Basics
Description
Respiratory distress syndrome (RDS) is an acute, developmental lung disease affecting primarily premature infants. Disease is characterized by alveolar collapse due to a lack of pulmonary surfactant owing to lung immaturity that results in increased work of breathing, hypoxemia, and respiratory acidosis. The term hyaline membrane disease (HMD) is often used synonymously.
Epidemiology
- RDS is the most common lung disease in premature infants, affecting approximately 60 " 80,000 infants per year in the United States.
- Risk increases with the degree of prematurity; nearly 100% of infants born at <26 weeks ' gestation affected.
- For near-term infants delivered operatively without benefit of labor, the risk of developing RDS increases roughly 2-fold for every week <39 weeks ' gestation.
Risk Factors
- Prematurity
- Low birth weight
- Maternal diabetes
- Delivery without labor
- Absence of antenatal steroid administration
- Male gender
- Caucasian race
- Perinatal depression
Pathophysiology
- Insufficient or dysfunctional surfactant results in alveolar instability and atelectasis, causing hypoventilation and ventilation " perfusion mismatch, leading to hypoxemia and respiratory acidosis.
- The lack of surfactant in conjunction with pulmonary immaturity also leads to transudation of fluid and alveolar edema.
- Surfactant inactivation from transudation of proteins or other substances into the alveolus
- Increased work of breathing generates high negative intrathoracic pressures to overcome alveolar collapse. Retractions result from the highly compliant newborn rib cage combined with poorly compliant lungs.
- Expiratory grunting is due to glottic closure at the end of expiration to prevent end-expiratory atelectasis and maintain functional residual capacity.
- Infants with a well-developed pulmonary arterial muscular bed can develop secondary pulmonary hypertension, with hypoxemia leading to pulmonary vasoconstriction.
General Prevention
- Prevention of prematurity
- Maternal antenatal steroids
Diagnosis
History
- Gestational age, birth weight
- Lack of antenatal steroids
- Delivery history: maternal diabetes, perinatal asphyxia, route of delivery, absence of labor, 2nd-born twin
- Resuscitation: need for supplemental oxygen, positive pressure, intubation, surfactant
Physical Exam
- Assessment of color (cyanosis), grunting, nasal flaring, accessory muscle usage
- Vital signs (including respiratory rate to assess for tachypnea) and pulse oximetry (to assess for hypoxemia)
- Pulmonary exam, including shallow or decreased breath sounds, symmetry of breath sounds, and inspiratory rales
Diagnostic Tests & Interpretation
Lab
- Blood gases (BGs): Arterial BGs allow for accurate determination of pH, Paco2, and Pao2 to avoid hyperoxia as well as hypoxemia.
- Capillary BGs obtained from appropriately warmed extremities can provide accurate determinations of pH and Pco2, but poor perfusion to the extremity or inadequate warming may result in inaccurate determinations.
- Oxygenation may be determined noninvasively through pulse oximetry.
Imaging
- Chest radiography
- Classic findings include hypoinflation, diffuse reticulogranular or "ground-glass " appearance, and air bronchograms.
- Lateral films may be helpful for determination of air leak.
- Other imaging modalities (CT, ultrasound) are generally unnecessary for the diagnosis and management of RDS but may be indicated if there is suspicion for other pulmonary pathology.
Differential Diagnosis
Common
- Transient tachypnea of the newborn (TTN)
- Infection (sepsis, pneumonia)
- Air leak (may also be a complication of RDS)
- Meconium aspiration syndrome
Unusual
- Pulmonary hypoplasia
- Congenital heart disease
- Primary ciliary dyskinesia
- Genetic surfactant dysfunction
Treatment
General Measures
Diet
Sufficient glucose infusion to prevent hypoglycemia. Hydration and nutrition for expected increased caloric needs with early initiation of IV nutrition while working to establish enteral nutrition
Supportive Care
- Radiant warmer or incubator for warmth
- Blood pressure support with volume expansion and/or pressors to maintain perfusion and normal blood pressure for gestational age
Medication
- Exogenous surfactant
- Both modified mammalian-derived surfactants and synthetic surfactants have been shown to reduce morbidity and mortality from RDS.
