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Persistent fetal circulation

Authors:

Abstract

Persistent fetal circulation (PFC), also known as persistent pulmonary hypertension of the newborn, is defined as postnatal persistence of right-to-left ductal or atrial shunting, or both in the presence of elevated right ventricular pressure. It is a relatively rare condition that is usually seen in newborns with respiratory distress syndrome, overwhelming sepsis, meconium and other aspiration syndromes, intrauterine hypoxia and ischemia, and/or neonatal hypoxia and ischemia. This condition causes severe hypoxemia, and, as a result, has significant morbidity and mortality. Improved antenatal and neonatal care; the use of surfactant; continuous monitoring of oxygenation, blood pressure and other vital functions; and early recognition and intervention have made this condition even more rare. In modern neonatal intensive care units, anticipation and early treatment of PFC and its complications in sick newborns are commonplace. Thus, severe forms of PFC are only seen on isolated occasions. Consequently, it is even more imperative to revisit PFC compared with the time when there were occasional cases of PFC seen in neonatal intensive care units, and to discuss evolving treatment and management issues that pertain to this syndrome.
Persistent fetal circulation
Chrysal D’cunha MD, Koravangattu Sankaran MD FRCPC FCCM
Division of Neonatal Research, Department of Pediatrics, Royal University Hospital, Saskatoon, Saskatchewan
Persistent fetal circulation (PFC), also known as per-
sistent pulmonary hypertension of the newborn, was
first described as “unripe births of mankind” by William
Harvey in 1628 in his book Exercitatio Anatomica De
Motu Cordis et Sanguinis in Animalibus (1). However,
the syndrome went unnoticed for a long time – until the
latter half of the 19th century. In the 1950s, several inves-
tigators independently rediscovered this syndrome.
Novelo et al (2) presented a paper that described postna-
tal persistence of fetal circulatory patterns. Lind and We-
gelius (3) demonstrated that “the foramen ovale has
either failed to close or reopened” in asphyxiated infants.
They also noted two cases in which “the ductus arteriosus
was found to be open with a direction of the foetal flow
from the pulmonary artery to the aorta” (3). Burchell et al
(4) showed that right to left ductal shunting was exacer-
bated by hypoxia. Berglund (5) observed that right to left
atrial shunting occurred in an infant with respiratory dis-
tress syndrome. Several publications that discussed vari-
ous aspects of this condition followed. In 1969, Gersony
et al (6) published case reports of two newborns with pul-
monary hypertension and described this condition as
‘persistent fetal circulation’.
FETAL AND POSTNATAL CIRCULATION
To appreciate the mechanism of PFC, one has to be fa-
miliar with fetal circulation and perinatal circulatory ad-
aptation. In utero, the fetus derives its oxygenated blood
744 Paediatr Child Health Vol 6 No 10 December 2001
REVIEW
Correspondence: Dr K Sankaran, Royal University Hospital, 103 Hospital Drive, Saskatoon, Saskatchewan S7N 0W8. Telephone 306-966-8131,
fax 306-975-3767, e-mail sankaran@duke.usask.ca
C D’cunha, K Sankaran. Persistent fetal circulation. Paediatr Child
Health 2001;6(10):744-750.
Persistent fetal circulation (PFC), also known as persistent pulmonary hy-
pertension of the newborn, is defined as postnatal persistence of right-to-
left ductal or atrial shunting, or both in the presence of elevated right ven-
tricular pressure. It is a relatively rare condition that is usually seen in new-
borns with respiratory distress syndrome, overwhelming sepsis, meconium
and other aspiration syndromes, intrauterine hypoxia and ischemia, and/or
neonatal hypoxia and ischemia. This condition causes severe hypoxemia,
and, as a result, has significant morbidity and mortality. Improved antena-
tal and neonatal care; the use of surfactant; continuous monitoring of oxy-
genation, blood pressure and other vital functions; and early recognition
and intervention have made this condition even more rare. In modern
neonatal intensive care units, anticipation and early treatment of PFC and
its complications in sick newborns are commonplace. Thus, severe forms of
PFC are only seen on isolated occasions. Consequently, it is even more im-
perative to revisit PFC compared with the time when there were occasional
cases of PFC seen in neonatal intensive care units, and to discuss evolving
treatment and management issues that pertain to this syndrome.
