Download ethical and medical considerations in heart transplantation in children

Romanian Journal of Bioethics, vol. 6, nr. 3, July – September 2008
ETHICAL AND MEDICAL
CONSIDERATIONS IN HEART
TRANSPLANTATION
IN CHILDREN
Amalia Făgărăşan*, Horaţiu Suciu**
Abstract
Heart transplantation in children has evolved from a simple experimental procedure to a
revolutionary therapy, unanimously accepted as the only therapeutic method capable of ensuring
survival for a large number of children diagnosed with final stage cardiomyopathy, left heart
hypoplasic syndrome, obstructive rabdiomyoma, multiple fibroma. The most serious aspect, from
which the main ethical problems in pediatric heart transplantation derive, is that of the small
amount of donors. Small children below 2 years of age rarely die in circumstances that would
offer them the possibility of becoming donors. Under these conditions, a large variety of ethical
dilemmas come into focus: is the anencephalic newborn or infant a viable source of organs?
How will the distribution of available organs take place? Can a patient who has already
benefited from transplant undergo other transplants while other patients die waiting for a new
heart? Who makes the decisions in the case of children and teenagers with dilating
cardiomyopathy (CMD) and how objective are these decisions? What is the role of pediatric
bioethical commissions in making decisions about children with CMD, which team is capable
enough of identifying and solving the ethical problems which come into perspective concerning
this disease, which has a high risk of premature death in the absence of transplant?
Key words: heart transplant, child, Bioethics.
Pediatric heart transplantation, due to
medical advances in the past 40 years, has
been substantial evolving from a simple
experimental procedure to complex therapy,
unanimously accepted as the only therapy
of a certain patients class (children with
*
Lecturer, MD Pediatric Cardiology, Section of Pediatric Cardiology, Institute of Cardio-vascular diseases
and Transplant of Târgu Mureş, UMF Târgu Mureş, [email protected]
**
Lecturer, MD Cardio-vascular Surgery, Pediatric Cardiac Surgery and Transplant Clinical Section, Institute
of Cardio-vascular diseases and Transplant of Târgu Mureş, UMF Târgu Mureş
41
severe heart failure at end stages of
cardiomyopathy, which no longer respond
to complex drug therapy or infants born
with severe heart disease with no-access to
corrective surgical corrections and die
without trans-plantation).
From a surgical perspective, heart
transplant means the surgical removal of
the heart and great vessels from a brain
dead
donor
followed
by
their
implantation in a recipient with a severe
heart disease.
There are many types of transplant:
• Homograft – transplant from one
individual to another;
• Heterotrophic and heart – lung
transplantation;
• Orthopic graft – the transplanted
organ is placed in its normal anatomical
site;
• Syngeneic graft – transplant
between two identical twins;
• Xenograft – transplant between
different species (from animals to
humans).
Xenograft is considered by certain
individuals and religions as unethical,
because it affects human dignity. The first
xenotransplant in a child was performed in
1984 when Baby Fae, an infant born with
severe heart failure, received a heart from
a chimpanzee and survived 21 days. This
event raised an ethic dilemma at the time:
when does medical experimentation
become medical benefit? The response
was shortly found; 1 year later a human
donor transplant was taking place.
Therefore, all this effort led to the birth of
a human-heart-to-human-heart transplanttation program giving to hundreds of
children second chances to survive [1, 14].
transplant in a human being. In 1968 an
infant suffering from Ebstein’s disease
was provided with the heart of an
anencephalic infant, and managed to
survive 5 hours after the procedure was
completed. Between 1970 and 1980, at
the University of Stanford children
occasionally benefited from heart
transplants. The veritable success is
reputed by dr. Bailey LL and his team in
1985, at Loma Linda University
Children’s Hospital California, who
managed to complete an orthopic cardiac
transplant on a 4 day old infant who
turned 20 in 2005 as the longest surviving
person with a heart transplant. Since then,
Bailey and his team have completed more
than 485 transplant procedures [4].
At European level, pediatric heart
transplant have known great successes.
