an

intractable and unbearable pain; the

child’s parents and the medical team

must approve the request.94

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Luxembourg and Uruguay legalized

euthanasia for terminally ill patients,

who have received the approval of

two doctors and a panel of

experts.94,95

Switzerland allows PAS for both

adult citizens and foreigners,

whereas PAS is legal in Canada only

for all adult Canadian citizens with a

terminal illness that has progressed

to the point where natural death is

“reasonably foreseeable” (the

Assisted Dying for the Terminally Ill

Bill).96–100 Likewise, Colombia

approved euthanasia for terminally ill

patients with cancer, acquired

immunodeficiency syndrome (AIDS),

kidney or liver failure, and

degenerative diseases (including

Alzheimer’s, Parkinson’s, and

amyotrophic lateral sclerosis) that

cause extreme suffering.101 In

Germany, PAS is legal as long as the

lethal drug is taken without any help,

meaning there is no one guiding or

supporting the patient’s hand.102

Active euthanasia is illegal

throughout most of the United

States, whereas the passive form

(i.e., refusing medical treatment

even if this choice may hasten death)

is legal, with PAS being legal in five

states (Oregon, Washington,

Vermont, California, Montana, and

one county in New Mexico). The

legislation passed in Oregon,

Washington, and California was

based on Oregon’s “Death with

Dignity” Act,103–107 which states that a

“competent adult resident who has

been diagnosed by a physician with a

terminal illness, which will kill the

patient within six months, may

request in writing, from his or her

physician, a prescription for a lethal

dose of medication for the purpose of

ending the patient’s life. The

exercise of the option, under this

law, is voluntary, and the patient

must initiate the request. Any

physician, pharmacist, or healthcare

provider who has moral objections

may refuse to participate.” Two

witnesses, one of whom is not

related to the patient in any way,

must confirm the request. After the

request is made, another physician

must examine the patient’s medical

records and confirm the diagnosis.

The patient must be determined to

be free of a mental condition that

impairs his or her judgment. If the

request is authorized, the patient

must wait at least 15 days and make

a second oral request before the

prescription may be written. The

patient has a right to rescind the

request at any time. The patient

must be referred for a psychological

evaluation if the physician has

concerns about the patient’s ability

to make an informed decision or if he

or she suspects the patient’s request

may be motivated by depression or

coercion.103–107

Oregon’s Death with Dignity Act

protects doctors from liability

provided the adult patient is

competent and is in compliance with

the statute’s restrictions; at the same

time, this Act also guarantees and

regulates the access to the right to

die. Participation by physicians,

pharmacists, and healthcare

providers is voluntary. The law also

specifies that a patient’s decision to

end his or her life shall not “have an

effect upon a life, health, or accident

insurance or annuity policy.”

According to the Oregon Death with

Dignity Act: Data Summary 2015

Report,106 about 64 percent of the

people in Oregon who filled

prescriptions for lethal medications

died. There were no significant

differences concerning age, gender,

or levels of instruction. The primary

end of life concerns were the loss of

autonomy, the inability to make life

enjoyable, and loss of dignity.

Notably, there was no evidence of

heightened risk for euthanasia in the

elderly, women, the uninsured,

people with low educational status,

the poor, the physically and mentally

disabled, the chronically ill or

unconscious, minors, people with

psychiatric illnesses including

depression, or racial or ethnic

minorities compared with

background populations.108

In Oregon, futile or

disproportionately burdensome

treatments, including ANH, may be

withheld or interrupted under

specified circumstances and only

with the informed consent of the

patient or, as in the case of VS, with

the informed consent of the legal

surrogate.The United States Patient

Self Determination Act does not

address quality of life issues and

does not make a clear distinction

between active and passive

euthanasia when there is clear and

convincing evidence that the

informed consent to euthanasia,

passive or active, has been obtained

from a competent patient or the legal

surrogate of an incompetent patient.

