Following is the description of
five cases who were already receiving oral sildenafil
when they were referred to us.
Case Reports
Case 1: A 35-days-old baby,
product of full term normal delivery with Apgar score of
7,9,9 at 1,5 and 10 minutes, discharged on 2nd
day of life, developed severe respiratory distress on 3rd
postnatal day associated with vomiting and got
hospitalized in a peripheral centre. The sepsis screen
showed leucocytosis, high C reactive protein (CRP) and
positive blood culture. The child was ventilated and
started broad spectrum antibiotics. Chest X-ray
showed no cardiomegaly but there was patchy atelectesis
in lung parenchyma. Echocardiography showed severe left
ventricle (LV) dysfunction, severe pulmonary arterial
hypertension (PAH) with no mention of any septal defect.
As there was difficulty in weaning off from ventilator
in spite of repeated attempts till 24th
day of life and there was progressive increase in
cardiomegaly and pulmonary plethora, he was referred to
us. We repeated echocardiography that showed very large
patent ductus arteriosus (PDA) shunting left to right
with large run-off in descending aorta suggestive of
large left to right shunt. LV function was normal. His
pulmonary vasodilator therapy was stopped and he was
subjected to surgical ligation of PDA.
Case 2: A-45-day old female baby
was referred to us for evaluation as there was
persistence of cyanosis and respiratory distress since
birth; and high PA pressure and moderate-sized PDA with
bidirectional shunt on echocardiography. On examination,
there were features of CHF, PAH and cyanosis (room air
oxygen saturation was 80%). Sepsis screen was negative.
Chest X-ray revealed decreased pulmonary blood
flow, normal lung parenchyma and no cardiomegaly. Repeat
echocardio-graphy revealed large PDA with right-to-left
shunt and severe PAH. Pulmonary veins could not be
profiled. Therefore CT pulmonary angiography was done to
define pulmonary veins. CT pulmonary angiography
revealed streak like all pulmonary veins and large PDA.
Case 3: A-30-day old male baby,
product of full term normal delivery with normal APGAR
at birth got discharged on 2nd
day of life. On 5th
day of life, baby developed bluishness and respiratory
distress requiring hospitalization. Echocardiography
revealed small ASD with right to left shunt and severe
PAH. As the condition of the child did not improve and
there was continued requirement for oxygen, he was
referred to our centre. On examination, there was
tachycardia, tachypnea and mild cyanosis (room air
saturation 85%). Chest X-ray showed
dextroposition of heart, cardiomegaly, smaller right
lung volume with no definite lung parenchymal lesion.
Repeat echo showed small fossa ovalis ASD right to left
shunt, mild TR with peak gradient of 98 mmHg (systemic
BP = 88 mmHg), no VSD/AP window/PDA and confluent branch
pulmonary arteries with LPA grossly dilated measuring 10
mm (expected= 4mm) while RPA being smaller (3.6 mm).
Left sided pulmonary veins were normally connecting
while right sided pulmonary veins could not be profiled.
CT pulmonary angiography revealed right pulmonary veins
very thin in calibre becoming atretic before joining
left atrium.
Case 4 and 5: Two full term
neonates with normal APGAR at birth, 20 days and 28
days, old respectively were referred to us for
persistence of signs of PAH, CHF and oxygen dependency.
Chest X-ray showed cardiomegaly, pulmonary
plethora but no lung parenchymal lesion.
Echocardiography revealed moderate tricuspid
regurgitation with peak gradient of 70 mmHg, PFO right
to left shunt, dilated right atrium and right ventricle
with no structural heart defect. Ultrasound head
revealed large vein of Galen malformation which was
confirmed on CT head. Vein of Galen malformation is one
of the rare form of arteriovenous malformation which can
lead to features of CHF even during fetal life.
Discussion
Etiology of pulmonary arterial
hypertension in pediatric patients is multifactorial
[1]. Persistent pulmonary hypertension (PPHN) in term or
near-term infants is reported to vary between 0.43 and
6.8 of 1000 live births [2]. The treatment for PPHN has
evolved over the past few years considerably which has
reduced its morbidity significantly.
The pulmonary vascular resistance is
often increased in sepsis, especially in the presence of
acute lung injury. Contributing factors are decreased
production of nitric oxide (an endogenous vasodilator)
and increased levels in circulating vasoactive
substances, such as thromboxane and endothelin.
Serotonin contribute to increased pulmonary vascular
resistance (PVR) and pulmonary hypertension in sepsis
[3-5]. Acute lung injury leads to hypoxic pulmonary
vasoconstriction, and this pulmonary pressor response is
enhanced by hypercarbia or acidosis. Case 1 was
an example of increased PVR secondary to sepsis and
leading to bidirectional flow across PDA thus giving
false impression of PPHN. Sildenafil worsened the
situation by inducing CHF in an underlying condition of
large PDA as soon as the sepsis got better. Explanation
for LV dysfunction in the earlier echo cardiography
report could be due to sepsis and PDA might have been
missed probably due to right to left shunt resulting
from very high PVR. Here hemodynamic implication of
large PDA in the setting of sepsis was important to
understand.
Pulmonary vein atresia is a rare
congenital abnormality resulting from failure of
incorporation of the common pulmonary vein into the left
atrium [6]. It can involve either lung, and usually
presents in infants [7,8]. Pulmonary artery hypertension
is a frequent association [9]. Congenital stenosis or
atresia of pulmonary veins (Case 2 and 3) are not the
conditions where pulmonary vasodilator therapy works due
to obvious reasons.
The majority of cases of vein of
Galen malformation (94%) are diagnosed in the neonatal
period and present with high-output cardiac failure.
Severe pulmonary hypertension is a complicating factor
[10]. In the past, the mortality rate for this group was
close to 100%. Recent advances made in the management of
these patients, particularly by the use of endovascular
techniques have significantly altered the prognosis
[10]. We do USG cranium in all neonates in whom CHF and
PAH are unexplained as in the case 4 and 5. Sildenafil
will not work in such a situation until the root cause
of PAH is addressed.
We conclude, that in clinical
suspicion of PPHN, common causes such as pneumonia and
septal defects should be excluded. Unnecessary use of
pulmonary vasodilators will do more harm than any
benefit if given in such conditions.
Contributors: All the authors
have drafted, designed and approved the study.
Funding: None; Competing
interests: None stated.
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