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Respiratory Distress Syndrome in Neonates

(Hyaline Membrane Disease)

by James W. Kendig, MD, Ursula Nawab, MD

Respiratory distress syndrome is caused by pulmonary surfactant deficiency in the lungs of neonates, most commonly in those born at < 37 wk gestation. Risk increases with degree of prematurity. Symptoms and signs include grunting respirations, use of accessory muscles, and nasal flaring appearing soon after birth. Diagnosis is clinical; prenatal risk can be assessed with tests of fetal lung maturity. Treatment is surfactant therapy and supportive care.

Etiology

Surfactant is not produced in adequate amounts until relatively late in gestation (34 to 36 wk); thus, risk of respiratory distress syndrome (RDS) increases with greater prematurity. Other risk factors include multifetal pregnancies, maternal diabetes, and being male and white.

Risk decreases with fetal growth restriction, preeclampsia or eclampsia, maternal hypertension, prolonged rupture of membranes, and maternal corticosteroid use.

Rare cases are hereditary, caused by mutations in surfactant protein (SP-B and SP-C) and ATP-binding cassette transporter A3 ( ABCA3 ) genes.

Pathophysiology

Pulmonary surfactant is a mixture of phospholipids and lipoproteins secreted by type II pneumocytes (see Pulmonary function). It diminishes the surface tension of the water film that lines alveoli, thereby decreasing the tendency of alveoli to collapse and the work required to inflate them.

With surfactant deficiency, a greater pressure is needed to open the alveoli. Without adequate airway pressure, the lungs become diffusely atelectatic, triggering inflammation and pulmonary edema (see Pulmonary Edema). Because blood passing through the atelectatic portions of lung is not oxygenated (forming a right-to-left intrapulmonary shunt), the infant becomes hypoxemic. Lung compliance is decreased, thereby increasing the work of breathing. In severe cases, the diaphragm and intercostal muscles fatigue, and CO 2 retention and respiratory acidosis develop.

Complications

Complications of RDS include intraventricular hemorrhage (see Intraventricular and/or intraparenchymal hemorrhage), periventricular white matter injury, tension pneumothorax (see Pneumothorax (Tension)), bronchopulmonary dysplasia (see Bronchopulmonary Dysplasia (BPD)), sepsis (see Neonatal Sepsis), and neonatal death. Intracranial complications have been linked to hypoxemia, hypercarbia, hypotension, swings in arterial BP, and low cerebral perfusion (see Intracranial Hemorrhage and see Hemorrhagic Shock and Encephalopathy Syndrome (HSES)).

Symptoms and Signs

Symptoms and signs include rapid, labored, grunting respirations appearing immediately or within a few hours after delivery, with suprasternal and substernal retractions and flaring of the nasal alae. As atelectasis and respiratory failure progress, symptoms worsen, with cyanosis, lethargy, irregular breathing, and apnea.

Neonates weighing < 1000 g may have lungs so stiff that they are unable to initiate or sustain respirations in the delivery room.

On examination, breath sounds are decreased. Peripheral pulses may be decreased with peripheral extremity edema and decreased urine output.

Diagnosis

  • Clinical evaluation

  • ABG (hypoxemia and hypercapnia)

  • Chest x-ray

  • Blood, CSF, and tracheal aspirate cultures

Diagnosis is by clinical presentation, including recognition of risk factors; ABGs showing hypoxemia and hypercapnia; and chest x-ray. Chest x-ray shows diffuse atelectasis classically described as having a ground-glass appearance with visible air bronchograms; appearance correlates loosely with clinical severity.

Differential diagnosis includes group B streptococcal pneumonia and sepsis, transient tachypnea of the newborn (see Transient Tachypnea of the Newborn), persistent pulmonary hypertension, aspiration, pulmonary edema, and congenital cardiopulmonary anomalies. Neonates typically require cultures of blood, CSF, and possibly tracheal aspirate. Clinically, group B streptococcal pneumonia is extremely difficult to differentiate from RDS; thus, antibiotics should be started pending culture results.

Screening

RDS can be anticipated prenatally using tests of fetal lung maturity, which are done on amniotic fluid obtained by amniocentesis or collected from the vagina (if membranes have ruptured) and which can help determine the optimal timing of delivery. These are indicated for elective deliveries before 39 wk when fetal heart tones, human chorionic gonadotropin levels, and ultrasound measurements cannot confirm gestational age and for nonelective deliveries between 34 wk and 36 wk.

Amniotic fluid tests include the

  • Lecithin/sphingomyelin ratio

  • Foam stability index test (the more surfactant in amniotic fluid, the greater the stability of the foam that forms when the fluid is combined with ethanol and shaken)

  • Surfactant/albumin ratio

Risk of RDS is low when lecithin/sphingomyelin ratio is > 2, phosphatidyl glycerol is present, foam stability index = 47, or surfactant/albumin ratio is > 55 mg/g.

