Persistent fetal circulation

Persistent fetal circulationChrysal 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 WilliamHarvey 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 thelatter 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 haseither failed to close or reopened” in asphyxiated infants.They also noted two cases in which “the ductus arteriosuswas 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 leftatrial shunting occurred in an infant with respiratory dis-tress syndrome. Several publications that discussed vari-ous aspects of this condition followed. In 1969, Gersonyet al (6) published case reports of two newborns with pul-monary hypertension and described this condition as‘persistent fetal circulation’.

FETAL AND POSTNATAL CIRCULATIONTo 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 [email protected]

C D’cunha, K Sankaran. Persistent fetal circulation. Paediatr ChildHealth 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, meconiumand other aspiration syndromes, intrauterine hypoxia and ischemia, and/orneonatal 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 recognitionand intervention have made this condition even more rare. In modernneonatal intensive care units, anticipation and early treatment of PFC andits complications in sick newborns are commonplace. Thus, severe forms ofPFC are only seen on isolated occasions. Consequently, it is even more im-perative to revisit PFC compared with the time when there were occasionalcases of PFC seen in neonatal intensive care units, and to discuss evolvingtreatment and management issues that pertain to this syndrome.

Key Words: Newborns; Persistent fetal circulation; Persistent pulmonaryhypertension of the newborn; Respiratory distress syndrome

La circulation fœtale persistanteRÉSUMÉ : La circulation fœtale persistante (CFP), également désignéehypertension artérielle pulmonaire persistante du nouveau-né, sedéfinit comme une persistance postnatale du canal artériel, du shuntauriculaire ou de ces deux pathologies en présence d’une pressionélevée du ventricule droit. C’est une pathologie relativement rare,observée chez les nouveau-nés souffrant d’un syndrome de détresserespiratoire, de septicémie foudroyante, d’aspiration de méconium etd’autres syndromes d’aspiration ainsi que d’hypoxie et d’ischémieintra-utérines ou néonatales. Elle cause une hypoxémie grave ets’accompagne donc d’un taux élevé de morbidité et de mortalité. Demeilleurs soins anténatals et néonatals, le recours au surfactant, lasurveillance constante de l’oxygénation, de la tension artérielle et desautres fonctions vitales, de même qu’un dépistage et une interventionprécoces rendent cette pathologie encore plus rare. Dans les unités desoins intensifs néonatals modernes, la prévention et le traitementprécoce de la CFP et de ses complications chez les nouveau-nésmalades sont monnaie courante. Par conséquent, les formes graves deCFP ne se produisent que dans des cas isolés. Il est donc encore plusimpératif de réévaluer la CFP par rapport à l’époque où on observaitdes cas occasionnels de CFP dans les unités de soins intensifsnéonatals et d’aborder l’évolution du traitement et de la prise encharge de ce syndrome.

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and nutrients from the placenta through the umbilicalvein. Most of this blood bypasses the liver through theductus venosus and enters the inferior vena cava, whichends in the right atrium. Once again, the flow of blood issuch that most of it passes through the foramen ovale intothe left atrium and then into the left ventricle. This blood,rich in oxygen and nutrients, is pumped out from the leftventricle to the brain and the upper part of the body.Some of this blood in the right atrium from the inferiorvena cava, mixed with superior venacaval blood, goes intothe right ventricle, enters the pulmonary arterial trunkand then bypasses the lungs through the ductus arterio-sus to the descending aorta. This mixed blood is used tonourish 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 isrelatively richer in oxygen than those portions distal tothe ductus and aorta junction (postductal aorta). As a re-sult, the head, neck and right upper extremity (suppliedby branches from the preductal aorta) receive more oxy-gen than the trunk, the left upper extremity and bothlower 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) decreasesremarkably while the systemic vascular pressure risesabove the PVR. This allows blood from the right ventricleto enter the lungs for oxygenation. In most cases, this in-creased oxygenation, along with other factors, causes theductal wall to constrict and the ductus arteriosus to closefunctionally. Within days, anatomical occlusion occurs,with extensive neointimal thickening and loss of smoothmuscle cells, and the ductus becomes a strand-like struc-ture with no lumen (8).