Key Words: Newborns; Persistent fetal circulation; Persistent pulmonary
hypertension of the newborn; Respiratory distress syndrome
La circulation fœtale persistante
RÉSUMÉ : La circulation fœtale persistante (CFP), également désignée
hypertension artérielle pulmonaire persistante du nouveau-né, se
définit comme une persistance postnatale du canal artériel, du shunt
auriculaire ou de ces deux pathologies en présence d’une pression
élevée du ventricule droit. C’est une pathologie relativement rare,
observée chez les nouveau-nés souffrant d’un syndrome de détresse
respiratoire, de septicémie foudroyante, d’aspiration de méconium et
d’autres syndromes d’aspiration ainsi que d’hypoxie et d’ischémie
intra-utérines ou néonatales. Elle cause une hypoxémie grave et
s’accompagne donc d’un taux élevé de morbidité et de mortalité. De
meilleurs soins anténatals et néonatals, le recours au surfactant, la
surveillance constante de l’oxygénation, de la tension artérielle et des
autres fonctions vitales, de même qu’un dépistage et une intervention
précoces rendent cette pathologie encore plus rare. Dans les unités de
soins intensifs néonatals modernes, la prévention et le traitement
précoce de la CFP et de ses complications chez les nouveau-nés
malades sont monnaie courante. Par conséquent, les formes graves de
CFP ne se produisent que dans des cas isolés. Il est donc encore plus
impératif de réévaluer la CFP par rapport à l’époque où on observait
des cas occasionnels de CFP dans les unités de soins intensifs
néonatals et d’aborder l’évolution du traitement et de la prise en
charge de ce syndrome.
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and nutrients from the placenta through the umbilical
vein. Most of this blood bypasses the liver through the
ductus venosus and enters the inferior vena cava, which
ends in the right atrium. Once again, the flow of blood is
such that most of it passes through the foramen ovale into
the left atrium and then into the left ventricle. This blood,
rich in oxygen and nutrients, is pumped out from the left
ventricle to the brain and the upper part of the body.
Some of this blood in the right atrium from the inferior
vena cava, mixed with superior venacaval blood, goes into
the right ventricle, enters the pulmonary arterial trunk
and then bypasses the lungs through the ductus arterio-
sus to the descending aorta. This mixed blood is used to
nourish the lower half of the body and to return to the pla-
centa for reoxygenation via the umbilical arteries. Thus,
portions of the aorta proximal to the point where the duc-
tus joins the aorta (preductal aorta) carry blood that is
relatively richer in oxygen than those portions distal to
the ductus and aorta junction (postductal aorta). As a re-
sult, the head, neck and right upper extremity (supplied
by branches from the preductal aorta) receive more oxy-
gen than the trunk, the left upper extremity and both
lower extremities (7).
After birth, the infant takes its first breath and is ex-
posed to myriads of stimuli. The pulmonary vessels di-
late, and pulmonary vascular resistance (PVR) decreases
remarkably while the systemic vascular pressure rises
above the PVR. This allows blood from the right ventricle
to enter the lungs for oxygenation. In most cases, this in-
creased oxygenation, along with other factors, causes the
ductal wall to constrict and the ductus arteriosus to close
functionally. Within days, anatomical occlusion occurs,
with extensive neointimal thickening and loss of smooth
muscle cells, and the ductus becomes a strand-like struc-
ture with no lumen (8).
Furthermore, as left-sided pressures rise higher than
right-sided pressures, the foramen ovale functionally
closes (9). With the clamping of the umbilical cord and
the cessation of blood flow, pressures in the portal sinus
decrease. This causes the muscle in the sinus wall near
the ductus venosus to contract (10). The lumen of the
duct becomes filled with connective tissue, and, in two
months, the ductus venosus becomes a fibrous strand
embedded in the wall of the liver (11), thus establishing
adult circulation.
If, for any reason, right-sided pressures remain high
relative to those on the left side, fetal circulation will most
likely persist through one or both of the fetal channels
mentioned above. Therefore, PFC is defined as postnatal
persistence of right to left ductal or atrial shunting, or
both in the presence of elevated right ventricular pres-
sure.
FACTORS AFFECTING PVR
Because a lower PVR generally promotes functional
closure of the ductus and foramen ovale while a high PVR
encourages PFC, it is useful to know which substances in-
crease and which substances decrease PVR. Factors
known to lower PVR include oxygen, nitric oxide, prosta-
cyclin, prostaglandins E2and D2, adenosin, magnesium,
bradykinins, atrial natriuretic factor, alkalosis, hista-
mine, acetylcholine, beta-adrenergic stimulation and
potassium channel activation. Factors that increase PVR
are hypoxia, acidosis, endothelin-1, leukotrienes, throm-
boxanes, platelet activating factors, prostaglandin F2-
alpha, alpha-adrenergic stimulation and calcium channel
activation (12). Thus, it is important to recognize clinical
conditions that affect PVR and to treat them appropri-
ately.
EPIDEMIOLOGY AND COURSE
PFC was seen in one/1500 live births in the 1980s (13).
It occurs more commonly in males, and appears to occur
more frequently at higher altitudes (14). Most cases of
PFC result in either complete recovery or death. Occa-
sionally, there may be long term sequelae such as chronic
lung disease (15), cerebral infarction (16) resulting in
specific motor and/or cognitive deficits (17), and sensor-
ineural hearing loss (18). An association with sudden in-
fant death syndrome has also been suggested (19). The
underlying cause determines the prognosis (20).