Medical logs show the accomplishments of
a prestigious pediatric heart transplant
center in Padova, Italy which has performed
over 60 transplant procedures between 1985
and 2005, the average of children with
transplants being 9,7 years old, and the
percentage shows 73% cardiomyopathy,
21% heart diseases and 1% cardiac tumors.
The survival rate was 82% in the first year
after the procedure, 73% in 5 years, 72% in
10 years, 62,1% in 15 years and 49,3%
post-transplant [10].
In October 2000, in Romania, the
team of cardiovascular surgeons made up
of prof. dr. Radu Deac and dr. Horatiu
Suciu performed for the first time in The
Institute of Cardiovascular Diseases and
Transplantation Targu Mures an orthopic
cardiac transplant on a 12 year-old girl, in
final stages of severe cardiomyopathy
with extended myocardial fibrosis,
NYHA IV heart failure, the patient
surviving 2 years after the procedure,
followed by a sudden death due to
malignant arrhythmia.
Short history of heart transplant
1967 is the year in when Christiaan
Barnard in Cape Town, South Africa
performed the first orthopic heart
42
Index classification), with progressive
deterioration of ventricular functions or
functional status despite optimal medical
treatment. Dilatative cardiomyopathy is
the most frequent form of child
cardiomyopathy, with an incidence of 0,
58 in 100000 children, over 50% of
cardiomyopathies take place during
childhood. Considering data collected
from PHTSG (The Pediatric Health
Transplant Study Group), 76% of heart
transplants were performed in patients
with dilatative cardiomyopathy. The
survival rate of children with transplants
was 90% after a year, 83% after 5 years.
•
Other forms of cardiopathy to
benefit of heart transplant during final
stages are hypertrophic cardiomyopathies
(data collected from PHTSG suggested
that only 5% of children with transplants
were diagnosed with this disease) and
restrictive cardiomyopathies (2-3% of the
total cases). Data collected from PHTSG
suggested that 12% of children with
transplants suffered from this disease.
The mortality rate of children diagnosed
with restrictive cardiomyopathy is 63% in
the first 3 years after diagnosis, 75% 6
years after the diagnosis [7, 17].
•
Malignant arrhythmia or survivors
of heart arrest, who do not respond well
to drug treatment, ablation or the
implanting of a cardiac defibrillator.
•
Patients with congenital heart
disease who have benefited from surgical
treatment, but despite these their quality
of life is unacceptable due to the
persistence of severe hemodynamical
phenomena.
•
Cardiac tumors which cannot benefit
from surgical correction (multiple
fibroma or obstructive rabdiomioma) [5,
6].
Following over 25 years of
experience in pediatric heart transplants,
the best results have been proven to occur
Who is eligible for heart transplants?
Newborn over 36 weeks, weighing
over 2000 g and suffering from:
•
Congenital heart disease which
can’t be surgically corrected:
Primary criteria:
- Hypoplastic left heart syndrome;
- Aortic valve hypoplasia, stenosis,
or atresia (diameter ≤ 5mm newborn
over 36 weeks, weighing over 2500 g);
- Mitral valve hypoplasia, stenosis,
or atresia valve (diameter ≤ 8 mm in
newborn over 2500g), Shone’s
complex- severe mitral valve stenosis
(atresia), left ventricular outflow
obstruction, coarctation of the aorta;
- L-TGA with single ventricle and
heart block;
- D-TGA with hypoplastic right
ventricle and aortic tract;
- Single ventricle with hypoplastic
aortic tract;
- Symptomatic severe Ebstein’s
anomaly with normal pulmonary
arteries.
- Secondary criteria:
- Ductus-dependent
systemic
circulation (exception: critical aortic
stenosis
with
hypoplastic
left
ventricle);
- Ascending
aortic
hypoplasia
(diameter ≤ 5 mm);
- Aortic arch hypoplasia.
• Other congenital heart diseases
which can be included:
- Anomalous pulmonary venous
connection;
- Interrupted aortic arch;
- Complex truncus arteriosus;
- Atrial isomerism;
End stage cardiomyopathy, which
constitute the second largest category of
children viable for transplant, patients
with signs of heart failure (Ross and New
York University Pediatric Heart Failure
43
The essential question that comes up
while waiting for a heart transplant is:
“how long should we wait for a heart?”
