ROAD TO MERITISSIMUS

Written by: Dapoy Peralta, MD

Transcribed by: Angiegenesis

RESPIRATORY DISTRESS SYNDROME

Definition
- RDS is a respiratory disorder usually developing in the first few hours of life in
premature infants <36 weeks AOG
- It was first described as HYALINE MEMBRANE DISEASE in 1903 due to the
presence of preoteinaceous exudates along the walls of the alveoli on
histopathologic sections.
- It is different from Acute RDS which is primarily seen in adults
- The primary cause of RDS is related to
1. Structural lung immaturity in preterm infants accompanied by,
2. Quantitative or qualitative deficiency in pulmonary surfactant

Incidence and Risk Factors

ü Generally, the incidence and severity of RDS increases with decreasing gestational
age at birth, the risk being highest in extremely preterm infants
ü It is a major cause of morbidity and mortality in preterm infants
ü Incidence wise, RDS occurs in
§ 60-80% of infants <28 weeks AOG
§ 15-30% of those between 32 to 35 weeks
§ and rarely in the >37 weeks
ü Incidence is highest in preterm males and preterm white infants
ü Androgen slow down fetal lung development (decreased EGf & TGF-B) &
development of type II alveolar cells
ü Estrogen promotes synthesis of surfactant and SP-A & SP-B
ü Factors that increase the risk of RDS
1. Gestational DM (also maternal infection)
o Increased insulin decreases surfactant production
2. Perinatal asphyxia
o causes acute lung injury cesarian delivery – lower activity of Amiloride-
sensitive Na+ channels in alveolar epithelium leading to reduced fluid
clearance
3. Precipitous delivery
4. Multiple births
 o Often premature, second twin mostly affected
5. Cold stress
o Decreased surfactant production
6. Maternal history of previously affected infant
ü Factors that decrease the risk of RDS
1. Chronic or pregnancy-associated hypertension
o Chronic stress (increased cortisol) accelerates fetal lung maturation
2. Maternal heroin use
o Increases surfactant production by promoting binding of choline to
phosphate
3. Prolonged rupture of membranes
4. Antenatal corticosteroid prophylaxis

Pathophysiology
ü Knowledge of the normal fetal lung development is vital to understanding the
pathophysiology of neonatal RDS, which is due to inadequate surfactant activity
resulting from lung maturity
ü Normal fetal lung development occurs in 4 stages
1. Embryonic stage (26-33 days)
2. Pseudoglandular stage (5th – 16th week)
3. Canalicular stage (16th – 25th week)
4. Saccular stage (25th week – 2 years)
ü It is during the CANALICULAR STAGE that respiratory bronchioles and alveolar
ducts are formed allowing gas exchange with the surrounding capillaries
ü At around 25th week AOG cuboidal epithelial cells begin to differentiate into
alveolar type II cells with formation of cytoplasmic lamellar bodies, the presence of
which corresponds to the earliest surfactant production
ü However, it is not until the 35th week AOG that enough surfactant is produced
necessary to prevent RDS
ü During the SACCULAR STAGE, gas exchange becomes more effective as saccules
subdivide into anatomic alveoli
ü These alveoli increase from 0 at 32 weeks AOG to 50-150 million at birth in term
infants “ALVEOLARIZATION“
ü Alveolar growth continues for at least 2 years after birth reaching about 200 millin
alveoli in adults

PULMONARY SURFACTANT
ü As mentioned, the primary cause of RDS, is deficiency of pulmonary surfactant,
which is developmentally regulated