ETIOLOGY
PFC can be primary or secondary to other factors. The
majority of cases are secondary to insults that cause hy-
poxia and ischemia in utero. In primary PFC, there is hy-
pertrophy and increased muscularization of the walls of
the pulmonary vessels. Thus, after birth, these vessels
have a greater tendency to continue to stay constricted. As
such, these vessels do not dilate as expected, resulting in
high right-sided pressures. Cases in which vessels fail to
dilate with time and treatment prove to be fatal. Diagnosis
is usually made by autopsy (21).
Idiopathic PFC seemingly has no predisposing factors.
Any number of problems or situations can result in idio-
pathic PFC, including hypoxia, acidosis, hypothermia,
hypoglycemia, etc, and some of them may not have been
documented. Investigative and interventive efforts in the
future are most likely to make this subset of PFC occur in
fewer patients (22).
Secondary PFC is most commonly seen in infants with
lung diseases, the most common cause being meconium
aspiration (23). The resulting hypoxia and acidosis cause
pulmonary vasoconstriction and increased right-sided
pressures. Other common causes are diaphragmatic her-
nia (24), hyaline membrane disease (25), sepsis syn-
drome (22) and pulmonary thromboembolism (26).
Several congenital heart defects can produce pulmo-
nary hypertension in the newborn (27). Paediatric cardi-
ologists are frequently consulted to differentiate between
PFC, which implies a structurally normal heart, and a
congenital heart defect, which is responsible for pulmo-
nary hypertension. A discussion of pulmonary hyperten-
sion in the newborn secondary to a cardiac cause is
Paediatr Child Health Vol 6 No 10 December 2001 745
Persistent fetal circulation
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beyond the scope of the present paper. Consequently, this
paper only describes PFC in the neonate with a structur-
ally normal heart.
PFC has also been noted in cases of sepsis syndromes
caused by group B streptococcus (28), Listeria monocy-
togenes,Escherichia coli and Haemophilus influenzae
type b (29). It is believed that the increased release of the
pulmonary vasoconstrictor thromboxane is responsible
for PFC.
Several perinatal factors trigger PFC. Because hypoxia
and acidosis are known pulmonary vasoconstrictors, any
condition that disrupts utero-placental circulation, such
as placental abruption or placental insufficiency, causes
‘priming’ of fetal pulmonary vasculature, with hypertro-
phy and thickening of the muscular layer of pulmonary
vessels. This priming makes the neonate more suscepti-
ble to PFC, and more sensitive to secondary triggers of
PFC such as neonatal hypoxia and cold stress (30). Late
clamping of the umbilical cord allows a larger placental
transfusion, thereby, increasing the hematocrit. This rise
in hematocrit may result in increased viscosity and sludg-
ing of pulmonary circulation, which in turn cause hypoxia
and ventilation profusion mismatch, thereby increasing
PVR and resulting in higher pressures on the right side
relative to the left side (31). Maternal ingestion of cyclooxy-
genase inhibitors, such as acetylsalicylic acid, indometha-
cin, salicylates and naproxen, can induce constriction of
the fetal arterial duct in utero (32). Arterial constriction
leads to excessive pulmonary blood flow in the fetus and
subsequent hypertrophy of the pulmonary vessels, result-
ing in pulmonary hypertension and severe PFC postna-
tally.
DIAGNOSIS
When the right arm and head remain pink, while the
left arm and lower body are cyanotic, a clinical condition
with differential cyanosis occurs. This condition is due to
the difference in oxygen content in preductal and post-
ductal blood, and is relatively specific for PFC. However,
not all cases of PFC present with this picture.
Thus, the above condition lacks sensitivity (22). When
pulmonary hypertension is present, closure of the pul-
monic valve is more forceful, resulting in a loud second
heart sound (P2). However, loud P2s are also heard in pa-
tients with aortic atresia, pulmonary atresia, transposi-
tion of the great vessels and truncus arteriosus, etc (22);
thus, this sign lacks specificity.
A positive partial pressure of arterial oxygen (PaO2)
gradient greater than 15 mmHg between the right radial
artery and the descending aorta blood suggests PFC, but
it is not present in every case (33). The hyperoxia test in-
volves the inhalation of 100% oxygen. Blood gases before
and after inhalation are recorded. A change of less than
20 mmHg in PaO2can indicate either PFC or congenital
cyanotic heart disease (34), particularly when these con-
ditions cannot be corrected by improved ventilation,
whereas a change in PaO2of 20 mmHg or greater implies
a respiratory disorder. This blood gas test is not specific.
Modified versions include the hyperoxia-continuous
positive airway pressure test (applying 6 to 10 cmH2Oof
continuous positive airway pressure) and the hyperoxia-
hyperventilation test (the infant is hyperventilated me-
chanically to achieve a partial pressure of carbon dioxide
in the low 20s and a pH greater than 7.55). These tests
are not very reliable. Furthermore, they are very aggres-
sive, with the potential for permanent injury to the patient
(35); as a result, they have been abandoned.
