Introduction

Background
Respiratory distress syndrome (RDS), also known as hyaline membrane disease (HMD), occurs almost exclusively in
premature infants. The incidence and severity of respiratory distress syndrome are related inversely to the gestational
age of the newborn infant.
Enormous strides have been made in the understanding of the pathophysiology and management of these infants,
leading to improvements in morbidity and mortality. Advances include (1) the use of antenatal steroids to enhance
pulmonary maturity; (2) appropriate resuscitation facilitated by placental transfusion and immediate use of continuous
positive airway pressure (CPAP) for alveolar recruitment; (3) early administration of surfactant; (4) the use of gentler
modes of ventilation, including early use of "bubble" nasal CPAP to minimize damage to the immature lungs; and (5)
supportive therapies, such as diagnosis and management of patent ductus arteriosus (PDA), fluid and electrolyte
management, trophic feeding and nutrition, and use of prophylactic fluconazole. These therapies have also resulted in
the survival of extremely premature infants, some of whom who continue to be ill with complications ofprematurity.
Although reduced, the incidence and severity of complications of respiratory distress syndrome can result in clinically
significant morbidities. Sequelae of respiratory distress syndrome include septicemia,bronchopulmonary dysplasia
(BPD), PDA, pulmonary hemorrhage, apnea/bradycardia, necrotizing enterocolitis (NEC), retinopathy of prematurity
(ROP), hypertension, failure to thrive, intraventricular hemorrhage (IVH), and periventricular leukomalacia (PVL) with
associated neurodevelopmental and audiovisual handicaps. Direct attention to anticipating and minimizing these
complications and to preventing premature delivery whenever possible are strategic goals.

Schematic outlines the pathology of respiratory distress syndrome (RDS). Infants may recover completely or
develop chronic lung damage, resulting in bronchopulmonary dysplasia (BPD). FiO 2 = fraction of inspired oxygen;
HMD = hyaline membrane disease; V/Q = ventilation perfusion.
[ CLOSE WINDOW ]

Schematic outlines the pathology of respiratory distress syndrome (RDS). Infants may recover completely or
develop chronic lung damage, resulting in bronchopulmonary dysplasia (BPD). FiO 2 = fraction of inspired oxygen;
HMD = hyaline membrane disease; V/Q = ventilation perfusion.

Pathophysiology
Considerable advances have been made in the understanding of the pathophysiology of respiratory distress syndrome,
lung development, ontogeny of surfactant proteins (SPs), protein leakage, and the role of cytokines in inducing lung
damage. The cause of respiratory distress syndrome is relative deficiency of surfactant, which decreases lung
compliance (see Media file 1) and functional residual capacity with increased dead space. The resulting large
ventilation-perfusion (V/Q) mismatch and right-to-left shunt may involve as much as 80% of the cardiac output.

Bottom curve reflects findings from lungs obtained at postmortem from an infant with hyaline membrane disease
(HMD). Lungs with HMD require far more pressure than to achieve a given volume of inflation than do lungs
obtained from an infant dying of a nonrespiratory cause. Arrows indicate inspiratory and expiratory limbs of the
pressure-volume curves. Note the decreased lung compliance and increased critical opening and closing pressures,
respectively, in the premature infant with HMD.
[ CLOSE WINDOW ]

Bottom curve reflects findings from lungs obtained at postmortem from an infant with hyaline membrane disease
(HMD). Lungs with HMD require far more pressure than to achieve a given volume of inflation than do lungs
obtained from an infant dying of a nonrespiratory cause. Arrows indicate inspiratory and expiratory limbs of the
pressure-volume curves. Note the decreased lung compliance and increased critical opening and closing pressures,
respectively, in the premature infant with HMD.

Upon macroscopic evaluation, the lungs appear airless and ruddy (ie, liverlike). Therefore, the lungs of affected
newborn infants require an increased critical opening pressure to inflate (see Media file 1). Diffuse atelectasis of
distal airspaces along with distension of distal airways and perilymphatic areas are observed microscopically.
Progressive atelectasis, barotrauma or volutrauma, and oxygen toxicity, damages endothelial and epithelial cells lining
these distal airways, resulting in exudation of fibrinous matrix derived from blood.

Hyaline membranes that line the alveoli (see Media file 2) may form within a half hour after birth. In larger premature
infants, the epithelium begins to heal at 36-72 hours after birth, and endogenous surfactant synthesis begins.

Microscopic appearance of lungs of an infant with respiratory distress syndrome. Hematoxylin and eosin stain
shows hyaline membranes (pink areas).
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Microscopic appearance of lungs of an infant with respiratory distress syndrome. Hematoxylin and eosin stain
shows hyaline membranes (pink areas).

The recovery phase is characterized by regeneration of alveolar cells, including type II cells, with a resultant increase
in surfactant activity. The healing process is complex (see Media file 3).

Schematic outlines the pathology of respiratory distress syndrome (RDS). Infants may recover completely or
develop chronic lung damage, resulting in bronchopulmonary dysplasia (BPD). FiO 2 = fraction of inspired oxygen;
HMD = hyaline membrane disease; V/Q = ventilation perfusion.
[ CLOSE WINDOW ]

Schematic outlines the pathology of respiratory distress syndrome (RDS). Infants may recover completely or
develop chronic lung damage, resulting in bronchopulmonary dysplasia (BPD). FiO 2 = fraction of inspired oxygen;
HMD = hyaline membrane disease; V/Q = ventilation perfusion.

A chronic process often ensues in infants who are extremely immature and critically ill and in infants born to mothers
with chorioamnionitis, resulting in BPD. In extremely premature infants, an arrest in lung development often occurs
during the saccular stage, resulting in chronic lung disease termed "new" BPD.
Surfactant is a complex lipoprotein (see Media file 4) composed of 6 phospholipids and 4 apoproteins.

Bar chart demonstrates the composition of lung surfactant. About 1% of the 10% protein component comprises
surfactant apoproteins; the remaining proteins are derived from alveolar exudate.
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Bar chart demonstrates the composition of lung surfactant. About 1% of the 10% protein component comprises
surfactant apoproteins; the remaining proteins are derived from alveolar exudate.

Surfactant recovered by alveolar wash from most mammals contains 70-80% phospholipids, 8-10% protein, and 10%
neutral lipids, primarily cholesterol. Dipalmitoyl phosphatidylcholine (DPPC), or lecithin, is functionally the principle
phospholipid. Phosphatidylglycerol comprises 4-15% of the phospholipids; although it is a marker for lung maturity, it
is not necessary for normal lung function.
Of the 4 surfactant apoproteins identified, SP-B and SP-C are 2 small hydrophobic proteins that comprise 2-4% of the
surfactant mass and are present in commercially available surfactant preparations. SP-B and SP-C work in concert to
facilitate rapid adsorption and spreading of DPPC as a monolayer to lower the surface tension at the alveolar air-fluid
interface in vivo during expiration, thus preventing atelectasis. The SP-B gene is on human chromosome 2, and its
primary translation product is 40 kDa, which is clipped to become a 8-kDa protein in the type II cells before entering
lamellar bodies to be cosecreted with phospholipids. The SP-C gene is on chromosome 8; its primary translation

product is 22 kDa and is processed to an extremely hydrophobic 4-kDa protein that is associated with lipids in
lamellar bodies.
SP-A is an innate host defense, large molecular, hydrophobic protein that regulates lung inflammation. SP-A binds to
multiple organisms, such as group B streptococcus, Staphylococcus aureus, influenza virus, adenovirus,
and respiratory syncytial virus. SP-A facilitates phagocytosis of pathogens by macrophages and their clearance from
the airways. Mice that lack SP-A have no tubular myelin and have normal lung function and surfactant metabolism,
indicating that SP-A is not a critical regulator of surfactant metabolism. Patients with SP-A deficiency have not been
described.
SP-D is also a hydrophobic protein of 43 kDa that is a collectin with structural similarities to SP-A. It has a collagenlike
domain and a glycosylated region that gives it its lectinlike functions. SP-D is a large multimer that also binds
pathogens and facilitates their clearance. The absence of SP-D results in increased surfactant lipid pools in the
airspaces and emphysema in mice. No humans with SP-D deficiency have been described.
The components of pulmonary surfactant are synthesized in the Golgi apparatus of the endoplasmic reticulum of the
type II alveolar cell (see Media file 5).

Schematic show surfactant metabolism, with a single alveolus is shown and the location and movement of
surfactant components. Surfactant components are synthesized from precursors in the endoplasmic reticulum and
transported through the Golgi apparatus by multivesicular bodies. Components are ultimately packaged in lamellar
bodies, which are intracellular storage granules for surfactant before its secretion.
After secretion (exocytosis) into the liquid lining of the alveolus, surfactant phospholipids are organized into a
complex lattice called tubular myelin. Tubular myelin is believed to generate the phospholipid that provides
material for a monolayer at the air-liquid interface in the alveolus, which lowers surface tension. Surfactant
phospholipids and proteins are subsequently taken back into type II cells, possibly in the form of small vesicles,
apparently by a specific pathway that involves endosomes, and probably transported for storage into lamellar
bodies for recycling.
Alveolar macrophages also take up some surfactant in the liquid layer. A single transit of the phospholipid
components of surfactant through the alveolar lumen normally requires a few hours. The phospholipid in the lumen
is taken back into type II cell and is reused 10 times before being degraded. Surfactant proteins are synthesized in
polyribosomes and extensively modified in the endoplasmic reticulum, Golgi apparatus, and multivesicular bodies.
Surfactant proteins are detected in lamellar bodies or secretory vesicles closely associated with lamellar bodies
before they are secreted into the alveolus.
[ CLOSE WINDOW ]

Schematic show surfactant metabolism, with a single alveolus is shown and the location and movement of
surfactant components. Surfactant components are synthesized from precursors in the endoplasmic reticulum and

transported through the Golgi apparatus by multivesicular bodies. Components are ultimately packaged in lamellar
bodies, which are intracellular storage granules for surfactant before its secretion.
After secretion (exocytosis) into the liquid lining of the alveolus, surfactant phospholipids are organized into a
complex lattice called tubular myelin. Tubular myelin is believed to generate the phospholipid that provides
material for a monolayer at the air-liquid interface in the alveolus, which lowers surface tension. Surfactant
phospholipids and proteins are subsequently taken back into type II cells, possibly in the form of small vesicles,
apparently by a specific pathway that involves endosomes, and probably transported for storage into lamellar
bodies for recycling.
Alveolar macrophages also take up some surfactant in the liquid layer. A single transit of the phospholipid
components of surfactant through the alveolar lumen normally requires a few hours. The phospholipid in the lumen
is taken back into type II cell and is reused 10 times before being degraded. Surfactant proteins are synthesized in
polyribosomes and extensively modified in the endoplasmic reticulum, Golgi apparatus, and multivesicular bodies.
Surfactant proteins are detected in lamellar bodies or secretory vesicles closely associated with lamellar bodies
before they are secreted into the alveolus.

