2d:I[856015,["/_next/static/immutable/chunks/1xzisbplk9czp.js","/_next/static/immutable/chunks/3j2i1faptc_-9.js","/_next/static/immutable/chunks/0fma7nlq6immz.js","/_next/static/immutable/chunks/08tq8rmv423j5.js","/_next/static/immutable/chunks/1chr5wkk3j58k.js","/_next/static/immutable/chunks/37kmmh_zm4dov.js","/_next/static/immutable/chunks/311zvdjfxff-f.js","/_next/static/immutable/chunks/1a_hqhrsle_n_.js"],"default"] 2e:T70f9,

Summary Table

Domain	Details
Risk Factors	Prematurity (the single most important risk factor, especially < 34 weeks), maternal gestational diabetes (hyperinsulinemia delays surfactant maturation), cesarean delivery without labor, male sex, white ethnicity, second-born twin, perinatal asphyxia, family history of RDS
Etiology	Deficiency of pulmonary surfactant due to immature type II pneumocytes
Patient Presentation	Preterm neonate with progressive respiratory distress within the first few minutes to hours of life: tachypnea, expiratory grunting, nasal flaring, intercostal and subcostal retractions, cyanosis
Classic Physical Exam	Grunting respiration (the hallmark), chest wall retractions, nasal flaring, diminished breath sounds bilaterally, cyanosis unresponsive to supplemental oxygen in severe cases
Key Diagnostic Results	Chest X-ray: bilateral diffuse ground-glass (reticulogranular) opacities with air bronchograms and low lung volumes. Prenatal: lecithin-to-sphingomyelin (L/S) ratio < 2.0 suggests lung immaturity
Management	Prevention: antenatal corticosteroids (betamethasone). Treatment: exogenous surfactant replacement therapy, continuous positive airway pressure (CPAP), mechanical ventilation for refractory cases
Keywords	"Premature infant," "grunting," "ground-glass opacities," "air bronchograms," "surfactant deficiency," "hyaline membrane disease," "L/S ratio"

1. Pathophysiology

Surfactant is a phospholipid-protein complex produced by type II pneumocytes beginning around 24 weeks of gestation, but reaching adequate levels only near 34 to 36 weeks. Its primary function is to reduce alveolar surface tension at the air-liquid interface, thereby preventing alveolar collapse at end-expiration. The dominant phospholipid component is dipalmitoylphosphatidylcholine (DPPC, also called lecithin), and the key surfactant proteins are SP-B and SP-C, which facilitate surfactant spreading and adsorption.

In a premature infant, type II pneumocytes are structurally and functionally immature. They cannot produce sufficient surfactant. Without surfactant, alveolar surface tension increases dramatically, leading to widespread atelectasis (alveolar collapse) at end-expiration. This collapse reduces the functional residual capacity (FRC) of the lungs, meaning the neonate must generate enormous inspiratory pressures with each breath just to re-expand collapsed alveoli. This is why you see grunting: the infant is exhaling against a partially closed glottis to create auto-PEEP, an instinctive attempt to maintain alveolar patency.

The atelectasis creates significant ventilation-perfusion (V/Q) mismatch and intrapulmonary shunting. Blood passes through non-ventilated alveoli without gas exchange, resulting in hypoxemia and hypercarbia. The resulting hypoxia and acidosis cause pulmonary vasoconstriction, which further reduces pulmonary blood flow, worsens gas exchange, and damages the alveolar epithelium. Damaged capillaries leak proteinaceous fluid into the alveolar space, which forms eosinophilic hyaline membranes on histology, hence the historical name "hyaline membrane disease."

This creates a vicious cycle: surfactant deficiency leads to atelectasis, which leads to hypoxia, which leads to epithelial injury, which further impairs any residual surfactant production. Without intervention, the cycle progresses to respiratory failure.

Why does maternal diabetes increase risk? Fetal hyperinsulinemia (driven by maternal hyperglycemia crossing the placenta) directly inhibits the production of surfactant phospholipids. Insulin antagonizes the stimulatory effect of cortisol on type II pneumocyte maturation. So even at equivalent gestational ages, infants of diabetic mothers have less mature lungs.

Why does cesarean delivery without labor increase risk? The process of labor itself triggers a catecholamine surge and cortisol release in the fetus, which stimulates surfactant secretion and promotes lung fluid absorption. A scheduled cesarean section performed before labor onset bypasses this hormonal preparation.

Protective factors are worth noting because they appear as distractors. Chronic intrauterine stress (such as preeclampsia, intrauterine growth restriction, or prolonged rupture of membranes) actually accelerates fetal lung maturation through sustained cortisol exposure, reducing RDS risk.