Electrocardiogram can be normal or abnormal and,
thus, cannot distinguish PFC from congenital heart dis-
ease (22). At one time, cardiac catheterization and dye
demonstration of the right to left shunt was the most con-
clusive diagnostic test. The hazards involved with this
procedure have limited its use (34). Currently, echocardi-
ography with a pulse Doppler probe has become the diag-
nostic test. It is a noninvasive method that can rule out
the presence of congenital heart disease. It accurately de-
termines both the pressure and velocity of blood flow in
major vessels of fetuses and newborns, including the di-
rection of blood flow through the ductus and the foramen
ovale (36). A depth-gated pulse Doppler probe can estimate
right to left shunts. It can also help to assess biventricular
function and to provide an estimation of pulmonary artery
pressures (37), thus making the diagnosis relatively easy in
the absence of congenital heart disease.
MANAGEMENT
Upon the birth of any infant, reversible events, such as
hypothermia, hypoxia, acidosis and hypoglycemia, should
be sought, and corrected as quickly and as early as possi-
ble. Any obvious underlying cause of cardio-respiratory
distress should be treated, and the infant should be
watched carefully for signs of improvement and/or dete-
rioration. The vital functions of such infants must be
monitored continuously. Despite the measures men-
tioned above, if the fraction of inspired oxygen (FiO2)
rises, to maintain oxygen saturation above 95%, PFC
should be a part of the differential diagnosis and a tertiary
care centre should be notified.
Infants with PFC are very sensitive to their environ-
ment and tend to be extremely unstable. They are, in gen-
eral, mechanically ventilated, sedated and often paralyzed
with muscle relaxants. Therefore, procedures such as suc-
tioning, changing endotracheal tubes, bathing and reposi-
tioning should be kept to a minimum. If cyanosis is
present, congenital heart defects have to be ruled out be-
fore the cyanosis is attributed to PFC. Vital functions have
to be monitored continuously. Stable infants with PFC
and with initially acceptable oxygen saturations have been
known to suddenly drop their saturations to very low lev-
els when saturations drop below a critical level, usually
below 95% (the flip-flop phenomenon). Therefore, it is
important to recognize this crisis, and oxygen saturations
should be kept above 95% until FiO2levels are in an ac-
ceptable range (below 50%). Aggressive treatment should
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D’cunha and Sankaran
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be reserved only for patients who are unresponsive to
conservative management, as described above (38).
Tolazaline is believed to cause the release of histamine
(38), a pulmonary vasodilator, thereby, decreasing PVR.
Complications with its use include systemic hypotension,
gastrointestinal bleeding, increased gastrointestinal se-
cretions and acute tubular necrosis (39,40). Because of
myriad untoward effects, its use has been abandoned.
Corticosteroids transiently improve lung function. They
also help to increase systemic blood pressure over the
pulmonary pressure, thereby creating a gradient that
helps to increase pulmonary blood flow, thereby im-
proving oxygenation.
Surfactant, besides its use in premature babies with
hyaline membrane disease, is believed to improve lung
function in term babies with congenital diaphragmatic
hernia (41), meconium aspiration syndrome (42) and
bacterial pneumonia (43). Thus, early treatment with sur-
factant prevents the development of PFC. Modified natu-
ral surfactants have demonstrated superior ability in
improving oxygenation, decreasing mortality, and lower-
ing the frequency of retinopathy and bronchopulmonary
dysplasia in neonates (44,45) compared with artificial
surfactants. The above abilities may be due to the reten-
tion of the hydrophobic surfactant-associated proteins.
Early or prophylactic treatment of respiratory distress
syndrome (RDS) with surfactant appears to be more ef-
fective than treatment once RDS has developed. This may
be related to the avoidance of ventilator-induced lung in-
jury and/or more uniform distribution of surfactant when
it is given before lung injury occurs. Most protocols in-
clude doses, scheduled 6 to 12 h apart, beginning either
in the delivery room or at the first clinical sign of respira-
tory distress (46). Direct bolus instillation of surfactant
down the endotracheal tube has proved to have both de-
creased mortality and morbidity in neonatal RDS (47),
whereas aerolized surfactants have proved to be ineffec-
tive (48). Adverse effects of surfactant therapy include
changes in cerebral perfusion in premature infants (49)
and transient airway obstruction from bolus administra-
tion. The latter can be avoided by slower administration
of surfactant (50). Although surfactant therapy may not
cure the underlying cause, it decreases mortality from
acute lung injury (50) and PFC.
Controlled hyperventilation has been used to decrease
PVR by making the blood more alkalotic (40). This
method has to be employed with extreme caution because
decreased partial pressure of carbon dioxide levels may
result in cerebral ischemia (51) and susequent neurode-
velopmental deficits. Other complications include pneu-
mothorax, bronchopulmonary dysplasia and chronic
lung disease (51); in some cases, an increased rate of
hearing loss has also been noted (18). Another way to
treat acidosis is to administer sodium bicarbonate
and/or tromethamine. Adverse effects include fluid and
sodium overload, especially in renally compromise in-
fants (52).
Eicosanoids may be used as adjuncts in the manage-
ment of PFC. Prostacyclin is a potent vasodilator that
may have some specificity for pulmonary vasculature
(53). Prostaglandin E1is a nonspecific pulmonary vaso-
dilator. Prostaglandin D2is a vasodilator specific to
pulmonary circulation (54).