The components are packaged in multilamellar vesicles in the cytoplasm of the type II alveolar cell. They are secreted
by a process of exocytosis, the daily rate of which may exceed the weight of the cell. Once secreted, the vesicles
unwind to form bipolar monolayers of phospholipid molecules that depend on the apoproteins SP-B and SP-C to
properly configure in the alveolus. The lipid molecules are enriched in dipalmitoyl acyl groups attached to a glycerol
backbone that pack tightly and generate low surface tension. Tubular myelin stores surfactant and depends on SP-B.
Corners of the myelin lattice appear to be glued together with the large apoprotein SP-A, which may also have an
important role in phagocytosis. Surfactant proteins are expressed in the fetal lung with increasing gestational age.
In premature infants, respiratory distress syndrome develops because of impaired surfactant synthesis and secretion
leading to atelectasis, V/Q inequality, and hypoventilation with resultant hypoxemia and hypercarbia. Blood gases
show respiratory and metabolic acidosis that causes pulmonary vasoconstriction, resulting in impaired endothelial and
epithelial integrity with leakage of proteinaceous exudate and formation of hyaline membranes (hence the name).
Hypoxia, acidosis, hypothermia, and hypotension may impair surfactant production and/or secretion. In many
neonates, oxygen toxicity with barotrauma and volutrauma in their structurally immature lungs causes an influx of
inflammatory cell, which exacerbates the vascular injury, leading to BPD. Antioxidant deficiency and free-radical injury
worsens the injury.
The hydrophobic SP-B and SP-C are essential for lung function and pulmonary homeostasis after birth. These proteins
enhance the spreading, adsorption, and stability of surfactant lipids required to reduce surface tension in the alveolus.
SP-B and SP-C participate in regulating intracellular and extracellular processes critical for maintaining respiratory
structure and function. SP-B deficiency is an inherited deficiency caused by a pretranslational mechanism implied by
the absence of messenger RNA (mRNA).
SP-B deficiency leads to death in term or near-term neonates and clinically manifests as respiratory distress syndrome
with pulmonary hypertension, or congenital alveolar proteinosis. The genetic absence of SP-B is most often caused by
a 2-base pair insertion (121 ins 2) that produces a frame shift and premature terminal signal, resulting in a complete
absence of SP-B. Approximately 15% of term infants who die of a syndrome similar to respiratory distress syndrome
have SP-B deficiency. The lack of SP-B causes a lack of normal lamellar bodies in type II cells, a lack of SP-C, and the
appearance of incompletely processed SP-C in the airspaces. These pro SP-C forms are diagnostic of SP-B deficiency.
Analysis of lung tissue with immunologic and biologic methods reveals an absence of one of the surfactant specific
proteins, SP-B, and its mRNA. In an in-vitro study, critical structure and function in the N-terminal region of pulmonary
SP-B was noted. W9 is critical to optimal surface activity, whereas prolines may promote a conformation that
facilitates rapid insertion of the peptide into phospholipid monolayers compressed to the highest pressures during
compression-expansion cycling.
Mutations of SP-B and SP-C cause acute respiratory distress syndrome and chronic lung disease that may be related
to the intracellular accumulation of injurious proteins, extracellular deficiency of bioactive surfactant peptides, or both.
Mutations in the gene for SP-C are a cause of both familial and sporadic interstitial lung disease and emphysema as
they age. Mutations in other genes that cause protein misfolding and misrouting may contribute to the pathogenesis
of chronic interstitial lung disease.
Mutations in the adenosine triphosphate (ATP)binding casette gene ( ABCA3) in newborns result in fatal surfactant
deficiency. ABCA3 is critical for proper formation of lamellar bodies and surfactant function and may also be important
for lung function in other pulmonary diseases. Because it is closely related to the ABCA1 and ABCA4 -encoded

proteins that transport phospholipids in macrophages and photoreceptor cells, it may have a role in surfactant
phospholipid metabolism.
The incidence of genetic abnormalities of pulmonary surfactant disorders is unknown. In a review of 300 term infants
presenting as severe respiratory distress syndrome, 14% had SP-B deficiency and 14% had a deficiency of ABCA3.
Hydrophilic SP-A and SP-D are lectins. In vivo and in vitro studies provide compelling support for SP-A and SP-D as
mediators of various immune-cell functions. Studies have shown novel roles for these proteins in the clearance of
apoptotic cells, direct killing of microorganisms, and initiation of parturition. None of the currently available surfactant
preparations to treat respiratory distress syndrome have SP-A and SP-D.
Frequency
United States
In the United States, respiratory distress syndrome has been estimated to occur in 20,000-30,000 newborn infants
each year and is a complication in about 1% pregnancies. Approximately 50% of the neonates born at 26-28 weeks'
gestation develop respiratory distress syndrome, whereas less than 30% of premature neonates born at 30-31 weeks'
gestation develop respiratory distress syndrome. In one report, the incidence rate of respiratory distress syndrome
was 42% in infants weighing 501-1500 g, with 71% reported in infants weighing 501-750 g, 54% reported in infants
weighing 751-1000 g, 36% reported in infants weighing 1001-1250 g, and 22% reported in infants weighing 12511500 g among the 12 university hospitals participating in the National Institute of Child Health and Human
Development (NICHD) Neonatal Research Network.1
International
Respiratory distress syndrome has been reported in all races worldwide, occurring most often in white premature
infants. Respiratory distress syndrome is encountered less frequently in the developing countries than elsewhere,
primarily because most premature infants who are small for their gestation are stressed in utero because of
malnutrition or pregnancy-induced hypertension. Most deliveries occur at home; therefore, accurate records are
unavailable to determine the frequency of respiratory distress syndrome and other illness in developing countries.
Race
White infants are at increased risk for respiratory distress syndrome.
Clinical
History

Respiratory distress syndrome (RDS) frequently occurs in the following individuals:

o

White male infants

Infants born to mothers with diabetes

Infants born by means of cesarean delivery

Second-born twins

Infants with a family history of respiratory distress syndrome

In contrast, the incidence of respiratory distress syndrome decreases with the following:
o

Use of antenatal steroids

Pregnancy-induced or chronic maternal hypertension

Prolonged rupture of membranes

Maternal narcotic addiction

Secondary surfactant deficiency may occur in infants with the following:

o

Intrapartum asphyxia

Pulmonary infections (eg, group B beta-hemolytic streptococcal pneumonia)

Pulmonary hemorrhage

Meconium aspiration pneumonia

Oxygen toxicity along with barotrauma or volutrauma to the lungs

Congenital diaphragmatic hernia and pulmonary hypoplasia

Physical

Physical findings are consistent with the infant's maturity assessed by using the Dubowitz examination or its
modification by Ballard.

Progressive signs of respiratory distress are noted soon after birth and include the following:
o

Tachypnea

Expiratory grunting (from partial closure of glottis)

Subcostal and intercostal retractions

Cyanosis

Nasal flaring

Extremely immature in neonates may develop apnea and/or hypothermia.

Several diagnoses may coexist and complicate the course of respiratory distress syndrome, including the
following:
o

Pneumonia is usually secondary to group B beta-hemolytic streptococci and often coexists with
respiratory distress syndrome.

Metabolic problems (eg, hypothermia, hypoglycemia) may occur.

Hematologic problems (eg, anemia, polycythemia, jaundice) may occur.

Transient tachypnea of the newborn usually occurs in term or near-term neonates, often after
cesarean delivery. The chest radiograph of an infant with transient tachypnea shows good lung
expansion and, often, fluid in the horizontal fissure.

Aspiration syndromes may result from aspiration of amniotic fluid, blood, or meconium. Aspiration
syndrome is observed in more mature infants and is differentiated by obtaining a history and by
viewing the chest radiographs.

Pulmonary air leaks (eg, pneumothorax, interstitial emphysema, pneumomediastinum,

pneumopericardium) may occur. In premature infants, these complications may be due to excessive
positive-pressure ventilation. In rare cases, spontaneous pneumothorax may occur in large infants.

Congenital anomalies of the lungs (eg, diaphragmatic hernia, chylothorax, congenital cystic
adenomatoid malformation of the lung, lobar emphysema, bronchogenic cyst, pulmonary
sequestration) and heart (eg, cardiac anomalies) are uncommon in premature infants. These
entities can be diagnosed on the basis of chest radiographic or echocardiographic findings. On rare
occasions, they coexist with respiratory distress syndrome.

Causes

The greatest risk factor for respiratory distress syndrome is prematurity.