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 ü Because it is developmentally regulated, it follows that the most common cause of
surfactant deficiency is preterm delivery.
ü Surfactants may also be inactivated by meconium (term) and blood
ü In terms of composition, pulmonary surfactant consists of 90% lipids, 80% of which
are phospholipids composed primarily of Dipalmifoylphosphatidylcholine,
phosphatidyl glycerol and inositol. 10% of these lipids are cholesterol.
ü The rest 10% is composed of surfactant-specific apoproteins which contribute to the
biophysical surface tension decreasing properties (SP-A, SP-B, SP-C, SP-D)
• SP-A – responsible for tubular myelin formation than contributes to the
surface film within the alveoli. Also, a non-immune host defense protein &
regulator of inflammation
• SP-B – mostly contributes to surface tension lowering property since it
facilitates surface absorption of lipids
• Hereditary deficiency in males is FATAL due to loss of lamellar bodies (even
in term)
ü After being secreted, surfactants move from airspaces back to Type II alveolar cells
for recycling and contributes to the intracellular surfactant pool
ü With inadequate surfactant activity, high surface tension within the alveolar wall
develops leading to instability of the lungs at end-expiration, low lung volume, and
decreased lung compliance. Law of Laplace: P = 2T/R. Distending pressure is equal
to surface tension over radius.
ü The resulting atelectasis leads to V/Q mismatch impairing efficient gas exchange
ü HYPOXEMIA and HYPERCARBIA develop with subsequent metabolic & respiratory
acidosis. Acidosis decreases surfactant production
ü Combination of these factors leads to pulmonary vasoconstriction comprising blood
flow to the alveoli
ü With chronic administration of high flow O2 (increases susceptibility),
BAROTRAUMA ensues. (inflammatory mediators enhances conversion of surfactant
to its inactive vesicular form)
ü Alveolar epithelial and capillary endothelial cells become damaged, inflammation
ensues.
ü Eventually, lung injury becomes irreversible and there will be bronchopulmonary
dysplasia characterized by a “bubbly lung pattern” on CXR seen as
o Focal areas of radiolucency representing normal lung parenchyma
o Curvilinear densities representing fibrosis. (normally aerated lung trapped
between fibrotic changes)
ü This must be differentiated from WILSON-MIKITY SYNDROME, a syndrome
characterized by pulmonary dysmaturity wherein alveoli do not mature at the same
time
o Focal areas if radiolucency represent mature distended alveoli
o Curvilinear densities represent immature collapsed alveoli

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 ü Differentiating factor would be based on history
o BPD - (+) history ofdx RDS and high O2 administration
o WMS – (-) history of RDS and high O2 administration

CLINICAL MANIFESTATIONS

ü Clinical manifestations of RDs result primarily from abnormal pulmonary function

and hypoxemia
ü It typically presents within the first minutes or hours after birth
ü Common signs and symptoms include:
o Difficulty in initiating normal respiration
o Tachypnea
o Nasal flaring
o Expiratory grunting
§ Decrease in grunting may be the first sign of improvement
§ Neonate’s attempt to maintain FRC by forcefully closing the glottis
o Retractions
§ During inspiration, the highly compliant chest wall is drawn inward
by the high negative intrathoracic pressures required to expand the
poorly compliant lungs
o Apnea
§ Sign of respiratory fatigue in severe RDS
o Cyanosis
§ Reflects an increase in deoxygenated hemoglobin due to hypoxia
o Decreased activity
§ Due to hypoxia or attempt by infant to conserve energy
ü On physical exam, auscultation may reveal decreased breath sounds, infant may be
pale with diminished peripheral pulsed
ü Urine outputs often low in the first 24-48 hours
ü Peripheral edema is common

DIAGNOSIS

ü In the diagnosis of RDS, a good prenatal, birth, and neonatal transition history is
crucial more than that of the physical examination findings which are nonspecific.
History should also include the different risk factors.
ü Infant, in a pregnant woman expected to deliver preterm, RDS must already be
anticipated and appropriate interventions be prepared.

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 PRENATAL

ü Prenatally, lung maturity may be determined by assessing the amniotic fluid

lecithin to sphingomyelin (L:S) ratio. A value of more than 2:1 is indicative of lung
maturity.
ü Another test is the foam stability index or clement’s test. In the presence of
ethanol, a nonfoaming competitive surfactant, the presence of complete ring of
bubbles at the meniscus (stable foam) is suggestive of fetal lung maturity.
ü Lamellar bodies on the amniotic fluid can also be quantified using the same
machine used to count platelets (coulter counter placed on platelet mode) and
values >50,00/uL are suggestive of fetal lung maturity
ü Other tests include use of 3D ultrasound (noninvasive) to assess fetal lung maturity.
Parameters being measured are:
o Fetal lung volume (FLV) - >50 mL
o Fetal lung to liver intensity ratio (FLLIR) - >1.1
o Breathing related nasal fluid flow (BRNFF)

POSTNATAL

ü Postnatally, the diagnosis of RDS is based on a clinical picture of a preterm infant

with an acute onset of progressive respiratory failure shortly after birth, in
conjunction with a chest radiograph.
ü CXR features of RDS include:
o Low lung volume
o Classic diffuse reticulogranular ground glass pattern (alveolar atelectasis
contrasting with aerated airways) with air bronchograms (peripherally
located patent terminal bronchioles)
ü On severe RDS, there may be homogenous opacification of both lungs “WHITE
OUT PATTERN”
ü Pneumothorax and air leaks are uncommon findings in the initial CXR and are more
commonly observed when lung compliance improves
ü Other ancillary tests may be requested to rule out or to differentiate RDS from
other causes of respiratory distress.
ü This may include CBC, blood culture, 2d-echo, blood glucose, etc.