Unfortunately, there is no definitive
answer to this question (days, weeks or
months).
in children diagnosed with left cord
hypoplasic syndrome. This serious
congenital heart disease has prevalence
between 0,162 and 0,267 in every 1000
newborns, thus it is estimated that 8001000 will be born with this disease every
year, to which heart transplant is the only
effective primary therapy. Since 1985,
when dr. Bailey LL and his team
performed the first heart transplant on a
newborn using a human donor, up to
1996, 176 children were on the transplant
list. Awaiting heart transplant, a series of
palliative surgical procedures were
applied in order to ensure the survival of
the children. 19% of patients included on
the list died during the waiting period,
and 142 underwent heart transplant. The
age of the patients was between 1, 5
hours and 6 months (the average was 29
days old). The mortality rate was 13
deaths in the first days after transplant, 22
patients within the first month after
transplant. The survival rate was 91%
after a month, 85% after 5 years, and
70% after 7 years. 5 patients had to be
retransplanted (4 for vasculopathy and 1
for reject) [13].
A revolutionary step in the evolution
of heart transplantation was the discovery
of the immunosuppressive treatment,
namely cyclosporine. The optimum time
for conducting a heart transplant in a
child is the neonatal period, considered
the period of an “immunologic privilege”,
the easiest period to control and the least
aggressive [3].
Another congenital heart with
transplantation as single treatment is
aortic athresy. Jacobs and colab.
published results that show that of 323
patients diagnosed with this disease from
January 1994 to January 1997, 49
underwent heart transplants, the survival
rate being 67% after 1 month, 59% after 3
months and 51% after 3 years [11].
Who does not benefit from a heart
transplant?
• Prematurely born children and
newborns under a certain weight limit
that do not have access to bypass;
• Children
with
severe
homodynamic and metabolic instability
despite supportive treatments;
• Clinically active infections;
• Significant neurological deficits
• Severe renal malformations in
children under 1 year;
• Chromosomal anomalies or
various syndromes with limited survival
rates;
• A history of alcohol abuse, drug
abuse in the past 6 months or
psychosocial anamnesis which would
limit the compliance to the pre and post
transplant treatment;
• Lack of compliance to post
transplant treatment.
Who could be a donor for heart
transplant?
This is a quite delicate issue because
it raises a series of medical and ethical
controversies. Any child who has died in
various circumstances (except the
counter-indications for donation) and
whose parent has agreed that the heart be
used in a transplant procedure is a
suitable donor.
The necessary stages until the actual
transplant are: recognition of the clinical
status of brain death, in the absence of an
intoxication with a drug which suppresses
the central nervous system (criteria which
may vary from one country to another).
44
Unanimously accepted criteria for brain
death are: lack of response to external
stimuli/coma; lack of the brain stem
reflexes; lack of the pupillary; corneal
oculocephalic, oculovestibular, gag and
cough reflex; apnea in the presence of
adequate carbon dioxide stimulation.
Neurological testing is also required.
Brain death will be pronounced by two
physicians.
Another important step in heart
transplantation is the existence of an
ABO compatibility between the donor
and the potential recipient.
The size of the heart must be
roughly the same as the one of the
recipient (it is impossible to transplant the
heart of a small child to a teenager).
Children born with anencephaly are
possible donors and infants who die due
to sudden infant death syndrom – SIDS
(if cardiac function is satisfactory).
Ethical issues in pediatric heart
transplantation
A critical aspect is the reduced
number of donors. This determines the
most serious ethical dilemmas. Small
children under 2 years of age rarely die in
medical circumstances making them
eligible as donors. Data offered by The
International Transplant Registry suggest
that 30-50% of patients die while waiting
for a donor. Data offered by The United
Network for Organ Sharing (UNOS),
suggest that 247 children were awaiting a
new heart in 2007 in the US, 28 under a
year old, 78 between 1 and 5 years old,
63 between 6 and 10 years old and 78
between 11 and 17 years old.