Active euthanasia is explicitly

illegal in Australia, Austria, China,

Denmark, Finland, France, Ireland,

Italy, Latvia, Lithuania, New Zealand,

Norway, the Philippines, Russia,

Spain, Turkey, and the United

Kingdom, though some will allow

access to advanced care directive

options and offer reduced penalties

for those who assist patients in

dying. In Denmark and France, a sort

of “Right to Die with Dignity” act is

under debate.92

Passive euthanasia, as described

earlier, is legal in India, Sweden, and

Ireland. Moreover, passive euthanasia

is tolerated in the United States,

Mexico, Canada, Israel, Argentina,

Hungary, Finland, Thailand (even for

foreign individuals), Portugal (with

the exception of ANH interruption,

which is not allowed), and Germany.

In Japan, there is a law plan for

active euthanasia and PAS. The plan

includes clauses related to an

unbearable and untreatable suffering

(for which the physician must have

ineffectively exhausted all other

measures of pain relief), inevitable

and approaching death, and a written

consent (living wills and family

consent will not suffice).

Interestingly, Japan’s government

instituted “bioethics SWAT teams,”

which are made available to the

families of terminally ill patients in

order to help them, along with the

doctors, come to an informed

decision based on the personal facts

of the case. In Mexico, terminally ill

patients or, if they are unconscious,

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their closest relatives are permitted

to refuse medication or further

medical treatment to extend life in

Mexico City, the central state of

Aguascalientes, and the Western

state of Michoacán.92,108–110

In Italy, active euthanasia is under

the penal law (as being equated to

intentional homicide), as is assisted

suicide. Nevertheless, the extensive

use of pain-relieving drugs, which

could cause premature death (i.e.,

indirect euthanasia), is not

considered a form of euthanasia;

neither is the abstention from

aggressive treatments (i.e., those

therapies that can only prolong a

state without chances of

amelioration). The Italian

government is still in the

developmental stage in regard to

right to die policy, but theirs is

mainly directed at limiting an

individual’s personal autonomy and

the possibility of writing a personal

living will. Indeed, advanced care

directives, which are not yet broadly

recognized in Italy, probably

represent the best way to safeguard

the principle of autonomy.

AUTHORS’ POINT OF VIEW AND

FUTURE PERSPECTIVES

We believe that all patients with

DOC (i.e., their surrogates) should

be put in the position to freely

choose their own way to end their

lives, in full respect of the personal

and inviolable principles of the

dignity and sanctity of human life. In

our opinion, all patients should be

free to manage their own deaths, or

to empower someone to do it if they

are incapacitated, when they

perceive their quality of life as

severely impaired by physical or

psychological suffering (e.g.,

incontinence, nausea and vomiting,

breathlessness, paralysis, difficulty in

swallowing, depression, fearing a loss

of control or dignity, feeling like a

burden, having a dislike for being

dependent) and when there is no

chance of improvement.

It is urgent that governments

establish safeguards, criteria, and

protocol that protect the right to a

worthy death (in keeping the

patient’s lucid and conscious will and

the personal concepts of dignity and

the sanctity of life), ensure societal

oversight, and prevent euthanasia

and PAS from being abused or

misused (i.e., moving from being a

measure of ‘last resort to one of early

intervention).111 In fact, euthanasia is

progressively moving from terminally

ill people to those who are

chronically ill, and from physical

illness to mental illness or

psychological distress or suffering

(even “tired of living”), and from

conscious to unconscious patients.

This means that the actual laws may

fail to detect and prevent situations

in which people could be subjected

to undue pressure to access or

provide euthanasia and could

circumvent the safeguards that are in

place.

A balanced law should guarantee

and regulate the access to

euthanasia/PAS. Such laws should

require that all patients and their

surrogates are properly educated

regarding the law and their rights

and are capable of making ELDs.

