Merck Manual

Please confirm that you are a health care professional

honeypot link

Respiratory Distress Syndrome in Neonates

(Hyaline Membrane Disease)

By

Arcangela Lattari Balest

, MD, University of Pittsburgh, School of Medicine

Last full review/revision Jul 2021| Content last modified Jul 2021
Click here for Patient Education

Respiratory distress syndrome is caused by pulmonary surfactant deficiency in the lungs of neonates, most commonly in those born at < 37 weeks 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

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 Neonatal pulmonary function Neonatal pulmonary function The transition from life in utero to life outside the womb involves multiple changes in physiology and function. Also see Perinatal Problems. (See also Liver Structure and Function and Neonatal... read more ). 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 Pulmonary Edema Pulmonary edema is acute, severe left ventricular failure with pulmonary venous hypertension and alveolar flooding. Findings are severe dyspnea, diaphoresis, wheezing, and sometimes blood-tinged... read more 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 Respiratory Acidosis Respiratory acidosis is primary increase in carbon dioxide partial pressure (Pco2) with or without compensatory increase in bicarbonate (HCO3−); pH is usually low but may be near normal. Cause... read more develop.

Complications

Complications of RDS include intraventricular hemorrhage Intraventricular hemorrhage and/or intraparenchymal hemorrhage The forces of labor and delivery occasionally cause physical injury to the infant. The incidence of neonatal injury resulting from difficult or traumatic deliveries is decreasing due to increasing... read more Intraventricular hemorrhage and/or intraparenchymal hemorrhage , periventricular white matter injury, tension pneumothorax Pneumothorax (Tension) Tension pneumothorax is accumulation of air in the pleural space under pressure, compressing the lungs and decreasing venous return to the heart. (See also Overview of Thoracic Trauma.) Tension... read more Pneumothorax (Tension) , bronchopulmonary dysplasia Bronchopulmonary Dysplasia (BPD) Bronchopulmonary dysplasia is chronic lung disease of the neonate that typically is caused by prolonged ventilation and is further defined by age of prematurity and extent of supplemental oxygen... read more Bronchopulmonary Dysplasia (BPD) , sepsis Neonatal Sepsis Neonatal sepsis is invasive infection, usually bacterial, occurring during the neonatal period. Signs are multiple, nonspecific, and include diminished spontaneous activity, less vigorous sucking... read more , and neonatal death. Intracranial complications have been linked to hypoxemia, hypercarbia, hypotension, swings in arterial blood pressure, and low cerebral perfusion (see Intracranial Hemorrhage Intracranial Hemorrhage The forces of labor and delivery occasionally cause physical injury to the infant. The incidence of neonatal injury resulting from difficult or traumatic deliveries is decreasing due to increasing... read more Intracranial Hemorrhage ).

Symptoms and Signs

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

  • Clinical evaluation

  • Arterial blood gases (ABGs; hypoxemia and hypercapnia)

  • Chest x-ray

  • Blood, cerebrospinal fluid (CSF), and tracheal aspirate cultures

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 Diagnosis reference Respiratory distress syndrome is caused by pulmonary surfactant deficiency in the lungs of neonates, most commonly in those born at 37 weeks gestation. Risk increases with degree of prematurity... read more ). 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 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

  • 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.

Diagnosis reference

  • 1. Srinivasan L, Harris MC, Shah SS: Lumbar puncture in the neonate: Challenges in decision making and interpretation. Semin Perinatol 36(6):445–453, 2012. doi: 10.1053/j.semperi.2012.06.007

Prognosis

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.

Treatment

  • Intratracheal surfactant if indicated

  • Supplementary oxygen as needed

  • Mechanical ventilation as needed

There is increasing evidence supporting use of less invasive ventilation techniques, such as nasal continuous positive airway pressure (CPAP Continuous Positive Airway Pressure (CPAP) Initial stabilization maneuvers include mild tactile stimulation, head positioning, and suctioning of the mouth and nose followed as needed by Supplemental oxygen Continuous positive airway... read more ), even in very premature infants (1 Treatment references Respiratory distress syndrome is caused by pulmonary surfactant deficiency in the lungs of neonates, most commonly in those born at 37 weeks gestation. Risk increases with degree of prematurity... read more ). 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 Treatment references Respiratory distress syndrome is caused by pulmonary surfactant deficiency in the lungs of neonates, most commonly in those born at 37 weeks gestation. Risk increases with degree of prematurity... read more ). 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 Treatment references Respiratory distress syndrome is caused by pulmonary surfactant deficiency in the lungs of neonates, most commonly in those born at 37 weeks gestation. Risk increases with degree of prematurity... read more ).

  • 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 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.

Animal-derived surfactants are generally considered superior to synthetic ones.

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.

Treatment references

  • 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

Prevention

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 Preterm Labor Labor (contractions resulting in cervical change) that begins before 37 weeks gestation is considered preterm. Risk factors include prelabor rupture of membranes, uterine abnormalities, infection... read more .)

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 Pneumothorax Pulmonary air-leak syndromes involve dissection of air out of the normal pulmonary airspaces. (See also Overview of Perinatal Respiratory Disorders.) Extensive physiologic changes accompany... read more ).

Key Points

  • 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.

Click here for Patient Education
NOTE: This is the Professional Version. CONSUMERS: Click here for the Consumer Version
Professionals also read
Test your knowledge
Mumps
Mumps is an acute, contagious, systemic viral disease caused by a paramyxovirus. It is spread by droplets or saliva and probably enters through the nose and mouth. After a 12- to 24-day incubation period, headache, anorexia, malaise, and low-grade fever usually develop. Then several other symptoms develop over the next few days. Of these symptoms, edema of which of the following structures is most likely to peak on the 2nd day and typically last 5 to 7 days? 
Download the Manuals App iOS ANDROID
Download the Manuals App iOS ANDROID
Download the Manuals App iOS ANDROID
 

Also of Interest

 
TOP