DIFFERENTIAL DIAFNOSES
1. TRANSIENT TACHYPNEA OF NEWBORN/RETAINED LUNG FLUID SYNDROME
ü This is due to delayed resorption of fetal lung fluid and is generally seen in
more mature infants who were delivered through CS without labor.
ü It is during LABOR when lung fluid starts to be reabsorbed

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 ü In addition, during vaginal deliveries, the vagina can squeeze the excess
fluid out from the lungs
ü The major presenting symptom is persistently elevated respiratory rate with
milder respiratory distress than RDS
ü It is self-limited and mostly resolves within 6-8 hours with significant clinical
improvement
ü On CXR, there is hyperaeration and prominent pulmonary markings (linear
densities) representing engorged lymphatic vessels trying to remove excess
fluid
2. NEONATAL PNEUMONIA
ü It is often difficult to differentiate between infants with RDS and those with
bacterial pneumonia due to overlap of both clinical and radiographic
findings
ü A good maternal history is very important. There should also be a high
index of suspicion
ü Investigate for:
o UTI
o PROM – patients are usually term >18 hours
o Chorioamnionitis
o Foul discharge
o Maternal fever
ü Also, because of this overlap, blood cultures or tracheal cultures must be
obtained in all preterm infants presenting with respiratory distress
ü Empiric antibiotic should be given that will cover common organisms while
waiting for the results of the culture
o GBS
o E. coli
o Listeria monocytogenes
o Klebsiella sp.
o Enterococcus
ü Drug of choice: AMPICILLIN (100mkd BID) + GENTAMICIN (5mkd BID) 7-
10 days
ü Do NOT give ceftriaxone it increases CHON binding
3. CYANOTIC CONGENITAL HEART DISEASE
ü Most patients with cyanotic congenital heart disease have milder
respiratory distress than that seen in RDS
ü In addition, there is also the absence of characteristic CXR finding in RDS
ü If the lung function does not improve with respiratory support and
surfactant administration, a 2D-echo should be done to rule out structural
heart disease or persistent pulmonary hypertension of newborn.

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 4. NON-PULMONARY SYSTEMIC DISORDERS
ü Several non-pulmonary systemic disorders ma also present with respiratory
distress
o Hypothermia
o Hypoglycemia
o Anemia/polycythemia
o Metabolic acidosis
ü Appropriate laboratory tests may be requested such as blood glucose,
CBC, and ABG

MANAGEMENT
ü Corticosteroids
o Improve lung mechanics and gas exchange
o Upregulate gene expression of epithelial Na+ channel
o Accelerate development of Type 1 & 2 pneumocytes
o Increase production of surfactant and surface proteins (increased
phospholipid synthetase)
o Upregulated pulmonary B2 receptors
o Induces fetal lung antioxidant system

Preventive Measures
ü Generally, the best way to prevent RDS is to prevent preterm delivery
ü However, this is not always possible
ü Thus, we can administer antenatal corticosteroids to the mother to accelerate fetal
lung maturation and prevent or decrease the severity of RDS
ü Antenatal corticosteroids should be administered to all pregnant women who are
on their 24-34th week AOG who are at increased risk of preterm delivery within 7
days.
ü Either BETAMETHASONE or DEXAMETHASONE can be given
ü But BETHAMETHASONE has the added benefit of decreasing the risk of
periventricular leukomalacia and has also been proven to be more effecting in
preventing RDS
o BETAMETHASONE 12 mg IM q24 x 2 doses
o DEXAMETHASONE 6 mg IM q12 x 4 doses
ü If the woman did not deliver after 14 days from the time the steroid were given, a
single rescue dose may be given to women who are <34 weeks AOG at risk of
preterm delivery within 7 days
ü Antenatal corticosteroid administration also has the added benefit of
o Reducing the incidence of necrotizing enterocolitis and intraventricular
hemorrhage

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 o Reduction in need for ventilatory support and NICU stay
o Reduction in the risk of infection
o Overall reduction in neonatal mortality

