All you need to know about respiratory distress syndrome, also hyaline membrane disease

1. RESPIRATORY DISTRESS
SYNDROME
(Hyaline membrane disease)
PAEDS REFRESHER- 2023, SEPTEMBER
Presented by Dr DA Koli
MOIVOI CRH

2. Neonatal respiratory distress syndrome (RDS) occurs from
a deficiency of surfactant, due to either inadequate
surfactant production, or surfactant inactivation in the
context of immature lungs. Prematurity affects both these
factors, thereby directly contributing to RDS
Most commonly in those born at < 37 weeks gestation.
Risk increases with degree of prematurity.

3. INTRODUCTION
 RDS occurs in babies born early(premature) whose lungs are not fully developed.The
earlier the infant is born, the more likely it is for them to have RDS and need extra oxygen
and help to breathe.
 Cause- baby does not have enough surfactant(anti-surface tension) in the lungs.
 Surfactant is a liquid substance made in the lungs at about 26-34 weeks of
gestation/pregnancy.As the fetus grows, the lungs make more surfactant.
 The surfactant coats the lining of the tiny air sacs(alveoli) in the lungs and help keep them
from collapsing on self.The air sacs must be open to allow oxygen to enter the blood from
the lungs and carbon dioxide release from the capillaries into the lung.
 While RDS is common in prematures, other newborns can also get it. More common in
those born before 37-39 weeks, and uncommon in full-term babies(after 39 weeks).

4. PATHOPHYSIOLOGY
 Surfactant deficiency increases surface tension within small airways and alveoli,
thereby reducing the compliance of the lung.
 Usually there is a delicate balance of pressures at the air-fluid interface essentoial
to prevent the compliance of the alveoli or filling of the alveoli with fluid.
 Can be described using LaPlace law……P=2T/R, where P is pressure,T is surface
tension, and R is the radius of the alveoli. Describes the relationship between the
pressure difference across the interface of two static fluids to the shape of the
surface
 As the surface tension increases at the alveolar level, the amount of pressure
required to maintain alveolar shape increases. With reduced surfactant
production, atelectasis occurs throughout the lung, causing reduced gas
exchange.

5.  Widespread and repeated atelectasis eventually damages the respiratory epithelium, causing a cytokine-
mediated inflammatory response. As pulmonary edema develops as a result of the inflammatory
response, increasing amounts of protein-rich fluid from the vascular space to leak into the alveoli, which
further inactivate surfactant.
 Furthermore, many infants with RDS require mechanical ventilation, which may have deleterious effects
on the lung.
 Overdistension of the alveoli during positive pressure ventilation leads to further damage and
inflammation.
 Besides, oxidative stress generated both by high oxygen tensions from mechanical ventilation and
inflammatory processes within the lung also promotes the conversion of surfactant into an inactive form
through protein oxidant damage and lipid peroxidation.
 Thus RDS can cause hypoxemia through alveolar hyperventilation, diffusion abnormality, ventilation-
perfusion mismatch, intrapulmonary shunting, or a combination of these mechanisms.This hypoxemia
and tissue hypoperfusion ultimately lead to increased anaerobic metabolism at a cellular level with
resultant lactic acidemia.

6. HISTOPATHOLOGY
 Historically, neonatal respiratory distress syndrome was known as hyaline
membrane disease, owing to an eosinophilic membrane that lines the distal
airspaces, usually terminal bronchioles or alveolar ducts, in autopsies of neonates
with RDS.
 Macroscopically, lung tissue from infants with RDS appears similar to hepatic
tissue with a ruddy appearance.
 The hyaline membrane mentioned above is composed of fibrin, cellular debris
from lung epithelium, red blood cells, and leukocytes.
 Microscopic histological examination may also reveal pulmonary tissue with few
dilated alveoli among diffuse areas of atelectasis

7. STAGES OF FETAL LUNG DEVELOPMENT
 Development of the lower respiratory tract begins on day 22 of embryogenesis
and continues to form the trachea, lungs, bronchi and alveoli.
 The process divides into 5 stages: embryonic, pseudo-glandular, canalicular,
saccular and alveolar stage.

