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Patent ductus arteriosus
Highlights
Summary Overview
Basics
Definition Epidemiology Aetiology Pathophysiology Classification
Prevention
Primary Screening
Diagnosis
History & examination Tests Differential Step-by-step Guidelines Case history
Treatment
Details Step-by-step Guidelines Evidence
Follow Up
Recommendations Complications Prognosis
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History & exam

Key factors
presence of risk factors presentation in infancy
Other diagnostic factors

tachypnoea/SOB
failure to thrive exercise intolerance widened pulse pressure machine-like continuous murmur/Gibson murmur in children born at term pulmonary rales apnoea low diastolic BP irritability diaphoresis increased respiratory symptoms with URTI murmur heard only during systole hyperdynamic precordium systolic thrill third heart sound heard at apex mid-diastolic rumble heard at apex bounding peripheral pulses History & exam details
Diagnostic tests
1st tests to order
CXR ECG echo
Tests to consider
cardiac catheterisation and angiography Diagnostic tests details
Treatment details
Presumptive
premature very-low-birth weight infants: prophylactic therapy intravenous indometacin
Acute
premature infants (<32 weeks) intravenous indometacin or ibuprofen surgical ligation
term infants and children: small-to-moderate-sized ducts percutaneous catheter device closure diuretics term infants and children: large ducts and/or symptomatic infants too small for device closure adults percutaneous catheter device closure surgical ligation Treatment details surgical ligation
Summary
A ductus arteriosus is a vascular fetal structure that usually closes in the first 48 hours after birth. Persistence of the ductus arteriosus can result in heart failure, increased pulmonary pressures, and endarteritis. The incidence and sequelae of a patent ductus arteriosus (PDA) are more significant in premature infants than infants born at full-term. Clinical history and presentation can vary significantly depending on age of the child and the size of the ductus. Patients may be entirely asymptomatic or have signs and symptoms of heart failure and haemodynamic instability. Treatment options vary depending on the age of the patient and the size of the ductus. Practice may vary significantly between institutions.
Definition
Patent ductus arteriosus (PDA) describes the persistence of a fetal structure, known as the ductus arteriosus, after birth. This vascular structure, which connects the main pulmonary artery to the aorta, allows blood to bypass the lungs in utero. In term infants it functionally closes, usually in the first 48 hours of life. [1]
Epidemiology
The persistence of a PDA is much more common in preterm than term infants. [2] This is secondary to the immaturity of the ductus. [3] Since the advent of echocardiography, the incidence of PDA in children born at term has been reported as approximately 1 to 2 per 1000.[4] This estimate is higher than previously thought since it includes clinically silent PDAs. [5]This higher estimate comes with inclusion of clinically silent PDAs. [5] There is globally a higher incidence in females as well as in children born at higher altitudes. [6] [7]
Aetiology
In the fetus, the patency of the duct is maintained by a low-oxygen environment and circulating prostaglandins PGE2 and PGI2, produced by the placenta. [8] After birth, oxygen saturation increases and contributes to the constriction of the duct through potassium-mediated channels. [9] [10] Post-natally, the level of circulating prostaglandins falls as the placenta is removed from the circulation. In addition, pulmonary blood flow increases
resulting in increased metabolism of prostaglandins. There may be several other unknown factors that contribute to ductal closure. [8] [11] Haemodynamic constriction is later followed by complete structural closure mediated by histological changes that obliterate the ductal lumen. [12] While the process of ductal closure is fairly well understood, the factors that result in persistence of the ductus are less clear. In preterm infants, there may be a decreased response to oxygen and a continued sensitivity to prostaglandins when compared to term infants. [13] [14] On histological examination, differences between the tissue of a persistent ductus versus a physiological ductus have been noted suggesting an anatomic reason for persistence. [12]
Pathophysiology
The pathophysiology occurs as a result of shunting of blood from the aorta to the pulmonary artery across this vascular connection. Clinical effects depend on the magnitude of the shunt, which in turn depends on the relative systemic and pulmonary artery pressures. [15] After birth, pulmonary vascular resistance falls while systemic resistance remains unchanged leading to left-to-right shunting through the ductus. The degree of shunting depends on both the systemic-to-pulmonary artery pressure ratio as well as the size of the duct. A small duct in the setting of near systemic pulmonary pressures will have limited flow. However, the larger ductus will have less resistance to flow and will initially be associated with a greater degree of shunting as pulmonary resistance falls in the newborn period. This will result in an increased left ventricular volume, left ventricular output, and pulmonary over-circulation. [16] Increased flow to the lungs leads to decreased pulmonary compliance and increased work of breathing. With the increased pre-load, the left ventricle dilates and left ventricular end diastolic pressures and left atrial pressures increase. The increase in left-sided pressure inhibits pulmonary venous return, furthering pulmonary congestion. In preterm infants, the effects of pulmonary over-circulation and systemic steal are more pronounced. Increased pulmonary blood flow not only leads to pulmonary oedema, but also to pulmonary haemorrhage, [17] respiratory distress syndrome, and bronchopulmonary dysplasia. [18] [B Evidence] Decreased systemic perfusion may be responsible for the increased incidence of necrotising enterocolitis and interventricular haemorrhage seen in preterm infants with PDA.[B Evidence] Additionally, a large PDA can impact myocardial perfusion by decreasing diastolic BP. This, along with the shorter diastolic time caused by compensatory tachycardia, can reduce coronary flow. [19]
Classification
Small, moderate, or large If the ductus is widely patent, such that the vessel itself provides no resistance to flow, then it is considered large. The amount of shunting across a large PDA will be dependant upon the relative pulmonary and systemic vascular resistance. A large ductus is usually of equal or greater diameter than 1 of the proximal branch pulmonary arteries. A moderate-sized ductus will provide some resistance to flow. However, the amount of shunting will be great enough to result in some degree of left atrial dilation. A small ductus will significantly restrict flow such that there will be no dilation of the left atrium or left ventricle.
Primary prevention
There are currently no recognised strategies for primary prevention. There is some literature that suggests that the use of antenatal corticosteroids may decrease the incidence of PDAs in premature infants, though there are other risks to the infant associated with this intervention that may outweigh this benefit. [32]
Screening
Premature infants
Screening is usually reserved for preterm infants. As early as 1989, it was found that early screening and treatment of PDAs in this population might be advantageous. [39] Centres differ in practice, with some centres routinely screening for PDA by echo for infants less than a certain gestational age and weight (<28 weeks or <1000 g) at 2 to 3 days of life because of concerns of lack or reliability of clinical signs and perceived benefits of early treatment. [35] Some centres prefer to prophylactically treat without any screening to confirm the diagnosis, although evidence for this is controversial. [40] [41]
History & examination