Specific Therapy
1. Ensure adequate ventilation and oxygenation (warmed and humidified using a
hood)
ü To prevent atelectasis, pulmonary vasoconstriction and V/Q mismatch
ü Continuous positive airway pressure (CPAP) via mask, nasal cannula or ET
tube must be employed to provide Positive End-Expiratory Pressure (PEEP).
4-6 cm H2O sedate the infant
ü This will maintain the arterial oxygen tension between 60-80 mmHg
ü If the infant cannot maintain a PaO2 >50 mmHg while breathing 70-100%
O2, intubation and mechanical ventilation with PEEP is required (or an FiO2
exceeds 0.40 on CPAP)
ü If other indications for mechanical ventilation
o Arterial pH <7.20
o PaCO2 >60 mmHg
o Severe persistent apnea
o ET size
§ <1000g - 2.5
§ 1000-2000g – 3.0
§ 2000-3000g – 3.5
§ >3000g – 3.5 to 4.0
o ET depth
§ Weight in kg + 6
ü The optimal mode of ventilation to reduce risk of barotrauma remains
unclear
ü Based on available literature, use of synchronized volume-targeted
ventilation with tidal volumes set at 4-6 ml/kg with permissive hypercarbia
is appropriate
ü Regardless of the choice of ventilator, the goal is to minimize barotrauma
and oxygen toxicity while still reaching target PaO2 and PaCO2
ü Blood gas monitoring every 4-6 hours with an indwelling arterial line
(umbilical) may be contemplated
2. Surfactant Replacement Therapy
ü Surfactants are indicated for those with:
o Persistent severe respiratory distress
§ Requiring a FiO2 of 0.40 or higher to maintain SpO2 >90%
o Apneic patients
ü The standard technique for surfactant administration is through an ET tube

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 o May be complicated by transient airway obstruction or inadvertent
instillation only into the right main bronchus
o Oxygen saturation should be monitored since desaturation may
occur
ü Less invasive measures include aerosolized surfactant, laryngeal mask
airway-aided delivery of surfactant, pharyngeal instillation or the use of thin
intrathecal catheters
ü Surfactant preparations include natural and synthetic surfactants
ü Although both are effective, natural surfactants are superior since they
contain SP-B and SP-C
ü Natural surfactants – contains DPPC, neutral lipids, and SP-B, SP-C
o PORACTANT ALFA (curosurf) – Porcine lung minced extract
o CALFACTANT (infasurf) – Bovine lung lavage extract
o BERACTANT (survanta) – Bovine lung minced extract
ü Synthetic surfactants
o COLFOSCERIL PALMITATE (exosurf)
o LUCINACTANT (surfaxin) - discontinued
ü “Prophylactic dose” may be given immediately after birth of a premature
infant (prevention)
ü “Rescue dose” is given during the first 24 hours of life after diagnosis of
RDS is established
3. Supportive Care
ü THERMOREGULATION
o Maintain in thermoneutral environment to minimize hea loss and
maintain core body temperature, thereby reducing oxygen
consumption, carbon dioxide production and caloric needs
ü FLUIDS
o Should maintain in a slightly negative water balance since excessive
fluid intake increased the risk of PDA, NEC, and BPD.
o Increased left-to-right shunting
ü NUTRITION
o To cover both metabolic expenditure and growth
o Increased PGE2 – increasing patency of DA
o IV glucose 60 ml/kg on the 1st day, 80-100 ml/kg on the 2nd day
(10%)
ü CONTINUOUS VITAL SIGNS MONITORING
o noninvasive
ü ANTIBIOTICS
o Obtain blood culture and treat with AMPICILLIN 100mkd +
GENTAMICIN 5mkd BID for 7-10 days until cultures are available
ü ELECTROLYTES

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 ü ACID-BASE BALANCE
o Limit NaHCO3 to 8 mEq/kg/day to prevent hypernatremia
ü BLOOD TRANSFUSION
o If Hct <35 to maintain oxygen carrying capacity
ü CARDIAC SUPPORT
o Inotropic agents like dopamine and dobutamine if needed

PROGNOSIS

ü Generally, survival rates directly correlate to the AOG and birth weight
ü The use of surfactant replacement has greatly reduced mortality by approximately
40%
ü Survivors of severe RDS may have significant complications
ü Acute complications include:
o Alveolar rupture/Air leaks
§ Pneumomediastinum/pericardium/thorax
§ Interstitial emphysema
o Infections
§ Septicemia secondary to S. epidermidis, Candida sp.
o Intracranial hemorrhage and periventricular leukomalacia
§ Posthemorrhagic hydrocephalus
§ Perform Cranial UTZ: (+) cystic changes, for all <1500g
o Patent ductus arteriosus
§ 2D echo
§ Tx: ibuprofen/indomethacin/paracetamol/surgery
o Pulmonary hemorrhage
o Necrotizing enterocolitis
§ SFA (pneumoperitoneum, pneumatosis intestinalis, bloody stool,
portal vein gas)
o Apnea of prematurity
§ Give CPAP
ü Chronic complications include:
o Bronchopulmonary dysplasia
o Retinopathy of prematurity/Retrolental fibroplasia
§ BW <1500g, AOG <32 weeks, 4 weeks after birth
§ Laser photocoagulation
o Neurologic impairment
§ Cerebral palsy (spastic diplegia), visual and cognitive defects

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