Other risk factors include maternal diabetes, cesarean delivery, and asphyxia.

Not all prematurely born newborn infants develop respiratory distress syndrome.

Surfactant deficiency and risk factors are outlined in History.

Differential Diagnoses
Anemia, Acute
Aspiration Syndromes
Gastroesophageal Reflux
Hypoglycemia
Hypothermia, Circulatory Arrest and Cardiopulmonary Bypass
Pneumomediastinum
Pneumonia

Pneumothorax
Polycythemia
Sudden Infant Death Syndrome
Transient Tachypnea of the Newborn

Other Problems to Be Considered

Pneumonia
Metabolic problems
Hematologic problems
Transient tachypnea
Aspiration syndromes
Pulmonary air leaks
Congenital anomalies of the lungs
Workup
Laboratory Studies

Blood gases are usually obtained in respiratory distress syndrome (RDS), as clinically indicated, from an
indwelling peripheral or central (umbilical) arterial catheter or by means of arterial puncture. In a multicenter

study by Billman and colleagues, an in-line, ex-vivo point-of-care monitor was shown to be reliable in critically
ill neonates and infants.2 It can be reliably used without adverse consequences associated with serial
phlebotomy.

Blood gases show respiratory and metabolic acidosis along with hypoxia.
o

Respiratory acidosis occurs because of alveolar atelectasis and/or overdistension of terminal

airways.

Metabolic acidosis is primarily lactic acidosis, which results from poor tissue perfusion and
anaerobic metabolism.

Hypoxia occurs from right-to-left shunting of blood through the pulmonary vessels, patent ductus
arteriosus (PDA), and/or patent foramen ovale.

Pulse oximetry is used as a noninvasive tool to monitor oxygen saturation, which should be maintained at 9095%. However, it is unreliable for determining hyperoxia because of the flat-top portion of the S -shaped
oxygen-hemoglobin dissociation curve. In the past, continuous, in-line arterial partial pressure of oxygen
(PaO2) monitoring and transcutaneous monitoring was used. Transcutaneous CO 2 monitors should be used in
infants with ongoing respiratory distress to monitor ventilation if it correlates with paCO 2 .

Imaging Studies

Chest radiographs of a newborn infant with respiratory distress syndrome reveal bilateral, diffuse reticular
granular or ground-glass appearances, air bronchograms, and poor lung expansion (see Media file 6).

Chest radiographs in a premature infant with respiratory distress syndrome before and after
surfactant treatment. Left: Initial radiograph shows poor lung expansion, air bronchogram, and
reticular granular appearance. Right: Repeat chest radiograph obtained when the neonate is aged
3 hours and after surfactant therapy demonstrates marked improvement.
[ CLOSE WINDOW ]

Chest radiographs in a premature infant with respiratory distress syndrome before and after surfactant
treatment. Left: Initial radiograph shows poor lung expansion, air bronchogram, and reticular granular
appearance. Right: Repeat chest radiograph obtained when the neonate is aged 3 hours and after
surfactant therapy demonstrates marked improvement.

The prominent air bronchograms represent aerated bronchioles superimposed on a background of

collapsed alveoli.

The cardiac silhouette may be normal or enlarged. Cardiomegaly may be the result of prenatal
asphyxia, maternal diabetes, PDA, an associated congenital heart anomaly, or simply poor lung
expansion.

These findings may be altered with either early surfactant therapy (see Media file 6) or a PDA or with
mechanical ventilation.

The radiologic findings of respiratory distress syndrome cannot be reliably differentiated from those
of pneumonia, which is most commonly caused by group B beta-hemolytic streptococci. If the
radiograph shows streaky opacities, the diagnosis of Ureaplasma orMycoplasma pneumonia should
be considered and confirmed by means of tracheal aspirate cultures grown in the appropriate
medium.

Echocardiographic evaluation is performed in selected infants to assist in diagnosing PDA and in determining
the direction and degree of shunting on Doppler study. It is also useful in diagnosing pulmonary hypertension,
assessing cardiac function, and excluding structural heart disease.

Other Tests

Although pulmonary mechanics testing (PMT) has primarily been used as a research tool in the past, newer
ventilators are equipped with PMT capabilities to assist the neonatologist in adequately managing the
changing pulmonary course of premature newborn infants with respiratory distress syndrome.

Constant PMT may be helpful in preventing volutrauma due to alveolar and airway overdistension. Monitoring
may also facilitate weaning the infant from the ventilator after surfactant therapy or in determining if the
infant can be extubated. However, clinical studies of PMT to date have not proven its long-term outcome
benefits in neonates with respiratory distress syndrome.

Infants with respiratory distress syndrome have substantially decreased lung compliance with a range of
0.0005-0.0001 L/cm H2 O. Therefore, for the same pressure gradient, the delivered tidal volume is reduced
in premature infants with respiratory distress syndrome compared with healthy newborn infants.
o

Pulmonary compliance may considerably improve after surfactant administration. Hence, the
patient's lung compliance and end-expiratory tidal volume should be monitored closely after
surfactant therapy, and the peak inspiratory pressure should be adjusted accordingly.

The resistance (airway and tissues) may be normal or increased. The time constant and the
corresponding pressure and volume equilibration are shortened. The anatomic dead space and the
functional residual capacity are increased.

Procedures

Sedation, analgesia, or anesthesia whenever feasible

Arterial puncture, venous puncture, and capillary blood sampling

Vascular access
o

Intravenous line placement

Umbilical arterial catheterization

Umbilical artery cut down

Peripheral artery cannulation

Umbilical venous catheterization

Tracheal intubation or tracheostomy

Bronchoscopy

Placement of thoracotomy tubes

Placement of pericardial tubes

Placement of gastric tubes

Transfusion of blood, blood products, and exchange transfusion

Lumbar puncture

Suprapubic bladder aspiration and bladder catheterization

Histologic Findings

See Pathophysiology and Media file 2.

Microscopic appearance of lungs of an infant with respiratory distress syndrome. Hematoxylin

and eosin stain shows hyaline membranes (pink areas).
[ CLOSE WINDOW ]

Microscopic appearance of lungs of an infant with respiratory distress syndrome. Hematoxylin and eosin
stain shows hyaline membranes (pink areas).
Treatment
Medical Care

Prenatal prevention and prediction of respiratory distress syndrome (RDS)

o

Obstetricians with experience in fetal medicine should care for mothers whose infants are at an
increased risk for respiratory distress syndrome, preferably at a tertiary perinatal center. Strategies
to prevent premature birth include bed rest, tocolytics, antibiotics, and antenatal steroids.

The following has been reported with the use of antenatal corticosteroids:

One course of antenatal corticosteroids reduces the risk of respiratory distress syndrome
and neonatal death; however, in a recent Canadian study of 1858 women at 25-32 weeks'
gestation who remained undelivered after a single course of antenatal corticosteroids,
multiple courses did not improve outcomes and were associated with decrease in weight,
length, and head circumference at birth. 3 In another trial in which a single repeat dose of
prenatal betamethasone treatment was given in women with imminent preterm birth before
34 weeks' gestation, the requirement for surfactant therapy was increased. However, in
contrast, several large clinical trials in which much higher fetal corticosteroid exposure
occurred showed benefit with less severe lung disease and no increased risks.

The increased incidence of cerebral palsy in the study from Wapner and associates could
be avoided by limiting retreatment to less than 4 weekly treatments. 4 The results of the
studies from Crowther and colleagues and Wapner and associates are not consistent with
the result of the other strategy (ie, a single treatment when delivery is
imminent).5 Nevertheless, these weekly retreatment trials demonstrate considerable safety
for retreatment. Other trials with different retreatment intervals are in progress.

Corticosteroid treatment at recognition of a risk of preterm delivery is indicated. If the

mother does not deliver within 1 week, retreatment may be considered; most
perinatologists administer a single, 12-mg dose of betamethasone, rather than 2 doses.

Clinical judgment should be used about the risk for preterm delivery before any repeat
dose is administered. If cervical dilation or signs of labor persist, a repeat dose may help.
If the pregnancy appears to be at lower risk, retreatment may be deferred. Multiple
retreatment (>4 times) may increase risk; however, the effect of corticosteroid retreatment
for the risk of preterm delivery remains unclear.

Tests to predict fetal lung maturity are done by estimating the lecithin-to-sphingomyelin ratio and/or
by the presence of phosphatidylglycerol in the amniotic fluid obtained with amniocentesis. Antenatal
diagnosis of SP-B deficiency, a rare genetic disease, can also be antenatally diagnosed by analyzing
the amniotic fluid; this diagnostic testing should be undertaken in previously affected siblings.

Delivery and resuscitation: A neonatologist experienced in the resuscitation and care of premature infants
should attend the deliveries of fetuses born at less than 28 weeks' gestation. These neonates are at a high
risk for maladaptation, which further inhibits surfactant production. In the delivery room, continuous nasal
positive airway pressure (CPAP) is often used in spontaneously breathing premature infants immediately after
birth as a potential alternative to immediate intubation and surfactant replacement to minimize the severity
of bronchopulmonary dysplasia (BPD). Several centers have reported success with the use of nasal bubble
CPAP to decrease the complications associated with intubation and mechanical ventilation. 6,7 By avoiding
intubation, lung injury may be diminished.

Surfactant replacement therapy

o

The mortality rate of respiratory distress syndrome decreased by approximately 50% over the last
decade with the advent of surfactant therapy.