Furthermore, as left-sided pressures rise higher thanright-sided pressures, the foramen ovale functionallycloses (9). With the clamping of the umbilical cord andthe cessation of blood flow, pressures in the portal sinusdecrease. This causes the muscle in the sinus wall nearthe ductus venosus to contract (10). The lumen of theduct becomes filled with connective tissue, and, in twomonths, the ductus venosus becomes a fibrous strandembedded in the wall of the liver (11), thus establishingadult circulation.

If, for any reason, right-sided pressures remain highrelative to those on the left side, fetal circulation will mostlikely persist through one or both of the fetal channelsmentioned above. Therefore, PFC is defined as postnatalpersistence of right to left ductal or atrial shunting, orboth in the presence of elevated right ventricular pres-sure.

FACTORS AFFECTING PVRBecause a lower PVR generally promotes functional

closure of the ductus and foramen ovale while a high PVRencourages PFC, it is useful to know which substances in-

crease and which substances decrease PVR. Factorsknown to lower PVR include oxygen, nitric oxide, prosta-cyclin, prostaglandins E2 and D2, adenosin, magnesium,bradykinins, atrial natriuretic factor, alkalosis, hista-mine, acetylcholine, beta-adrenergic stimulation andpotassium channel activation. Factors that increase PVRare hypoxia, acidosis, endothelin-1, leukotrienes, throm-boxanes, platelet activating factors, prostaglandin F2-alpha, alpha-adrenergic stimulation and calcium channelactivation (12). Thus, it is important to recognize clinicalconditions that affect PVR and to treat them appropri-ately.

EPIDEMIOLOGY AND COURSEPFC was seen in one/1500 live births in the 1980s (13).

It occurs more commonly in males, and appears to occurmore frequently at higher altitudes (14). Most cases ofPFC result in either complete recovery or death. Occa-sionally, there may be long term sequelae such as chroniclung disease (15), cerebral infarction (16) resulting inspecific 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). Theunderlying cause determines the prognosis (20).

ETIOLOGYPFC 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 ofthe pulmonary vessels. Thus, after birth, these vesselshave a greater tendency to continue to stay constricted. Assuch, these vessels do not dilate as expected, resulting inhigh right-sided pressures. Cases in which vessels fail todilate with time and treatment prove to be fatal. Diagnosisis 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 beendocumented. Investigative and interventive efforts in thefuture are most likely to make this subset of PFC occur infewer patients (22).

Secondary PFC is most commonly seen in infants withlung diseases, the most common cause being meconiumaspiration (23). The resulting hypoxia and acidosis causepulmonary vasoconstriction and increased right-sidedpressures. 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 betweenPFC, which implies a structurally normal heart, and acongenital heart defect, which is responsible for pulmo-nary hypertension. A discussion of pulmonary hyperten-sion in the newborn secondary to a cardiac cause is

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Persistent fetal circulation

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beyond the scope of the present paper. Consequently, thispaper only describes PFC in the neonate with a structur-ally normal heart.

PFC has also been noted in cases of sepsis syndromescaused by group B streptococcus (28), Listeria monocy-

togenes, Escherichia coli and Haemophilus influenzae

type b (29). It is believed that the increased release of thepulmonary vasoconstrictor thromboxane is responsiblefor PFC.