10. EPIDEMIOLOGY
In the United States, estimated to occur in 20,000-30,000 newborn infants each
year and is a complication in about 1% pregnancies.
Approximately 50% of the neonates born at 26-28 weeks' gestation develop rds,
whereas less than 30% of premature neonates born at 30-31 weeks' gestation
develop the condition.
In one report, the incidence rate of respiratory distress syndrome was 42% in
infants weighing 501-1500g, with 71% reported in infants weighing 501-750g, 54%
reported in infants weighing 751-1000g, 36% reported in infants weighing 1001-
1250g, and 22% reported in infants weighing 1251-1500g, among the 12 university
hospitals participating in the National Institute of Child Health and Human
Development (NICHD) Neonatal Research Network.

11. International data
 Respiratory distress syndrome is encountered less frequently in developing
countries than elsewhere, primarily because most premature infants who are
small for their gestation are stressed in utero because of malnutrition or
pregnancy-induced hypertension.
 In addition, because most deliveries in developing countries occur at home,
accurate records in these regions are unavailable to determine the frequency of
respiratory distress syndrome.
Race-related demographics
 Rds has been reported in all races worldwide, occurring most often in white
premature infants.

12. DIFFERENTIALS FOR NEONATAL
RESPIRATORY DISTRESS

13. DIFFERENTIALS IN RESPIRATORY DISTRESS
 There are numerous causes of neonatal respiratory distress syndrome, including
transient tachypnea of the newborn, pulmonary air leak disorders
(pneumothorax, pneumomediastinum), neonatal pneumonia, meconium
aspiration, persistent pulmonary hypertension of the newborn, and the broad
categories of cyanotic congenital heart disease and interstitial lung disease.
 Infants with transient tachypnea of the newborn have impaired resorption of the
fetal lung fluid and have marked tachypnea soon after birth, but symptoms
generally improve after 24 hours. Chest radiograph shows perihilar streaking,
representing perihilar interstitial edema, without the diffuse reticulo-granular
ground glass appearance of RDS.

14.  Pulmonary air leak syndromes such as pneumothorax and pneumomediastinum may also
present as respiratory distress, but the onset of symptoms may be more acute. Other clinical
clues include chest rise asymmetry, and diminished breath sounds on one side of the chest.
Hyperlucent areas on chest radiography can be appreciated if the air leak is significant.
Pulmonary interstitial emphysema affects infants who are mechanically ventilated; symptoms
of respiratory distress often occur later than expected with RDS, and the trapped air within the
perivascular tissues has a characteristic appearance of cystic lucencies on chest radiography.
 Bacterial pneumonia, especially related to Group B Streptococcus in a newborn is often
clinically and radiographically indistinguishable from RDS.The preferred treatment includes
empirical antibiotics in addition to respiratory management.
 Infants with cyanotic congenital heart disease may have similar symptoms clinically, but will
not have the diffuse reticulo-granular ground glass appearance on chest radiography.The
radiological findings depend on the underlying anatomic abnormality.

15. RISK FACTORS
 Siblings that had RDS
 Twin or multiple births
 C-section delivery without labor
 Diabetic mother
 Asthmatic mother
 Infections in pregnancy
 Sick baby at time of delivery
 Hypothyroidism
 Cold, stress, or hypothermia….baby cannot keep body temperature warm at birth.
 Genetic problems with lung development
 Male gender
 White race more than other races
 Prematurity
 Perinatal asphyxia
 Monozygotic more than dizygotic twins
 Rare recessive mutations of SP-B and SP-C genes
 Associated with deletions in ATP BINDING CASSETTE SUB-FAMILY A, member 3(ABCA-3)

16. PRESENTATION…HISTORY AND PHYSICAL
Symptoms and signs include:
- grunting…”ugh” sound with each breath
- fast breathing soon after birth
- use of accessory muscles
- nasal flaring (widening of nostrils with each breath)
appearing soon after birth.
- Xiphoid (supra and sub),subcostal/lower chest wall and
intercostal retraction
- Cyanosis….lips, fingers , toes, body colour
- Reduced urine output
- A premature infant…low ballard score
- In obvious respiratory distress usually immediately after
birth, or within minutes
- May have decreased breath sounds
- Possible diminished peripheral pulses

