Respiratory Distress Syndrome (RDS) is a condition seen primarily in premature infants caused by a lack of pulmonary surfactant. This deficiency leads to alveolar collapse and respiratory failure. The risk of developing RDS increases the younger the gestational age. Clinical presentation includes tachypnea, retractions, and hypoxemia. Diagnosis is made based on clinical features and chest x-ray showing diffuse lung opacities. Treatment focuses on supportive care including oxygen therapy and mechanical ventilation. Surfactant replacement therapy is also used to reduce mortality from RDS.

1. P H O N G T H O R N T U N T I V A R A R U T
P R E S E N T E R
U R A R O M P A N T U M A P O L
A D V I S O R
Respiratory Distress Syndrome

2. Respiratory Distress Syndrome (RDS)
 Also known as Hyaline Membrane Disease (HMD)
 RDS occurs primarily in premature infants; its
incidence is inversely related to gestational age and
birthweight
Gestational age Percentages
Less than 28 wks 60-80%
32-36 wks 15-30%
37-39 wk 5%
Term Rare
Nelson Textbook of Pediatrics, 18th Ed.

3. Incidence of RDS
 The risk of developing RDS increases with :
 Maternal diabetes, multiple births, cesarean section delivery,
perinatal asphyxia, cold stress, and a history of previously
affected infants
 The risk of RDS is reduced in pregnancies with :
 Chronic or pregnancy-associated hypertension, maternal
heroin use, prolonged rupture of membranes, and antenatal
corticosteroid prophylaxis

4. Etiology & Pathophysiology
 Surfactant deficiency (decreased production and
secretion) is the primary cause of RDS
 The failure to attain an adequate FRC and the tendency of
affected lungs to become atelectatic correlate with high surface
tension and the absence of pulmonary surfactant
 The major constituents of surfactant
 Dipalmitoyl phosphatidylcholine (lecithin) <- Major component
 Phosphatidylglycerol
 Apoproteins (surfactant proteins SP-A, -B, -C, -D)
 Cholesterol

5. Nelson Textbook of Pediatrics, 18th Ed.

6. Etiology & Pathophysiology
 Surfactant is produced by Type II pneumocytes
(Great alveolar cells) and present in high
concentrations in fetal lung by 20 wk of gestation,
but it does not reach the surface of the lungs
 Surfactant appears in amniotic fluid between 28 and
32 wk of gestation
 Mature levels of pulmonary surfactant are usually
present after 35 wk (L/S ratio = 2:1)

7. Etiology & Pathophysiology
Advancing gestational age
Increasing amounts of phospholipids are
synthesized and stored in type II alveolar cells
Surface-active agents are released into the alveoli
(Air-Liquid Interface)
Reduce surface tension of the water and help
maintain alveolar stability by preventing the
collapse of small air spaces at end-expiration

8. Etiology & Pathophysiology
 Genetic disorders may contribute to respiratory
distress :
 Abnormalities in surfactant protein B and C genes
 Abnormalities in gene responsible for transporting surfactant
across membranes (ABC transporter 3 [ABCA3])

9. Fetal rat lung, day 20
(term, day 22)
showing developing type
II cells, stored glycogen
(pale areas), secreted
lamellar bodies, and
tubular myelin
Nelson Textbook of Pediatrics, 18th Ed.

10. Etiology & Pathophysiology
 Synthesis of surfactant depends in part on
 Normal pH
 Temperature
 Perfusion
 The epithelial lining of the lungs may also be injured
by high oxygen concentrations and the effects of
respirator management, thereby resulting in a
further reduction in surfactant

11. Etiology & Pathophysiology
 The highly compliant chest wall of preterm infants
offers less resistance to the natural tendency of the
lungs to collapse
 At end-expiration, the volume of the thorax and
lungs tends to approach residual volume, and
atelectasis may develop

13. Etiology & Pathophysiology
Deficient
synthesis or
release of
surfactant
Atelectasis and
results in
perfused but
not ventilated
alveoli
Hypoxia
Small respiratory
units and a
compliant chest
wall

14. Nelson Textbook of Pediatrics, 18th Ed.

15. Pathology
 The lungs appear deep purplish red and are liver-
like in consistency
 Extensive atelectasis
with engorgement of
the interalveolar
capillaries and
lymphatics

16. Liver-like consistency
of the lungs

17. Clinical manifestations
 Characteristically, tachypnea, prominent (often
audible) grunting, intercostal and subcostal
retractions, nasal flaring, and duskiness are noted
 Signs of RDS usually appear within minutes of birth,
although they may not be recognized for several
hours in larger premature infants until rapid,
shallow respirations have increased to 60/min
or greater