Hence, ELDs must be voluntary, well

considered, informed, and, above all,

persistent over time. The requesting

person must have provided explicit,

written consent and must be

competent at the time the request

was made. In this regard, some states

require that the voluntariness of the

request has to be confirmed by at

least two witnesses.

A law would avoid non-voluntary

euthanasia in patients with DOC by

confirming the lack of chances of

recovery based on an accurate

clinical assessment corroborated by

advanced paraclinical approaches

and by demonstrating the will of the

patient to not live in such a

condition. In cases with no living will

in place, the best interest of the

patient should be pursued according

to evidence-based medicine and the

opinion of the patient’s surrogate.

The role of the physician is

imperative when making informed

ELDs. Indeed, the so-called

“therapeutic alliance” between the

patient and doctor should be

fundamental in ELD (as well as in

life) and only when this alliance

enforces the patient’s autonomy.

Physicians have a great responsibility

to use their knowledge and skill in

the primary interest of their patients,

and should not only aim to relieve

the burden of sorrow but also strive

to educate and enable patients and

their loved ones to understand,

evaluate, and make their own choices

concerning ELD. Only trained

healthcare clinicians can make

evidence-based diagnoses and

prognoses of DOC conditions, thus

the determination made by the

physician on whether a DOC patient

has any chance to improve is

evidence-based and carefully

considered. The pivotal role the

medical staff plays in ELDs has been

highlighted and regulated in

countries where euthanasia and/or

PAS are legal. Switzerland, however,

allows non-physicians to assist in

suicide. In the Netherlands and

Belgium, a second doctor must see

the patient to confirm the request to

die is valid and the suffering

unbearable, and a network of doctors

is trained to undertake these

consultations. In the United States,

in all five of the states that allow

PAS, it is required that a second

doctor must examine the patient to

confirm the terminal illness before

the request is approved. In Oregon,

Washington, and Vermont, the

patient must also see a mental health

professional when either the

attending or consulting doctor

suspects that the patient may be

suffering from a psychological

disorder (such as depression) that is

impairing his or her judgement. In

addition, ad hoc committees (even if

this is delayed) are used to revise

cases with potential mistakes in the

euthanasia or PAS procedures.

Unfortunately, these committees are

largely underutilized.

Governments and magistrates

must work to establish and

communicate the proper protocol for

ELDs to their citizens in order to

guarantee the rights of patients to a

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peaceful and worthy death and to

limit SSA. Indeed, no additional

requirement relating to the patient’s

experience of the disease or any

minimum level of suffering would

easily extend the application of

euthanasia. On the other hand,

narrowing euthanasia to unbearable

suffering would limit the accessibility

of the right to die for all the other

patients. Likewise, limiting the right

to die from a terminal illness (as in

the United States) could result in the

courts excluding patients with VS

from this right, given that they are

not terminally ill and their prognosis

can only be established with

sufficient confidence using advanced,

non-standard neurophysiological or

neuroimaging approaches. In

addition, the acceptance of solely

passive or indirect euthanasia for

patients in VS would limit their

accessibility to their right to die. In

fact, these patients deserve the same

accessibility to the right to die as

other people and do not deserve a

“worse” euthanasia than the others

(i.e., a slow and agonizing death

because of starvation and

dehydration).

Finally, the people who have the

duty of informing and educating the

public seek to help people cope with

the finiteness of the human

condition, the intrinsic limits of

medicine, and the responsibility to

explore the values surrounding

ELDs.

Hence, there is no reason why any

single moral view of physicians,

magistrates, politicians, or educators

should prevail. A conciliation of the

different currents of thought on

euthanasia may be reached by

placing, at the center, the patient’s

rights to freely manage his or her life

and death while keeping the

principles of dignity and sanctity of

human life intact. ELDs should be

guaranteed in patients with DOCs

when negative prognoses have been

well defined, possibly through the

use of advanced neurophysiological

and functional neuroimaging

techniques, and the desires of the

patients to not live in such

conditions have been clearly

expressed by living wills or by

surrogates. Finally, ad hoc

committees to oversee the proper

access and application of euthanasia

should be instituted and potentiated.