17. DIAGNOSIS
 Diagnosis is clinical….history plus physical assessment of the infant
 prenatal risk can be assessed with tests of fetal lung maturity.- amniocentesis for
biochemical markers(usually after 32 weeks’ gestation), lecithin: sphingomyelin ratio,
presence or absence of phospatidyl -glycerol, lamellar body counts, gray scale ultrasound
scan and MRI.
 Normal L/S ratio is 2.0-2.5. Less than 2.0 suggests immature fetal lung
 Fetal crown-rump length on son0graphy (CRL) in centimeters plus 6.5 equals gestational
age in weeks
 Blood tests- cbcs, esr, cultures, bga’s, blood glucose
 Chest xrays of the infant…..pronounced hypoaeration, xtic ground glass
appearance(bilateral fine granular opacities in the pulmonary parenchyma), and
peripherally extending air bronchograms

18. EVALUATION
 Since the definition of neonatal respiratory distress syndrome is imprecise,
prompt diagnosis and treatment require an overall assessment of prenatal and
delivery history to identify perinatal risk factors, clinical presentation,
radiographic findings, and evidence of hypoxemia on blood gas analysis.
 Chest Radiography
Chest radiography findings pathognomonic of RDS include homogenous lung
disease with diffuse atelectasis, classically described as having a ground-glass
reticulo-granular appearance with air bronchograms, as well as low lung volumes.
The air-tissue interface formed between microalveolar collapse in the background
with the air-filled larger airways in the foreground creates the classic appearance of
air bronchograms.

19.  Arterial Blood Gas Analysis
 Arterial blood gas analysis may show hypoxemia that responds to increased oxygen
supplementation and hypercapnia. Serial blood gases may show evidence of worsening
respiratory and metabolic acidosis, including lactic acidemia in infants with worsening
RDS.
 Other Investigations
 An echocardiogram may show the presence of a patent ductus arteriosus that might
complicate the clinical course of RDS.
 Complete blood counts may show evidence of anemia and abnormal leukocyte counts,
suggesting infection.At times, a workup for infectious etiologies may be necessary,
including blood, cerebrospinal fluid, and tracheal cultures (when appropriate).

21. TREATMENT
 Treatment is surfactant therapy and supportive care.
 The goals of optimal management of neonatal respiratory distress syndrome include decreasing
incidence and severity using antenatal corticosteroids, followed by optimal management using
respiratory support, surfactant therapy, and overall care of the premature infant.
- Antenatal corticosteroids…dexamethasone 12mg bd for 24 hrs before delivery
- Monitoring oxygenation and ventilation
- Assisted ventilation of the neonate
- Exogenous surfactant therapy
- Supportive care, including thermoregulation, nutritional support, fluid and electrolyte management,
antibiotic therapy, etc.
 In untreated RDS, the symptoms will progressively worsen over 48 to 72 hours towards respiratory failure,
and the infant may become lethargic and apneic.The infant may also develop peripheral extremity edema
and show signs of decreased urine output.

22. MonitoringOxygenation andVentilation
 Serial blood gas monitoring may be necessary to optimize oxygenation and ventilation.
Ideally, the neonates undergo blood gas monitoring using an umbilical or peripheral
arterial catheter placed using a sterile technique.The partial pressure of arterial oxygen
(PaO2) on an arterial blood gas is maintained between 50 to 80 mmHg, and partial
pressure of arterial carbon dioxide (PaCO2) is maintained between 40 to 55 mmHg, with
the pH >7.25.
 Non-invasive pulse oximetry is now the standard of care to monitor oxygen saturation
(SaO2). Unclear higher limits often limit the utility of pulse oximetry, since PaO2 could be
significantly higher at the SaO2 levels >95%.
 Non-invasive capnography and transcutaneous carbon dioxide monitoring are used as
adjuncts for monitoring ventilation.

23. AssistedVentilation of the Neonate
 To reduce atelectasis by providing a constant distending positive airway pressure.
The current preferred strategy is the early initiation of continuous positive airway
pressure (CPAP) with selective surfactant administration.
 In most institutions, non-invasive modalities are preferred over invasive
ventilation as they decrease the risk of mortality, and bronchopulmonary
dysplasia (BPD) compared to invasive ventilation with or without surfactant.