Several perinatal factors trigger PFC. Because hypoxiaand acidosis are known pulmonary vasoconstrictors, anycondition that disrupts utero-placental circulation, suchas placental abruption or placental insufficiency, causes‘priming’ of fetal pulmonary vasculature, with hypertro-phy and thickening of the muscular layer of pulmonaryvessels. This priming makes the neonate more suscepti-ble to PFC, and more sensitive to secondary triggers ofPFC such as neonatal hypoxia and cold stress (30). Lateclamping of the umbilical cord allows a larger placentaltransfusion, thereby, increasing the hematocrit. This risein hematocrit may result in increased viscosity and sludg-ing of pulmonary circulation, which in turn cause hypoxiaand ventilation profusion mismatch, thereby increasingPVR and resulting in higher pressures on the right siderelative to the left side (31). Maternal ingestion of cyclooxy-genase inhibitors, such as acetylsalicylic acid, indometha-cin, salicylates and naproxen, can induce constriction ofthe fetal arterial duct in utero (32). Arterial constrictionleads to excessive pulmonary blood flow in the fetus andsubsequent hypertrophy of the pulmonary vessels, result-ing in pulmonary hypertension and severe PFC postna-tally.

DIAGNOSISWhen the right arm and head remain pink, while the

left arm and lower body are cyanotic, a clinical conditionwith differential cyanosis occurs. This condition is due tothe 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). Whenpulmonary hypertension is present, closure of the pul-monic valve is more forceful, resulting in a loud secondheart 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 radialartery and the descending aorta blood suggests PFC, butit is not present in every case (33). The hyperoxia test in-volves the inhalation of 100% oxygen. Blood gases beforeand after inhalation are recorded. A change of less than20 mmHg in PaO2 can indicate either PFC or congenitalcyanotic heart disease (34), particularly when these con-ditions cannot be corrected by improved ventilation,whereas a change in PaO2 of 20 mmHg or greater implies

a respiratory disorder. This blood gas test is not specific.Modified versions include the hyperoxia-continuouspositive airway pressure test (applying 6 to 10 cmH2O ofcontinuous positive airway pressure) and the hyperoxia-hyperventilation test (the infant is hyperventilated me-chanically to achieve a partial pressure of carbon dioxidein the low 20s and a pH greater than 7.55). These testsare 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 dyedemonstration of the right to left shunt was the most con-clusive diagnostic test. The hazards involved with thisprocedure 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 outthe presence of congenital heart disease. It accurately de-termines both the pressure and velocity of blood flow inmajor vessels of fetuses and newborns, including the di-rection of blood flow through the ductus and the foramenovale (36). A depth-gated pulse Doppler probe can estimateright to left shunts. It can also help to assess biventricularfunction and to provide an estimation of pulmonary arterypressures (37), thus making the diagnosis relatively easy inthe absence of congenital heart disease.

MANAGEMENTUpon the birth of any infant, reversible events, such as

hypothermia, hypoxia, acidosis and hypoglycemia, shouldbe sought, and corrected as quickly and as early as possi-ble. Any obvious underlying cause of cardio-respiratorydistress should be treated, and the infant should bewatched carefully for signs of improvement and/or dete-rioration. The vital functions of such infants must bemonitored continuously. Despite the measures men-tioned above, if the fraction of inspired oxygen (FiO2)rises, to maintain oxygen saturation above 95%, PFCshould be a part of the differential diagnosis and a tertiarycare 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 paralyzedwith muscle relaxants. Therefore, procedures such as suc-tioning, changing endotracheal tubes, bathing and reposi-tioning should be kept to a minimum. If cyanosis ispresent, congenital heart defects have to be ruled out be-fore the cyanosis is attributed to PFC. Vital functions haveto be monitored continuously. Stable infants with PFCand with initially acceptable oxygen saturations have beenknown to suddenly drop their saturations to very low lev-els when saturations drop below a critical level, usuallybelow 95% (the flip-flop phenomenon). Therefore, it isimportant to recognize this crisis, and oxygen saturationsshould be kept above 95% until FiO2 levels are in an ac-ceptable range (below 50%). Aggressive treatment should


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be reserved only for patients who are unresponsive toconservative 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 ofmyriad untoward effects, its use has been abandoned.Corticosteroids transiently improve lung function. Theyalso help to increase systemic blood pressure over thepulmonary pressure, thereby creating a gradient thathelps to increase pulmonary blood flow, thereby im-proving oxygenation.