ACKNOWLEDGMENT

The authors would like to thank

Prof. Anthony Pettignano for his

editing services.

REFERENCES

1. Zeman A. Consciousness: concepts,

neurobiology, terminology of

impairments, theoretical models

and philosophical background.

Handb Clin Neurol. 2008;90:3–31.

2. Zeman A. What do we mean by

“conscious” and “aware?”

Neuropsychol Rehabil.

2006;16:356–376.

3. Laureys S, Perrin F, Brédart S.

Self-consciousness in non-

communicative patients.

Conscious Cogn. 2007;16:722–741.

4. von Wild K, Laureys ST,

Gerstenbrand F, et al. The

vegetative state—a syndrome in

search of a name. J Med Life.

2012;5:3–15.

5. Laureys S, Celesia GG, Cohadon F,

et al. Unresponsive wakefulness

syndrome: a new name for the

vegetative state or apallic

syndrome. BMC Med. 2010;8:68.

6. Formisano R, D’Ippolito M, Risetti

M, et al. Vegetative state,

minimally conscious state, akinetic

mutism and Parkinsonism as a

continuum of recovery from

disorders of consciousness: an

exploratory and preliminary study.

Funct Neurol. 2011;26:1–10.

7. Formisano R, D’Ippolito M, Catani

S. Functional locked-in syndrome

as recovery phase of vegetative

state. Brain Inj. 2013;27:1332.

8. Formisano R, Pistoia F, Sarà M.

Disorders of consciousness: a

taxonomy to be changed? Brain

Inj. 2011;25:638.

9. Bruno MA, Vanhaudenhuyse A,

Thibaut A, et al. From

unresponsive wakefulness to

minimally conscious PLUS and

functional locked-in syndromes:

recent advances in our

understanding of disorders of

consciousness. J Neurol. 2011;

258:1373–1384.

10. Multi-Society Task Force on PVS.

Medical aspects of the persistent

vegetative state. N Engl J Med.

1994;330:1499–1508.

11. Demertzi A. Multiple fMRI system-

level baseline connectivity is

disrupted in patients with

consciousness alterations. Cortex.

2014;52:35–46.

12. Bernat JL. Chronic disorders of

consciousness. Lancet. 2006;

367:1181–92.

13. Rubin EB, Bernat JL. Ethical

aspects of disordered states of

consciousness. Neurol Clin.

2011;29:1055–1071.

14. Chochinov HM. Dignity Therapy:

Final Words for Final Days. New

York: Oxford, UK University Press;

2011.

15. Rabiu AR, Sugand K. Has the

sanctity of life law “gone too far?”

analysis of the sanctity of life

doctrine and English case law

shows that the sanctity of life law

has not “gone too far.” Philos

Ethics Humanit Med. 2014;9:5.

16. Duttge G. End-of-life decisions in

cases of vegetative state from the

legal point of view. Fortschr

Neurol Psychiatr.

2011;79:582–587.

17. Jox RJ. Best interests in the

“vegetative state.” Fortschr Neurol

Psychiatr. 2011;79:576–581.

18. Maggiore SM, Antonelli M.

Euthanasia, therapeutic obstinacy

or something else? An Italian case.

Int Care Med. 2005;31:997–998.

19. Bernardin J. Consistent Ethic of

Life. Lake Barrington, IL: Sheed &

Ward; 1988.

20. Barry RL. The Sanctity of Human

Life and Its Protection. Lanham:

University Press of America; 2002.

21. Bayertz K. Sanctity of Life and

Human Dignity: Philosophy and

Medicine. Boston: Kluwer

Academic; 1996.

22. Lanken PN, Ahlheit BD, Crawford

S, et al. Withholding and

withdrawing life-sustaining

therapy. Am Rev Respir Dis.