The administration of cardiotonic drugs should be re-
served for infants in whom myocardial dysfunction
and/or persistent hypotension is documented. The ideal
pressors would increase myocardial contractility and car-
diac output without increasing oxygen consumption,
thereby increasing systemic blood pressure above the
pulmonary pressure and forcing blood flow to lungs and
high risk organs such as the brain, liver, heart, kidneys
and intestine. Dopamine at low doses combined with high
doses of dobutamine is commonly used. At high doses,
dopamine acts as an alpha-adrenergic stimulator, which
increases PVR (55) and results in a negative outcome.
Several vasoactive substances are made endogenously.
Endothelin type 1, made by vascular endothelium, is a
pulmonary vasoconstrictor. The vascular endothelium
produces an endothelium-derived relaxing factor, which
was later identified as nitric oxide (12). Nitric oxide stimu-
lates a guanylate cyclase, which in turn produces cyclic-
guanosinemonophosphate. Cyclic-guanosinemonophos-
phate activates a protein kinase, which subsequently re-
moves calcium ions from inside the cells, thereby causing the
smooth muscle to relax (56).
Exogenous, inhaled nitric oxide at low doses causes
potent, sustained and selective pulmonary vasodilation
(57). High doses of nitric oxide improve oxygenation only
for brief periods (58) and may cause side effects (59). The
effects of nitric oxide may be suboptimal when lung vol-
umes are decreased, as seen in patients with conditions
such as pneumonia, atelectasis and pulmonary edema
(60). Interactions of nitric oxide with high frequency oscil-
latory ventilation have been shown to be therapeutically
successful (61). Other methods of alveolar recruitment,
such as prone positioning and the use of surfactant, may
also enhance the effects of nitric oxide. Nitric oxide has
demonstrated effectiveness in infants with RDS while
other vasodilators, such as nitroglycerin and sodium ni-
troprusside, have failed (62). One reason for the failure is
that nitric oxide is inactivated after binding to hemoglo-
bin and, thus, does not decrease systemic pressures. An-
other reason is that blood flow is redirected from poorly
aerated regions to better aerated areas at low doses of ni-
tric oxide, an event not seen in other modes of vasodilator
therapy (63). The loss of this selective effect at high doses
of nitric oxide is most likely due to the ability of nitric ox-
ide to reach poorly ventilated lung regions, a response not
seen at low doses. Potential toxicities of nitric oxide ther-
apy include methemoglobinemia (12), exposure to nitro-
gen dioxide and the generation of peroxynitrite.
Peroxynitrite can directly cause oxidation, peroxidation
and nitration of critical proteins and enzyme systems, in-
hibit surfactant function, and induce cell apoptosis and
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lung inflammation (64). However, these effects have been
noted at doses higher than those recommended for clinical
use. Furthermore, numerous studies have demonstrated
protective effects of nitric oxide, including decreased oxi-
dant injury (65) and decreased neutrophil accumulation
(66). Neurotoxicity, possibly resulting from DNA at high
doses, strand breakage and inhibition of DNA repair sys-
tems, has been observed (12,67). However, nitric oxide -
may also have tumoricidal effects (68). Other adverse
effects of nitric oxide include dependency (69) and pro-
longed bleeding times (nitric oxide inhibits platelet adhe-
sion (12,70). Nitric oxide is the treatment of choice for PFC
and can be potentially life-saving. The dose varies from 1
to 80 ppm, and is introduced through the inhalation limb
of the ventilator with a continuous nitric oxide monitor.
The usual starting dose in infants is 20 ppm. This dose can
be increased or decreased quickly every 15 to 30 min until
a steady state dose is reached, which can be as low as 1
ppm or as high as 80 ppm.
Extracorporeal membrane oxygenator (ECMO) therapy
is used in cases of severe PFC where all other modes of
therapy have failed. It is a modified form of cardiopulmon-
ary bypass and is used in situations such as congenital dia-
phragmatic hernia and meconium aspiration syndrome in
which the lungs need a ‘rest’ for recovery. Venous blood
from the right atrium is drained by a cannula, oxygen-
ated by a membrane lung and returned to the patient
through either the right common carotid artery (venoar-
terial [VA] ECMO) or through the femoral vein (venove-
nal [VV] ECMO). The membrane lung has two
compartments, one with flowing blood and the other
with flowing gas, that are separated by a silicon rubber
membrane through which gas exchange occurs. Patients
continue to be intubated and on ventilators, but at low
pressure, rate and fraction of inspired oxygen settings.
The purpose of this strategy is to prevent their lungs
from collapsing (71).