Key diagnostic factorshide all
presence of risk factors (common)
Risk factors include: prematurity of birth, maternal rubella infection, female sex, and age <3 months.
presentation in infancy (common)
Significantly large PDAs most often present as pulmonary resistance falls, usually before 2 to 3
months of age. Diagnosis in adolescence or adulthood is much more unusual but does occur. Other diagnostic factorshide all tachypnoea/SOB (common)
In moderate or large PDAs, pulmonary over-circulation often results in increased work of breathing and SOB. In older children this SOB can sometimes be mistaken for reactive airways disease.
failure to thrive (common) In moderate or larger PDAs, failure to thrive is a common presenting symptom for infants. exercise intolerance (common)
In moderate or larger PDAs, exercise intolerance is a common presenting symptom for older children.
widened pulse pressure (common)
With a haemodynamically significant shunt, a widened pulse pressure can be detected by BP measurement or by palpation of bounding pulses. In preterm infants, bounding pulses are a poor independent predictor for the presence of a PDA. [35]
machine-like continuous murmur/Gibson murmur in children born at term (common)
This classic murmur, known as a Gibson murmur or machinery murmur, is best heard in the left infraclavicular area and peaks in late systole and continues through into diastole. [33] However, some patients with a higher pulmonary pressure in diastole may have a murmur that is confined to systole. The lack of a continuous murmur does not rule out a PDA. [2] A murmur is a less reliable sign in preterm infants with a high specificity but poor sensitivity.[35]
apnoea (common) This is a symptom in premature infants. low diastolic BP (common) Low diastolic BP with circulatory instability may mimic sepsis in preterm infants. irritability (common) This is a non-specific symptom in full-term infants and children. diaphoresis (common) This is a non-specific symptom in full-term infants and children. increased respiratory symptoms with URTI (common) Full-term infants and children are prone to these infections. murmur heard only during systole (common) This is a sign in newborns, irrespective of the size of the ductus. hyperdynamic precordium (common) This is a sign in children with a moderate-to-large duct. systolic thrill (common)
A systolic thrill may be palpable in the upper left sternal border. This is a sign in children with a moderate-to-large duct.
third heart sound heard at apex (common) This is a sign in children with a moderate-to-large duct. mid-diastolic rumble heard at apex (common) This is a sign in children with a moderate-to-large duct. bounding peripheral pulses (common) This is a sign in children with a moderate-to-large duct. pulmonary rales (uncommon)
Can be heard as a result of pulmonary oedema or venous congestion secondary to higher left atrial pressures. factorshide all
Risk
Strong prematurity
The relationship between delayed closure of the ductus arteriosus and prematurity has long been recognised.[20] The incidence of PDA in all preterm infants is about 8 per 1000 births, which is almost 10 times that seen in term infants. [2] This increases with decreasing gestational age and birth weight with an incidence as high as 20% in preterm infants weighing <1750 g and 64% in preterm infants weighing <1000 g. [21] [22]Gestational age is related to ductal sensitivity to oxygen and prostaglandins with a decreased reaction to oxygen and an increased sensitivity to
prostaglandins seen in more premature infants. [14] There is some evidence that the use of prophylactic protein-free synthetic surfactant in preterm infants may increase the risk of PDA. [23]
maternal rubella
Maternal rubella infection in the first trimester is associated with an increased incidence of PDA. [24]While maternal rubella is associated with several congenital heart lesions, PDA is the most common, seen in up to 50% of cases in some early series. [25]The persistent ductus in these patients is histologically akin to an immature ductus. [26] The mechanism of this relationship is not well understood.
female gender
Seen predominantly in females. In one series, 64% of PDAs occurred in females (a ratio of almost 2:1). [6]
Weak respiratory distress syndrome (RDS)
There appears to be an association with severe RDS with a much higher incidence seen in premature infants ill with RDS. [27] PDA is also associated with a 4.5-fold increase in the occurrence of bronchopulmonary dysplasia. [18] [B Evidence] While the causal direction of this relationship would seem to place PDA at fault, the decreased oxygenation occurring as a result of RDS and lung pathology may result in decreased metabolism of prostaglandins, thereby contributing to the continued persistence of the duct. [28]
high altitude
Children living at higher altitudes are found to have a higher prevalence. [7] In addition, the effect of altitude is progressive with lower ambient oxygen levels likely contributing to persistence of the ductus.
family history
Development is multi-factorial with evidence for a genetic contribution in certain cases. Siblings of patients are at increased risk (3%) of the defect. [29] There is an increased occurrence with certain syndromes such as trisomy 21, 4p, and Holt-Oram syndrome. [26] In addition, Char syndrome, autosomal dominant inheritance of PDA, is sometimes seen. [30] Other investigators have found a recessive gene locus that may be associated. [31]
black race
Studies in the US have demonstrated a racial differential with a higher incidence found in black children compared with white children. [4]
Diagnostic tests
1st tests to orderhide all
Test
CXR
This test is not diagnostic or very sensitive, but it may be helpful in providing information with regard to the prese
absence of a clinically significant shunt. The definitive diagnostic test for a clinical indication is an echocardiogram
CXR can be completely normal for patients with smaller shunts. With more significant shunting it may show cardi
(left atrial and left ventricular enlargement), increased pulmonary markings, and a prominent main pulmonary art ECG
An ECG is not very sensitive for a PDA and is used only for corroborative purposes. It may be completely norma leads II, III, Avf, and the left precordial leads. Significant left atrial enlargement may manifest as widened P septal defect. echo
significant left-sided overload, left ventricular dilation and hypertrophy will result in deep Q waves and tall R wave
waves. [2] This test is also not specific as these findings can be seen with other left-sided shunts such as a ventr
Definitive diagnostic test for a PDA. [36] Echo is the chosen test for diagnosis of a PDA with direct 2-dimensiona
and measurement of the duct possible with larger ducts and colour Doppler evidence of the duct in smaller shunt determine the direction and velocity of the shunt to understand the ductal resistance and the relative systemic to
image In addition, the shunt flow characteristics can be determined by colour and Doppler imaging. [37] It is impo
pulmonary pressure. Echo also provides useful and reliable information regarding left-sided heart enlargement. I
early days of echo, when there was less spatial resolution than is present today, the sensitivity was 96% and spe as 100% sensitive, with catheterisation reserved for treatment purposes only.
was 100% compared to angiography. [38] However, in the present era, with echo's improved capabilities, it is ac
Tests to considerhide all