- Exogenous surfactant is delivered directly into the trachea through the endotracheal tube and thus currently requires that the infant be intubated, although alternative delivery methods are being explored.
- Timing of surfactant
- Prophylactic: as soon as infant is stabilized, usually less than 15 minutes of life, based on the risk for RDS without demonstrating that the infant has disease. Prophylaxis is usually reserved for those infants at highest risk for RDS, such as <26 weeks ' gestation.
- Rescue: after the diagnosis of RDS is established; usually after first hour and before 48 hours of life
- Additional doses are considered for persistently high FiO2 requirements (FiO2 >0.3 " 0.4) or for ongoing need for mechanical ventilation. Consultation with a neonatologist is recommended.
- Caffeine citrate
- Used for apnea of prematurity and may be helpful in RDS if it is able to minimize the duration of mechanical ventilation
Alert
- Occasionally, the surfactant material may clog the endotracheal tube, causing acute airway obstruction with resultant hypercapnia and hypoxemia, necessitating suctioning or removal and replacement of the endotracheal tube.
- Surfactant therapy can also result in acute improvements in pulmonary compliance. Monitor physical exam, Spo2, blood gasses, and tidal volumes to avoid inadvertent overventilation.
Additional Therapies
- Continuous positive airway pressure (CPAP)
- Can be delivered via nasal prongs or mask either using a ventilator, dedicated apparatus, or through "bubble CPAP "
- CPAP prevents end-expiratory atelectasis and can be started in the delivery room.
- Humidified high-flow nasal cannula (HFNC)
- May achieve CPAP benefit with easier handling of the patient and less risk of pressure necrosis of nasal septum
- Pressure delivery variable
- Mechanical ventilation
- May be required for infants with significant respiratory acidosis and hypoxemia. Can be initiated following intubation for surfactant delivery
- High-frequency ventilation (oscillatory or jet) may be valuable in very severe cases or with air leak (jet).
Ongoing Care
Follow-up Recommendations
- Very low-birth-weight and extremely low-birth-weight infants should receive follow-up in specialty clinics that can provide for their specialized needs, including neurodevelopmental, pulmonary (for those with bronchopulmonary dysplasia [BPD]), and ophthalmology (for those with retinopathy of prematurity).
- Immunizations are extremely important preventive measures to prevent subsequent respiratory morbidity and mortality. See chapter on "Bronchopulmonary Dysplasia " for recommendations for passive immunization against respiratory syncytial virus with palivizumab (Synagis).
Prognosis
Natural history: disease severity worsens over the first 24 " 72 hours, with improvement occurring after 5 " 10 days of age. With antenatal steroids, CPAP, newer modes of mechanical ventilation, and surfactant replacement therapy, more rapid improvement is often seen, and mortality from RDS is rare. Outcome is usually related to the degree of prematurity and its related complications.
Complications
Air-leak: pneumothorax, pneumomediastinum, pulmonary interstitial emphysema, pneumopericardium
- Pulmonary hemorrhage: typically occurs between 1 and 3 days of age with sudden respiratory deterioration and pink or red frothy fluid or bright red blood in the endotracheal tube. Associated with diffuse opacification of the lung fields and marked decrease in pulmonary compliance.
- Complications related primarily to prematurity that are often associated with RDS:
- Patent ductus arteriosus: Pulmonary edema and high-output congestive heart failure may develop as a consequence of left-to-right shunting through the ductus.
- Bronchopulmonary dysplasia: a chronic disease of multifactorial etiology involving abnormal lung development and abnormal repair following lung injury due in part to RDS as well as edema, infection, and other factors causing inflammation
Alert
- Emergency treatment of pneumothorax: Acute tension pneumothorax can occur as a complication of RDS and its management and can be life threatening, even in larger or term infants. Needle aspiration may provide temporary stabilization, and chest tube placement may be necessary.