Surfactant, besides its use in premature babies withhyaline membrane disease, is believed to improve lungfunction in term babies with congenital diaphragmatichernia (41), meconium aspiration syndrome (42) andbacterial pneumonia (43). Thus, early treatment with sur-factant prevents the development of PFC. Modified natu-ral surfactants have demonstrated superior ability inimproving oxygenation, decreasing mortality, and lower-ing the frequency of retinopathy and bronchopulmonarydysplasia in neonates (44,45) compared with artificialsurfactants. The above abilities may be due to the reten-tion of the hydrophobic surfactant-associated proteins.Early or prophylactic treatment of respiratory distresssyndrome (RDS) with surfactant appears to be more ef-fective than treatment once RDS has developed. This maybe related to the avoidance of ventilator-induced lung in-jury and/or more uniform distribution of surfactant whenit is given before lung injury occurs. Most protocols in-clude doses, scheduled 6 to 12 h apart, beginning eitherin the delivery room or at the first clinical sign of respira-tory distress (46). Direct bolus instillation of surfactantdown 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 includechanges in cerebral perfusion in premature infants (49)and transient airway obstruction from bolus administra-tion. The latter can be avoided by slower administrationof surfactant (50). Although surfactant therapy may notcure the underlying cause, it decreases mortality fromacute lung injury (50) and PFC.

Controlled hyperventilation has been used to decreasePVR by making the blood more alkalotic (40). Thismethod has to be employed with extreme caution becausedecreased partial pressure of carbon dioxide levels mayresult in cerebral ischemia (51) and susequent neurode-velopmental deficits. Other complications include pneu-mothorax, bronchopulmonary dysplasia and chroniclung disease (51); in some cases, an increased rate ofhearing loss has also been noted (18). Another way totreat acidosis is to administer sodium bicarbonateand/or tromethamine. Adverse effects include fluid andsodium 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 thatmay have some specificity for pulmonary vasculature(53). Prostaglandin E1 is a nonspecific pulmonary vaso-dilator. Prostaglandin D2 is a vasodilator specific topulmonary circulation (54).

The administration of cardiotonic drugs should be re-served for infants in whom myocardial dysfunctionand/or persistent hypotension is documented. The idealpressors would increase myocardial contractility and car-diac output without increasing oxygen consumption,thereby increasing systemic blood pressure above thepulmonary pressure and forcing blood flow to lungs andhigh risk organs such as the brain, liver, heart, kidneysand intestine. Dopamine at low doses combined with highdoses of dobutamine is commonly used. At high doses,dopamine acts as an alpha-adrenergic stimulator, whichincreases PVR (55) and results in a negative outcome.

Several vasoactive substances are made endogenously.Endothelin type 1, made by vascular endothelium, is apulmonary vasoconstrictor. The vascular endotheliumproduces an endothelium-derived relaxing factor, whichwas 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 thesmooth muscle to relax (56).

Exogenous, inhaled nitric oxide at low doses causespotent, sustained and selective pulmonary vasodilation(57). High doses of nitric oxide improve oxygenation onlyfor brief periods (58) and may cause side effects (59). Theeffects of nitric oxide may be suboptimal when lung vol-umes are decreased, as seen in patients with conditionssuch as pneumonia, atelectasis and pulmonary edema(60). Interactions of nitric oxide with high frequency oscil-latory ventilation have been shown to be therapeuticallysuccessful (61). Other methods of alveolar recruitment,such as prone positioning and the use of surfactant, mayalso enhance the effects of nitric oxide. Nitric oxide hasdemonstrated effectiveness in infants with RDS whileother vasodilators, such as nitroglycerin and sodium ni-troprusside, have failed (62). One reason for the failure isthat 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 poorlyaerated regions to better aerated areas at low doses of ni-tric oxide, an event not seen in other modes of vasodilatortherapy (63). The loss of this selective effect at high dosesof nitric oxide is most likely due to the ability of nitric ox-ide to reach poorly ventilated lung regions, a response notseen 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, peroxidationand 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 beennoted at doses higher than those recommended for clinicaluse. Furthermore, numerous studies have demonstratedprotective effects of nitric oxide, including decreased oxi-dant injury (65) and decreased neutrophil accumulation(66). Neurotoxicity, possibly resulting from DNA at highdoses, strand breakage and inhibition of DNA repair sys-tems, has been observed (12,67). However, nitric oxide -may also have tumoricidal effects (68). Other adverseeffects 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 PFCand can be potentially life-saving. The dose varies from 1to 80 ppm, and is introduced through the inhalation limbof the ventilator with a continuous nitric oxide monitor.The usual starting dose in infants is 20 ppm. This dose canbe increased or decreased quickly every 15 to 30 min untila steady state dose is reached, which can be as low as 1ppm or as high as 80 ppm.