Test Result
cardiac catheterisation and angiography Not routinely done for diagnostic evaluation of uncomplicated PDA. Angiography provides anatomic evidence of shunt. View image Role of catheterisation is chiefly therapeutic in facilitating transcatheter occlusion.
presence of shunt and any co-exist pulmonary HTN.
Differential diagnosis
Condition Venous hum Differentiating signs/symptoms Differentiating tests
A venous hum can be heard usually more on the right side. In
Physical examination will distinguish a venous hum as desc the echo will be normal.
there is still sufficient concern echo can be performed. In th
addition, it diminishes with supine positioning and with local compression.

Coronary artery fistula
This murmur is also continuous. However, it is usually heard lower in the precordium. [2 ]
Can be distinguished by echo. On echo evaluation a corona can be distinguished by location.
a small continuous jet of flow into the right ventricle or main
Left-sided shunts (ventricular septal defect, atrioventricular septal defect)
These lesions can present similarly with regard to clinical history, ECG, and CXR findings. However, the murmur of most left-toright shunts will only be heard in systole. The exception is an aortopulmonar y window, which is a large connection between aorta
Echo can definitively distinguish these lesions by their char
and location. Left heart enlargement if present will look sim
and pulmonary artery and will present with clinical findings identical to that of a large PDA. Aortic regurgitation
These patients often present at an older age. They can present with symptoms of exercise intolerance as well. The usually do not demonstrate tachypnoea. The murmur is characteristica lly a highpitched diastolic decrescendo murmur best heard at the lower left sternal border.
Again echo can definitively distinguish aortic regurgitation f
the descending aorta may similarly demonstrate diastolic flo seen at the level of the aortic valve.
on the degree of aortic regurgitation. However, a diastolic r
Step-by-step diagnostic approach