Major disadvantages of VA ECMO include the require-
ment of artery ligation after ECMO and embolization of air,
clots or debris returning from the ECMO circuit into the
arterial circulation (72). As a result, it is less commonly
used. Some centres repair arterial vessels during decan-
nulation (73). The preferred route in many centres is VV
ECMO because it limits the risk of embolization to the cen-
tral nervous system (74). However, because the portion of
cardiac output that is drained into the ECMO circuit is less
with VV ECMO than that with VA ECMO, the arterial satu-
ration in VV ECMO is usually lower. In most patients, arte-
rial saturations of 80% to 85% are adequate to maintain
tissue needs and are obtainable with VV ECMO. Patients
who do not receive sufficient oxygen may require a switch
to VA ECMO (75). A double-lumen single cannula also ex-
ists for use in VV ECMO. The advantage is that only a sin-
gle surgical site is required. This technique avoids the risk
of cerebral emboli seen in VA ECMO and reduces recircula-
tion problems noted in VV ECMO (76). For ECMO therapy
to be successful, it is imperative to avoid complications that
may result in early discontinuation of ECMO before ade-
quate lung function has been restored (77). Heparaniza-
tion is required to prevent clotting of the ECMO circuit.
To limit the risk of bleeding, the platelet count must be
kept above 100,000/mm3. Low levels of platelets and/or
fibrinogen may necessitate the administration of plate-
lets, fresh frozen plasma, cryoprecipitate and blood
transfusions (71,78). Positive end-expiratory pressure
must be maintained to prevent atelectasis (79). Patients
generally require parenteral nutrition; however, enteral
feeding is encouraged to retain the integrity of the gut
mucosa. If enteral feeding cannot be tolerated by the pa-
tient, supplementation of hyperalimentation with low
levels of feeding can be an alternative (80).
Many patients are volume overloaded from treatment
for hemodynamic instability before ECMO (81). Further-
more, the nonpulsatile flow of blood during ECMO may
alter renal blood flow and result in increased levels of
renin, aldosterone or antidiuretic hormone. Decreased
atrial filling pressures in VA ECMO may give rise to in-
creased amounts of atrial natriuretic factor. The com-
bined effects of these events may result in fluid retention.
Diuretics, low dose dopamine or hemofiltration can all
be used to maintain fluid balance (82). Sedation and an-
algesia are required for infants on ECMO. Tolerance to
medications often develops, necessitating higher doses.
Alterations in drug clearance and volume of distibution
during ECMO may require modification of standard
dosing regimens (83). Only patients who have not re-
sponded to less stressful modes of therapy should re-
ceive ECMO because it is quite aggressive and can have
serious complications. Complications include throm-
boembolism, air embolism, bleeding, stroke, seizures,
systemic hypertension, atelectasis and hemolysis. A
typical duration of ECMO is 3.5 days (71).
CONCLUSIONS
Even though PFC is seen less often than in previous
years, it is a serious condition that requires early diagno-
sis and prompt treatment. Treatment can be gentle or
aggressive, depending on the response. Hypothermia,
hypoxia, acidosis and hypoglycemia should be corrected
quickly and efficiently. Vital functions of infants must be
monitored continuously, with particular attention given
to maintain oxygen saturation above 95%. Underlying
causes of PFC should be sought and treated. If there is no
improvement, a tertiary care centre should be consulted.
Supportive treatments, such as sedation, paralysis, me-
chanical ventilation and blood pressure support, should
be introduced as necessary.
Administration of nitric oxide through the ventilator
should be introduced as soon as the diagnosis of PVC is
confirmed. ECMO is used as a last resort. With improv-
ing technology, early diagnosis and early treatment with
nitric oxide, the use of ECMO has become very mini-
mal. It would be wonderful to see PFC as a disease of
the past.
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... It is relatively a rare condition which is seen in newborn with respiratory distress syndrome, septicemia, meconium aspiration syndrome, diaphragmatic hernia or perinatal asphyxia or ischemia. 8,9 In utero the fetus derives its oxygen and nutrients from placenta through the umbilical vein. Most of this blood bypasses the liver and enter into right atrium (RA). ...
... During last trimester, the fetal pulmonary circulation becomes progressively responsive to vasoactive Stimuli. [8][9][10] Immediately after birth, pulmonary artery pressure falls and blood flow increases in response to birth related stimuli. Those includes establishment of air liquid interface, rhythmic lung distension, increased oxygen tension and altered production of vasoactive substances like nitric oxide and prostaglandin. ...