24. CPAP
Continuous Positive Airway Pressure (CPAP):
Nasal CPAP is an initial intervention in preterm infants with RDS or risk of RDS
without respiratory failure.
Multiple modalities available for CPAP delivery, including ventilator derived CPAP as
well as a less expensive bubble CPAP device.
Infants who received CPAP fared as well as infants who received prophylactic
surfactant therapy along with mechanical ventilation in the SUPPORT trial
(Surfactant Positive Airway Pressure and Pulse Oximetry RandomizedTrial), and
those who received early CPAP had a reduced need for surfactant therapy.
Also, the incidence of BPD decreased with the use of CPAP.
The goals of treatment include keeping SpO2 between 90-95%, and PaCO2
between 45-65 mmHg.

25. NIPPVVS CPAP
Non-invasive Respiratory Support:
Nasal Intermittent Positive PressureVentilation (NIPPV) appears superior to CPAP
alone for decreasing extubation failure, the need for intubation in preterm infants,
but the same in cost and safety.
The primary difference in NIPPV and CPAP is that NIPPV requires a ventilator to
provide positive pressure ventilation, while CPAP may use a less expensive device
such as bubble CPAP to deliver the appropriate pressures.

26. High Flow Nasal Canula:
 Heated humidified high-flow nasal cannulas (HFNC) are also used in some centers as an alternative to CPAP to provide
positive distending pressure ventilation to neonates with RDS. As seen in a clinical trial by Roberts et al., HFNC was
found to be inferior to CPAP.
MechanicalVentilation:
 Patients who do not respond to CPAP, develop respiratory acidosis (PH < 7.2 and PaCo2 > 60-65 mm of Hg), hypoxemia
(PaO2 < 50 mm of Hg or Fio2 > 0.40 on CPAP), or severe apnea are managed with endotracheal intubation and
mechanical ventilation.
 The goals of mechanical ventilation include providing adequate respiratory support while balancing the risks of
barotrauma, volutrauma, and oxygen toxicity.
 Time-cycled pressure limited ventilation is the preferred initial mode of ventilation in preterm infants with RDS.
 High-frequency oscillatory ventilation (HFOV) and high-frequency jet ventilation (HFJV) are often used as rescue
modalities when requiring high conventional ventilator support or concerns for pulmonary air leaks.
 Other strategies include the use of high-frequency ventilation empirically in extremely preterm infants to minimize lung
injury.

27.  Role of minimal handling of the severely premature neonate…..?

28. Exogenous SurfactantTherapy
 The targeted treatment for surfactant deficiency is intratracheal surfactant replacement therapy via an
endotracheal tube.
 Surfactant administered within 30 to 60 minutes of the birth of a premature neonate is found to be
beneficial. Surfactant hastens recovery and decreases the risk of pneumothorax, interstitial emphysema,
intraventricular hemorrhage (IVH), BPD, and neonatal mortality in the hospital and at one year.
 However, neonates who receive surfactant for established RDS, have an increased risk of apnea of
prematurity.According to European census guidelines, the surfactant is administered to immature babies
with FiO2 > 0.3, and mature babies with FiO2 > 0.4. Currently, there are no clinically significant
advantages of using one type over another when used in similar doses:
 Beractant:This is a modified natural surfactant prepared from minced bovine lungs with the additives
 Poractant alfa:This is a modified natural surfactant derived from minced porcine lung extract
 Calfactant:This is a natural surfactant obtained from lavaging calf lung alveoli and contains 80%
phosphatidylcholine with only 1% protein
 Synthetic surfactant: Clinical trials are ongoing

29.  Surfactant is administered either by standard endotracheal intubation, which needs experienced practitioner or through
less invasive surfactant administration (LISA) technique like aerosolized nebulized surfactant preparations, laryngeal
mask, pharyngeal instillation, and thin intratracheal catheters
 The standard technique of surfactant administration by endotracheal intubation and mechanical ventilation may result
in transient airway obstruction, pulmonary injury, pulmonary air leak, and airway injury
 Emerging evidence shows that the LISA technique is associated with a lower rate of BPD, death, and need for
mechanical ventilation compared to surfactant administration through endotracheal intubation.
 Still, further investigations are required to prefer the LISA technique as the standard technique of surfactant
administration in place of endotracheal intubation.
 If the neonates maintain adequate respiratory drive with FiO2 <0.3, it should be planned to stop surfactant and switch
to CPAP.
 Oxygen saturation (>90%), thermoregulation (36.5 to 37.5 C), and fluid and nutrition status should be monitored.