Clinical history and presentation can vary significantly depending on age of the child and the size of the ductus. Patients may be entirely asymptomatic or have signs and symptoms of heart failure and haemodynamic instability.
History
The clinical history varies depending on the age of the patient and the size of the shunt. In premature babies the clinical history can be somewhat nonspecific. They can have worsening respiratory status with tachypnoea and/or apnoea and increased ventilator requirements. They can also have circulatory instability associated with low diastolic BP, which may mimic sepsis. In full-term infants and children with a small PDA there may be no significant clinical history. With a moderate or large PDA, infants may present with such non-specific symptoms as tachypnoea, irritability, poor feeding, diaphoresis, and failure to gain weight. They may be prone to increased respiratory symptoms with URTIs. An older child may present with SOB and exercise intolerance.
Physical examination
Irrespective of size, the PDA in the newborn is associated with a murmur heard only during systole. However, the murmur later becomes more continuous in nature.
Small duct: on cardiac examination, there is usually normal precordial activity with a normal S1 and S2. A continuous murmur is best heard in the second left intercostal space. It may radiate to the back. The murmur is accentuated late in systole and continues into diastole.[33] The lung examination and respiratory rate are usually normal. Moderate or large duct: these children usually have a hyperdynamic precordium. A systolic thrill may sometimes be palpable in the upper left sternal border. The first and second heart sounds are sometimes masked by the murmur. A third heart sound is often heard at the apex. There may also be a mid diastolic rumble heard at the apex. The peripheral pulses are often bounding. On respiratory examination, these children may be tachypnoeic. If they are in heart failure they may have pulmonary rales.
On BP measurement there may be a widened pulse pressure if the ductus is large.
Diagnostic testing
Generally, if there is concern for a PDA based on clinical findings, a CXR may be helpful in providing information with regard to the presence or absence of a clinically significant shunt. The definitive diagnostic test for a clinical indication is an echocardiogram.
A CXR in a patient with a moderate or large haemodynamically significant duct will demonstrate an enlarged heart and increased pulmonary vascular markings. The main pulmonary artery segment will be prominent. Left atrial dilation, best seen on the lateral film, will be present. During early infancy, the ECG is often normal. However, in older infants and children it may demonstrate left ventricular enlargement with a deep Q wave and tall R waves in leads II, III, Avf, V5, and V6. Left atrial enlargement with widened P waves may also be seen. Based on these findings and the historical findings above, these patients can be referred to a paediatric cardiologist. In patients with smaller shunts, the CXR and ECG can be completely normal. In this case the decision to refer will have to be based on the physical examination finding of a concerning murmur. The definitive test to confirm the diagnosis is an echo. [26] Echo was first shown to be useful for direct imaging and measurement of the ductus in 1978. [34] This is usually performed along with an evaluation by a paediatric cardiologist. Echo can evaluate the presence and size of the ductus as well as the direction of shunting. Left heart chamber dimensions can be evaluated to determine the significance of the duct. Cardiac catheterisation with angiography is usually not necessary for the diagnosis of an uncomplicated PDA. The role of this procedure in most cases is the facilitation of closure via transcatheter occlusion. If used diagnostically, it provides evidence of the presence and severity of shunt and allows assessment of any associated pulmonary HTN. View image A silent ductus arteriosus is a patent ductus without clinical signs or symptoms. A murmur is absent. The ductus becomes evident as an incidental finding when an echo is performed for another purpose. There has been some controversy over the treatment of a silent PDA.
Click to view diagnostic guideline references.
Case history #1
A 1.5 month-old infant girl is brought to her paediatrician for poor feeding. Since she was last seen at 2 weeks she has had poor weight gain. She sweats with feeds and seems to tire out easily. There is no significant family history. On physical examination she is noted to be tachypnoeic and uninterested in her bottle after a few minutes of feeding. She has increased work of breathing. On cardiac examination, she has a grade 4 continuous murmur that is heard in the left infraclavicular region and back. She also has an early diastolic rumble best heard at the apex. Her liver is 3 cm below her costal margin. Her pulses are bounding. Her CXR reveals an enlarged heart
with a prominent main pulmonary artery segment and increased pulmonary markings.
Case history #2
A 28 week premature boy is treated with appropriate doses of surfactant. However, on his second day of life he has worsening symptoms of respiratory distress syndrome with increasing ventilatory requirements. He has also started demonstrating apnoeic episodes. He is noted to have a widened pulse pressure (30 mmHg) on his arterial line and he is starting to have some bloody stools. On physical examination, he is noted to have bounding pulses and a prominent precordial impulse. On auscultation a grade 3 systolic ejection murmur can be heard in the left infraclavicular area. His abdomen also appears distended. On CXR, his lung fields are almost completely opacified.
Other presentations
Clinical presentation depends on the age of the patient and the size of the shunt. Patients can be completely asymptomatic, have significant heart failure, or, if they present much later in life, may have signs and symptoms of pulmonary HTN. Premature infants with a haemodynamically significant PDA usually develop clinical signs in the first week of life. Full-term infants with a PDA may present in early infancy with signs of heart failure if they have a large shunt across the ductus. Conversely, they may not present until late childhood with mild exercise intolerance if the shunt is smaller. Haemodynamically insignificant shunts will not be associated with symptoms but may be picked up by the presence of a murmur on examination. Atypically, if a haemodynamically significant PDA is missed in childhood, it may present in adulthood with heart failure, atrial arrhythmias, endarteritis, or, most seriously, with irreversible pulmonary vascular disease characterised by desaturation and evidence of right heart failure.
Treatment Options
Treatment Patient group premature very-low-birth weight infants: prophylactic therapy line 1st Treatmenthide all
intravenous indometacin
The cut-off of very low-birth weight varies between centres, but is usually <1300 g or <1000 g. The treatment is used with the thought that treating a PDA in very low-birth weight premature infants will prevent the clinical sequelae of a haemodynamically significant shunt better than waiting for the PDA to become clinically evident.