Article
p> Background: Persistent pulmonary hypertension (PPHN) is the persistence of the high pulmonary arterial pressure after birth which is a characteristic of the fetal circulation. PPHN is associated with substantial infant mortality and morbidity. Various treatment protocol are used according to the need of the patient. This study aimed to see the spectrum of the disease and its outcome in Bangladesh. Methods: 181 newborn babies were diagnosed as persistent pulmonary hypertension or persistent fetal circulation. After establishing diagnosis, all cases were kept in NICU and various management plans were prescribed according to necessity of a specific case. Repeat echocardiography was done after 72 hours to see the response of treatment. Residual congenital cardiac lesions were managed later on. Results: Most of the patient (69.06%) was diagnosed at first week of life. Minimum age of the patient was 1 day and maximum age 23 days. Among 181 cases 109 (66.22%) were male and 72(39.77%) were female. Associated congenital lesions like atrial septal defect was found in 52 (28.72%) cases, patent ductus arteriosus (PDA) was found in 14 (7.73%) cases and ventricular septal defect (VSD) was found in 2 (1.10%) cases. Combination of ASD & PDA was found in 75 (44.33%) cases. Systolic pulmonary artery pressure was more than 60 mmHg in 103 (56.91%) cases, more than 50 mmHg in 53 (29.28%) cases and more than 30 mmHg in 25 (13.81%) cases. Most of the patient (100%) received high flow oxygen therapy along with anti failure (66.30%) and sildenafil 98 (54.14%) therapy as per requirement of the patient. Complete cure was achieved in 95.58% cases and mortality was only 1.10%. Conclusion: These data showed a very impressive outcome of the PPHN in Bangladeshi Newborn even with minimally invasive management. Cardiovasc. j. 2018; 11(1): 17-22</p
... In 1969, Gersony and coworkers were the first to document pulmonary hypertension [9]. A recent review described sildenafil alone or in combination with iNO to be the best option for managing PPHN. ...
Article
Background Persistent pulmonary hypertension of the newborn (PPHN) has been known for more than three decades, and lots of advancements have been made regarding its diagnosis and management. However, the exact causes of PPHN and the best treatment strategies remain debatable. This study aimed to compare the effectiveness of sildenafil and bosentan versus sildenafil and beraprost in the management of persistent pulmonary hypertension of the newborn (PPHN). Methodology This open-label, non-randomized, quasi-experimental study was conducted at the Department of Pediatric Cardiology and Neonatology, The Children's Hospital & The Institute of Child Health, Multan, Pakistan, from January 2021 to June 2021. We enrolled a total of 50 newborns (25 in each group) aged <10 days, gestational age above 34 weeks, who presented with respiratory distress and marked hypoxemia (PaO2 < 50 mmHg) as per arterial blood gas (ABG) analysis and confirmed echocardiographic diagnosis of PPHN within 24 hours of admission. A total of 25 cases were given sildenafil and bosentan, while the other 25 cases were given sildenafil and beraprost. Echocardiographic examination was done again after 72 and 120 hours, and the findings were noted. Outcomes were measured in terms of the reduction in tricuspid regurgitation (TR), mortality, and duration of hospital stay. Results Of the 50 neonates, 27 (54.0%) were male. Overall, the mean age was calculated to be 3.54 ± 0.7 days. The mean gestational age was 35.0 ± 0.7 weeks. The mode of delivery was cesarean section among 35 (70.0%) neonates. A significantly higher reduction in tricuspid regurgitation after 72 and 120 hours following the initiation of the treatment was observed in the sildenafil plus bosentan group in comparison with the sildenafil plus beraprost group (p < 0.05). No statistically significant difference was observed in terms of the duration of hospitalization between both study groups (p = 0.1776). Conclusion The combination of sildenafil and bosentan was found to be more effective than sildenafil and beraprost in reducing tricuspid regurgitation after 72 hours, while they have comparable efficacy at 120 hours of treatment in the management of persistent pulmonary hypertension of the newborn.
... ECMO specifically is considered a rescue therapy for neonates with severe PPHN and who are unresponsive to other RESEARCH treatment modalities; 40% of neonates with PPHN do not respond to the combination of HFOV and iNO and require ECMO as a last resort. [3,10,13] Of the 25 nonsurvivors in this study, 62.5% died within 24 hours of admission. Univariate analysis showed that the characteristics of survivors and non-survivors were similar, except for the need for inotropic support. ...
Article
Full-text available
Background. Persistent pulmonary hypertension of the newborn (PPHN) is a clinical syndrome characterised by high pulmonary pressures, low systemic pressures and severe hypoxaemia due to circulation transition failure after birth. Objective. To determine the incidence of and describe the risk factors, infant characteristics and treatment strategies for PPHN at Charlotte Maxeke Johannesburg Academic Hospital over the last 8 years. Methods. This was a retrospective descriptive study. Patient records of neonates who had a discharge diagnosis of PPHN were reviewed for the period from January 2006 to December 2013. Neonates’ PPHN diagnosis was based on clinical criteria and, where possible, echocardiography. Neonates with a congenital cyanotic heart defect were excluded. Results. A total of 81 neonates had a discharge diagnosis of PPHN, of whom 72 were included in the study. Of the 72 neonates, 37 (51.4%) were female, 38 (52.8%) were born by vaginal delivery and 44 (61.1%) were inborn. The mean (standard deviation (SD)) birth weight was 2.94 (0.69) kg while the mean (SD) gestational age was 38.2 (3.3) weeks. Meconium aspiration syndrome (MAS) was seen in 43 neonates (59.7%) and was the most common disease underlying PPHN. Of the 72 neonates, 67 (93.1%) required mechanical ventilation, but only18.1% required high-frequency oscillatory ventilation. Magnesium sulphate and sildenafil were used in 12 (16.7%) and 9 neonates (12.5%), respectively. Inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation treatments were not available. Of the 72 neonates, 25 (34.7%) died. The need for inotropic support was associated with a poor outcome (p=0.01). Conclusion. PPHN was uncommon in our unit, but its management proved challenging owing to the high mortality risk. The leading cause of PPHN was MAS. Consideration should be given to introducing iNO, given that extracorporeal membrane oxygenation (ECMO) treatment is expensive and labour intensive and probably not justified at this time. © 2018, Health and Medical Publishing Group. All rights reserved.
