Hi guys, This ppt shows the pathophysiology of pulmonary surfactant in newborn and respiratory distress syndrome. Main focus is towards management of RDS esp. exogenous surfactant administration. Your comments are welcome. Thank you.

1. Neonatal respiratory system
&
Respiratory Distress Syndrome
PRESENTED BY : DR SONALI PARADHI MHATRE

2. Introduction
• Molecular oxygen is one of the most essential components of our environment, as it is crucial to
the molecular reactions for running of our basic cellular machineries needed for survival ,
alongwith all the day today activities.
• Respiration is defined as the transport of oxygen from the outside air to the cells within tissues,
and the transport of carbon dioxide in the opposite direction.
• Breathing is the process that moves air in and out of the lungs. Breathing is also called
ventilation, which includes both inhalation and exhalation.
• The transition from fetal to neonatal life requires a rapid conversion from intermittent fetal
respiratory activity (not associated with gas exchange) to continuous breathing upon which gas
exchange is dependant.

3. Embryology
of
Lung
develoment

5. Pathophysiology
of
Pulmonary Surfactant

6. Basic Physics : Surface Tension
Attractive forces among liquid molecules are responsible for
phenomena of surface tension.
Each molecule is pulled equally in the
inside direction.
Thus, SPHERICAL SHAPE of water
molecule is seen.

8. The lung alveoli are coated with surfactant
molecules. Thus, preventing collapse on expiration
and reducing pressure needed for next inspiration.
Hydrophobic
head
Hydrophillic
tail

9. Before surfactant After surfactant

10. Pulmonary
Physiology

12. Stable alveolar volume depends on a
balance between:
1) Surface tension at the liquid-gas
interface.
2) Recoil of tissue elasticity.

13. Pulmonary Surfactant
Surface active lipoprotein
complex formed by Type 2
alveolar cells.
Contains both proteins
and lipids. Thus has both
hydrophilic and
hydrophobic regions.

14. Components
Of
Pulmonary
Surfactant.

15. Components & Functions
* Major Lipids (~90%)
Saturated Phosphatidylcholine DPPC (Lecithin) 60-80%
Unsaturated Phosphospholipids
Phosphatidylglycerol (PG) ~10%
* Proteins (~10%)
SP-A
Hydrophilic, Host defence. Surfactant homeostasis.
SP-B
Hydrophobic, Spreading,  surface tension
SP-C
Hydrophilic , Adsorption
SP-D: ? Phagocytic function

16. How it works…???
Starts at the terminal sac stage of lung
development the Type 2 cells.
At 20wk gestation, the lamellar bodies appear in
cytoplasm.
Lamellar bodies are secreted by exocytosis into
the surface water layer lining the alveolar
airspace.
Here, surfactant forms a meshwork of
tubular myelin.

17. Basic
Structure
of
Alveoli

18. Half life of alveolar
surfactant is 5-10 hrs
after secretion.
Broken down by
macrophages and/or
reabsorbed into the
lamellar bodies.

19. Functions of surfactant
Decreases the surface tension.
To promote lung expansion during inspiration.
To prevent alveolar collapse and loss of lung volume at
the end of expiration.
Facilitates recruitment of collapsed alveoli.

20. Normal Expiration
With Surfactant
Abnormal Respiration
Without Surfactant

21. Why Preterms..????
TERM BABIES :
have storage pool of approximately 100 mg/kg of
surfactant at birth.
PRETERM BABIES :
have a storage pool of approx. 4-5 mg/kg surfactant at
birth.

22. Deficiency of surfactant
Progressive Atelectasis.
Loss of functional residual capacity.
Alterations in ventilation perfusion ratios.
Uneven distribution of ventilation.

23. Respiratory
Distress
Syndrome

24. Respiratory distress syndrome
Transient tachypnea of newborn
Pneumonia / sepsis
Meconium aspiration syndrome
Congenital heart disease
Perinatal asphyxia
Persistent pulmonary hypertension
Spontaneous pneumothorax
Pulmonary haemorrhage
Diaphragmatic hernia/ pulmonary
hypoplasia.
Causes of Respiratory distress in a newborn …??