18. Clinical manifestations
 Breath sounds may be normal or diminished with a
harsh tubular quality
 Fine rales may be heard, especially posteriorly over
the lung bases
 Apnea and irregular respirations occur as
infants tire and are ominous signs requiring
immediate intervention

19. Clinical manifestations
 In most cases, the symptoms and signs reach a peak
within 3 days, after which improvement is gradual
 Death is rare on the 1st day of illness, usually occurs
between days 2 and 7
 associated with alveolar air leaks (interstitial emphysema,
pneumothorax), pulmonary hemorrhage, or IVH.
 Mortality may be delayed weeks or months if BPD
develops in mechanically ventilated infants with
severe RDS

20. Clinical diagnosis
 On X-ray, the lungs may have a characteristic, but
not pathognomonic appearance
 Fine reticular granularity of the parenchyma
 Air bronchograms
 More prominent early in the left lower lobe because of
superimposition of the cardiac shadow
 Typical pattern developing at 6–12 hr.
 Laboratory findings are initially characterized by
hypoxemia and later by progressive hypoxemia,
hypercapnia, and variable metabolic acidosis

21. Infant with respiratory distress syndrome. Note the granular lungs, air bronchogram, and air-filled
esophagus. ( A is the endotracheal tube; B is the umbilical venous catheter at the junction of the umbilical
vein, ductus venosus, and portal vein; C is the umbilical artery catheter passed up the aorta to T12)
Nelson Textbook of Pediatrics, 18th Ed.

22. Ground glass appearance
• Fine reticulogranular
• Air bronchogram

23. Progression of the disease
 Acute phase
 First 48-72 hr. after birth, newborn begins to have tachypnea,
chest tightness
 The sign and symptoms are peak on day 1-2
 Patients may death if they did not receive adequate treatment
 Recovery phase
 Started on day 3-5
 Type II Pneumocytes are regenerated
 Decreased oxygen requirement

24. Differential diagnosis
 Group B streptococcal pneumonia
 Transient tachypnea of the newborn (TTNB)
 Diaphragmatic hernia
 More common in term newborn
 Total anomalous pulmonary venous return (TAPVR)

25. Treatments
 Because most cases of RDS are self-limited, the goal
of treatment is to minimize abnormal physiologic
variations and superimposed iatrogenic problems
 There are 4 main treatments for RDS :
 Supportive treatments
 Oxygen therapy
 Mechanical ventilation
 Surfactant replacement therapy

26. Supportive treatment
 Body temporature
 Scheduled “touch times” to avoid hypothermia and minimize
oxygen consumption
 Placed in an isolette or radiant warmer to maintaine core
temperature between 37 ± 0.5 °C

27. Supportive treatment
 Nutritional support
 For the 1st 24 hr, 10%DW should be infused through a
peripheral vein at a rate of 65–75 mL/kg/day
 For VLBW and ELBW, TPN should be added
 Day 2-3, Na 3-4 mEq/kg/day and K 2-3 mEq/kg/day
should be added (TV not more than 90 ml/kg/day)
 Excessive fluids (>140 cc/kg/day) contribute to the
development of PDA and BPD
 On day 1, if good clinical, step feed by started at 0.5-1 ml/kg x
8 feeds drip in 1-2 hr with TPN (TV 80-100)

28. Supportive treatment
 Others
 Give a blood transfer when Hct is less than 40% (* Protocol)

29. Hgb RESPIRATORY SUPPORT AND/OR SYMPTOMS
TRANSFUSION
VOLUME
Hct ≤ 35/
Hgb ≤ 11
Infants requiring moderate or significant mechanical ventilation (MAP >
8 cm H2O and Fio2 > 0.4)
15 mL/kg PRBCs[*] over
period of 2–4 hr
Hct ≤ 30/
Hgb ≤ 10
Infants requiring minimal respiratory support (any mechanical
ventilation or endotracheal/nasal CPAP > 6 cm H2O and Fio2 ≤ 0.4)
15 mL/kg PRBCs over
period of 2–4 hr
Hct ≤ 25/
Hgb ≤ 8
Infants not requiring mechanical ventilation but who are receiving
supplemental O2 or CPAP with an Fio2 ≤ 0.4 and in whom 1 or more of
the following is present:
20 mL/kg PRBCs over
period of 2–4 hr (divide
into 2–10 mL/kg volumes
if fluid sensitive)
• ≤24 hr of tachycardia (HR > 180) or tachypnea (RR > 80)
• An increased oxygen requirement from the previous 48
hr, defined as a ≥4-fold increase in nasal canula flow (i.e.,
0.25 to 1 L/min) or an increase in nasal CPAP ≥ 20%
from the previous 48 hr (i.e., 5 to 6 cm H2O)
• Weight gain <10 g/kg/day over the previous 4 days while
receiving ≥100 kcal/kg/day
• An increase in episodes of apnea and bradycardia (>9
episodes in a 24-hr period or ≥2 episodes in 24 hr
requiring bag and mask ventilation) while receiving
therapeutic doses of methylxanthines
• Undergoing surgery
Hct ≤ 20/
Hgb ≤ 7
Asymptomatic and an absolute reticulocyte count <100,000 cells/μL
20 mL/kg PRBCs over
period of 2–4 hr (2–10
mL/kg volumes)
* RBC should be irradiated prior to transfusion Nelson Textbook of Pediatrics, 18th Ed.