The first dose of prophylactic indometacin is usually started within the first 12 hours of birth. Treatment can be given at day of life 0, before clinical evidence of a PDA becomes evident.
Evidence shows that while prophylactic indometacin might increase ductal closure and decrease the incidence of intraventricular haemorrhage, there are few other short-term or long-term benefits. [41]
Infants being treated must have electrolytes, creatinine, urine output, and platelets followed regularly during administration. Feeds are withheld.
Complications can include necrotising enterocolitis, bleeding, or renal dysfunction. [57] [74] B-type natriuretic peptide-guided treatment has been shown to reduce the number of primary indometacin doses in infants with PDA. [51] [B Evidence] Primary Options indometacin : 0.1 mg/kg intravenously once daily for 3 days
Presumptive
Treatment Patient group premature infants (<32 weeks) line 1st Treatmenthide all
intravenous indometacin or ibuprofen
Cyclo-oxygenase inhibitors such as NSAIDs inhibit
Presumptive
Treatment Patient group line Treatmenthide all
prostaglandins. They have been shown to be effective in ductal closure in preterm infants. [21] In
Presumptive
this case, treatment is given in the first few days of life after a PDA has become clinically evident or has
Presumptive
been diagnosed by echo. Treatment options include indometacin or ibuprofen.
Presumptive
Infants being treated with indometacin must have electrolytes, creatinine, urine output, and platelets
Presumptive
followed regularly during administration. Feeds are withheld. B-type natriuretic peptide-guided treatment
Presumptive
has been shown to reduce the number of primary indometacin doses in infants with PDA. [51] [B
Presumptive
Evidence] Complications can include necrotising enterocolitis, bleeding, or renal
Presumptive
dysfunction. [57] [74] If the duct persists after the first course of treatment, a second similar course is given.
Presumptive
Ibuprofen has been postulated to close a patent ductus without the same GI and cerebral perfusion
Presumptive
effects. [75] Two recent meta-analyses found no difference in terms of successful PDA closure
Presumptive
between these two treatments, but did have slightly differing results with regard to secondary morbidities.
Presumptive
One which compared both oral and intravenous ibuprofen to indometacin found a decreased risk of
Presumptive
necrotising enterocolitis in patients treated with ibuprofen but an increased incidence of chronic lung
Presumptive
disease compared with indometacin treatment. [53] The second meta-analysis only
Presumptive
compared intravenous forms of both drugs and found no difference in necrotising entercolitis or
Presumptive
interventricular haemorrhage risk, but did find an increased risk of chronic lung disease in patients
Presumptive
treated with ibuprofen compared with indometacin. [54]
Presumptive
Indometacin remains the standard of care, especially in the US where intravenous ibuprofen is not readily
Presumptive
available. However, in Europe, ibuprofen has an orphan license for the treatment of PDA in premature
Presumptive
neonates <34 weeks of gestational age. Some centres use oral ibruprofen; however, studies
Presumptive
regarding its efficacy and safety are limited. [76] [77]
Presumptive
Primary Options
Presumptive
indometacin : infants <48 hours of age: 0.2 mg/kg intravenously as a loading dose, followed by 0.1
Presumptive
mg/kg every 12 hours for 2 doses; infants 2-7 days of age: 0.2 mg/kg intravenously every 12 hours for 3
Presumptive
doses; infants >7 days of age: 0.2 mg/kg intravenously as a loading dose, followed by 0.25
Presumptive
mg/kg every 12 hours for 2 doses
Presumptive
Secondary Options
Presumptive
ibuprofen : 10 mg/kg intravenously as a loading dose,
Presumptive
followed by 5 mg/kg every 24 hours for 2 doses
Presumptive
Treatment Patient group line 2nd Treatmenthide all
surgical ligation
Surgical ligation is usually considered after medical
Presumptive
therapy has failed to result in ductal closure. Surgical
Presumptive
ligation of the duct generally has very high success
Presumptive
rates with low associated
Presumptive
morbidity. [56] [58] Complications are rare and
Presumptive
include recanalisation of the duct, pneumothorax,
Presumptive
effusion, haemorrhage, and wound infection. [78] A
Presumptive
review suggests that there may be little benefit to
Presumptive
prophylactic surgical ligation compared with no
Presumptive
therapy or medical therapy, with no significant
Presumptive
decrease in mortality or bronchopulmonary dysplasia,
Presumptive
though a decrease in the incidence of necrotising
Presumptive
enterocolitis was reported. [61] [B Evidence]
Presumptive
Videothorascopic surgical ligation is now being used
Presumptive
with increasing frequency in favourable cases with
Presumptive
good results. [62]
Presumptive
Treatment Patient group line 1st Treatmenthide all
term infants and children: small-to-moderate-sized ducts
percutaneous catheter device closure
In asymptomatic or symptomatic patients,
Presumptive
percutaneous catheter closure is the first-line treatment in order to treat heart failure and prevent
Presumptive
elevated pulmonary pressures or endarteritis. With infants who are symptomatic and aged > 6 months,
Presumptive
percutaneous catheter device closure is carried out as soon as possible. In symptomatic infants aged <6
Presumptive
months, intervention is delayed if at all possible. In these circumstances, provided that the child is
Presumptive
making adequate weight gain, temporary use of diuretic therapy with furosemide can control
Presumptive
symptoms and give time for the infant to grow to a more suitable size for percutaneous intervention.
Presumptive
Percutaneous catheter device closure is also the firstline treatment in asymptomatic patients, though again
Presumptive
this is delayed where possible until the patient is 1 year of age or more.
Presumptive
Catheter devices include coils, Amplatzer duct occluder, Rashkind umbrella device, and Gianturco-
Presumptive
Grifka occlusion device. Choice of device depends on ductal morphology and operator choice during the
Presumptive
procedure. [68] Patients are given sub-acute bacterial endocarditis prophylaxis for 6 months after the
Presumptive
procedure or longer if turbulent flow persists around the device. [79]
Presumptive
adjunct [?]
diuretics
Infants who are symptomatic may not be large
Presumptive
enough to undergo percutaneous device closure at
Presumptive
the time of presentation. In these circumstances,
Presumptive
provided that the child is making adequate weight
Presumptive
gain, temporary use of diuretic therapy with
Presumptive
furosemide can control symptoms and give time for
Presumptive
the infant to grow to a more suitable size for
Presumptive
percutaneous intervention.
Presumptive
Primary Options
Presumptive
furosemide : 0.5 to 2 mg/kg intravenously every 6-12
Presumptive
hours
Presumptive
term infants and children:
surgical ligation
Presumptive
large ducts and/or
Some patent ducts are too large to be closed by a
Presumptive
symptomatic infants too small