2. Classification and Clinical Manifestation

RDS severity is graded clinically and radiographically. The Silverman-Andersen score is used to assess clinical severity at the bedside, while chest X-ray findings are staged by the degree of opacification.

Clinical Severity (Silverman-Andersen Retraction Score)

Parameter	0 (No distress)	1 (Moderate)	2 (Severe)
Upper chest movement	Synchronized with abdomen	Lag on inspiration	Seesaw (paradoxical)
Lower chest retractions	None	Just visible	Marked
Xiphoid retractions	None	Just visible	Marked
Nasal flaring	None	Minimal	Marked
Expiratory grunt	None	Audible with stethoscope	Audible without stethoscope

A total score of 0 indicates no distress; a score of 7 to 10 indicates severe respiratory distress requiring immediate intervention.

Radiographic Staging

Stage	Chest X-ray Findings
Grade I (Mild)	Fine reticulogranular (ground-glass) pattern, air bronchograms limited to perihilar region
Grade II (Moderate)	Ground-glass opacities extending to lung periphery, air bronchograms more prominent
Grade III (Severe)	Dense opacification of both lung fields, heart borders becoming indistinct
Grade IV (Very Severe)	Complete "white-out" of both lung fields, heart and diaphragm borders obliterated (no aerated lung visible)

Temporal Course of Clinical Features

Timing	Manifestation
Within minutes of birth	Tachypnea (RR > 60/min), mild grunting
2 to 6 hours	Progressive retractions, nasal flaring, worsening cyanosis, audible grunting
6 to 24 hours	Peak severity; without treatment, progressive hypoxemia and respiratory failure
48 to 72 hours	If surviving, natural improvement begins as endogenous surfactant production increases (the "turning point")

3. Diagnostic Workup

Test	Purpose	Key Findings
Chest X-ray (Best Initial Test)	Confirm clinical suspicion, grade severity	Bilateral diffuse ground-glass (reticulogranular) opacities, air bronchograms, low lung volumes, uniform involvement
Arterial blood gas (ABG)	Assess gas exchange and acid-base status	Hypoxemia ($\downarrow PaO_2$), hypercarbia ($\uparrow PaCO_2$), respiratory +/- metabolic acidosis
L/S ratio (Prenatal, if available)	Assess fetal lung maturity before delivery	L/S ratio < 2.0 indicates immature lungs; phosphatidylglycerol (PG) absent confirms immaturity
Pulse oximetry	Continuous monitoring of oxygenation	$SpO_2$ target 90 to 95% in preterm neonates
Bubble stability (shake) test	Rapid bedside surfactant assessment	Absence of stable bubbles indicates surfactant deficiency
Complete blood count, blood culture	Exclude neonatal sepsis/pneumonia	Rule out infection as an alternative or coexisting etiology

The chest X-ray is the best initial test and the cornerstone of diagnosis. In a premature neonate presenting with early-onset respiratory distress, bilateral ground-glass opacities with air bronchograms on chest X-ray are virtually diagnostic. Air bronchograms appear because the air-filled bronchi become visible against the backdrop of collapsed, opacified alveoli. Lung volumes are characteristically low because of diffuse atelectasis. This pattern is uniform and bilateral, which helps distinguish RDS from focal processes like pneumonia.

An arterial blood gas is obtained to quantify the severity of gas exchange impairment. You will see hypoxemia with a widened alveolar-arterial ($A\text{-}a$) oxygen gradient, confirming intrapulmonary shunting. Progressive hypercarbia indicates ventilatory failure and suggests the need for mechanical ventilation.

The L/S ratio is a prenatal test performed on amniotic fluid (obtained via amniocentesis). An L/S ratio $\geq$ 2.0 indicates mature surfactant production. The presence of phosphatidylglycerol (PG) is an additional marker that confirms lung maturity. PG appears late in gestation (around 35 to 36 weeks) and is not affected by blood or meconium contamination, making it a more reliable marker when the amniotic fluid sample is contaminated. Importantly, PG is absent in immature lungs regardless of the L/S ratio, so the combination of L/S < 2.0 and absent PG is highly predictive of RDS.

A sepsis workup (CBC with differential, blood culture, and sometimes C-reactive protein) must be performed because neonatal pneumonia (particularly Group B Streptococcus) can present identically. These two conditions can coexist, and you cannot distinguish them on chest X-ray alone in many cases. Empiric antibiotics (typically ampicillin + gentamicin) are often started until cultures return negative.