30. Oxygen therapy
 Warm humidified oxygen should be provided at a
concentration initially sufficient to keep PaO2 50-80
mmHg, pH 7.25-7.45, PaCO2 40-50 mmHg and SpO2
90–95%
 to maintain normal tissue oxygenation while minimizing the
risk of oxygen toxicity
 O2 box is not recommended for newborn with VLBW
and ELBW because of high concentration of O2 may
increase risk of ROP

31. Oxygen therapy
 If the PaO2 cannot be maintained above 50 mmHg at
inspired oxygen concentrations of 60% or greater,
applying CPAP at a pressure of 5–10 cm H2O by
nasal prongs
 CPAP prevents collapse of surfactant-deficient alveoli,
improves FRC, and improves ventilation-perfusion matching
 The amount of CPAP required usually decreases
abruptly at about 72 hr of age, and infants can be
weaned from CPAP shortly thereafter

32. Mechanical ventilation
 Continue positive airway pressure (CPAP) is being
use with 4-8 cm·H2O
 To make Functional residual capacity (FRC) for the lung to
prevent atelectasis
 Usually started with 5 cm·H2O and increased by 1 cm·H2O in
subsequent with increase oxygen by 10%
 Routes of administration
 Nasal prongs
 Nasopharyngeal tube

33. Mechanical ventilation
 Indication for ventilator
 Apnea with no improvement
 Cyanosis or PaO2 ≤ 40 mmHg (when using CPAP and high
oxygen concentration)
 Signs of Respiratory failure
 PaCO2 > 60 mmHg
 Metabolic acidosis

34. Surfactant replacement therapy
 Surfactant replacement therapy can reduce mortality
and incidence of Chronic pulmonary disease
 There are 2 types of surfactant :
1. Natural surfactant extract
 Bovine(Survanta), Porcine(Curosurf), Surfacten, Alveofact and
Calf (Infasurf)
2. Synthetic surfactant
 Exosurf and ALEC (Artificial Lung Expanding Compound)

35. Surfactant replacement therapy
 Natural surfactants appear to be superior, perhaps
because of their surfactant-associated protein
content
 Natural surfactants have a more rapid onset and
are associated with a lower risk of
pneumothorax and improved survival

36. Surfactant replacement therapy
 The 2 main indications :
 Prophylactic treatment
 Being use for infant delivered during 23-29 wk of gestation and
birth weight 600-1250 g
 Results :
 Improve dyspnea in first 48-72 hr of life (Decrease O2
requirement, ventilation improved)
 Decreased incidence of pneumothorax and BPD
 Not affect the incidence of IVH and PDA
 Decrease mortality

37. Surfactant replacement therapy
 The 2 main indications :
 Therapeutic or Rescue treatment
 Initiated as soon as possible in the 1st 24 hr of life
 Repeated dosing is given via the endotracheal tube every 6–12 hr
for a total of 2 to 4 doses, depending on the preparation
 Results :
 Clinical improved (Decrease O2 requirement)
 Decreased incidence of pneumothorax
 Not affect the incidence of BPD, IVH and PDA
 Decrease mortality
There is no significantly difference between single dose and multiple dose
of surfactant replacement therapy (Dunn et al. and Speer et al.)