Innovations in CLINICAL NEUROSCIENCE [ V O L U M E 1 3 , N U M B E R 1 1 – 1 2 , N O V E M B E R – D E C E M B E R 2 0 1 6 ]22

1991;144:726–731.

23. Chan TK, Tipoe GL. The best

interests of persistently vegetative

patients: to die rather that to live?

J Med Ethics. 2014;40:202–204.

24. Ackermann RJ. Withholding and

withdrawing life-sustaining

treatment. Am Fam Physician.

2000;62:1555-60.

25. Rich BA. The ethics of surrogate

decision making. West J Med.

2002;176:127–129.

26. Schiavo ex rel. Schindler v.

Schiavo, 403 F.3d 1289 (11th Cir.

2005).

27. Luchetti M. Eluana Englaro—

chronicle of a death foretold:

ethical considerations on the

recent right-to-die case in Italy. J

Med Ethics. 2010;36:333–335.

28. ProCon.org. Explore pros and cons

of controversial issues. Landmark

euthanasia and physician-assisted

suicide legal cases. 2009.

http://euthanasia.procon.org/view.r

esource.php?resourceID=000131.

Accessed 1 December 2016.

29. Standler RB. Legal Right to Refuse

Medical Treatment in the USA.

12 July 2012.

http://www.rbs2.com/rrmt.pdf

Accessed 1 December 2016.

30. Pellegrino ED. Decisions to

withdraw life-sustaining treatment:

a moral algorithm. J Am Med

Assoc. 2000;283:1065–1067.

31. Kapp MB. Economic influences on

end-of-life care: empirical evidence

and ethical speculation. Death

Studies. 2001;25:251–263.

32. Lipman HI. Deactivation of

advanced lifesaving technologies.

Am J Geriatr Cardiol.

2001;16:109–111.

33. Gedge E, Giacomini M, Cook D.

Withholding and withdrawing life

support in critical care settings:

ethical issues concerning consent.

J Med Ethics. 2007;33:215–218.

34. Santiago C, Abdool S.

Conversations about challenging

end-of-life cases: ethics debriefing

in the medical surgical care unit.

Dynamics. 2011; 22:26–30.

35. Hirschberg R, Giacino JT. The

vegetative and minimally conscious

states: diagnosis, prognosis and

treatment. Neurolog Clinic.

2011;29:773–786

36. Lezak MD. Brain damage is a

family affair. J Clin Exp

Neuropsychol. 1988;10:111–123.

37. Stern J, Sazbon L, Becker E,

Costeff H. Severe behavioral

disturbance in families of patients

with prolonged coma. Brain Inj.

1988;21:256–262.

38. Jacobs HE, Muir CA, Cline JD.

Family reactions to persistent

vegetative state. J Head Trauma

Rehab. 1986;55–62.

39. Fins JJ. Neuroethics and

neuroimaging: moving toward

transparency. Am J Bioeth.

2008;8:46–52.

40. Fins JJ, Illes J, Bernat JL, et al.

Neuroimaging and disorders of

consciousness: envisioning an

ethical research agenda. Am J

Bioeth. 2008;8:3–12.

41. Vos PE. Biomarkers of focal and

diffuse traumatic brain injury. Crit

Care. 2011;15:183.

42. Owen AM, Coleman MR.

Functional MRI in disorders of

consciousness: advantages and

limitations. Curr Opin Neurol.

2007;20:632–637.

43. Coleman MR, Davis MH, Rodd JM,

et al. Towards the routine use of

brain imaging to aid the clinical

diagnosis of disorders of

consciousness. Brain.

2009;132:2541–2552.

44. Leon-Carrion J, Martin-Rodriguez

JF, Damas-Lopez J, et al. Brain

function in the minimally conscious

state: a quantitative

neurophysiological study. Clin

Neurophysiol.

2008;119:1506–1514.

45. Bagnato S, Boccagni C,

Prestandrea C, et al. Prognostic

value of standard EEG in traumatic

and non-traumatic disorders of

consciousness following coma. Clin

Neurophysiol. 2010;121:274–280.