Meta-analysis of clinical trials comparing early natural and synthetic surfactant therapy versus
controls showed a decrease in air leaks. Meta-analysis of comparisons of early versus delayed
selective treatment for neonatal respiratory distress syndrome suggested a decrease in pulmonary
air leaks and chronic lung disease. Early surfactant therapy in tiny neonates followed by rapid
extubation to nasal CPAP decreased the need for and duration of mechanical ventilation and
decreased the rate of pulmonary air leakage and 28-day mortality compared with selective
surfactant therapy in respiratory distress syndrome followed by ventilation. Rates of pulmonary

hemorrhage, necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), intraventricular

hemorrhage (IVH), periventricular leukomalacia (PVL), and BPD did not differ between the groups.
o

Neonates with respiratory distress syndrome who require assisted ventilation with a fraction of
inspiratory oxygen (FIO2) of >0.40 should receive intratracheal surfactant as soon as possible,
preferably within 2 hours after birth.

Stevens et al used meta-analysis of 6 studies to assess if early surfactant therapy with extubation
to nasal CPAP is associated with a decrease in the need for mechanical ventilation, air leak, and
BPD compared with later selective surfactant replacement and continued mechanical ventilation with
extubation from low ventilator support. 8 They concluded that treatment with surfactant by transient
intubation using a low treatment threshold (FIO 2 <0.45) is preferable to later, selective surfactant
therapy by transient intubation using higher threshold for study entry (FIO 2 >0.45) or at the time of
respiratory failure and initiation of mechanical ventilation. Extremely premature neonates
administered surfactant in the delivery room may have improvement in short-term outcomes and
milder BPD.

Because surfactant is protective to the immature lungs, several investigators have recommended its
prophylactic use after resuscitation in extremely premature neonates (<27 weeks' gestation). Also,
pulmonary inflammation leads to leakage of proteins inactivating the surfactant, damaging the
surfactant phospholipids and fatty acids, affecting hydrolytic activity on surfactant proteins by
proteolytic enzymes, and decreasing synthesis of surfactant by type II cells after oxidant injury.

In developing countries, surfactant is expensive and unnecessary in most instances because more
than 60% of premature infants do not have surfactant deficiency; they are intubated with its inherent
risks. Instead, nasal bubble CPAP has been widely used in recent years to manage respiratory
distress syndrome and apnea of prematurity.

Premature neonates with surfactant deficiency and respiratory distress syndrome have an alveolar
pool of about 5 mg/kg. Full-term animal models have pools of 50-100 mg/kg. Recommended
dosages of clinically available surfactant preparations are 50-200 mg/kg, approximately the
surfactant pool of term newborn lungs. Rapid bolus administration of surfactant after adequate lung
recruitment with 3-4 cm of positive end-expiratory pressure (PEEP) and adequate positive pressure
may improve its homogeneous distribution. Most neonates require 2 doses; however, as many as 4
doses given at 6-hour to 12-hour intervals were used in several clinical trials. If the patient rapidly
improves after 1 dose, respiratory distress syndrome is unlikely. Conversely, in infants who have a
poor or no response, patent ductus arteriosus (PDA), pneumonia, and complications of ventilation
(air leak) should be excluded, especially before subsequent surfactant doses are given.

Tables 1-6 summarize some complications from a meta-analysis of several clinical trials conducted
worldwide. Clinical trials showed fewer complications and more rapid improvement in the infant's
respiratory status using protein-containing natural surfactants compared with synthetic surfactants.
Currently marketed natural surfactants have various amounts of phospholipids (mostly desaturated
phosphatidylcholine) and apoprotein B and C but not apoprotein A and D. Apoprotein A and D may
be important for host defense. Table 7 shows the source, composition, and dosages of several
surfactant preparations.

The ideal surfactant preparation to treat premature infants with respiratory distress syndrome and
its sequelae has not been identified.

Two large international trials studied the KL4 polypeptide, Surfaxin, which has not yet been
approved by the US Food and Drug Administration (FDA). 9,10 The studies had several limitations
including the following:

They were designed as "equivalent to the approved surfactant products" studies,

presumably to satisfy product licensing requirements rather than to evaluate the role of

various surfactant components. In one study, Surfaxin was compared with colfosceril
palmitate, which has been discontinued. The second study was halted halfway and was
thus underpowered to establish equivalency of KL4 with Poractant.

Most patients were enrolled in centers outside the United States experienced in
conducting research. Data regarding the participation rate at each center and regarding the
range of outcome varied among the 55 and 22 centers in the 2 respective studies.

The dose of phospholipid ranged from 67.5-76 mg/kg, and the volume varied from 2.2-5.5
mL among the participating centers. This was apparently done for obtaining licensing
requirements to compare with existing surfactant products. Furthermore, KL4 polypeptide
does not lipid-associate as readily as SP-B and SP-C. Lucinactant forms a gel in its storage
form and must be heated to 44C and shaken before administration and placed on a
special heating block prior to administration. The metabolism reuptake of KL4 polypeptide
by type II pneumocyte and its interaction with natural surfactant in these infants is unclear.

In 2 reviews, Notter and Kresch et al summarized data from extensive biophysical studies, in vitro
and whole-animal biochemical studies, molecular and physiologic studies, and several large
international clinical trials.11,12

Oxygenation and CPAP

o

CPAP was introduced as the primary therapeutic modality when Gregory et al demonstrated a
marked reduction in respiratory distress syndrome mortality. 13 Oxygen was the primary therapeutic
mode before the introduction of CPAP.

Oxygen is administered a hood, nasal canula or in the isolette to treat infants with mild respiratory
distress syndrome or after discontinuation of CPAP or assisted ventilation.

CPAP keeps the alveoli open at the end of expiration, decreasing the right-to-left pulmonary shunt.

CPAP is often administered using nasal prongs. In the Cochrane database review, devices and
pressure sources for administration of nasal CPAP were assesed. 7 Short binasal-prongs devices
were found to be more effective than single prongs and also reduced the rate of reintubation.

A meta-analysis of studies on prophylactic use of nasal CPAP for preventing morbidity and mortality
in very preterm infants concluded that intermittent positive pressure ventilation (IPPV) was not
beneficial.14

In a study of nasal CPAP in infants born at less than 27 weeks' gestation in a retrospective,
observational study in one hospital, the probability of an individual baby remaining on nasal CPAP
was 66% (95% confidence interval [CI], 46-86%) on day 1 and 80% (95% CI, 60-99%) on day 2. 15

In a recent trial, 610 infants born at 25-28 weeks' gestation were randomly assigned to CPAP or
intubation 5 minutes after birth, their outcomes were assessed at age 28 days, at age 36 weeks,
and before discharge.16 These investigators found no reduction in death or BPD with early nasal
CPAP; the CPAP group had an increase in the incidence of pneumothorax (9% vs 3%) but also fewer
days on ventilator and fewer infants receiving oxygen at age 28 days.

Recently, Pillow and her colleagues have suggested that bubble CPAP promotes enhanced airway
patency during treatment of acute postnatal respiratory disease in preterm lambs. 17 Whether the
findings of this animal model of respiratory distress syndrome, wherein the nares length and gas
flow pattern is considerably different, can be mirrored to prematurely born infants is unclear. Air leak
from nasal prongs may also alter the findings.

CPAP is an adjunct therapy given after surfactant if prolonged assisted ventilation is not required.
Use of nasal CPAP after initial surfactant therapy has been successful in some infants. In a
retrospective study, bubble nasal CPAP was successful in 76% of infants who weighed less than
1250 g and in 50% of infants who weighed less than 750 g.18

CPAP may be used after extubation in individuals with respiratory distress syndrome to prevent
atelectasis and prevent apnea in premature infants. A randomized control trial compared
postextubation bubble CPAP with infant flow driver CPAP in preterm infants with respiratory distress
syndrome;6 although both were equally effective, bubble CPAP is associated with a significantly
higher rate of successful extubation and reduced duration of CPAP in infants younger than 14 days.

The goal of therapy for patients with respiratory distress syndrome is to maintain a pH of 7.25-7.4,
a PaO2 of 50-70 mm Hg, and a carbon dioxide pressure (PCO 2) of 40-65 mm Hg, depending on the
infant's clinical status.

Vapotherm: Vapotherm with heated and humidified high-flow nasal canula (>2 L/min) has been used for
respiratory support of neonates and to facilitate early extubation. 19 Neonatal units in the United States and
United Kingdom use Vapotherm as a means of providing respiratory support. This device allows the delivery
of high flows of gas at body temperature with close to 100% relative humidity. Evidence suggests that
Vapotherm may be an effective and well-tolerated method of providing babies with respiratory support. It has
numerous advantages over therapies such as nasal CPAP, including a reduction in the number of ventilator
days and reduced nasal trauma. It may be better tolerated than other forms of noninvasive respiratory
therapy. Some evidence suggests that weight gain is improved using Vapotherm and that oral feeding can be
introduced earlier. Further research is required, especially into the methods of weaning Vapotherm and, as
with all neonatal treatments, the long-term effects.

Assisted ventilation
o

Kirby and deLemos introduced assisted ventilation several decades ago. 20 Assisted ventilation
further decreased respiratory distress syndromerelated morbidity and mortality; however, early
ventilators were associated with complications, such as air leaks, BPD (secondary to barotrauma or
volutrauma), airway damage, and intraventricular hemorrhage. Advances in microprocessor-based
technology, transducers, and real-time monitoring have enabled patient-driven ventilator control and
synchronization of mechanical ventilation with patient effort. The novelty of the newer ventilation
techniques has generated controversies that remain to be resolved. Among these are signal
detection and transduction, optimal volume delivery (ventilation modes), and weaning from
mechanical ventilation.

Consider ventilation as a necessary physiologic support while the infant recovers from respiratory
distress syndrome. Several investigators suggested that permissive hypercapnia with arterial partial
pressure of carbon dioxide (PaCO2) of 45-55 mm Hg (with adequate lung volume) may facilitate
weaning during recovery from respiratory distress syndrome. To minimize the complications of
conventional intermittent mandatory ventilation, new ventilation techniques have been introduced,
as described below.