4. Management and Treatment

Phase	Intervention	Details
Prevention (Antenatal)	Betamethasone	12 mg IM, 2 doses 24 hours apart, given to the mother between 24 and 34 weeks if preterm delivery is anticipated
Prevention (Antenatal, alternative)	Dexamethasone	6 mg IM, 4 doses 12 hours apart (equivalent alternative to betamethasone)
Delivery Room	Initial stabilization	Gentle ventilation, CPAP at 5 to 8 cm $H_2O$, avoid aggressive bagging
First-Line Treatment	Exogenous surfactant	Poractant alfa (Curosurf): 200 mg/kg initial dose via endotracheal tube; or Beractant (Survanta): 100 mg/kg per dose, up to 4 doses every 6 hours
Respiratory Support	CPAP	Nasal CPAP at 5 to 8 cm $H_2O$; first-line non-invasive support
Respiratory Support	Mechanical ventilation	If CPAP fails ($FiO_2$ requirement > 0.40, persistent apnea, refractory hypoxemia/hypercarbia)
Oxygenation Target	Titrated $FiO_2$	Maintain $SpO_2$ 90 to 95%; avoid hyperoxia (retinopathy risk) and hypoxia
Supportive	Thermoregulation, IV fluids, glucose monitoring	Prevent hypothermia, hypoglycemia, and fluid overload

Prevention is the highest-yield testable concept in RDS management. Antenatal corticosteroids are the single most effective intervention to reduce both the incidence and severity of RDS. Betamethasone is preferred because it crosses the placenta effectively and has a longer duration of action compared to other corticosteroids. The standard regimen is 12 mg intramuscularly every 24 hours for 2 doses, administered to the mother when preterm delivery between 24 and 34 weeks is anticipated. The benefit is optimal when delivery occurs more than 24 hours but less than 7 days after the first dose. Corticosteroids accelerate type II pneumocyte maturation and stimulate surfactant synthesis.

If the neonate is born and develops RDS, the next step is respiratory support. The current approach favors early nasal CPAP, which maintains alveolar patency by providing constant distending pressure. CPAP splints the alveoli open at end-expiration (similar to what the infant's own grunting attempts to achieve, but more effectively). Many centers now practice the INSURE technique (Intubate, Surfactant, Extubate to CPAP), which delivers surfactant while minimizing the duration of mechanical ventilation. An emerging alternative is the LISA technique (Less Invasive Surfactant Administration), where surfactant is delivered through a thin catheter while the infant remains on CPAP, avoiding intubation entirely.

Exogenous surfactant is the definitive treatment. It is administered directly into the trachea via an endotracheal tube. Poractant alfa (a porcine-derived natural surfactant) at an initial dose of 200 mg/kg has been shown to produce a faster and more sustained response compared to beractant (bovine-derived) at 100 mg/kg. After administration, there is typically a rapid improvement in oxygenation and lung compliance within minutes.

Mechanical ventilation is reserved for infants who fail CPAP. Indications include persistent $FiO_2$ requirement above 0.40 to maintain target saturations, recurrent apnea, or worsening respiratory acidosis ($pH < 7.20$, $PaCO_2 > 60$ mmHg). Gentle ventilation strategies using low tidal volumes (4 to 6 mL/kg) and permissive hypercapnia ($PaCO_2$ targets of 45 to 55 mmHg) are preferred to minimize ventilator-induced lung injury, which is a precursor to bronchopulmonary dysplasia (BPD).

Oxygen must be carefully titrated. The target $SpO_2$ in preterm infants is 90 to 95%. Excessive oxygen (hyperoxia) increases the risk of retinopathy of prematurity (ROP) and contributes to oxidative lung injury. Insufficient oxygen increases mortality. This narrow therapeutic window is a frequently tested concept.

Complications to Anticipate

Complication	Mechanism	Prevention/Management
Bronchopulmonary dysplasia (BPD)	Chronic lung injury from ventilation and oxygen	Minimize ventilator support, use gentle ventilation, caffeine citrate
Patent ductus arteriosus (PDA)	Prematurity delays ductal closure	Indomethacin or ibuprofen; surgical ligation if refractory
Intraventricular hemorrhage (IVH)	Fragile germinal matrix vessels in preterm brain	Avoid fluctuations in blood pressure and ventilation
Retinopathy of prematurity (ROP)	Oxygen toxicity to developing retinal vessels	Strict $SpO_2$ monitoring, ophthalmologic screening
Necrotizing enterocolitis (NEC)	Intestinal ischemia and immaturity	Preferential use of breast milk, cautious feeding advancement
Pneumothorax	Alveolar overdistension from CPAP or ventilator	Monitor for acute deterioration, transillumination, needle decompression