percutaneous catheter device, yet closure is required
Presumptive
for device closure
either to treat or prevent heart failure from the left-to-
Presumptive
right shunt or to prevent endarteritis. This may be
Presumptive
recognised at initial work-up or when an attempted
Presumptive
device closure is made.
Presumptive
If the patient is symptomatic, surgical ligation is
Presumptive
undertaken as soon as possible. If asymptomatic,
Presumptive
ligation can be scheduled electively. Success is high
Presumptive
with few complications that can include operative
Presumptive
pneumothorax, haemorrhage, effusion, or long-term
Presumptive
recanalisation. [56] [58]
Presumptive
When infants <6 months old are significantly
Presumptive
symptomatic from the left-to-right shunt from a patent
Presumptive
ductus and cannot be controlled by diuretic therapy
Presumptive
while they develop and grow, they may be referred for
Presumptive
surgical ligation if they are felt to be too small for
Presumptive
catheter closure. However, with increased experience
Presumptive
with percutaneous device closure, smaller and
Presumptive
younger children are being taken to the
Presumptive
catheterisation laboratory, [63] [69] so referral for
Presumptive
surgical ligation is decreasing in this patient group,
Presumptive
although this is also dependent on institution.
Presumptive
adults
percutaneous catheter device closure
In certain adults with PDA, closure may be necessary
Presumptive
if there is significant left-to-right shunt and/or pulmonary HTN. Surgical or catheter-based closure is
Presumptive
advocated, provided that pulmonary vascular resistance is not prohibitively high. [70] Currently,
Presumptive
most advocate closure via a transcatheter device in adults with a small-to-moderate patent ductus, which
Presumptive
has been shown to be safe and effective in this age group. [71] [72] [C Evidence]
Presumptive
Treatment Patient group line 2nd Treatmenthide all
surgical ligation
In certain adults with PDA, closure may be necessary if there is significant left-to-right shunt and/or
Presumptive
pulmonary HTN. Concerns regarding ductal tissue friability in adults with larger patent ductus have led
Presumptive
some centres to pursue video-assisted thoracoscopic surgery (VATS) ligation with good results. [73] [C
Presumptive
Evidence]
Acute
Last
Treatment approach
The main goal of treatment in premature infants is to prevent related morbidity and mortality secondary to haemodynamic instability and such comorbidities as respiratory distress syndrome and necrotising enterocolitis. [42] [43] [44] [B Evidence] As a result, there are different treatment strategies for premature and term infants.
Premature infants
A great deal of controversy remains over how, when, and if to treat PDAs in premature infants.[45] [46] Initial options include prophylactic treatment with cyclo-oxygenase inhibitors like indometacin, medical treatment when a symptomatic ductus is noted to be present, or conservative observation. The most practiced are the former 2, though a few centres have reported small numbers of spontaneous closure in infants <30 weeks with simple fluid restriction and ventilator changes. [47] [48] [A Evidence] One study found a variety of treatment practices among a large national neonatology group with almost equal numbers of premature infants with a PDA receiving prophylactic indometacin or indometacin after day 1, and a smaller number of patients receiving no treatment. [46] Prophylactic indometacin involves treatment with indometacin at 0 days of life before a PDA becomes clinically evident. It is usually reserved for very lowbirth weight infants (depending on the centre <1300 g or <1000 g). A metaanalysis found that this treatment plan did decrease the rate of PDA, the need for surgical ligation for PDA, and the rate of intraventricular haemorrhage in this population. [49] However, there was no difference in incidence of necrotising enterocolitis, bronchopulmonary dysplasia, mortality, or long-term neurosensory outcome. [49] [A Evidence] Treatment with indometacin after clinical evidence of a significant ductus is present is usually undertaken in premature infants after day 2 or 3 of life and has shown to be successful in closing PDAs compared to placebo. [21] [A Evidence] While some centres practice a prolonged course of indometacin (>4 and usually 7 doses), no significant difference has been shown in successful PDA closure, need for re-treatment, need for surgical ligation, or such outcomes as mortality and the incidence of co-morbidities such as chronic lung disease or necrotising enterocolitis with this longer regimen. [50] [A Evidence] If the first course of indometacin fails to succeed, a second course is usually given. B-type natriuretic peptide (BNP)-guided treatment has been shown to reduce the number of primary indometacin
doses in infants with PDA.[B Evidence] In this study, subsequent indometacin doses were withheld (if a 12-hour or 24-hour BNP level after the first dose was <100) without any difference in PDA persistence found between the groups. [51] Attention has also been given to ibuprofen as an alternative to indometacin for treatment of PDAs in this population. [52] Two recent meta-analyses found no difference in terms of successful PDA closure between these two treatments, but did have slightly differing results with regard to secondary morbidities. One which compared both oral and intravenous ibuprofen to indometacin found a decreased risk of necrotising enterocolitis in patients treated with ibuprofen but an increased incidence of chronic lung disease compared with indometacin treatment. [53] The second meta-analysis only compared intravenous forms of both drugs and found no difference in necrotising entercolitis or interventricular haemorrhage risk, but did find an increased risk of chronic lung disease in patients treated with ibuprofen compared with indometacin. [54] Surgical ligation has historically been reserved as a second-line treatment when medical treatment has failed or is contra-indicated. [55] It can be performed on premature infants as small as 600 g. Surgical ligation of the duct generally has very high success rates with low associated morbidity. [56] [57] [C Evidence] While one study did show a relatively high late mortality in preterm infants this was felt to be related to the high risk of this population rather than to the surgery itself. [58] There has been some inquiry into the favourability of surgical ligation as first-line management in this population. [59] [60] [A Evidence] However, there are currently limited data to allow for adequate comparison of the 2 treatment approaches. [59] A review suggests that there may be little benefit to prophylactic surgical ligation compared to no therapy or medical therapy, with no significant decrease in mortality or bronchopulmonary dysplasia. Although a decrease in the incidence of necrotising enterocolitis was reported, authors concluded that prophylactic ligation was not indicated. [61] [B Evidence]Videothorascopic surgical ligation is now being used with increasing frequency in favourable cases with good results. [62] [C Evidence]
Full-term infants and children

