Jurnal Internasional Pda. Kelompok 1
Jurnal Internasional Pda. Kelompok 1
Jurnal Internasional Pda. Kelompok 1
Fakultas Keperawatan
Universitas Pembangunan Indonesia
Manado
2020
Brandão et al.; CA, 9(4): 5-14, 2020; Article no.CA.59903
Authors’ contributions
This work was carried out in collaboration among all authors. All authors read and approved
the final manuscript.
Article Information
DOI: 10.9734/CA/2020/v9i430140
Editor(s):
(1) Gen-Min Lin, National Defense Medical Center, Taiwan.
Reviewers:
(1) S. Ramakrishnan, India.
(2) José Luis García Serrano, University of Granada, Spain.
Complete Peer review History: http://www.sdiarticle4.com/review-history/59903
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Brandão et al.; CA, 9(4): 5-14, 2020; Article no.CA.59903
ABSTRACT
The Ductus Arteriosus (DA) is a vascular structure of the fetal heart that communicates the isthmus of the
aorta (at the junction of the aortic root with the descending aorta) to the roof of the bifurcation of the
pulmonary trunk. It is an essential structure of the fetal heart that connects the pulmonary circulation to de
systemic circulation bypassing the lungs. The DA is usually patent at birth. It undergoes through muscle
contraction between 10 and 15 hours of life and closes due to fibrous proliferation of the intimal layer by
the third week of life. The change in the natural history of DA, with consequent permeability beyond the
predicted period, promotes the Patent Ductus Arteriosus (PDA) a congenital acyanotic heart disease. The
most important risk factor for PDA is prematurity. Other risk factors are the congenital rubella,
chromosomal abnormalities, genetic factors, low birth weight, perinatal asphyxia and birth in high altitude
places. The clinical manifestations of a PDA are determined by the degree of left-to-right shunting, which is
dependent upon age, the size and length of the PDA and the difference between pulmonary and systemic
vascular resistances. The diagnosis of PDA is usually based on its characteristic clinical findings and
confirmation by echocardiography. The proper management of PDA depend on age, hemodynamic impact
and resource available and may include conservative management, pharmacologic treatment, surgical
approach and percutaneous closure. The complication rates for percutaneous and surgical closure are rare.
Keywords: Patent ductus arteriosus; congenital heart defects; therapy; treatment outcome.
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2. CAUSES AND RISK FACTORS heart disease in 60% of the patients and PDA
is the most frequent. The incidence of PDA is
The most important risk factor for PDA is also increased in high altitude locations
prematurity. Premature infants have a lower compared with those born at sea level, for the
blood oxygen concentration and therefore are same lower oxygen concentration typical of
more susceptible to PDA, since one of the such places [5].
prime mechanisms of ductal contraction is not
effective [1,3].
Mutations in the TFAP2B gene cause Char
syndrome, a rare condition that presents with
Another risk factor is the Congenital Rubella distinctive face appearance, PDA and hand
Syndrome that can present with congenital
blood is delivered by the placenta and not the within the DA lumen are the main factors that
lungs [1]. lead to DA syndromes associated with PDA are
CHARGE syndrome, Holt-Oram
closure through muscular contraction. 3. MORPHOLOGY
Thus, the functional closure of the DA occurs
within the first 24 to 48 hours and the In 1989, Krichenko developed an angiography
anatomical closure occurs in 2 to 3 weeks [1,2]. based classification in 5 categories: conical
(type The change in the natural history of DA, with A), window (type B), tubular (type C),
complex
descendingconsequent
aorta. permeability beyondofthe predicted (type D) and elongated (type E) [7].
This deviation
period, promotes the Patent Ductus abnormalities. The TFAP2B gene appears to
pulmonary blood to the systemic circulation does play a role in the normal formation of
structures not harm the fetus, since the oxygenated in the face, heart and limbs.
Other genetic
syndrome, Noonan syndrome and
DiGeorge syndrome [6]. There is a higher
The DA is usually patent at birth. It undergoes frequency in siblings, even without any
through muscle contraction between 10 and genetic disorder, with a recurrence rate of 5%.
15 hours of life and closes due to fibrous In addition to prematurity,
proliferation of the intimal layer by the third chromosomal abnormalities, genetic
week of life. Higher oxygen concentration at factors and infections, other etiological factors
the blood on the DA associated with a drop in are low birth weight, perinatal asphyxia and
the prostaglandin E2 production of the birth in high altitude places [3].
placenta and a decrease in blood pressure
Arteriosus (PDA) a congenital acyanotic heart In term infants, the reported incidence of
disease. isolated PDA ranges from 2 to 6 per 1000 live
births. Isolated PDA accounts for 5 to 10% of
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congenital heart defects. For unknown type A but is more elongated and also has a narrow
reasons, there is a female predominance for point at the pulmonary end (Fig. 1). Frequently PDA is
associated with other congenital heart diseases
PDA with a 2:1 female to male ratio [1]. In
(CHD), sometimes being the responsible for the
premature infants, its incidence is maintenance of the infant’s life. In the group of the
approximately 0.008%. Up to 30% of CHD that course with low pulmonary flow, the PDA
newborns weighing less than 2500 g develop compensates the deficiency of pulmonary circulation.