46. Giacino JT, Hirsch J, Schiff N,

Laureys S. Functional

neuroimaging applications for

assessment and rehabilitation

planning in patients with disorders

of consciousness. Arch Phys Med

Rehabil. 2006;87:S67–76.

47. Zandbergen EG, Koelman JH, de

Haan RJ, Hijdra A, PROPAC-Study

Group. SSEPs and prognosis in

post-anoxic coma: only short or

also long latency responses?

Neurology. 2006;67:583–586.

48. Stender J, Gjedde A, Laureys S.

Detection of consciousness in the

severely injured brain. Ann

Update Intensive Care Emerg

Med. 2015;495–506

49. Schnakers C, Giacino JT, Løvstad

M, et al. Preserved covert cognition

in non-communicative patients

with severe brain injury?

Neurorehabil Neural Repair.

2015;29:308–317

50. Candelieri A, Cortese MD, Dolce G,

et al. Visual pursuit: within-day

variability in the severe disorder of

consciousness. J Neurotrauma.

2011;28:2013–2017.

51. Schnakers C, Vanhaudenhuyse A,

Giacino J, et al. Diagnostic

accuracy of the vegetative and

minimally conscious state: clinical

consensus versus standardized

neurobehavioral assessment. BMC

Neurol. 2009;9:35.

52. Owen AM, Coleman MR, Boly M, et

al. Detecting awareness in the

Detecting awareness in the

vegetative state. Science.

2006;313:1402.

53. Giacino JT. Disorders of

consciousness: differential

diagnosis and neuropathologic

features. Semin Neurol.

1997;17:105–111.

54. Giacino JT, Fins JJ, Laureys S,

Schiff ND. Disorders of

consciousness after acquired brain

injury: the state of the science. Nat

Rev Neurol. 2014; 10:99–114.

55. Shultziner D. Human dignity:

functions and meanings. Global

Jurist. 2003;3:1–21.

56. World Medical Association.

Declaration of Helsinki: ethical

principles for medical research

involving human subjects. J Am

Med Assoc. 2013;310:2191–2194.

57. Andorno R. The Oviedo

Convention: a European legal

framework at the intersection of

human rights and health law. J Int

Biotechnol Law.

Innovations in CLINICAL NEUROSCIENCE [ V O L U M E 1 3 , N U M B E R 1 1 – 1 2 , N O V E M B E R – D E C E M B E R 2 0 1 6 23

2005;2(4):133–143.

58. United Nations Educational,

Scientific, and Cultural

Organization. Universal

Declaration on the Human

Genome and Human Rights. 9

December 1998.

59. Augé M. Non-places. Introduction

to an Anthropology of

Supermodernity. New York:

Verso; 1992.

60. Kollas CD, Boyer-Kollas B. Closing

the Schiavo case: an analysis of

legal reasoning. J Palliative Med.

2006;9:1145–1163.

61. Olsen ML, Swetz KM, Mueller PS.

Ethical decision making with end-

of-life care: palliative sedation and

withholding or withdrawing life-

sustaining treatments. Mayo Clin

Proc. 2010;85:949–954.

62. Royal College of Physicians.

Prolonged Disorders of

Consciousness: National Clinical

Guidelines. London: RCP; 2013.

63. American Academy of Neurology.

Position of the American Academy

of Neurology on certain aspects of

the care and management of the

persistent vegetative state patient.

Neurology. 1989;39:125–126.

64. Larriviere D, Bonnie RJ.

Terminating artificial nutrition and

hydration in persistent vegetative

state patients: current and

proposed state laws. Neurology.

2006;66:1624–1628.

65. Bacon D, Williams MA, Gordon J.

Position statement on laws and

regulations concerning life-

sustaining treatment, including

artificial nutrition and hydration,

for patients lacking decision-

making capacity. Neurology.

2007;68:1097–1100.