The goal of treatment in this group is to alleviate or prevent heart failure and to prevent increased pulmonary pressures with a significant shunt. With smaller shunts or silent PDAs, the goal of treatment is the prevention of endarteritis through routine closure. However, this remains controversial. Any infant or child who is symptomatic usually has closure as soon as possible.
Patients who present with symptoms outside of the neonatal period may not be large enough to undergo percutaneous device closure at the time of presentation. Provided that the child is making adequate weight gain, diuretic therapy with furosemide may be used on a temporary basis to improve symptoms and allow the patient to reach a suitable size for percutaneous intervention. First-line treatment in this group of patients is catheter device closure if patients are of sufficient size as it avoids surgery and can be done usually with just a day admission or overnight hospital stay. Safe device closure has been reported in patients as young as 6 months and as small as 5 kg. [63] [C Evidence] Transcatheter closure is also usually reserved for small- or moderate-sized ducts, although with newer devices larger ducts have been able to be treated with increasing efficacy. [64] If infants are asymptomatic, the procedure is often delayed until they are close to 1 year of age. In children >1 year, the procedure can be scheduled at the time of diagnosis, either electively or as needed depending on their symptoms and left heart overload. The procedure has an extremely high success rate of >95% with no mortality and few complications. [65] [66] Complications can include coil embolisation, persistent turbulent flow around the device and residual leak. [66] [67] Complications were more likely to occur in smaller children. [67] There are several types of devices that can be employed for catheter closure and choice of device usually depends on the morphology of the duct. [68] Surgical ligation in full-term infants and children is usually reserved for ducts that are thought to be too large for closure with a transcatheter device, or for symptomatic infants whose physical size and anatomy are thought to be too small for transcatheter device closure. However, the exact size below which transcatheter device closure is felt to be unsuitable may vary with clinician and institution. [63] [69]
Adults
In certain adults with PDA, closure may be necessary if there is significant left-to-right shunt and/or pulmonary HTN. Surgical or catheter-based closure is advocated, provided that pulmonary vascular resistance is not prohibitively high. [70] [36] Currently, most advocate closure via a transcatheter device in adults with a small-to-moderate patent ductus, which has been shown to be safe and effective in this age group. [71] [72] [C Evidence] Concerns regarding ductal tissue friability in adults with larger patent ductus have led some centres to pursue surgical ligation with good results. [73] [C Evidence]
Monitoring
Patients require monitoring until definitive closure is achieved. Generally, they are followed by a cardiologist with serial echos. In infants this is often done fairly regularly at 3-month intervals. In older children, follow-up is less frequent (and often closure is scheduled before a follow-up visit). After closure most patients are seen in follow-up at 1 month, and again between 6 months to 1 year. Most institutions will then discharge patients from care unless there is a residual lesion. Since long-term experience with catheter closure is more limited, some more conservative practitioners will continue to follow these patients every 2 years. Premature infants will need to be observed for a longer period as the ductus may re-open in some patients. However, they are often followed clinically by their primary physician or neonatal consultant.
Patient Instructions
Patients previously required sub-acute bacterial endocarditis (SBE) prophylaxis for dental procedures. However, new US and European guidelines do not require long-term SBE prophylaxis for dental procedures for a PDA because of the small numbers of cases of SBE felt to be prevented by antibiotic use. [79] [91] In contrast, after catheter closure with a device, patients should observe SBE prophylaxis for 6 months until the device is endothelialised. Additionally, patients will need to continue to observe SBE prophylaxis if there is a residual shunt near the device. [79] Patients with an untreated small PDA with normal left chamber size can participate in all levels of competitive sport. Those with a more significant shunt and left heart enlargement should undergo definitive closure prior to competitive athletics. They may return to full participation 3 months after closure if they have a normal cardiac examination without evidence of left ventricular enlargement or elevated pulmonary pressures. If patients demonstrate elevated pulmonary resistance (pulmonary pressures >30 mmHg), individual recommendations for levels of physical activity must be undertaken. [92]
Complications
Complicationhide all
respiratory distress syndrome (RDS) see our comprehensive coverage of Acute respiratory distress syndrome There also appears to be an association with severe RDS, with a much higher incidence seen in premature
infants ill with RDS. [27] necrotising enterocolitis in premature infants This complication is usually reserved to premature infants with increased haemodynamic instability. Left-to-right shunting at the level of the duct can lead to systemic steal. This can result in hypoperfusion of end organs including the gut. The presence of a duct has been found to be independently associated with the incidence of necrotising enterocolitis. [44] Treatment of this complication varies from medical therapy with gut rest to surgical intervention. Prevention is attempted by not feeding premature infants with suspected PDA and by attempting medical or surgical closure of significant ducts. pulmonary haemorrhage in premature infants Isolated to premature infants, pulmonary haemorrhage can result from increased pulmonary blood flow. This has been directly related to the size of the duct in one study. [17] pulmonary HTN see our comprehensive coverage of Idiopathic pulmonary arterial hypertension A large non-restrictive patent ductus can lead to the eventual development of pulmonary hypertensive disease in patients if left untreated. This occurs because of chronic volume and pressure overload on the pulmonary circulation that can lead to irreversible vascular changes. Elevated pulmonary pressures may eventually lead to right-to-left shunting at the duct resulting in cyanosis and clubbing. Other signs of elevated pulmonary pressures may be present and include a right ventricular heave and a loud pulmonic closure sound. A PDA is seen as a cause of unexplained pulmonary HTN in adolescents or adults. [85] In some patients this pulmonary HTN may be reversible with treatment of the PDA. [86] However, in patients with irreversible pulmonary HTN treatment options are limited to medical therapy including oxygen and pulmonary vasodilators. CHF see our comprehensive coverage of Chronic congestive heart failure An untreated patent ductus with a significant shunt can result in symptoms of CHF. When and if CHF occurs depends on the size of the shunt and the amount of volume overload on the heart. While patients with larger shunts may present in infancy, more moderate shunts may not present until later in childhood or into adulthood. [25] Once symptoms of heart failure are noted, patients can be initially managed medically with digoxin and diuretic medical therapy until the ductus can be dealt with definitively either by catheter closure or surgical ligation. endarteritis Prior to surgical and catheter closure, the incidence of infective arteritis associated with the lesion was as high as 1% per year. [25] However, in the current era this has decreased dramatically to almost negligible numbers of case reports. [81] When they occur, these vegetations usually form on the pulmonary end of the duct as a result of turbulent flow and can result in pulmonary emboli. If suspected endarteritis can be diagnosed by transthoracic or trans-oesophageal echo. Treatment usually consists of long-term antibiotics followed by definitive closure of the duct. aneurysm of the duct A ductal aneurysm is an enlargement of the ductal tissue near the point of attachment to the aorta. It is thought
to be related to abnormal elastin/ductal tissue. The reported incidence varies significantly from 1.5% to 8%. [87] [88]It usually presents in infancy but has been reported in adults. [89] While some of the aneurysms resolve on their own, complications such as thromboses or rupture can occur. [88] [90] The presence of a ductal aneurysm often points to an underlying connective tissue disorder. Spontaneous resolution of ductal aneurysms in infancy has been reported. If persistent or discovered at a later age, surgery is recommended.
Prognosis
Premature infants
Premature infants with a clinically significant PDA are at risk of increased mortality and morbidity from chronic lung disease, necrotising enterocolitis, and pulmonary haemorrhage.[17] [42] [44] One study found that premature infants with a persistent significant PDA (despite attempted closure) had 4 times the risk of death compared to premature infants without a significant PDA. [80] However, there was no difference in mortality in those who had had successful medical closure. Another study found an absolute risk difference of 2% in mortality in patients with an untreated PDA. [21] Their overall mortality rate at 1 year was 20%. However, it remains difficult to separate out the contribution of the PDA from other co-morbid factors of prematurity, such as respiratory distress syndrome. At 1 year of age, one study found 70% of these premature infants alive and without significant morbidity. [21] In successfully treated patients, there may still be some increased rates of bronchopulmonary dysplasia and retinopathy of prematurity, although this is again difficult to separate out from other co-morbid factors. [81]
Full-term infants and children