PDA [3]. Its prevalence is estimated at 14.2% The most common CHD in this group are Tetralogy of
in the total population (12.4% in children and Fallot, tricuspid atresia, pulmonary stenosis,
pulmonary atresia with intact ventricular septum and
16.3% The right definition of the morphology
single ventricle with pulmonary stenosis and
is important to define the proper treatment, transposition of great arteries. In the cases of
considering that some categories are more hypoplasic left heart disease, the PDA Large, tubular
challenging to be treated with percutaneous PDAs offer low resistance and makes aortic end
closure and should be consider closure with pressure similar to the pulmonary end pressure. It is
the surgical approach. known by the Ohm Law that pressure = flow x
resistance, therefore pulmonary extremity pressure
of the PDA = flow through the ductus x pulmonary
Type A is the most frequent and it is resistance. By similarity, aortic extremity pressure =
characterized by a conical shape with the flow through the ductus x systemic resistance. If no
narrowing points are present, pressure in both
narrowing point at the pulmonary end. On
extremities are similar and the proportion of
Type B PDAs there is no constrictive point and pulmonary and aortic flow (Qp/Qs) will be defined by
in adults). It is among the five most difficult , due to the lack of narrow point to hold
common diagnoses of congenital heart surgery the closure device. Type C is tubular shaped
and
[4]. is also related with higher complications when
is resembles aortopulmonary window. This the relation between systemic resistance (Rs) and
morphology makes percutaneous closure pulmonary resistance (Rp). At birth, the Rp is 25% the
Rs and therefore, pulmonary flow can be 4 times the
percutaneously closed. Type D is rare and has systemic (Table 1) [9].
multiple constrictive points. At last, type E resembles
represents the only path for systemic 5. SYMPTOMS AND PHYSICAL EXAM circulation. In
the presence of other CHC with left to right shunt, PDA can worsen left The PDA has great clinical
variability and may chambers overflow and therefore result in remain asymptomatic or be associated
with more precocious hemodynamic consequences symptoms of heart failure and pulmonary
[8]. vascular remodeling, leading to inversion of the shunt and characterization of Eisenmenger
4. PHATOPHYSIOLOGY Syndrome. The clinical manifestations of a PDA are determined by the
degree of left-to-right
The clinical features of the PDA depend on the shunting, which is dependent upon age, the size amount of
blood that deviates from the and length of the PDA and the difference systemic to pulmonary circulation.
The intrinsic between pulmonary and systemic vascular resistance of the PDA and the pulmonary resistances.
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In term infants, the most typical resistance regulate the flow that reach the presentation of PDA in the
absence of other lungs. congenital heart defects is murmur [10].
Type B
Type A Type C
Type D
Type E
Fig. 1. Krichenko PDA classification. Type A: Conical shape with the narrowing point at the
pulmonary end. Type B: No constrictive point and resembles aortopulmonary window. Type
C: Tubular shaped. Type D: Multiple constrictive points. Type E: Resembles type A but is more
elongated and also has a narrow point at the pulmonary end. Red vessel: Proximal aorta;
blue vessel: Pulmonary artery
Table 1. Relationship between volume, pressure and resistance
Pp = Qp x Rp and Ps = Qs x Rs
If Pp = Ps (present at tubular and window shaped PDA), then Qp x Rp = Qs x Rs
Pp: pulmonary pressure / Qp: pulmonary flow / Rp: pulmonary resistance / Ps: systemic pressure / Qs: systemic
flow / Rs: systemic resistance
produces a typical murmur described by
In preterm infants, typical signs are absent in Gibson in 1898 (a louder continuous or
the first hours of life, due to the transition of machinery murmur in the first or second left
the pulmonary vascular resistance that take intercostal space). As the myocardium
several hours or days to be complete. The performance improves, there can be seen
increased shunt velocity coinciding with hyperactive precordium, increased pulse
declining pulmonary vascular resistance volume and wide pulse pressure [3,9].