Synchronous intermittent mandatory ventilation is a technique in which some of the patient's

respirations are synchronized with breaths the ventilator deliver. In a randomized controlled trial, the
incidence of BPD (defined as oxygen requirement at a corrected gestational age of 36 wk) was
significantly reduced with this therapy compared with standard intermittent mandatory ventilation
(47% vs 72%, P < .05). Another study involved neonates born at 28-34 weeks gestational age with
respiratory distress syndrome who required surfactant with early extubation to synchronous,
intermittent positive-pressure ventilation. The duration of intubation was shortened and the need for
oxygen was decreased with this strategy compared with conventional ventilation.

Assist-control ventilation has been suggested to improve outcomes. In a comparison of pressureregulated volume control and the assist-control mode of ventilation from birth, the time to
extubation was not altered in infants with respiratory distress syndrome.

Some physicians use pressure-support ventilation to wean infants who develop chronic lung
changes. Further studies are required to evaluate its long-term benefits.

High-frequency ventilation (HFV)

o

With high-frequency ventilation (HFV), small tidal volumes (less than anatomic dead space) are
usually delivered at rapid frequencies, thus eliminating wide pressure swings seen with conventional
ventilators. These modes of ventilation received attention because the high tidal volumes, wide
pressure swings, and the resultant pulmonary trauma and cardiovascular compromise are believed
to be major contributing factors associated with mechanical ventilation.

HFV was originally designed to treat patients with air leak. Many studies in animal models of
respiratory distress syndrome demonstrated that HFV promoted uniform lung inflation; improved
lung mechanics and gas exchange; and reduced exudative alveolar edema, air leak, and lung
inflammation.

Early use of high-frequency oscillatory ventilation (HFOV) was clearly superior to conventional
ventilation. Several clinical trials showed that prophylactic HFOV may reduce the incidence of chronic
lung disease. Adequate clinical trials controlled for resuscitation techniques, time and type of
surfactant therapy, and similar strategies with the same types of HFV versus synchronous
intermittent mandatory ventilation are awaited to evaluate short-term and long-term respiratory and
neurologic outcomes.

HFV techniques involve a learning curve, and optimal ventilator strategies vary with the stage of
respiratory distress syndrome.

The HFV techniques are as follows:

High-frequency oscillatory ventilation (10-15 Hz): Because expiration actively occurs,

monitor patients for hypocarbia to prevent periventricular leukomalacia (PVL). Controlled
trials of HFOV to reduce BPD in infants with respiratory distress syndrome have been
controversial because of the varied types of ventilators used, time of recruitment,
differences in surfactant treatment, management of PDA and fluids. The unfavorable
outcome of HFOV in some studies has been attributed to (1) a low incidence of BPD with
antenatal steroid use and, therefore, an inadequate sample size to detect a difference; (2)
use of a suboptimal lung volume strategy in patients treated with HFOV; (3) definition and
differences in chorioamnionitis; and (4) differences in resuscitation techniques at birth.

High-frequency jet ventilation: Its frequency range is 4-11 Hz (usually 7 Hz). This treatment
has to be used in tandem with conventional ventilation to provide PEEP and sigh breaths. It
decreases air leaks. Because the solenoid valves open intermittently to provide jet
breaths, some neonatologists prefer to use high-frequency jet ventilation to treat infants
with pulmonary air leaks.

High-frequency flow interrupter: Its frequency range is 6-15 Hz, with the advantages of a
built-in conventional ventilator and an ability to provide sigh breaths. Its use is also
associated with a decreased incidence of air leaks in infants with RDS.

Nitric oxide (NO)

Although inhaled NO (iNO) is a safe and effective treatment for near-term and term newborn infants
with pulmonary hypertension and hypoxic respiratory failure, its role in premature infants with
respiratory distress is ill defined.

It has selective pulmonary vasodilation and, in premature infants, may have a role in decreasing
inflammation, reducing oxidative stress, and enhancing alveolarization and lung growth.

The effects of iNO in premature newborn infants with respiratory distress syndrome may be
dependent on the timing, dose and duration of iNO therapy, and the extent of the infant's lung
disease. Results of several clinical trials are summarized in the tables below.

Some evidence suggests that low-dose iNO may be safe and effective in reducing the risk of death
and BPD for a subset of premature infants with birth weight less than 1000 g. Also, a
neuroprotective effect of iNO has been demonstrated in large randomized clinical trials, although its
exact relationship and mechanism of action is unclear.

Hintz et al reported no improvement in the neurodevelopmental outcome at a mean corrected age of

20 months in premature infants with birth weight less than 1500g and severe respiratory failure
enrolled in a randomized, controlled trial of iNO. 1 They suggested that routine use of iNO in
premature infants should be limited to research settings. However, they lost more than 50% of their
patients to follow-up; therefore, interpretation of these results is difficult.

In premature neonates born at less than 32 weeks' gestation with respiratory distress syndrome
and hypoxic respiratory failure, low pulmonary blood flow, as determined with Doppler
echocardiography, may be helpful in determining which patients are likely to benefit from iNO
therapy.

Supportive therapy
o

Temperature regulation: Hypothermia increases oxygen consumption, further compromising

neonates with respiratory distress syndrome who are born prematurely. Therefore, prevent
hypothermia in neonates with respiratory distress syndrome during delivery, resuscitation, and
transport. Care for these patients in a neutral thermal environment with the use of a double-walled
incubator or radiant warmer.

Fluids, metabolic, and nutritional support

In infants with respiratory distress syndrome, initially administer 5% or 10% dextrose

intravenously at a rate of 60-80 mL/kg/d. Closely monitor blood glucose (with Dextrostix
testing), electrolytes, calcium, and phosphorous levels, as well as renal function, and
hydration (as determined by body weight and urine output) to prevent any imbalance. Add
calcium at birth to the initial intravenous fluid. Intravenous sodium bicarbonate is often
misused and is considered an unproven therapy. Electrolytes should be added as soon as
the patient voids and as indicated by estimated serum electrolyte levels. Gradually
increase fluid intake to 120-140 mL/kg/d. Extremely premature infants occasionally
require fluid intake of 200-300 mL/kg or more because of insensible water loss occurring
from their large body surfaces.

After the neonate is stable, intravenous nutrition with amino acids and lipid are
commenced within 24-48 hours of birth. As soon as the patient can tolerate oral feedings,
trophic feeding with small volumes (preferably breast milk) is commenced by using the
orogastric tube to stimulate gut development. Gastric feedings are increased as tolerated,
and intravenous nutritional support is decreased proportionately to maintain adequate fluid
and calorie intake. Recent data suggest that adequate supply of macronutrients,

micronutrients, vitamins, and antioxidants should be provided to maintain optimal lung,

brain, eye, and somatic growth.

Circulation and anemia: Assess the baby's circulatory status by monitoring his or her heart rate,
peripheral perfusion, and blood pressure. Administer blood or volume expanders, and use
appropriate vasopressors to support circulation. Closely monitor blood withdrawn for laboratory
tests in tiny patients and replace the blood with packed-cell transfusion when it reaches 10% of the
patient's estimated blood volume or if the hematocrit level is less than 40-45%. Anemia and blood
loss can be minimized by using placental transfusion at delivery, by limiting blood loss with in vivo
blood gas and electrolyte estimations, and by using erythropoietin with iron in extremely premature
neonates.

Antibiotic administration: Start antibiotics in all infants who present with respiratory distress at birth
after blood cultures, a CBC count with differential, and C-reactive protein levels are obtained.
Discontinue antibiotics after 2-5 days if blood cultures are negative and if no maternal risk factors
are found. Exceptions to the use of antibiotics include the absence of clinical or laboratory findings
suggestive of chorioamnionitis, adequate antenatal care, and a recent negative maternal cervical
culture for group B beta-hemolytic streptococci or a baby delivered by a mother with intact amniotic
membranes.

Support of parents and family

Parents often undergo much emotional and/or financial stress with the birth of a critically
ill premature baby with respiratory distress syndrome and its associated complications.
The parents may feel guilty, they may be unable to relate to the neonate in the intensive
care setting, and they may be anxious about their child's prognosis. In addition, the baby
may be unable to provide adequate cues to arouse mothering. These factors interact to
prevent maternal-infant bonding. Hence, provide adequate support for parents and other
family members to prevent or minimize these problems.

Staff members (preferably a physician and a nurse) should keep the parents well informed
by frequently talking to them, especially during the acute stage of respiratory distress
syndrome. Encourage parents and assist them in frequently visiting their child. Explain the
equipment and procedures to the parents, and encourage them to touch, feed, and care
for their baby as soon as possible. Before the patient is discharged from the hospital, he
or she is immunized, and follow-up care is arranged with a multidisciplinary team and
coordinated by a pediatrician experienced in the care of problems of premature infants.

Summary
o

Tables 1-6 summarize some of the complications from a meta-analysis of several clinical trials
conducted worldwide. Table 7 summarizes features of available surfactant preparations.

