Respiratory Distress Syndrome in Neonates
(Hyaline Membrane Disease)
(See also Overview of Perinatal Respiratory Disorders.)
Extensive physiologic changes accompany the birth process, sometimes unmasking conditions that posed no problem during intrauterine life. For that reason, a person with neonatal resuscitation skills must attend each birth. Gestational age and growth parameters help identify the risk of neonatal pathology.
Surfactant is not produced in adequate amounts until relatively late in gestation (34 to 36 weeks); thus, risk of respiratory distress syndrome (RDS) increases with greater prematurity. Other risk factors include multifetal pregnancies, maternal diabetes, and being a white male.
Rare cases are hereditary, caused by mutations in surfactant protein (SP-B and SP-C) and ATP-binding cassette transporter A3 (ABCA3) genes.
Pulmonary surfactant is a mixture of phospholipids and lipoproteins secreted by type II pneumocytes (see Neonatal 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. 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 CO2 retention and respiratory acidosis develop.
Complications of RDS include intraventricular hemorrhage, periventricular white matter injury, tension pneumothorax, bronchopulmonary dysplasia, sepsis, and neonatal death. Intracranial complications have been linked to hypoxemia, hypercarbia, hypotension, swings in arterial blood pressure, and low cerebral perfusion (see Intracranial Hemorrhage).
Symptoms and signs of RDS 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, and may ultimately lead to cardiac failure if adequate lung expansion, ventilation, and oxygenation are not established.
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, and crackles may be heard.
Diagnosis of RDS 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 and low lung expansion; appearance correlates loosely with clinical severity.
Differential diagnosis includes
Neonates typically require cultures of blood. CSF cultures are not routinely done after birth because there is low incidence of meningitis associated with early-onset sepsis, but they may be done in certain cases (eg, blood cultures are positive for gram-negative bacilli, concern of late-onset sepsis) (1). Clinically, group B streptococcal pneumonia is extremely difficult to differentiate from RDS; thus, antibiotics should be started pending culture results.
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 weeks when fetal heart tones, human chorionic gonadotropin levels, and ultrasound measurements cannot confirm gestational age and for nonelective deliveries between 34 weeks and 36 weeks.
Amniotic fluid tests include the
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.
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. Greater prematurity is associated with higher risk of chronic lung disease, bronchopulmonary dysplasia, or both.
Specific treatment of RDS is intratracheal surfactant therapy. This therapy requires endotracheal intubation, which also may be necessary to achieve adequate ventilation and oxygenation.
There is increasing evidence supporting use of less invasive ventilation techniques, such as nasal continuous positive airway pressure (CPAP), even in very premature infants (1). Infants with RDS who are receiving nasal CPAP and who need an increasing fraction of inspired oxygen (FIO2) have been shown to benefit from brief intubation to deliver surfactant followed by immediate extubation (1). Administration of intratracheal surfactant via a thin catheter is a newer technique that has also been shown to be beneficial in reducing the risk of BPD. Both of these techniques show a trend toward fewer cases of BPD but not fewer days of mechanical ventilation (2, 3).
Surfactant hastens recovery and decreases risk of pneumothorax, interstitial emphysema, intraventricular hemorrhage, bronchopulmonary dysplasia, and neonatal mortality in the hospital and at 1 year. Options for surfactant replacement include
Beractant is a lipid bovine lung extract supplemented with proteins B and C, colfosceril palmitate, palmitic acid, and tripalmitin; dose is 100 mg/kg every 6 hours as needed 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 hours apart as needed.
Calfactant is a calf lung extract containing phospholipids, neutral lipids, fatty acids, and surfactant-associated proteins B and C; dose is 105 mg/kg every 12 hours up to 3 doses as needed.
Lucinactant is a synthetic surfactant with a pulmonary surfactant protein B analog, sinapultide (KL4) peptide, phospholipids, and fatty acids; dose is 175 mg/kg every 6 hours 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, FIO2, rate) also may need to be reduced.
1. Blennow M, Bohlin K: Surfactant and noninvasive ventilation. Neonatology 107(4):330–336, 2015. doi: 10.1159/000381122.
2. Bohlin K, Gudmundsdottir T, Katz-Salamon M, et al: Implementation of surfactant treatment during continuous positive airway pressure. J Perinatol 27(7):422–427, 2007. doi: 10.1038/sj.jp.7211754.
3. Aldana-Aguirre JC, Pinto M, Featherstone RM, Kumar M: Less invasive surfactant administration versus intubation for surfactant delivery in preterm infants with respiratory distress syndrome: A systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 102(1):F17–F23, 2017. doi: 10.1136/archdischild-2015-310299.
When a fetus must be delivered between 24 weeks and 34 weeks, giving the mother 2 doses of betamethasone 12 mg IM 24 hours apart or 4 doses of dexamethasone 6 mg IV or IM every 12 hours at least 48 hours 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 who are at high risk of developing RDS (infants < 30 weeks 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).
Respiratory distress syndrome (RDS) is caused by pulmonary surfactant deficiency, which typically occurs only in neonates born at < 37 weeks 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.
Give respiratory support as needed and treat with intratracheal surfactant if the infant requires immediate intubation or has worsening respiratory status on nasal continuous positive airway pressure.
Give the mother several doses of a parenteral corticosteroid (betamethasone, dexamethasone) if time allows, and she must deliver between 24 weeks and 34 weeks gestation; corticosteroids induce fetal surfactant production and reduce the risk and/or severity of RDS.
Drugs Mentioned In This Article
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