On these conditions a new ethical
controversy arises: is the anencephalic
newborn or infant acceptable source of
organs? Anencephaly is a congenital
defect in which the cranium is not
developed and the cerebral cortex is
absent, yet vital organs like the heart and
kidneys are perfectly normal. 1000-2000
children are born with this disease every
year, and the lifespan of these children is
a few hours or days, rarely weeks. In the
last years more and more people are
speaking about using the organs collected
from these children in transplant. This is
possible only with the consent of the
parents to donate their anencephalic
child’s organs in order to give another
child with serious heart problems a
chance for life. Furthermore, the general
rules of organ donation apply to heart
donations as well: respecting human
dignity, the principle of anonymity, and
gratuity [16].
Other ethical dilemmas caused by
the short supply of donors, measured
against the number of patients in need of
heart transplants are:
Who can not be a donor
for a heart transplant?
• Patients with AIDS or HIV;
• Patients with hepatitis B or
carriers of HBs antigen carriers;
• Patients positive for hepatitis C
are relatively counter-indicated;
• Severe infections which are not
treatment responsive;
• ABO incompatibility with the
potential recipient;
• Inadequate size of the heart for
the potential recipient (size of the donor
heart must be close to the size of
recipient’s heart);
• Cardiac malformation other
than: simple septal defect and simple
patent ductus arteriosus;
• Evidence of severe myocardial
ischemic injury: ejection fraction < 40%,
shortening fraction < 20%, mitral
regurgitation
45
Who makes the decisions in case of
children and teenagers with CMD and
how objective are they?
How should the effect of the
treatment be compared to the impact on
the quality of life of these children?
What is the role of pediatric bioethics
commissions in making decisions regarding
children with CMD, and which team would
be capable enough to identify and solve the
ethical considerations that appear around
this disease, with a great risk of a
premature death without a transplant? [17]
The reality that heart transplant in
children with heart failure, due to the
unfavorable evolution of cardiomyopathies, is for the moment the only
treatment, is demonstrated by studies
which show a survival rate if 90% after a
year, the children being unbarred from
any day to day activity, and the psychomotor and cognitive development at 1, 3
and 5 years post transplant is normal in
over 80% of cases. A significant decrease
in psychological morbidity (depression)
has been recorded in 12-24 months post
transplantation, especially in teenagers
with cardiomyopathy [20].
Concerning the neuro-psycho-motor
development of infants post transplant,
medical logs show that the mental
development index was the same as the
average of the biologic age group, with
the exception of groups 18-23 and 24-36
months old, which showed slight degrees
of retardation [9].
The long term evolution and prognosis
of children who benefit from heart
transplantation are unknown. The longest
known survivor of heart transplant was 20
years old in 2005. The long term prognosis
is determined by a series of post transplant
complications such as: rejection, coronary
vasculopathy, infectious complications,
insulin-dependent diabetes, osteoporosis
and malignant affections [18].
How will the distribution of
available organs be carried out?
The concept of rightful distribution
or the criteria of equal access depending
on waiting time and age comes into
focus. The second criterion is that of
maximum benefit considering medical
criteria of severity (the most severely
affected has priority) and according to
elements of good prognosis (evolution
and longevity after transplant) [19].
Can a patient who has already
benefited from a transplant to receive a
new transplant seeing as how patients die
waiting for a heart transplant? Can a
teenager with suicide attempts or a drug
abuse history benefit from transplant?
Despite
several
difficulties
encountered and medical and ethical
issues, heart transplantation remains one
of the most revolutionary therapies, but
not a medical miracle as certain
enthusiasts have tried to label it, because
a miracle implies the curing of a disease
(for eg., the discovery of antibiotics)
while a transplant replaces one chronic
disease with another, improving life
quality while awaiting new technology to
be developed (stem cells, genetic
engineering). Children sentenced to death
because of severe afflictions with a grim
prognosis (left heart hypoplasic syndrome
dilating cardiomyopathy (CMD) in final
stages) are given a new life through
transplant.
Referring to dilatative cardiomyopathy (CMD) treatment, although the
last few years have brought significant
improvements by the discovery of new
classes of drugs which prolong the
compensation period of the disease, many
important aspects of the treatment for this
disease remain uncertain. As a result of
this uncertainty, parents and physicians
alike are faced with difficult decisions
which raise serious ethical problems:
46
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