Additional Reading
- Engle WA. Surfactant-replacement therapy for respiratory distress in the preterm and term neonate. Pediatrics. 2008;121(2):419 " 432. [View Abstract]
- Finer NN, Carlo WA, Walsh MC, et al. Early CPAP versus surfactant in extremely preterm infants. N Engl J Med. 2010;362(21):1970 " 1979. [View Abstract]
- Jobe AH. What is RDS in 2012? Early Hum Dev. 2012;88(Suppl 2):S42 " S44. [View Abstract]
- Morley CJ, Davis PG, Doyle LW, et al. Nasal CPAP or intubation at birth for very preterm infants. N Engl J Med. 2008;358(7):700 " 708. [View Abstract]
- Sweet DG, Carnielli V, Greisen G, et al. European consensus guidelines on the management of neonatal respiratory distress syndrome in preterm infants " 2013 update. Neonatology. 2013;103(4):353 " 368. [View Abstract]
- Tita AT, Landon MB, Spong CY, et al. Timing of elective repeat cesarean delivery at term and neonatal outcomes. N Engl J Med. 2009;360(2):111 " 120. [View Abstract]
Codes
ICD09
- 769 Respiratory distress syndrome in newborn
ICD10
- P22.0 Respiratory distress syndrome of newborn
SNOMED
- 46775006 Respiratory distress syndrome in the newborn (disorder)
FAQ
- Q: Should all babies with a diagnosis of RDS be started on antibiotics?
- A: It is important to consider sepsis/pneumonia in all infants with a diagnosis of RDS, particularly infection with group B Streptococcus (GBS). Risk factors to be considered include maternal GBS colonization, evidence of chorioamnionitis, intrapartum antibiotic use, and route of delivery. Antibiotics may sometimes be held if the risk factors for sepsis are low compared to those for RDS, such as in a baby delivered electively by caesarean section for maternal indications. However, as congenital pneumonia can radiographically appear identical to RDS, it is often common practice to screen for sepsis in all infants with RDS by performing blood cultures and looking for other laboratory evidence of infection including complete blood counts with differentials and acute-phase reactants such as C-reactive protein, and start empiric antibiotic therapy with ampicillin or penicillin in combination with an aminoglycoside. Duration of antibiotics is typically 48 hours depending on results of blood cultures as well as the clinical picture and other laboratory data. Therapy may be narrowed if a specific organism is identified.
- Q: What is the most worrisome acute complication of RDS?
- A: Acute air leak (primarily tension pneumothorax) can be life threatening, even in near-term or full-term infants with RDS, and such infants should be cared for in centers that are prepared to properly handle this emergent situation in a timely fashion (i.e., availability of a provider who can perform an emergent needle aspiration and chest tube placement). In smaller infants, pulmonary hemorrhage can also be life threatening.
- Q: Because the risk of a baby developing RDS for a baby born at 26 weeks ' gestation is so high, should such babies automatically receive prophylactic surfactant?
- A: Not necessarily. Early prospective, randomized, placebo-controlled studies did demonstrate that mortality from RDS was reduced with prophylactic surfactant in preterm infants ≤26 weeks ' gestation. However, those studies were conducted in an era before widespread use of antenatal steroids and early use of CPAP. Recent prospective, randomized trials of different approaches to extremely low-birth-weight infants in the delivery suite have demonstrated that such infants treated with early and continued CPAP alone may have outcomes comparable to those immediately intubated and treated with surfactant replacement therapy.
- Q: As some surfactant preparations are prepared from cow lungs, is there an increased risk that babies receiving such surfactants will develop a milk protein allergy?
- A: It is very unlikely that surfactant treatment with preparations derived from animal lungs increases the risk of immune responses. The two proteins in replacement surfactants are present in low amounts and are extremely hydrophobic and unlikely to generate an immune response given the limited number of surfactant doses (usually maximum of 4) administered. They are also not structurally related to proteins found in human milk, and their amino acids sequences are highly conserved between species, such that it is unlikely that they would be seen as foreign antigens by the baby 's immune system.