30. SUPPORTIVE CARE
 Preterm infants with apnea of prematurity may require caffeine therapy. Caffeine
can also be administered to preterm infants < 28 weeks with extremely low birth
weight (BW <1000 g) to increase respiratory drive and enhance the use of CPAP.
There was a low incidence of BPD and earlier extubation in preterm infants who
received caffeine compared to placebo.[39]
 Optimal fluid and electrolyte management is critical in the initial course of RDS.
Some neonates may require volume resuscitation using crystalloids as well as
vasopressors for hypotension.
 Furthermore, the overall care of a preterm infant also includes optimizing
thermoregulation, nutritional support, blood transfusions for anemia, treatment
for hemodynamically significant PDA, and antibiotic therapy as necessary.

31. PROGNOSIS
 Prognosis of infants managed with antenatal steroids, respiratory support, and
exogenous surfactant therapy is excellent.
 Mortality is less than 10%, with some studies showing survival rates of up to 98%
with advanced care.
 Increased survival in developed countries is in stark comparison to babies who
received no intervention in low-income countries, where the mortality rate for
premature infants with RDS is significantly higher, at times close to 100%.
 With adequate ventilatory support alone, surfactant production eventually
begins, and once surfactant production begins along with the onset of diuresis,
RDS improves within 4 or 5 days.
 Untreated disease leading to severe hypoxemia in the first days of life can result
in multiple organ failure and death.

32. COMPLICATIONS
Complications of neonatal respiratory distress syndrome are related mainly to the
clinical course of RDS in neonates and the long-term outcomes of the neonates.
While surfactant therapy has decreased the morbidity associated with RDS, many
patients continue to have complications during and after the acute course of RDS.
 Acute complications due to positive pressure ventilation or invasive mechanical
ventilation include air-leak syndromes such as pneumothorax,
pneumomediastinum, and pulmonary interstitial emphysema.There is also an
increase in the incidence of intracranial hemorrhage and patent ductus arteriosus
in very low birth weight infants with RDS, although independently linked to
prematurity itself.

33.  BPD(bronchopulmonary dysplasia) is a chronic complication of RDS.The pathophysiology
of BPD involves both arrested lung development as well as lung injury and inflammation.
- Besides a surfactant deficiency, the immature lung of the premature infant has decreased
compliance, decreased fluid clearance, and immature vascular development, which
predisposes the lung to injury and inflammation, further disrupting the normal
development of alveoli and pulmonary vasculature.
- Also, oxidative stress from hyperoxia secondary to mechanical ventilation, and decreased
anti-oxidant capabilities of the premature lung, both lead to further damage to the lung
through the increased production onTGF-β1 and other pro-inflammatory cytokines.
 Neurodevelopmental delay is another complication of RDS, especially with infants who
received mechanical ventilation long-term.
-The incidence of cerebral palsy also was increased in infants with RDS, with decreasing
incidence as gestational age increased.The length of time on mechanical ventilation
correlates with increased rates of both cerebral palsy and neurodevelopmental delay.

34. DETERRENCE AND PATIENT EDUCATION
 While the goal of preventing preterm birth altogether continues to be investigated, RDS can be reduced
by the administration of antenatal corticosteroids.
 Administration of antenatal corticosteroids significantly reduces the incidence of RDS and the need for
mechanical ventilation.The use of antenatal corticosteroids decreased the incidence of RDS in a review of
21 studies and 4083 infants with a reduction in neonatal and fetal death in a review of 3627 infants in 13
studies.
 It has also been shown to reduce infant mortality and periventricular leukomalacia.
 Of note, there were no statistically significant increases in maternal mortality with the administration of
antenatal corticosteroids.
 The beneficial effect of antenatal corticosteroid use after 34 weeks of gestation is controversial due to the
lack of information in long term developmental outcomes.
 Maternal antenatal corticosteroids are recommended for possible preterm delivery in the next seven days
between 23rd and 34th week gestational age. Some institutions offer antenatal corticosteroids at 22
weeks if anticipating delivery within the next week. Despite multiple interventions targeting various
etiologies, the goal of preventing preterm birth remains elusive.

35. SILVERMANN-ANDERSEN RETRACTION
SCORE(SARS SCORE)
 0-3….mild respiratory distress
 4-6… moderate resp distress
 >6….impending respiratory failure
 Score of 10…..severe respiratory failure

36.  THANKYOU