Treatment

  • Surfactant

  • Supplementary O 2 as needed

  • Mechanical ventilation as needed

Prognosis with treatment is excellent; mortality is < 10%. With adequate ventilatory support alone, surfactant production eventually begins, and once production begins, RDS resolves within 4 or 5 days. However, in the meantime, severe hypoxemia can result in multiple organ failure and death.

Specific treatment is intratracheal surfactant therapy. This therapy requires endotracheal intubation, which also may be necessary to achieve adequate ventilation and oxygenation. Less premature infants (those> 1 kg) and those with lower O 2 requirements (fraction of inspired O 2 [F io 2 ] < 40 to 50%) may respond well to supplemental O 2 alone or to treatment with nasal continuous positive airway pressure (see Continuous positive airway pressure (CPAP)). A treatment strategy of early (within 20 to 30 min after birth) surfactant therapy is associated with significant decrease in duration of mechanical ventilation, lesser incidence of air leak syndromes (see Pulmonary Air-Leak Syndromes), and lower incidence of bronchopulmonary dysplasia.

Surfactant hastens recovery and decreases risk of pneumothorax, interstitial emphysema, intraventricular hemorrhage, bronchopulmonary dysplasia, and neonatal mortality in the hospital and at 1 yr. However, neonates who receive surfactant for established RDS have an increased risk of apnea of prematurity (see Apnea of Prematurity). Options for surfactant replacement include

  • Beractant

  • Poractant alfa

  • Calfactant

  • Lucinactant

Beractant is a lipid bovine lung extract supplemented with proteins B and C, colfosceril palmitate, palmitic acid, and tripalmitin); dose is 100 mg/kg q 6 h prn up to 4 doses.

Poractant alfa is a modified porcine-derived minced lung extract containing phospholipids, neutral lipids, fatty acids, and surfactant-associated proteins B and C; dose is 200 mg/kg followed by up to 2 doses of 100 mg/kg 12 h apart prn.

Calfactant is a calf lung extract containing phospholipids, neutral lipids, fatty acids, and surfactant-associated proteins B and C; dose is 105 mg/kg q 12 h up to 3 doses prn.

Lucinactant is a synthetic surfactant with a pulmonary surfactant protein B analog, sinapultide (KL4) peptide, phospholipids, and fatty acids; dose is 175 mg/kg q 6 h up to 4 doses.

Lung compliance can improve rapidly after therapy. The ventilator peak inspiratory pressure may need to be lowered rapidly to reduce risk of a pulmonary air leak. Other ventilator parameters (eg, F io 2 , rate) also may need to be reduced.

Prevention

When a fetus must be delivered between 24 wk and 34 wk, giving the mother 2 doses of betamethasone 12 mg IM 24 h apart or 4 doses of dexamethasone 6 mg IV or IM q 12 h at least 48 h before delivery induces fetal surfactant production and reduces the risk of RDS or decreases its severity. (See Preterm Labor.)

Prophylactic intratracheal surfactant therapy given to neonates that are at high risk of developing RDS (infants < 30 wk completed gestation especially in absence of antenatal corticosteroid exposure) has been shown to decrease risk of neonatal death and certain forms of pulmonary morbidity (eg, pneumothorax).

Key Points

  • Respiratory distress syndrome (RDS) is caused by pulmonary surfactant deficiency, which typically occurs only in neonates born at < 37 wk gestation; deficiency is worse with increasing prematurity.

  • With surfactant deficiency, alveoli close or fail to open, and the lungs become diffusely atelectatic, triggering inflammation and pulmonary edema.

  • In addition to causing respiratory insufficiency, RDS increases risk of intraventricular hemorrhage, tension pneumothorax, bronchopulmonary dysplasia, sepsis, and death.

  • Diagnose clinically and with chest x-ray; exclude pneumonia and sepsis by appropriate cultures.

  • If premature delivery is anticipated, assess lung maturity by testing amniotic fluid for lecithin/sphingomyelin ratio, foam stability, or the surfactant/albumin ratio.

  • Treat with intratracheal surfactant and give respiratory support as needed.

  • Give the mother several doses of a parenteral corticosteroid (betamethasone, dexamethasone) if she must deliver between 24 wk and 34 wk gestation; corticosteroids induce fetal surfactant production and reduce the risk and/or severity of RDS.

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • SURVANTA
  • INFASURF
  • CELESTONE SOLUSPAN, DIPROLENE, LUXIQ
  • OZURDEX

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