Table 1. Results of a Meta-Analysis of Separate Clinical Trials of the Treatment of

Respiratory Distress Syndrome With Natural or Synthetic Surfactant Preparations
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Table

Outcome

Natural Surfactant Treatment

Number of
Relative Risk (95% CI)
Trials
Relative Difference (95% CI)

Synthetic Surfactant Treatmen

Number of
Relative Risk (95%
Trials
Relative Difference (9

Pneumothorax
BPD
Mortality
BPD or death

Outcome
Pneumothorax
BPD
Mortality
BPD or death

12

0.43 (0.35, 0.52)

-17% (-21%, -13%)
9
0.94 (0.72, 1.22)
-2% (-9%, 4%)
12
0.68 (0.57, 0.80)
-9% (-13%, -5%)
10
0.76 (0.65, 0.90)
-14% (-21%, -7%)
Natural Surfactant Treatment
Number of
Relative Risk (95% CI)
Trials
Relative Difference (95% CI)
12
0.43 (0.35, 0.52)
-17% (-21%, -13%)
9
0.94 (0.72, 1.22)
-2% (-9%, 4%)
12
0.68 (0.57, 0.80)
-9% (-13%, -5%)
10
0.76 (0.65, 0.90)
-14% (-21%, -7%)

0.64 (0.55, 0.76

-9% (-12%, -6%)
5
0.75 (0.61, 0.92
-4% (-6%, -1%)
6
0.73 (0.61, 0.88
-5% (-7%, -2%)
4
0.73 (0.65, 0.83
-8% (-11%, -5%)
Synthetic Surfactant Treatmen
Number of
Relative Risk (95%
Trials
Relative Difference (9
5
0.64 (0.55, 0.76
-9% (-12%, -6%)
5
0.75 (0.61, 0.92
-4% (-6%, -1%)
6
0.73 (0.61, 0.88
-5% (-7%, -2%)
4
0.73 (0.65, 0.83
-8% (-11%, -5%)

Table 2. Results of a Meta-Analysis of Separate Clinical Trials of the Prophylactic Use of

Natural or Synthetic Surfactant Preparations
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Table

Outcome
Pneumothorax
BPD
Mortality
BPD or death

Outcome
Pneumothorax
BPD
Mortality
BPD or death

Natural Prophylaxis
Relative Risk (95% CI)
Relative Difference (95% CI)
0.35 (0.26, 0.49)
-13% (-20% -11%)
7
0.93 (0.80, 1.07)
-4% (-9%, -3%)
7
0.60 (0.44, 0.83)
-7% (-12%, -3%)
7
0.84 (0.75, 0.93)
-10% (-16%, -4%)
Natural Prophylaxis
Number of
Relative Risk (95% CI)
Trials
Relative Difference (95% CI)
8
0.35 (0.26, 0.49)
-13% (-20% -11%)
7
0.93 (0.80, 1.07)
-4% (-9%, -3%)
7
0.60 (0.44, 0.83)
-7% (-12%, -3%)
7
0.84 (0.75, 0.93)
-10% (-16%, -4%)
Number of
Trials
8

Synthetic Prophylaxis
Number of
Relative Risk (95%
Trials
Relative Difference (9
6
0.67 (0.50, 0.90
-5% (-9%, -2%)
4
1.06 (0.83, 1.36
1% (-4%, 6%)
7
0.70 (0.58, 0.85
-7% (-11%, -3%)
4
0.80 (0.77, 1.03
-4% (-10%, 1%)
Synthetic Prophylaxis
Number of
Relative Risk (95%
Trials
Relative Difference (9
6
0.67 (0.50, 0.90
-5% (-9%, -2%)
4
1.06 (0.83, 1.36
1% (-4%, 6%)
7
0.70 (0.58, 0.85
-7% (-11%, -3%)
4
0.80 (0.77, 1.03
-4% (-10%, 1%)

Table 3. Results of a Meta-Analysis of Head-to-Head Trials With Natural Versus Synthetic

Surfactants

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Table
Outcome
Pneumothorax
BPD
Mortality
BPD or death
Outcome
Pneumothorax
BPD
Mortality
BPD or death

Number of
Trials
5
4
7
2
Number of
Trials
5
4
7
2

Relative Risk
(95% CI)
0.68 (0.56, 0.83)
0.97 (0.88, 1.07)
0.88 (0.76, 1.02)
0.94 (0.87, 1.01)
Relative Risk
(95% CI)
0.68 (0.56, 0.83)
0.97 (0.88, 1.07)
0.88 (0.76, 1.02)
0.94 (0.87, 1.01)

Relative Difference
(95% CI)
-4.1% (-6.3%, -2.0%)
-1.2% (-5.4%, -2.9%)
-2.2% (-4.7%, 0.4%)
-3.6% (-8.0%, 0.8%)
Relative Difference
(95% CI)
-4.1% (-6.3%, -2.0%)
-1.2% (-5.4%, -2.9%)
-2.2% (-4.7%, 0.4%)
-3.6% (-8.0%, 0.8%)

Table 4. Meta-Analysis of Clinical Trials Comparing Prophylactic Use of Surfactant Versus

Rescue Treatment of Infants With Respiratory Distress Syndrome
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Table
Outcome
Pneumothorax
BPD
Mortality
BPD or death
Infants <30 wk of gestation
Mortality
BPD or death
Outcome
Pneumothorax
BPD
Mortality
BPD or death
Infants <30 wk of gestation
Mortality
BPD or death

Number of
Trials
6
7
6
7

Relative Risk
(95% CI)
0.62 (0.42, 0.89)
0.95 (0.81, 1.11)
0.59 (0.46, 0.76)
0.85 (0.76, 0.95)

Relative Difference
(95% CI)
-2.1% (-3.7%, -0.55)
-0.9% (-3.5%, 1.7%)
-4.6% (-6.8%, -2.5%)
-4.5% (-7.4%, -1.5%)

6
7
Number of
Trials
6
7
6
7

0.60 (0.47, 0.77)

0.86 (0.77, 0.96)
Relative Risk
(95% CI)
0.62 (0.42, 0.89)
0.95 (0.81, 1.11)
0.59 (0.46, 0.76)
0.85 (0.76, 0.95)

-6.5% (-9.6%, -3.4%)

-5.5% (-9.6%, -1.5%)
Relative Difference
(95% CI)
-2.1% (-3.7%, -0.55)
-0.9% (-3.5%, 1.7%)
-4.6% (-6.8%, -2.5%)
-4.5% (-7.4%, -1.5%)

6
7

0.60 (0.47, 0.77)

0.86 (0.77, 0.96)

-6.5% (-9.6%, -3.4%)

-5.5% (-9.6%, -1.5%)

Table 5. Results of a Meta-Analysis of Early Versus Delayed Treatment of Respiratory

Distress
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Table
Outcome
Pneumothorax
BPD
Mortality
BPD or death
Outcome
Pneumothorax
BPD
Mortality
BPD or death

Number of
trials
3
3
4
3
Number of
trials
3
3
4
3

Relative Risk
(95% CI)
0.70 (0.59, 0.82)
0.97 (0.88, 1.06)
0.87 (0.77, 0.99)
0.94 (0.88, 1.00)
Relative Risk
(95% CI)
0.70 (0.59, 0.82)
0.97 (0.88, 1.06)
0.87 (0.77, 0.99)
0.94 (0.88, 1.00)

Relative Difference
(95% CI)
-5.2% (-7.5%, -2.9%)
-1.2% (-4.6%, 2.2%)
-2.8% (-5.5%, 0.0%)
-3.7% (-7.2%, 0.0%)
Relative Difference
(95% CI)
-5.2% (-7.5%, -2.9%)
-1.2% (-4.6%, 2.2%)
-2.8% (-5.5%, 0.0%)
-3.7% (-7.2%, 0.0%)

Table 6. Results of a Meta-Analysis of Clinical Trials to Compare Multiple Doses With a

Single Dose of Surfactant
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Table
Outcome
Pneumothorax
BPD
Mortality
BPD or death
Outcome
Pneumothorax
BPD
Mortality
BPD or death

Number of
Trials
2
1
2
1
Number of
Trials
2
1
2
1

Relative Risk
(95% CI)
0.51 (0.30, 0.88)
1.10 (0.63, 1.93)
0.63 (0.57, 1.11)
0.80 (0.57, 1.11)
Relative Risk
(95% CI)
0.51 (0.30, 0.88)
1.10 (0.63, 1.93)
0.63 (0.57, 1.11)
0.80 (0.57, 1.11)

Relative Difference
(95% CI)
-8.7% (-15.4%, -2.0%)
1.2% (-5.8%, 8.3%)
-7.0% (-14%, 0%)
-6.6%, (-16.2%. 3%)
Relative Difference
(95% CI)
-8.7% (-15.4%, -2.0%)
1.2% (-5.8%, 8.3%)
-7.0% (-14%, 0%)
-6.6%, (-16.2%. 3%)

Table 7. Type, Source, Composition, Dosages, and Other Information for Currently Available
Surfactant Preparations
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Table
Type
Beractant (Survanta)
Surfactant-TA (Surfacten)

Source
Composition
Dosing
Bovine lung Dipalmitoyl
4 mL/kg (100
mince
phosphatidylcholine (DPPC), mg/kg), 1-4 doses
tripalmitin, SP-B <0.5%, SP- every 6 h

Comm
Refrigerate

Bovactant (Alveofact)