25. Introduction
• Respiratory Distress Syndrome occurs in preterm babies.
• Incidence is approx. 60-80% in infants <28wks, 15-30% in infants between
32-36wks, rarely in those above 37wks.
• Risk for development of RDS increases with maternal diabetes, multiple
births, C-section, asphyxia, cold stress, maternal history of previously
affected infant.
• Risk is reduced in chronic or pregnancy associated hypertension, antenatal
corticosteroid use.

26. Respiratory Distress Syndrome is
characterized by :
 Generalised Atelectasis
 Ventillation – perfusion mismatch
 Subsequent hypoxemia & Respiratory
acidosis.

27. Pathophysiology of RDS
Breathing
• ‘Shear stress’ in the alveoli and terminal bronchioles due
to repetitive reopening of collapsed alveoli and
overdistension of the open alveoli
Lung
damage
• Forces damage the fragile
lung architecture
Hyaline
deposits
• Proteinaceous debris leak in the
membranes
Surfactant
def.
Respiratory
Failure /
Death.
• Debris collected impairs the function
of the already little surfactant.

28. Pressure Volume Loop

29. Clinical Presentation
• Tachypnea (Respiratory Rate >60/min)
• Increased work of breathing
( Retractions, Nasal Flaring)
• Grunt
• Cyanosis (Central & Peripheral)
• Poor perfusion / Pallor
• Lethargy
• Not feeding well
• Apnea
Onset of symptoms are within minutes to hours of birth.
Very severe cases can be manifested in first few breaths.

31. Investigations
• Chest Xray.
• Arterial blood gas analysis
• Random blood sugar
• Complete blood count
• Blood culture (suspected cases)
• SOS : 2D ECHO.

32. Shake test / Gastric aspirate shake test (GAST).
• Take a test tube
• Mix 0.5 ml gastric aspirate + 0.5 ml ethanol
• Shake for 15 seconds
• Allow to stand 15 minutes for the interpretation of
results.
• If no bubbles were present, the test was negative
(no surfactant)
• If bubbles are seen at the top of the fluid, it is
intermediate (some surfactant present).
• If bubbles are seen right across the surface of the
fluid, it was positive result. (surfactant present)
Antenally, amniotic fluid can be used for the same procedure.

33. •Stage 1
Slight reticular
(granular) pattern.
Decrease in
transparency of the
lung, no certain
difference to normal
findings.
Radiologic changes in RDS..

34. Stage 2
Soft decrease in
transparency with an
aerobronchogram,
which overlaps the
heart .
(= always a sign of an
alveolar lung reaction!)
Radiologic changes in RDS (cont…)

35. Stage 3
Like stage 2, but with
gradual stronger
decrease in
transparency, as well as
a blurry diaphragm and
heart.
Radiologic changes in RDS (cont…)

36. Stage 4
White lung:
practically
homogenic lung
opacity
Radiologic changes in RDS (cont…)

37. Management
Of
RDS..!!!

38. Goals in Management of Respiratory
Distress Syndrome
1. Avoid hypoxemia and acidosis.
2. Optimize fluid management: avoid fluid overload and resultant body and
pulmonary edema, while averting hypovolemia and hypotension .
3. Reduce metabolic demands and maximize nutrition.
4. Minimize lung injury secondary due to volutrauma, barotrauma and oxygen
toxicity

39. Management
1. Provide Warmth . (Radiant warmer / Incubator)
2. Maintain good hydration . (60-80ml/kg/d)
3. Nutrition :
Nil by mouth (if tachypnea/ distress)
If stable, gavage feeding can be started.
If delay in enteral feeds is anticipated, Start Parenteral nutrition.
4. Antibiotics (If risk of pneumonia / sepsis)

40. Management (cont…)
5. Respiratory support :
 Supplemental Oxygen :
• Primary goal – to maintain adequate oxygen
availability to tissues esp. CNS and heart.
• When supplemental O2 administered to a
hypoxaemic neonate, continuous monitoring
is needed, to avoid hyperoxemia.
• Warming and humidification of O2 helps in
better prognosis.
• Can be delivered through hood / nasal
cannula.