66. Aquinas T. Aristotle. On

Interpretation c. 9 18b 30. In:

Summa Theologica. Part 1, Q.83

a1.

67. Gigli GL, Zasler ND. Life-

sustaining Treatments in

Vegetative State: Scientific

Advances and Ethical Dilemma.

Pontifical Academy of Sciences,

FIAMC. Amsterdam: IOS Press;

2004.

68. Kinney HC, Korein J, Panigrahy A,

et al. Neuropathological findings in

the brain of Karen Ann Quinlan—

the role of the thalamus in the

persistent vegetative state. N Engl

J Med. 1994;330:1469–1475.

69. Quinlan J, Quinlan JD. Karen Ann:

The Quinlans Tell Their Story.

New York: Bantam Books. 1977.

70. Cruzan v. Director. Missouri Dept.

of Health, 497 U.S. 261. 1990.

71. Lo B, Dornbrand L. The case of

Claire Conroy: will administrative

review safeguard incompetent

patients? Ann Intern Med. 1986;

104:869–873.

72. Nelson L. Persistent

Indeterminate State: Reflections

on the Wendland Case. Santa

Clara, CA: Santa Clara University;

2011.

73. Eisenberg JB, Kelso JC. The

Robert Wendland case. West J

Med. 2002;176:124.

74. Kahane G, Savulescu J. Brain

damage and the moral significance

of consciousness. J Med Philos.

2009;34:6–26

75. Weber LJ, Campbell ML. Medical

futility and life-sustaining

treatment decisions. J Neurosci

Nurs. 1996;28:56–60.

76. Syd L, Johnson M. The right to die

in the minimally conscious state. J

Med Ethics. 2011;37:175–178.

77. State of California. Natural Death

Act. Health and Safety Code—

HSC. Division 1. Administration of

Public Health [135 - 1179.80]. Part

1.85. End of Life Option Act

[443–443.22].

78. 101st United States Congress

(1989–1990). House: Ways and

Means; Energy and Commerce.

H.R.4449—Patient Self

Determination Act of 1990.

79. Rothschild A. Physician-assisted

death: an Australian perspective.

In: Birnbacher D, Dahl E (eds).

Giving Death a Helping Hand:

Physician-Assisted Suicide and

Public Policy: An International

Perspective. Springer:

International Library of Ethics,

Law, and the New Medicine;

2008:104.

80. Johnston C, Liddle J. The Mental

Capacity Act 2005: a new

framework for healthcare decision

making. J Med Ethics.

2007;33:94–97.

81. Docker C. Advance directives/living

wills. In: McLean SAM (ed).

Contemporary Issues in Law,

Medicine and Ethics. Dartmouth:

Aldershot; 1996.

82. The Commission on Assisted

Dying. The Current Legal Status

of Assisted Dying is Inadequate

and Incoherent. London: Demos;

2011.

83. Mallia P, Daniele R, Sacco S, et al.

Ethical aspects of vegetative and

minimally conscious states. Curr

Pharm Des. 2014;20:4299–304.

84. Hartling OJ. Euthanasia: the

illusion of autonomy. Med Law.

2006;25:189–199.

85. Boyle, JMJr. Toward understanding

the principle of double

effect.ZEthics. 1980;90:527–538.

86. Fine RL. From Quinlan to Schiavo:

medical, ethical, and legal issues in

severe brain injury. Proc (Bayl

Univ Med Cent). 2005;18:303–310.

87. Mueller PS. The Terri Schiavo saga:

ethical and legal aspects and

implications for clinicians. Pol

Arch Med Wewn.

2009;119:574–581.

88. Merrell DA. Erring on the side of

life: the case of Terri Schiavo. J

Med Ethics. 2009;35:323–325.

89. Quill TE. Terri Schiavo: a tragedy

compounded. N Engl J Med.

2005;352:1630–1633.

