1. Rational Surfactant Therapy
Ajay Agade
Jawaharlal Nehru Hospital And
Research Centre, Steel Plant Bhilai

2. What are the interventions
available?
• Oxygen
• CPAP
• Mechanical Ventilation
• Surfactant
Dr Ajay Agade

3. Surfactant Replacement Therapy
• Does it work?
• When to give?
• Which one to give?
• How often to give?
• How to give?
• Does it cause any problems?
Dr Ajay Agade

4. Does Surfactant Replacement Therapy Work?
Dr Ajay Agade

5. Most widely researched with maximum
RCT’ s in neonatology
Dr Ajay Agade

6. • Odds of death in hospital for VLBW infants were
reduced by 30 % after surfactant was introduced.
• 80% of decline in the U.S. neonatal mortality rate
between 1989 & 1990 could be attributed solely to
the use of surfactant.
NEJM May 1994
Dr Ajay Agade

7. Exogenous surfactant replacement has been
established as an appropriate preventive and
treatment therapy for prematurity-related
surfactant deficiency
AMERICAN ACADEMY OF PEDIATRICS
Committee on Fetus and Newborn March 1999, pp 684-685
Dr Ajay Agade

8. Indian Experience
• The mean duration of ventilation 44.1 hours
lesser, and the hospital stay 4.37 days lesser in
babies who received surfactant.
• The incidence of
sepsis, pneumonia, PDA, IVH and CLD was
lower in babies who received surfactant.
Narang et al Indian Pediatrics 2001
Dr Ajay Agade

9. What is Surfactant?
Dr Ajay Agade

10. TYPES OF SURFACTANT
SYNTHETIC MODIFIED NATURAL
(Exosurf, Surfact) (Survanta, Curosurf)
Phospholipids DPPC Animal lung extract
Spreading Cetyl alcholol Surfactant proteins
agents + (SP-B, SP-C)
Tyloxapol
Dr Ajay Agade

11. 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 currently available synthetic
surfactants.
Cochrane 2005
Dr Ajay Agade

12. Recommendation
Natural surfactants should be used in
preference to any
of the synthetic surfactants available
(grade A).
Cochrane 2005
Dr Ajay Agade

13. •The animal surfactants have phospholipid compositions similar to
that of natural surfactant; they contain some SP-B and SP-C, but
no SP-A.
• The surfactant approved for use in the United States is Survanta
(beractant, Ross Laboratories, Columbus, Ohio) prepared by
mincing bovine lungs in saline and extracting the lipids, SP-B, and
SP-C with organic solvents.
Dipalmitoylphosphatidylcholine, palmitic acid, and triglyceride are
then added to improve the surface properties of the extract
•. The surface properties of organic-solvent extracts of lung tissue
also can be improved by removing neutral lipids by
chromatography, as is done with Curosurf
Dr Ajay Agade

14. Absence of Surfactant
High Distending Pressures
Airway Stretch / Distortion
What happens ?
Cellular Membrane Disruption
Edema / Hyaline Membrane Formation
Higher FIO2 / Pressures
Barotrauma, BPD
Dr Ajay Agade

15. SURFACTANT : DEFICIENCY
Dr Ajay Agade

16. PRESSURE VOLUME LOOP
Dr Ajay Agade

17. There is no indication that exogenously administered
surfactant inhibits the synthesis and secretion of
endogenous surfactant
Two major benefits result from surfactant treatment:
The biophysical effects of the surfactant on the
surfactant-deficient lungs
And the provision of phospholipids as substrate
for recycling pathways
Dr Ajay Agade

18. Timing
Prophylactic
or Rescue
Dr Ajay Agade

19. The meta-analysis (50) indicated that there
would be two fewer pneumothoraces and
five fewer deaths for every 100 babies
treated prophylactically with surfactant.
Dr Ajay Agade

20. •Prophylactic treatment during the first 15 minutes of life
appears to be more effective
BUT 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.
Dr Ajay Agade

21. ARE MULTIPLE DOSES MORE BENEFICIAL ?
Dr Ajay Agade

22. Multiple doses of surfactant have been given in most
trials because the response to an individual dose is often
transient.
In preterm animals, exogenously administered surfactant
is can be inhibited by soluble proteins and other factors in
the small airways and alveoli.
Multiple doses are thought to be useful because they can
overcome this functional inactivation of surfactant.
Pediatrics 1991
Dr Ajay Agade

23. Antenatal steroid and Surfactant goes hand in hand
Dr Ajay Agade

24. Antenatal steroids & surf
• Synergistic effect
Prenatal steroids + Surfactant is better than
either alone
•  neonatal mortality
•  air leaks Give both
•  severe IVH
Am J Obst Gynec Suppl, 1995
Dr Ajay Agade

25. • A secondary analysis of data from
surfactant trials also indicates a greater
reduction in disease severity in babies
who received antenatal steroids
(evidence level 4).
• Combination of antenatal steroids is
more effective than exogenous
surfactant alone (evidence level 2b).
Dr Ajay Agade

26. How Do We Do It
http://www.youtube.com/watch?v=86OA4to66hQ
http://www.youtube.com/watch?v=j9z3fb3dV1A&f
eature=related
Dr Ajay Agade

27. INSURE procedure
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
Dr Ajay Agade

28. HOW SHOULD VENTILATORY MANAGEMENT
AFTER SURFACTANT THERAPY BE
APPROACHED?
“ Options for ventilatory management that are
to be considered after surfactant therapy
include very rapid weaning and extubation to
CPAP (grade B evidence).”
Dr Ajay Agade

29. Ventilatory strategy-INSURE
Dr Ajay Agade

30. WHAT ARE THE RISKS OF EXOGENOUS SURFACTANT
THERAPY?
Dr Ajay Agade

31. The short-term risks of surfactant replacement therapy
• Bradycardia and hypoxemia during instillation,
• Blockage of the endotracheal tube
• Increase in pulmonary hemorrhage following surfactant
treatment
• However, mortality ascribed to pulmonary hemorrhage
is not increased and overall mortality is lower after
surfactant therapy.
Dr Ajay Agade

32. Is Surfactant
beyond the
reach of the
common
man?
Dr Ajay Agade

33. Cost implications
• Surfactant is expensive
• 22% reduction in hospital charges per
survivor
• 52 % Reduction in ancillary charges
Dr Ajay Agade

34. Does surfactant fail?
• Extremely preterm infants with structurally lung
immaturity
• Pneumonia or pulmonary hypoplasia
• Perinatal asphyxia
• Pulmonary edema from lung damage or fluid
overload
• Pulmonary edema from L-R shunting through
PDA
• Congenital B protein deficiency
Dr Ajay Agade

35. Got Surfactant!
Dr Ajay Agade