Prior to the era of antibiotics, surgery and catheter closure, natural history studies demonstrated a risk of death as 0.42% per year (ages 2 to 19 years), 1.0% per year (20 to 29 years), and 1.8% per year (30 to 39 years). [25] The estimated risk of endarteritis has been estimated at 0.45% per year for an untreated duct. [25] With current treatment strategies, mortality and endarteritis occur rarely. [82] Spontaneous closure of a patent ductus after 3 months of age is relatively rare. If a significant shunt is left untreated, it can result in the development of pulmonary obstructive disease that can become manifest as early as 15 months of life. A more moderate untreated shunt may not present with such symptoms until later in life. In patients with smaller ducts, the risk of morbidity is very low and is mainly related to the risk of endarteritis. Clinically silent PDAs appear to carry a relatively low risk for endarteritis with only a few case reports in the literature. [83] [84] However,
most patients regardless of shunt size are now referred for either catheter or surgical closure. Overall prognosis of these patients is very good and typically after closure, patients are well and the procedure is considered curative. However, there are rare instances when increased pulmonary resistance may remain even after closure of the duct. This is thought to be related to a primary abnormality of the pulmonary vasculature. [26]

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Patent ductus arteriosus

History & exam

Other diagnostic factors

History & examination

presentation in infancy (common)

widened pulse pressure (common)

machine-like continuous murmur/Gibson murmur in children born at term (common)

Weak respiratory distress syndrome (RDS)

Tests to considerhide all

presence of shunt and any co-exist pulmonary HTN.

A venous hum can be heard usually more on the right side. In

there is still sufficient concern echo can be performed. In th

addition, it diminishes with supine positioning and with local compression.

Can be distinguished by echo. On echo evaluation a corona can be distinguished by location.

a small continuous jet of flow into the right ventricle or main

Left-sided shunts (ventricular septal defect, atrioventricular septal defect)

Echo can definitively distinguish these lesions by their char

and location. Left heart enlargement if present will look sim

Again echo can definitively distinguish aortic regurgitation f

on the degree of aortic regurgitation. However, a diastolic r

Step-by-step diagnostic approach

On BP measurement there may be a widened pulse pressure if the ductus is large.

intravenous indometacin or ibuprofen

Cyclo-oxygenase inhibitors such as NSAIDs inhibit

been diagnosed by echo. Treatment options include indometacin or ibuprofen.

Evidence] Complications can include necrotising enterocolitis, bleeding, or renal

treated with ibuprofen compared with indometacin. [54]

regarding its efficacy and safety are limited. [76] [77]

mg/kg every 12 hours for 2 doses

ibuprofen : 10 mg/kg intravenously as a loading dose,

followed by 5 mg/kg every 24 hours for 2 doses

Surgical ligation is usually considered after medical

therapy has failed to result in ductal closure. Surgical

ligation of the duct generally has very high success

rates with low associated

morbidity. [56] [58] Complications are rare and

include recanalisation of the duct, pneumothorax,

effusion, haemorrhage, and wound infection. [78] A

review suggests that there may be little benefit to

prophylactic surgical ligation compared with no

therapy or medical therapy, with no significant

decrease in mortality or bronchopulmonary dysplasia,

though a decrease in the incidence of necrotising

enterocolitis was reported. [61] [B Evidence]

Videothorascopic surgical ligation is now being used

with increasing frequency in favourable cases with

good results. [62]

term infants and children: small-to-moderate-sized ducts

percutaneous catheter device closure

In asymptomatic or symptomatic patients,

procedure or longer if turbulent flow persists around the device. [79]

Infants who are symptomatic may not be large

enough to undergo percutaneous device closure at

the time of presentation. In these circumstances,

provided that the child is making adequate weight

gain, temporary use of diuretic therapy with

furosemide can control symptoms and give time for

the infant to grow to a more suitable size for

furosemide : 0.5 to 2 mg/kg intravenously every 6-12

term infants and children:

large ducts and/or

Some patent ducts are too large to be closed by a

symptomatic infants too small

percutaneous catheter device, yet closure is required