39. Complication
 Bronchopulmonary dyaplasia (BPD)
 Result of lung injury in infants requiring mechanical
ventilation and supplemental oxygen
 disease of more mature preterm infants with RDS treated with
positive pressure ventilation and oxygen
 BPD is usually defined as a need for supplemental oxygen at 36
wk after conception
 Another definition of BPD is based on the severity of disease
 Neonates on positive pressure support or receiving >30%
supplemental oxygen are diagnosed with BPD

40. GA <32 WK ≥32 WK
Time point of
assessment
36 wk PMA or discharge home
Treatment with >21% oxygen
for at least 28 days plus
> 28 days but < 56 days
postnatal age or discharge home
Treatment with 21% oxygen for
at least 28 days plus
Mild BPD Breathing room air at 36 wk
PMA or discharge
Breathing room air by 56 days
postnatal age or discharge
Moderate BPD Need[*] for < 30% oxygen at 36
wk PMA or discharge
Need[*] for < 30% oxygen at 56
days postnatal age or discharge
Severe BPD Need[*] for ≥ 30% oxygen
and/or positive pressure (PPV
or NCPAP) at 36 wk PMA or
discharge
Need[*] for ≥ 30% oxygen
and/or positive pressure (PPV
or NCPAP) at 56 days' postnatal
age or discharge
* A physiologic test confirming that the oxygen requirement at the assessment
time point remains to be defined.
Nelson Textbook of Pediatrics, 18th Ed.

41. Complication
 Physiologic test
 Those receiving 30% oxygen or less undergo a stepwise 2%
reduction in supplemental oxygen to room air while under
continuous observation and oxygen saturation monitoring.
 Outcomes are “no BPD” (saturations 88% or greater for 60
min) or “BPD” (saturation <88%)
 This test is highly reliable and correlated with
discharge home in oxygen, length of hospital stay,
and hospital readmissions in the 1st yr of life

42. Complication
 Patent ductus arteriosus (PDA)
 Delayed closure of the PDA is associated with hypoxia,
acidosis, increased pulmonary pressure secondary to
vasoconstriction, systemic hypotension, immaturity, and local
release of prostaglandins, which dilate the ductus
 As RDS resolves, pulmonary vascular
resistance decreases, and left-to-right
shunting may occur and lead to left
ventricular volume overload and pulmonary
edema

43. Complication
 Patent ductus arteriosus (PDA)
 Manifestations of PDA may include :
 Apnea for unexplained reasons in an infant recovering from RDS
 Hyperdynamic precordium, bounding peripheral pulses, wide
pulse pressure, and a continuous or systolic murmur with or
without extension into diastole or an apical diastolic murmur,
multiple clicks resembling the shaking of dice
 Carbon dioxide retention
 Increasing oxygen dependence
 X-ray evidence of cardiomegaly and increased pulmonary vascular
markings
 Hepatomegaly

44. Complication
 Intraventricular hemorrhage (IVH)
 Commonly occurs on day 3-4 in preterm newborn with low
birth weight and severe RDS
 Can be detected by Brain ultrasonography

45. Complication
 Intraventricular hemorrhage (IVH)
 Grading of IVH
 Grade 1 - bleeding occurs just in a small area of the ventricles
 Grade 2 - bleeding also occurs inside the ventricles
 Grade 3 - ventricles are enlarged by the blood
 Grade 4 - bleeding into the brain tissues around the ventricles

46. Prevention
 Avoidance of preterm labor
 Avoidance of unnecessary cesarean section
 Evaluation of L/S ratio for lung maturity
 L/S ratio = 2:1 in mature lung
 Foam test (Shake test)
 Administration of corticosteroid before labor

47. Prevention
 Corticosteroid administration is recommended for
all women in preterm labor (24–34 wk gestation)
who are likely to deliver a fetus within 1 wk
Betamethasone 12 mg IM q 24 hr for 2 doses
 Repeated weekly doses of betamethasone until 32 wk
Dexamethasone 6 mg IM q 12 hr for 4 doses

48. Prevention
 Prenatal dexamethasone may be associated with a
higher incidence of periventricular
leukomalacia than betamethasone
 The relative risk of RDS, IVH and death is higher
with antenatal dexamethasone treatment when
compared with betamethasone

49. Prevention
Administration of a 1st dose of surfactant into
the trachea of symptomatic premature infants
immediately after birth (prophylactic) or during the
1st few hours of life (early rescue) reduces air leak
and mortality from RDS

50. References
 Robert M. Kliegman, Richard E. Behrman, Hal B.
Jenson, Bonita M.D. Stanton. Nelson Textbook of
Pediatrics. Saunders; 18th edition, 2007:
 พิมลรัตน์ ไทยธรรมยานนท์. การดูแลทารกแรกเกิด. ชัยเจริญ,
2554: 149-157

51. …Thank you…