Article
To protect the identity of the neonate and her family, pseudonyms and fictitious dates have been used, so as to ensure confidentiality as directed by the Nursing Midwifery Council (NMC, 2004). This article explores the aetiology of persistent pulmonary hypertension (PPHN) in a term neonate and discusses nursing management and the management of neonates on high frequency oscillation and inhaled nitric oxide therapy. It is imperative that all staff nursing a neonate on high frequency oscillation and inhaled nitric oxide therapy has a knowledge of the concept, be aware of the problems that may arise and be capable of taking steps in avoiding their occurrence.
Article
Birth hypoxia, asphyxia and ischemia have often been thought to be major causes of early hearing loss or deafness. The purpose of the present review is to focus on the role of these particular factors for perinatal auditory disorders. On the whole, only a small proportion of neonatal hearing loss is caused by perinatal factors. The exact etiology of neonatal hearing loss in children with complicated deliveries is difficult to evaluate due to the large number of causative factors that might be involved. After reviewing the literature covering the past 15-20 years, it is not possible to say that we understand the relative importance of different factors and their interactions. However, in the majority of studies, birth asphyxia is not correlated with hearing loss in babies with complicated deliveries Prolonged artificial ventilation, the presence of severe hypoxic ischemic encephalopathy or persistent pulmonary hypertension are important factors. The brain is more susceptible to anoxia than the ear and both are more likely to be damaged after prolonged pre-, peri- and postnatal hypoxia-ischemia than pure hypoxia during delivery. Perinatal hypoxia is more likely to cause a temporary hearing loss than a permanent one. Preterm babies are more vulnerable than term babies. The total number of risk factors, e.g. medicated by total length of stay in the neonatal intensive care unit and length of artificial ventilation, is the best predictor of risk for hearing loss of perinatal origin. The similarities between hearing loss and cerebral palsy are pointed out; only 8% of the cases of cerebral palsy are considered to be caused by conditions during delivery.
Article
Background Neonates with pulmonary hypertension have been treated with inhaled nitric oxide because of studies suggesting that it is a selective pulmonary vasodilator. We conducted a randomized, multicenter, controlled trial to determine whether inhaled nitric oxide would reduce mortality or the initiation of extracorporeal membrane oxygenation in infants with hypoxic respiratory failure. Methods Infants born after a gestation of >34 weeks who were 14 days old or less, had no structural heart disease, and required assisted ventilation and whose oxygenation index was 25 or higher on two measurements were eligible for the study. The infants were randomly assigned to receive nitric oxide at a concentration of 20 ppm or 100 percent oxygen (as a control). Infants whose partial pressure of arterial oxygen (PaO2) increased by 20 mm Hg or less after 30 minutes were studied for a response to 80-ppm nitric oxide or control gas. Results The 121 infants in the control group and the 114 in the nitric oxide group had similar base-line clinical characteristics. Sixty-four percent of the control group and 46 percent of the nitric oxide group died within 120 days or were treated with extracorporeal membrane oxygenation (P = 0.006). Seventeen percent of the control group and 14 percent of the nitric oxide group died (P not significant), but significantly fewer in the nitric oxide group received extracorporeal membrane oxygenation (39 percent vs. 54 percent, P = 0.014). The nitric oxide group had significantly greater improvement in PaO2 (mean [±SD] increase, 58.2±85.2 mm Hg, vs. 9.7±51.7 mm Hg in the controls; P<0.001) and in the oxygenation index (a decrease of 14.1±21.1, vs. an increase of 0.8±21.1 in the controls; P<0.001). The study gas was not discontinued in any infant because of toxicity. Conclusions Nitric oxide therapy reduced the use of extracorporeal membrane oxygenation, but had no apparent effect on mortality, in critically ill infants with hypoxic respiratory failure.
• Sixty neonates who were transferred to a neonatal intensive care unit during a four-year period had diagnoses of persistent fetal circulation (PFC). Six of these 60 neonates had β-hemolytic streptococcal infection. The clinical appearance of these six neonates included respiratory distress, cyanosis, and/or apnea. The chest roentgenograms showed mild to moderate lung disease. All six neonates had progressive acidosis with hypoxemia. The diagnosis of PFC was made by cardiac catheterization or contrast echoangiography. The neonates were treated with mechanical ventilation, antibiotics, and supportive therapy, including tolazoline hydrochloride. Mortality was high; only one of the six neonates survived. Streptococcal infection should be added to the growing list of conditions associated with PFC. (Am J Dis Child 1982;136:725-727)