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vascular marking can be found if significant then systemic pressure and the shunt at the
pulmonary overflow [3,10]. PDA instead of from left to right turns to right
to left. This is called Eisenmenger Syndrome
[8]. Once that endpoint is reached, there is no
Echocardiogram is the current main diagnostic benefit in PDA closure, since vascular
tool for PDA. PDA can be well identified remodeling will continue despite closure [12].
between the origin of the left pulmonary
artery and descending aorta, distal the left
subclavian artery at the parasternal and Other possible complications are endarteritis
suprasternal views. Chamber enlargements and formation of aneurysms of the DA.
measures and shunt velocity are important to Endarteritis is the endocarditis inside the DA
define the hemodynamic consequences of the which can be difficult to diagnose for general
PDA. Typically, there is no need to magnetic physicians if the patient does not have the
resonance or tomography to diagnose PDA. PDA diagnosis [13]. The risks of aneurysm are
Sometimes, however, it is an additional finding rupture and bleeding.
when examining different structure [10].
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after birth. This occur due to the comparative 8.1.1 Conservative management
hypoxemia preterm children have comparing
to term infants. For infants with a hemodynamically significant
PDA, an initial conservative approach can
include fluid restriction, maintenance of a
Some important questions remain difficult to higher hematocrit, use of diuretic and minimal
answer regarding the most advantageous way respiratory support. Excessive fluid
and the impact of PDA closure in preterm administration is associated with an increased
infants. First, does the PDA need to be closed? incidence of PDA and, therefore, a moderate
It is well known that a significant portion of daily intake of 120-130ml/kg is suggested.
symptomatic PDA can close spontaneously; When diuretic therapy is considered, it is wise
therefore, which ones should be treated not choosing furosemide, as it stimulates renal
before? And if so, how to perform the synthesis of prostaglandin E2, a potent
closure? There is still a lack of studies vasodilator that maintains ductus arteriosus
supporting any answers to those questions yet patency. Hematocrit at 35 to 40 percent can
[14]. The 2020 Indian Guidelines for increase pulmonary vascular resistance and
Management of Congenital Heart disease reduce left to right shunting, and minimal
recommend treating the preterm infants with mechanical ventilation minimize further
heart failure with 2 courses of drug therapy or pulmonary injury [14].
surgical ligation when pharmacological
8.1.2 Pharmacologic treatment
approach is unsuccessful [15].
When the conservative approach fails and
The first line of treatment is the conservative there is still hemodynamic impact of the PDA,
management in which general supportive pharmacologic intervention may be needed.
measures are applied with no drugs or The drugs that show effectiveness on PDA
procedures. If those measures do not work, closure are those who target inhibiting
and the child remains on mechanical prostaglandin synthetase, as prostaglandin
ventilation when other factors have been promotes ductal patency. The best choices are
excluded, such as infection or non-selective cyclooxygenase (COX) inhibitors
bronchopulmonary dysplasia, pharmacologic such as ibuprofen and indomethacin and
closure can be performed. In a very low acetaminophen, which interferes the
number of cases, and when the less invasive peroxidase segment [16].
treatments were ineffective, surgical or
percutaneous closure may be the final option The choice of drug is center-bases. It is known
[5]. that between the two COX inhibitors,
ibuprofen has lower risk of necrotizing
enterocolitis and transient renal insufficiency
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Brandão et al.; CA, 9(4): 5-14, 2020; Article no.CA.59903
then indomethacin, but shows no difference available) are used. The administered dose of
on mortality, intraventricular hemorrhage, acetaminophen is 60mg/kg per day over a two
pulmonary hemorrhage, bowel hemorrhage, to seven days program. This dosage is
sepsis or retinopathy rates. significantly higher than the pain and fever
dose used, so attention to hepatotoxicity
should be considered and liver blood test
The standard dose for ibuprofen is an initial
performed [5].
dose of 10 mg/kg followed by two additional
doses of 5 mg/kg given at 24 hours interval.
This dosing is the same for both oral and There is still a lack of trials to determine the
intravenous administration. IV ibuprofen is best
typically used in developed countries because
treatment choice. Recent Cochrane
of availability and because it is more
metaanalysis, however, states that
expensive then the oral form.
prophylactic treatment exposes a large
However, studies have shown the same proportion of infants unnecessarily to a drug
effectiveness and developing countries that has important side effects without
continue to use the oral form with same conferring any important short term benefits.
results [16]. Some studies suggest high dose Current evidence does not support the use of
ibuprofen as an alternative and point higher ibuprofen for prevention of patent ductus
likelihood of success. In these cases, an arteriosus. Until long term follow up results of
initially dose of 15-20mg/kg followed by two the trials included in this review have been
additional doses of 7,5-10mg/kg administered published, no further trials of
every 12 to 24 hours can be used. prophylactic ibuprofen are recommended
[17].