C 99% of TP wt/wt
Bovine lung 99% PL, 1% SP-B and SP-C 45 mg/mL
lavage

From the F
Republic o
Germany
Bovine lipid extract surfactant
Bovine lung 75% PC and 1% SP-B and 135 mg/kg/dose (5 Canadian
(bLES)
lavage
SP-C
mL/kg), 1-4 doses
every 12 h
Infasurf
Calf lung
DPPC, tripalmitin, SP-B 290 3 mL/kg (105
6-mL vials
lavage
g/mL, SP-C 360 g/mL
mg/kg), 1-4 doses refrigerate
every 6-12 h
Calf lung surfactant extract (CLSE) Similar to Infasurf
Poractant alpha (Curosurf)
Minced pig Phospholipids (DPPC, PG), Initially 2.5 mL/kg 1.5 and 3
lung
neutral lipids, fatty acids;
(200 mg/kg),
SP-B and SP-C; 80 mg/mL followed by 1.25 mL
of PL/mL [54 mg PC (30.5 (100 mg)/kg
mg DPPC and 1 mg protein
includes 0.3 mg of SP-B)]
Colfosceril Palmitate (Exosurf)
Synthetic
85% DPPC, 9%
5 mL/kg (67.5
No longer
hexadecanol, 6% tyloxapol mg/kg),
available;
1-4 doses every 12 lyophilized
h
dissolve in
Lucinactant (Surfaxin)
Synthetic
Protein: KL4 (sinapultide)
175 mg/kg/dose
Not licens
resembles SP-B;
phospholipid
FDA; warm
Phospholipids: DPPC, POPG
15 min at
on a heati
followed b
vigorous s
until a uni
free-flowin
suspensio
Artificial lung expanding compound Synthetic
70% DPPC, 30%
No data
Discontinu
(ALEC)
unsaturated
phosphatidylglycerol
Type
Source
Composition
Dosing
Comm
Beractant (Survanta)
Bovine lung Dipalmitoyl
4 mL/kg (100
Refrigerate
mince
phosphatidylcholine (DPPC), mg/kg), 1-4 doses
Surfactant-TA (Surfacten)
tripalmitin, SP-B <0.5%, SP- every 6 h
C 99% of TP wt/wt
Bovactant (Alveofact)
Bovine lung 99% PL, 1% SP-B and SP-C 45 mg/mL
From the F
lavage
Republic o
Germany
Bovine lipid extract surfactant
Bovine lung 75% PC and 1% SP-B and 135 mg/kg/dose (5 Canadian
(bLES)
lavage
SP-C
mL/kg), 1-4 doses
every 12 h
Infasurf
Calf lung
DPPC, tripalmitin, SP-B 290 3 mL/kg (105
6-mL vials
lavage
g/mL, SP-C 360 g/mL
mg/kg), 1-4 doses refrigerate
every 6-12 h
Calf lung surfactant extract (CLSE) Similar to Infasurf
Poractant alpha (Curosurf)
Minced pig Phospholipids (DPPC, PG), Initially 2.5 mL/kg 1.5 and 3
lung
neutral lipids, fatty acids;
(200 mg/kg),
SP-B and SP-C; 80 mg/mL followed by 1.25 mL
of PL/mL [54 mg PC (30.5 (100 mg)/kg
mg DPPC and 1 mg protein
includes 0.3 mg of SP-B)]
Colfosceril Palmitate (Exosurf)
Synthetic
85% DPPC, 9%
5 mL/kg (67.5
No longer
hexadecanol, 6% tyloxapol mg/kg),
available;

Lucinactant (Surfaxin)

Synthetic

Artificial lung expanding compound Synthetic

(ALEC)

Protein: KL4 (sinapultide)

resembles SP-B;
Phospholipids: DPPC, POPG

70% DPPC, 30%

unsaturated
phosphatidylglycerol

1-4 doses every 12

h
175 mg/kg/dose
phospholipid

No data

lyophilized
dissolve in
Not licens
FDA; warm
15 min at
on a heati
followed b
vigorous s
until a uni
free-flowin
suspensio
Discontinu

Table 8. Inhaled Nitric Oxide Therapy in Preterm Infants and Outcome Measures
Open table in new window
[ CLOSE WINDOW ]
Table
Study

Number
Enrolled

Mean
Gestational
Age (wk)

Kinsella et
al 21
Schreiber et
al 22
Van Meurs et
al 23
Ballard et
al 24
Kinsella et
al 25
Study

80

Kinsella et
al 21
Schreiber et
al 22
Van Meurs et
al 23
Ballard et
al 24
Kinsella et
al 25
Consultations

Mean
Oxygen
Index

Placebo
Death
Rate

Therapy
duration
(d)

Maximum
dose

27

Mean
Birth
Weight
(g)
1000

% Cha
Death

30

53%

5 ppm

-1

201

27.2

970

10

22.5%

10 ppm

-1

420

26

839

22

44%

10 ppm

-2

587

26

760

6%

24

20 ppm

-1

793

25

792

25%

14

5 ppm

-4

Number
Enrolled

Mean
Gestational
Age (wk)

Mean
Oxygen
Index

Placebo
Death
Rate

Therapy
duration
(d)

Maximum
dose

80

27

Mean
Birth
Weight
(g)
1000

30

53%

5 ppm

-1

201

27.2

970

10

22.5%

10 ppm

-1

420

26

839

22

44%

10 ppm

-2

587

26

760

6%

24

20 ppm

-1

793

25

792

25%

14

5 ppm

-4

% Cha
Death

Premature infants with respiratory distress syndrome are prone to various complications. Appropriate
specialists may be consulted as indicated.

See fluids, metabolism, and nutrition in the Medical Care section.

Diet

Medication
The goals of pharmacotherapy in respiratory distress syndrome (RDS) are to reduce morbidity and prevent
complications.
Lung surfactants
Exogenous surfactant can be helpful in treating airspace disease (eg, respiratory distress syndrome [RDS]). After
inhaled administration of these agents, surface tension is reduced, and alveoli are stabilized to decrease the work of
breathing and increasing lung compliance.
In head-to-head clinical trials to compare synthetic surfactant with animal-derived preparations, animal-derived
surfactants were superior, with immediate benefits in pulmonary air leaks, intraventricular hemorrhage,
bronchopulmonary dysplasia (BPD), and mortality.
In recent years, the evolution of surfactants from modified animal surfactant has included use of selective peptide
sequences of SP-B; synthetic peptide mimics, including RL4 and KL4; modification of SP-C; and peptoids of SP-B and
SP-C, A number of studies have demonstrated the critical function of SP-B or specific SP-B peptide sequences in
pulmonary surfactant, particularly the highly conserved amino- and carboxyl-terminal sequences consisting of a repeat
arginine-lysine (R-L) motif (RL4).

Beractant (Survanta, Alveofact)

Natural/modified bovine lung extract that lowers surface tension on alveolar surfaces during respiration and stabilizes
alveoli against collapse at resting transpulmonary pressures. For ET use only. Survanta contains 10% SP-B.

Dosing

Interactions

Contraindications

Precautions

Adult
Pediatric
ET: 4 mL/kg (100 mg/kg) divided in 4 aliquots administered at least 6 h apart for 1-4 doses within the first 48 h.
Swirl vial gently if settling occurs. Do not shake. Warm in room temperature for 20 min or by holding the vial in the
hand for 8 min. Do not use artificial warming methods. For prevention, begin warming prior to birth. Do not let sit
outside the refrigerator for longer than 24 h. Only warm to room temperature once, otherwise discard.
The tip of the catheter should be positioned just beyond the end of the ET tube above the carina. Do not instill into the
mainstem bronchus. Administration works best with 2 people, one positions the infant while the other administers the
dose.

Dosing

Interactions

Contraindications

Precautions

None reported

Dosing

Interactions

Contraindications

Precautions

Documented hypersensitivity

Dosing

Interactions

Contraindications

Precautions

Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits
outweigh risk to fetus
Precautions
Must be warmed to room temperature; administer only under carefully supervised conditions because of risk of acute
airway obstruction
Marked improvement in oxygenation may occur after administration; hence, decrease oxygen and ventilator pressures
(expired tidal volume) as blood gases suggest; monitor systemic oxygenation to avoid hyperoxia or hypoxia; surfactant
may reflux into ET tube (hence, administer rapidly followed by positive-pressure ventilation); monitor heart rate and
blood pressure; because ET tube becomes occluded in rare cases, suction infant's ET tube (preferably by using closed
suction system) before administering surfactant; pulmonary hemorrhage may occur in extremely premature infants
(exclude PDA); apnea and nosocomial sepsis may occur

Lucinactant (Surfaxin)
US Food and Drug Administration (FDA) approval pending. ATI-02;KL4-surfactant. Mixture of sinapultide (peptide that
mimics action of human SP-B), colfosceril palmitate, sodium palmitoyloleaylphosphatidyl glycerol, and palmitic acid.
Contains 30 mg phospholipids per milliliter. Lowers surface tension on alveolar surfaces during respiration and
stabilizes alveoli against collapse at resting transpulmonary pressures.
In phase III clinical trial versus colfosceril palmitate and beractant, RDS-related mortality significantly decreased
through day 14 (Mayo, 2005).

Dosing

Interactions

Contraindications

Precautions

Adult
Pediatric
100-200 mg/kg based on phospholipid content ET; may repeat q6h if infant requires FIO 2 >0.40 and if PDA with
significant left-to-right shunt is excluded

Dosing

Interactions

Contraindications

Precautions

None reported

Dosing

Interactions

Contraindications

Precautions

Documented hypersensitivity

Dosing

Interactions

Contraindications

Precautions

Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits
outweigh risk to fetus
Precautions
Must be warmed to room temperature; administer only under carefully supervised conditions because of risk of acute
airway obstruction
Marked improvement in oxygenation may occur after administration, hence, decrease oxygen and ventilator pressures

(expired tidal volume) as blood gases suggest; monitor systemic oxygenation to avoid hyperoxia or hypoxia; surfactant
may reflux into ET tube (hence, administer rapidly followed by positive-pressure ventilation); monitor heart rate and
blood pressure; because ET tube becomes occluded in rare cases, suction infant's ET tube (preferably by using closed
suction system) before administering surfactant; pulmonary hemorrhage may occur in extremely premature infants
(exclude PDA); apnea and nosocomial sepsis may occur

Calfactant (Infasurf)
Natural calf lung extract containing phospholipids, fatty acids, and surfactant-associated proteins B (260 mcg/mL) and
C (390 mcg/mL). For ET use only.