5. Differential Diagnosis and Distractors

Differential	Why It Looks Similar	Key Discriminator
Transient tachypnea of the newborn (TTN)	Also presents with tachypnea shortly after birth; also associated with cesarean delivery	TTN occurs in term or near-term infants, resolves within 24 to 72 hours without surfactant, and chest X-ray shows prominent perihilar streaking, fluid in fissures, and hyperinflated lungs (not ground-glass with low volumes)
Neonatal pneumonia (GBS)	Early-onset respiratory distress in a newborn; chest X-ray can show bilateral opacities	Look for maternal risk factors: prolonged rupture of membranes (> 18 hours), maternal fever, GBS colonization without prophylaxis. CXR may show focal or asymmetric infiltrates. CBC may show leukocytosis or leukopenia with left shift
Meconium aspiration syndrome (MAS)	Respiratory distress at birth with abnormal chest X-ray	Occurs in term or post-term infants with meconium-stained amniotic fluid. CXR shows coarse, irregular, patchy opacities with hyperinflation (air trapping), not the uniform ground-glass of RDS
Congenital diaphragmatic hernia (CDH)	Severe respiratory distress at birth, abnormal chest X-ray	Scaphoid (concave) abdomen on exam, bowel sounds in the chest, CXR shows bowel loops in the thorax with mediastinal shift. No ground-glass pattern
Persistent pulmonary hypertension of the newborn (PPHN)	Severe cyanosis and hypoxemia in a newborn	Typically term infant with a history of perinatal stress. Key finding: differential cyanosis (pre-ductal $SpO_2$ higher than post-ductal). CXR may show clear lung fields or minimal disease (disproportionate hypoxemia relative to CXR findings)
Congenital heart disease (cyanotic)	Cyanosis shortly after birth, may have tachypnea	Cyanosis that does not improve with supplemental oxygen (failed hyperoxia test: $PaO_2$ remains < 100 mmHg on 100% $FiO_2$). Murmur may be present. Echocardiography is diagnostic

6. Traps and High-Yield Pearls

The most common way students lose points on RDS questions is by confusing it with transient tachypnea of the newborn (TTN). Both present with respiratory distress shortly after birth and are associated with cesarean delivery. The critical discriminator is gestational age and chest X-ray pattern: RDS occurs in premature infants and shows ground-glass opacities with low lung volumes, while TTN occurs in term or near-term infants and shows hyperinflated lungs with perihilar streaking and fluid in the fissures. If the vignette describes a 28-week neonate with grunting and ground-glass opacities, that is RDS. If it describes a 38-week infant born via elective cesarean with tachypnea and streaky perihilar markings that resolve in 48 hours, that is TTN.

Another common trap involves maternal diabetes. Students often assume that a large-for-gestational-age (LGA) baby of a diabetic mother is "healthy" because of the large size. In reality, the fetal hyperinsulinemia delays surfactant maturation, putting this infant at higher risk for RDS even at later gestational ages than expected.

Watch for questions testing the timing of antenatal corticosteroids. The benefit requires at least 24 hours to take effect. If a mother presents in active preterm labor and delivers within 2 hours, the corticosteroids will not have had time to work. The vignette may present this scenario and then ask about the neonate's risk for RDS, and the answer is that the risk remains elevated despite receiving the first dose.

Finally, understand the oxygen management principle. A question may present an improving preterm infant on supplemental oxygen and ask about the target $SpO_2$. The answer is 90 to 95%. Targeting higher saturations (> 95%) increases retinopathy of prematurity risk, while targeting lower saturations (< 85%) increases mortality. This narrow range is a favorite testing point, and students who default to "normal" adult oxygen saturation goals will choose the wrong answer.

The core competency being tested across all RDS questions is the ability to integrate gestational age, clinical presentation, radiographic findings, and the pathophysiology of surfactant deficiency into a coherent clinical picture, and then to sequence the management correctly: prevent with corticosteroids, support with CPAP, treat with surfactant, and escalate to mechanical ventilation only when necessary.

1e:["$","$L2d",null,{"article":{"id":"49809dbc-1b73-4182-aa1e-a71e337ef0fa","title":"Respiratory Distress Syndrome (RDS)","content":"$2e","category":"Respirologi","created_at":"2026-07-02T02:04:06.903939+00:00","status":"published","subcategory":null},"questionCount":0,"sections":[{"id":"section-pathophysiology","num":"01","title":"Pathophysiology"},{"id":"section-classification-and-clinical-manifestation","num":"02","title":"Classification and Clinical Manifestation"},{"id":"section-diagnostic-workup","num":"03","title":"Diagnostic Workup"},{"id":"section-management-and-treatment","num":"04","title":"Management and Treatment"},{"id":"section-differential-diagnosis-and-distractors","num":"05","title":"Differential Diagnosis and Distractors"},{"id":"section-traps-and-high-yield-pearls","num":"06","title":"Traps and High-Yield Pearls"}],"hasSummaryTable":true}]