41. Management (cont…)
5. Respiratory support :
 CPAP (Continuous Positive airway pressure)
• Nasal CPAP can be used early to delay or
prevent the need for endotracheal
intubation and mechanical ventilation.
• Current recommendations are starting
nCPAP at birth to all infants at risk of RDS,
as those born <30wks gestation.
• Can be provided to infants via nasal mask,
nasal prongs or endotracheal tube.

43. Management (cont…)
5. Respiratory support :
 High Flow nasal O2:
• This has been introduced to neonatal respiratory
care as a way to provide positive distending
pressure, even comparable to CPAP, to a neonate
with respiratory distress.
• It aims to maximize patient tolerance by using
heated, humidified gas flow (>1L/min)
• Further studies comparing nCPAP with high flow
nasal O2 are currently ongoing.

44. Management (cont…)
5. Respiratory support :
 Mechanical Ventillation :
• Indications include :
1. <27wks (+ no antenatal steroids)
2. For other infants ANY of the following indications:
• FiO2 requirement >0.4
• pH <7.25
• Increased work of breathing (esp Grunt)
• PaCO2 >60
• Recurrent apnea
• CPAP failure.

45. Management (cont…)
6.) Exogenous Surfactant Administration:
When to Administer ???
• Surfactant is administered in preterm infants using three different timing
strategies.
1) Prophylactic surfactant therapy, which is administered at the time of delivery to
infants at risk of RDS.
2) Early rescue therapy, which is administered by two hours of age frequently before the
diagnosis of RDS
3) Late Rescue surfactant therapy, which is given once the diagnosis of RDS is
established.

46. Management (cont…)
6.) Exogenous Surfactant Administration:
When to Administer ??? (cont….)
• In all three strategies, surfactant therapy improves mortality and morbidity in preterm infants
when compared to untreated patients
• However, clinical trials suggest that prophylactic or early therapy is superior to rescue therapy
alone in infants at high-risk for RDS (below 30 weeks gestation)
• In at-risk infants, prophylactic or early rescue treatment is associated with a decrease in
morbidity and mortality compared to rescue treatment for established RDS.
• However , not all infants that would appear to be at risk of developing RDS, actually develop
the condition. May lead to some infants being over treated, and possibly being exposed to
adverse effects, unnecessarily.

47. Management (cont…)
6.) Exogenous Surfactant Administration: (cont…)
What to Administer ?
• Comparative trials demonstrate greater early improvement in the requirement for ventilator
support, fewer pneumothoraces, & deaths associated with natural surfactant.
• Natural surfactant may be associated with an increase in IVH, though the more serious
hemorrhages (Grade 3 and 4) are not increased.
• Despite these concerns, natural surfactant extracts would seem to be the more desirable choice
when compared to the currently available synthetic surfactants.
• Natural surfactants should be used in preference to any of the synthetic
surfactants available. (Cochrane 2005)

48. Types of Surfactants
Exogenous Surfactant
Synthetic
Non-protein synthetic
surfactant
1. Adsurf
2. Exosurf
Peptide containing
synthetic surfactant
1. Venticute
2. Surfaxin
Natural
1.Survanta
2. Neosurf
3. Curosurf
4. Infasurf

49. Protein containing Natural (Animal) surfactants:
Trade name Active ingredient Source dosing
Survanta Beractant Bovine lung
extract
4ml/kg, maximum upto 4 times 6
hrly
Infasurf Calfactant Calf lung lavage 3ml/kg, maximum up to 3 doses 12
hrly
Curosurf Poractant alfa Porcine lung
extract
2.5ml/ kg 1st dose maximum upto
1.25ml//kg up to 2 doses 12hrly
Neosurf Beractant Bovine lung lavage 5ml/kg 1st dose maximum upto 3
doses 12hrly

50. Management (cont…)
6.) Exogenous Surfactant Administration:
How to Administer ???
INSURE Technique :
• Intubate
• Give Surfactant
• Extubate
• Put on Ncpap.
Early surfactant replacement therapy with extubation to N CPAP compared with continued
mechanical ventilation with extubation is associated with a reduced need for mechanical
ventilation and increased utilization of exogenous surfactant therapy. (Cochrane 2005)

51. Management (cont…)
6.) Exogenous Surfactant Administration:
How to Administer ??? (cont….)
• INSURE technique may decrease the need and duration of mechanical
ventilation versus CPAP alone
• It also reduces the incidence of BPD. And is associated with fewer air leak
syndromes.