Dosing

Interactions

Contraindications

Precautions

Adult
Pediatric
ET: 3 mL/kg (105 mg/kg) q6-12h for 1-4 doses

Dosing

Interactions

Contraindications

Precautions

None reported

Dosing

Interactions

Contraindications

Precautions

Documented hypersensitivity

Dosing

Interactions

Contraindications

Precautions

Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits
outweigh risk to fetus
Precautions
Administer only under carefully supervised conditions because of risk of acute airway obstruction
Marked improvement in oxygenation may occur in minutes, hence, wean infant's inspired oxygen and/or ventilator
pressure (expired tidal volume) as blood gases indicate; monitor systemic oxygenation with pulse oximetry to avoid
hypoxia and/or hyperoxia; surfactant may reflux into ET tube (hence, administer rapidly followed by positive-pressure
ventilation); cyanosis, bradycardia, or changes in blood pressure have occurred during dosing procedures; because ET
tube becomes occluded in rare cases, suction infant's tube (preferably by using closed system) before administering
surfactant

Poractant (Curosurf)
Lowers surface tension on alveolar surfaces during respiration and stabilizes alveoli against collapse at resting
transpulmonary pressures. Indicated to treat RDS in premature infants. For ET use only. Curosurf has SP-B content of
30%.

Dosing

Interactions

Contraindications

Precautions

Adult
Pediatric
ET: 2.5 mL/kg (200 mg/kg); then 1.25 mL/kg (100 mg/kg) at 12-h intervals prn in 2 subsequent doses

Dosing

Interactions

Contraindications

Precautions

None reported

Dosing

Interactions

Contraindications

Precautions

Documented hypersensitivity

Dosing

Interactions

Contraindications

Precautions

Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits
outweigh risk to fetus
Precautions
Correction of acidosis, hypotension, anemia, hypoglycemia, and hypothermia recommended before administration;
marked improvement in oxygenation may occur in minutes; monitor systemic oxygenation to avoid hyperoxia

Colfosceril (Exosurf Neonatal)

Lowers surface tension on alveolar surfaces during respiration and stabilizes alveoli against collapse at resting
transpulmonary pressures. For ET use only.

Dosing

Interactions

Contraindications

Precautions

Adult
Pediatric
ET: 5 mL/kg (67.5 mg/kg) q12h for 1-4 doses

Follow-up
Further Inpatient Care

See the Treatment section.

Further Outpatient Care

See the Treatment section.

Inpatient & Outpatient Medications

See the Medication section.

Transfer

Transfer the following patients to a tertiary care center:

o

Mothers with high-risk pregnancy

Mothers in premature labor

Newborn infants with respiratory failure

Deterrence/Prevention

See Medical Care section.

Complications

Acute complications
o

Alveolar rupture: Suspect an air leak (eg, pneumomediastinum, pneumopericardium, interstitial

emphysema, pneumothorax [see Treatment]) when an infant with respiratory distress syndrome
suddenly deteriorates with hypotension, apnea, or bradycardia or when metabolic acidosis is
persistent.

Infection: Infections may complicate the management of respiratory distress syndrome and may
manifest in various ways, including failure to improve, sudden deterioration, or a change in WBC
count or thrombocytopenia. Also, invasive procedures (eg, venipuncture, catheter insertion, use of
respiratory equipment) and use of postnatal steroids provide access for organisms that may invade
the immunologically compromised host. With the advent of surfactant therapy, small and ill infants
are surviving, with increased incidence of septicemia secondary to staphylococcal epidermidis
and/or candidal infection. When septicemia is suspected, obtain blood cultures from 2 sites and
start appropriate antibiotics until culture results are obtained.

Intracranial hemorrhage and periventricular leukomalacia: Intraventricular hemorrhage is observed in

20-40% of premature infants with greater frequency in infants with respiratory distress syndrome
who require mechanical ventilation. Cranial ultrasonography is performed in the first week and
thereafter as indicated in premature neonates younger than 32 weeks' gestation. Prophylactic
indomethacin therapy and antenatal steroids have decreased the frequency of intracranial
hemorrhage in these patients with respiratory distress syndrome. Hypocarbia and chorioamnionitis
are associated with an increase in periventricular leukomalacia.

Patent ductus arteriosus (PDA) with increasing left-to-right shunt: This shunt may complicate the
course of respiratory distress syndrome, especially in infants weaned rapidly after surfactant
therapy. Suspect PDA in any infant who deteriorates after initial improvement or who has bloody
tracheal secretions. Although helpful in the diagnosis of PDA, cardiac murmur and wide pulse
pressure are not always apparent in critically ill infants. An echocardiogram enables the clinician to
confirm the diagnosis. Treat PDA with ibuprofen or indomethacin, which can be repeated during the

first 2 weeks if the PDA reopens. In refractory incidents of respiratory distress syndrome or in
infants in whom medical therapy is contraindicated, surgically close the PDA.

Pulmonary hemorrhage: The occurrence of pulmonary hemorrhage increases in tiny premature

infants, especially after surfactant therapy. Increase positive end-expiratory pressure (PEEP) on the
ventilator and administer intratracheal epinephrine to manage pulmonary hemorrhage. In some
patients, pulmonary hemorrhage may be associated with PDA; promptly treat pulmonary hemorrhage
in such individuals. In a retrospective study, intratracheal surfactant therapy was used successfully,
with the rationale that blood inhibits pulmonary surfactant.

Necrotizing enterocolitis (NEC) and/or GI perforation: Suspect NEC and/or GI perforation in any
infant with abnormal abdominal findings on physical examination. Radiography of the abdomen
assists in confirming their presence. Spontaneous perforation (not necessarily as part of NEC)
occasionally occurs in critically ill premature infants and has been associated with the use of
steroids and/or indomethacin.

Apnea of prematurity: Apnea of prematurity is common in immature infants, and its incidence has
increased with surfactant therapy, possibly because of early extubation. Manage apnea of
prematurity with methylxanthines (caffeine) and/or bubble or continuous flow nasal continuous
positive airway pressure (CPAP), or with assisted ventilation in refractory incidents. Exclude
septicemia, seizures, gastroesophageal reflux, and metabolic and other causes in infants with
apnea of prematurity.

Chronic complications
o

Bronchopulmonary dysplasia (BPD)

BPD is a chronic lung disease defined as a requirement for oxygen at a corrected

gestational age of 36 weeks. BPD is related directly to the high volume and/or pressures
used for mechanical ventilation or to manage infections, inflammation, and vitamin A
deficiency. BPD increases with decreasing gestational age.

Postnatal use of surfactant therapy, gentler ventilation, vitamin A, low dose steroids and
inhaled nitric oxide may reduce the severity of BPD.

Clinical studies have demonstrated various incidences of BPD, which has been attributed
to increased survival of small and ill infants with respiratory distress syndrome after the
introduction of the therapies discussed above (see Treatment). BPD may also be
associated with Gastroesophageal Reflux or Sudden Infant Death Syndrome. Hence,
consider these entities in infants with unexplained apnea before discharging them from the
hospital.

Retinopathy of prematurity (ROP): Infants with respiratory distress syndrome and a PaO 2>100 mm
Hg are at increased risk for ROP. Hence, closely monitor PaO 2 and maintain it at 50-70 mm Hg.
Although pulse oximetry is used in all premature infants, it is not helpful in preventing ROP in tiny
infants because of the flat portion of the oxygen-hemoglobin dissociation curve. An ophthalmologist
examines the eyes of all premature infants at 34 weeks' gestation and thereafter as indicated. If
ROP progresses, laser therapy or cryotherapy is used to prevent retinal detachment and blindness.
Closely monitor infants with ROP for refractive errors.

Neurologic impairment: Neurologic impairment occurs in approximately 10-70% of infants and is

related to the infant's gestational age, the extent and type of intracranial pathology, and the
presence of hypoxia and infections. Hearing and visual handicaps may further compromise
development in affected infants. They may develop a specific learning disability and aberrant

behavior. Therefore, periodically follow up these infants to detect those with neurologic impairment,
and undertake appropriate interventions.
o

Familial psychopathology

Infants with respiratory distress syndrome are at increased risk for child abuse and failure
to thrive; therefore, obtain home clearance in conjunction with a nurse and social worker
before discharging the patient from the hospital. Encourage and document parental visits
and the parent's interaction with the infant.

Advise parents to spend time with their infants with respiratory distress syndrome in a
separate room before discharge, especially if the parents are at high social risk (eg,
teenagers) who also have extremely premature infants.

Advise parents of infants who are discharged with oxygen and/or an apnea monitor, with a
gastrostomy or a requirement for tube feeding, or with a tracheostomy or other special
needs to spend time with their infants with respiratory distress syndrome in a separate
room before discharge.

Physicians who are skilled in recognizing the problems encountered in these infants should
be involved with their ongoing care because of the high risk of morbidity and mortality in
infancy.

Prognosis

See Treatment.

Patient Education

Because the risk of prematurity and respiratory distress syndrome is increased for subsequent pregnancies,
counsel the parents.

Promptly manage high-risk factors, such as diabetes, hypertension, incompetent cervix, and chorioamnionitis.

Educating and counseling of the parents, caregivers, and families of premature infants must be undertaken
as part of discharge planning. They should be advised of the potential problems infants with respiratory
distress syndrome may encounter during and after their nursery stay. Audiovisual aids and handouts
supplement such education.

Miscellaneous
Medicolegal Pitfalls

Trained and experienced professionals at a tertiary care facility should treat infants with respiratory distress
(RDS) whenever possible, because complications of premature births, respiratory distress, and the
procedures performed on infants with respiratory distress are associated with an increase in medicolegal
action against health care professionals and institutions.

To minimize such actions, adequately document the infant's clinical progress, including discussions with the
families and/or caregivers.

Obtain written informed consent before transport, elective procedures, or administration of blood products.

from (http://emedicine.medscape.com/article/976034-followup)