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pharmacologic therapy fail and the patient Once the patients are not newborns anymore,
remain with hemodynamic impact and need they do not respond to pharmacologic closure.
for maximum mechanical ventilation. It is If they are asymptomatic, it is recommended
associated with risk of infection, chylothorax, to delay closure until proper weight for
recurrent laryngeal nerve paralysis, percutaneous closure is achieved. If
bronchopulmonary dysplasia, pressure symptomatic, medical management as digoxin
fluctuations, intraventricular hemorrhage and and diuretics can help waiting to suitable
death. It still remains uncertain, however if weight for percutaneous closure. In
the surgical ligation is the major contributor to symptomatic nonresponders to medical
morbidity and mortality or if patients who treatment, surgical closure is preferable.
undergo surgical ligation are more severely Although there have been many devices used
compromised to begin with [18]. for smaller children with a huge success rate,
the smaller the child less than 6kg is, the
higher chance for procedure complication. In
8.2 Term Infants and Children
children over 6kg, percutaneous occlusion is
generally preferred over surgical ligation
In term infants and children with moderate to
because it is less invasive and less expensive
large PDA or in whom there is a prior episode
or at least as cost-effective [18].
of endocarditis, the closure
decision is straightforward,
whereas in small or silent PDA without Therefore, the timing of PDA closure depends
significant left-to-right shunt the decision for on the PDA’s size and hemodynamic
closure is less clear. In case of small audible
consequences. Large to moderate PDA with
PDA (i.e, those presenting with murmur), the
significant left heart volume overload,
closure is recommended because it prevent
congestive heart failure or pulmonary
occurrence of bacterial endocarditis, a rare
but recognized complication of small PDA. hypertension must have early closure (by 3
Some physicians, however, believe that the months). When there is some degree of left
chances of endocarditis in patients with small heart overload, mild or no congestive heart
PDA is similar then general population, and failure and/or mild pulmonary arterial
therefore should be left untreated [18]. hypertension, it is considered moderate. In
this case, it can be closed when the child is
Small silent PDA usually are incidentally between 6 and 12 months old. Small PDA
detected by imaging studies performed for should be closed by the age of 12-18 months
other indications. Silent PDA do not have and if silent PDA, the closure is not
hemodynamic consequences, and thus, the recommended [15].
only impetus for closure is the theoretical risk
of bacterial endocarditis or family/personal
preference. 8.3 Adults
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be used for small PDA and, for moderate to contemplating all anatomical variants of the
large PDA, other devices such as ductal ductus arteriosus.
occluder or general vascular plugs are
available.
Ideally, the occlusion should be total so that
there is no residual shunt, no part of the
It is important to point out that once there is device should remain exposed, and there
irreversible pulmonary hypertension, there should be no protrusion of the device into the
will be no benefit in performing the procedure pulmonary artery and/or aorta (Fig. 2).
and progressive pulmonary vascular disease Calibrated tubular channels, with small aortic
will continue despite PDA closure. If ampulla and angled channels, especially in low
Eisenmenger Syndrome is weight patients, are at higher risk of
present (severe pulmonary complications.
hypertension that results in right to left
shunt), closing the PDA may worsen clinical
Currently, the proper devices for
symptoms because they depend on the shunt
percutaneous closure of the DA are
to avoid heart failure and maintain cardiac
prostheses specifically designed for DA
output [20].
closure. Coils used to be particularly useful in
closing small DA with reduced performance
8.4 Interventional Options for large ductus. In those cases, sometimes it
was necessary to use more than one coil to fill
8.4.1 Catheter-based treatment a single DA, increasing the procedure time and
the risk of embolization. Specific designed
Percutaneous closure of the ductus arteriosus prostheses, on the other hand, come in
began in 1966 when Portsmann was different sizes and brands; however, their use
successful in percutaneous prosthesis is limited due to cost, both at public and
implantation in a 17year-old patient [21]. In private levels [22].
the last 5 decades, there have been great
advances in the development of prostheses
In patients with an DA diameter of less than 8
and sheaths, making it possible to reduce the
mm, there is ductal closure in more than 85%
duration of the procedure and include less
of cases during the 1-year follow-up and with
weight children.
less than 1% mortality [23].
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Brandão et al.; CA, 9(4): 5-14, 2020; Article no.CA.59903
Fig. 2. Right anterior oblique (RAO) aortogram showing the device placed
into the PDA ampulla by retrograde approach
8.4.2 Surgical treatment
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Brandão et al.; CA, 9(4): 5-14, 2020; Article no.CA.59903
10.1161/CIRCULATIONAHA.105.592063.
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Brandão et al.; CA, 9(4): 5-14, 2020; Article no.CA.59903
© 2020 Brandão et al.; This is an Open Access article distributed under the terms of the Creative Commons Attribution License
(http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium,
provided the original work is properly cited.
Peer-review history:
The peer review history for this paper can be accessed here:
http://www.sdiarticle4.com/review-history/59903
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