52. Management (cont…)
6.) Exogenous Surfactant Administration:
What about Repeat administration ?
Retreatment strategies may be dependent on which preparation is used, as some are more
prone to protein inactivation. The timing of retreatment has been fairly arbitrarily determined
in most of the surfactant trials, but comparisons of the timing of retreatment have been limited
and there have been no comparisons of the timing of retreatment between surfactant
preparations.
Multiple doses of surfactant have been given in most trials because the response to an
individual dose is often transient.
• Recommendation
• Retreatment should be considered when there is a persistent or recurrent oxygen requirement
of 30% or more and it may be given as early as 2 h after the initial dose or, more commonly, 4
h to 6 h after the initial dose

53. Management (cont…)
6.) Exogenous Surfactant Administration :
Side effects ..??
• Bradycardia and hypoxemia during instillation.
• Blockage of the endotracheal tube .
• Increase in pulmonary hemorrhage.
• Sepsis.
• Cost limitations

54. Role of Antenatal Corticosteroids
• Stimulation of developmentally regulated gene expression and physiologic
functions resulting in lung maturation.
• Accelerate development of Type1 & Type2 pneumocytes, leading to structural and
biochemical changes that improve both lung mechanics (max lung volumes,
compliance) and gas exchange.
• Induction of Type 2 pneumocytes increases surfactant production by inducing
enzyme responsible for surfactant proteins and phospholipid synthesis.
• Enhances the neonatal response to postnatal surfactant administration.

55. Role of Antenatal Corticosteroids (cont…)
• Other effects that help in lung fluid resorption :
1. Induction of pulmonary beta receptors which play a role in surfactant
release and absorption of alveolar fluid.
2. Induction of fetal lung antioxidant enzyme.
3. Upregulation of gene expression for the epithelial Na+ channel , which is
important for the absorbtion of lung fluid after birth.

56. Which steroid to use…???
• The steroids used are generally Betamethasone or Dexamethasone.
• They are identical biologically and readily cross the placenta.
• They have little mineralocorticoid activity and are relatively weak in immune
suppression.
• Dosage recommended :
2 doses of Betamethasone 12mg given 24 hrs apart
OR
4 doses of Dexamethasone 6mg given 12 hrs apart.

57. Take Home Message…!!!!
• The lung alveoli are coated with surfactant molecules which act by reducing the surface tension at
the fluid-air interface.
• Thus, preventing collapse on expiration and reducing pressure needed for next inspiration.
• The introduction of corticosteroids for fetal lung maturity in patients at risk of preterm labor was a
major milestone in reducing the neonatal morbidity and mortality from RDS.
Betamethasone and Dexamethasone are the steroids of choice.
• Recommended dosages are :
2 doses of Betamethasone 12mg given 24 hrs apart
OR
4 doses of Dexamethasone 6mg given 12 hrs apart.

58. Take Home Message…!!!!
• The administration of antenatal corticosteroid, and prophylactic or early surfactant therapy to
high risk preterm infants reduces the incidence and severity of RDS.
• The use of Oxygen therapy in preterm neonates have to be monitored well to prevent
hyperoxemic damage. Recommended SPO2 = 90 – 95%.
• Initial postnatal management includes detailed evaluation of the infant and providing warmth,
management of fluid, nutrition, Ventillation strategies and exogenous surfactant administration.
• Prophlactic or early rescue treatment modalities with exogenous surfactant are proved to be
better than late rescue therapy for RDS as well as reducing the incidences of BPD, air leaks.

59. • Natural surfactants should be used in preference to any of the artificial surfactants.
• Options for ventilatory management that are to be considered after prophylactic surfactant therapy
include very rapid weaning and extubation to CPAP within 1 h
• Surfactant administration is done using the INSURE (Intubate, Surfactant administration,
Extubate) method and patient to be taken on Nasal CPAP post procedure.
• Infants with RDS who have persistent or recurrent oxygen and ventilatory requirements within the
first 72 h of life should have repeated doses of surfactant.
Take Home Message…!!!!

60. Thank
You !!