90. Solarino B, Bruno F, Frati G, et al.

A national survey of Italian

physicians’ attitudes towards end-

of-life decisions following the death

of Eluana Englaro. Intensive Care

Med. 2011;37:542–549.

91. Striano P, Bifulco F, Servillo G.

The saga of Eluana Englaro:

another tragedy feeding the media.

Intensive Care Med.

2009;35:1129–1131.

92. De Lima L, Woodruff R, Pettus K,

et al. International Association for

Hospice and Palliative Care

position statement: euthanasia and

physician-assisted suicide. J

Palliat Med. 2017;20:8–14.

93. Chervenak FA, McCullough LB,

Arabin B. The Groningen Protocol:

Innovations in CLINICAL NEUROSCIENCE [ V O L U M E 1 3 , N U M B E R 1 1 – 1 2 , N O V E M B E R – D E C E M B E R 2 0 1 6 ]24

is it necessary? Is it scientific? Is it

ethical? J Perinat Med.

2009;37:199–205.

94. No authors listed. Euthanasia in

Belgium, the Netherlands and

Luxembourg. Prescrire Int.

2013;22:274–278.

95. Brinkman-Stoppelenburg A,

Vergouwe Y, van der Heide A,

Onwuteaka-Philipsen BD.

Obligatory consultation of an

independent physician on

euthanasia requests in the

Netherlands: what influences the

SCEN physicians judgment of the

legal requirements of due care?

Health Policy. 2014;115:75-81.

96. Hurst SA, Mauron A. Assisted

suicide and euthanasia in

Switzerland: allowing a role for

non-physicians. BMJ. 2003;

326:271–273.

97. Lindblad A, Löfmark R, Lynöe N.

Physician-assisted suicide: a survey

of attitudes among Swedish

physicians. Scand J Public

Health. 2008;36:720–727.

98. Müller-Busch HC, Oduncu FS,

Woskanjan S, Klaschik E. Attitudes

on euthanasia, physician assisted

suicide and terminal sedation–a

survey of the members of the

German Association for Palliative

Medicine. Med Health Care

Philos. 2004;7:333–339.

99. Lemaire A. Law for end of life care

in French. Intensive Care Med.

2004; 30:2120.

100. Emanuel EJ. Euthanasia and

physician-assisted suicide: a review

of the empirical data from the

United States. Arch Intern Med.

2002;162:142–152.

101. Ceaser M. Euthanasia in legal limbo

in Colombia. Lancet.

2008;371(9609):290–291.

102. Horn R. Euthanasia and end-of-life

practices in France and Germany: a

comparative study. Med Health

Care Philos. 2013;16:197–209.

103. The State of Oregon. The Oregon

Death with Dignity act. Oregon

State Legislature

1997;127:800–995.

104. Washington vs. Glucksberg, 521

U.S. 702 (1997).

105. Gonzales v. Oregon, 546 U.S. 243

(2006).

106. Oregon Public Health Division.

Oregon Death with Dignity Act:

Data Summary 2015. Oregon:

Secretary of the State of Oregon;

2016.

107. Oregon Blue Book. Initiative,

Referendum and Recall: 1996-

1999. Oregon: Secretary of the

State of Oregon; 2006.

108. Battin P, van der Heide A, Ganzini

L, et al. Legal physician-assisted

dying in Oregon and the

Netherlands: evidence concerning

the impact o” groups. J Mel

Ethics. 2007;33:591–597.

109. McDougall JF, Gorman M.

Contemporary World Issues:

Euthanasia. Santa Barbara, CA:

ABC-CLIO; 2008.

110. del Río AÁ, Marván ML. On

euthanasia: exploring psychological

meaning and attitudes in a sample

of Mexican physicians and medical

students. Dev World Bioeth.

2011;11(3):146–153.

111. Smets T, Bilsen J, Cohen J, et al.

The medical practice of euthanasia

in Belgium and the Netherlands:

legal notification, control and

evaluation procedures. Health

Policy. 2009;90:181–187.

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