Extracorporeal membrane oxygenator (ECMO) therapyis used in cases of severe PFC where all other modes oftherapy 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 inwhich the lungs need a ‘rest’ for recovery. Venous bloodfrom the right atrium is drained by a cannula, oxygen-ated by a membrane lung and returned to the patientthrough either the right common carotid artery (venoar-terial [VA] ECMO) or through the femoral vein (venove-nal [VV] ECMO). The membrane lung has twocompartments, one with flowing blood and the otherwith flowing gas, that are separated by a silicon rubbermembrane through which gas exchange occurs. Patientscontinue to be intubated and on ventilators, but at lowpressure, rate and fraction of inspired oxygen settings.The purpose of this strategy is to prevent their lungsfrom 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 thearterial circulation (72). As a result, it is less commonlyused. Some centres repair arterial vessels during decan-nulation (73). The preferred route in many centres is VVECMO because it limits the risk of embolization to the cen-tral nervous system (74). However, because the portion ofcardiac output that is drained into the ECMO circuit is lesswith 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 maintaintissue needs and are obtainable with VV ECMO. Patientswho do not receive sufficient oxygen may require a switchto 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 riskof cerebral emboli seen in VA ECMO and reduces recircula-tion problems noted in VV ECMO (76). For ECMO therapyto 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 bekept above 100,000/mm3. Low levels of platelets and/orfibrinogen may necessitate the administration of plate-lets, fresh frozen plasma, cryoprecipitate and bloodtransfusions (71,78). Positive end-expiratory pressuremust be maintained to prevent atelectasis (79). Patientsgenerally require parenteral nutrition; however, enteralfeeding is encouraged to retain the integrity of the gutmucosa. If enteral feeding cannot be tolerated by the pa-tient, supplementation of hyperalimentation with lowlevels of feeding can be an alternative (80).

Many patients are volume overloaded from treatmentfor hemodynamic instability before ECMO (81). Further-more, the nonpulsatile flow of blood during ECMO mayalter renal blood flow and result in increased levels ofrenin, aldosterone or antidiuretic hormone. Decreasedatrial 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 allbe used to maintain fluid balance (82). Sedation and an-algesia are required for infants on ECMO. Tolerance tomedications often develops, necessitating higher doses.Alterations in drug clearance and volume of distibutionduring ECMO may require modification of standarddosing 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 haveserious complications. Complications include throm-boembolism, air embolism, bleeding, stroke, seizures,systemic hypertension, atelectasis and hemolysis. Atypical duration of ECMO is 3.5 days (71).

CONCLUSIONSEven 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 oraggressive, depending on the response. Hypothermia,hypoxia, acidosis and hypoglycemia should be correctedquickly and efficiently. Vital functions of infants must bemonitored continuously, with particular attention givento maintain oxygen saturation above 95%. Underlyingcauses of PFC should be sought and treated. If there is noimprovement, a tertiary care centre should be consulted.Supportive treatments, such as sedation, paralysis, me-chanical ventilation and blood pressure support, shouldbe introduced as necessary.

Administration of nitric oxide through the ventilatorshould be introduced as soon as the diagnosis of PVC isconfirmed. ECMO is used as a last resort. With improv-ing technology, early diagnosis and early treatment withnitric oxide, the use of ECMO has become very mini-mal. It would be wonderful to see PFC as a disease ofthe past.



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Persistent fetal circulation