Rational Surfactant Therapy
Ajay Agade
Jawaharlal Nehru Hospital And
Research Centre, Steel Plant Bhilai
What are the interventions
available?
•Oxygen
•CPAP
•Mechanical Ventilation
•Surfactant
Dr Ajay Agade
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
Does Surfactant Replacement Therapy Work?
Dr Ajay Agade
Most widely researched with maximum
RCT’ s in neonatology
Dr Ajay Agade
•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 useof surfactant.
NEJM May 1994
Dr Ajay Agade
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
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
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
Recommendation
Natural surfactants should be used in
preference to any
of the synthetic surfactants available
(grade A).
Cochrane 2005
Dr Ajay Agade
•The animal surfactants have phospholipid compositionssimilar to
that of natural surfactant; they contain some SP-Band 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 thesurface properties of the extract
•. The surface propertiesof organic-solvent extracts of lung tissue
also can be improvedby removing neutral lipids by
chromatography, as is done withCurosurf
Dr Ajay Agade
Absence of Surfactant
High Distending Pressures
Airway Stretch / Distortion
Cellular Membrane Disruption
Edema / Hyaline Membrane Formation
Higher FIO2 / Pressures
Barotrauma, BPD
What happens ?
Dr Ajay Agade
SURFACTANT : DEFICIENCY
Dr Ajay Agade
PRESSURE VOLUME LOOP
Dr Ajay Agade
There is no indication that exogenouslyadministered
surfactant inhibits the synthesis and secretionof
endogenous surfactant
Two majorbenefits result from surfactant treatment:
The biophysical effectsof the surfactant on the
surfactant-deficient lungs
And theprovision of phospholipids as substrate
for recycling pathways
Dr Ajay Agade
Timing
Prophylactic
or Rescue
Dr Ajay Agade
The meta-analysis (50) indicated that there
would be two fewer pneumothoracesand
five fewer deaths for every 100 babies
treated prophylacticallywith surfactant.
Dr Ajay Agade
•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
ARE MULTIPLE DOSES MORE BENEFICIAL ?
Dr Ajay Agade
Multiple doses of surfactant have been given in most
trialsbecause the response to an individual dose is often
transient.
In preterm animals, exogenously administered surfactant
is can be inhibited bysoluble proteinsand other factors in
the small airways andalveoli.
Multiple doses are thought to be useful because theycan
overcome this functional inactivation of surfactant.
Pediatrics 1991
Dr Ajay Agade
Antenatal steroid and Surfactant goes hand in hand
Dr Ajay Agade
Antenatal steroids & surf
•Synergistic effect
Prenatal steroids + Surfactant is better than
either alone
•neonatal mortality
•air leaks
•severe IVH
Give both
Am J Obst Gynec Suppl, 1995
Dr Ajay Agade
•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
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
INSURE procedure
Earlysurfactant 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
HOW SHOULD VENTILATORY MANAGEMENT
AFTER SURFACTANT THERAPY BE
APPROACHED ?
“ Options for ventilatorymanagement that are
to be considered after surfactant therapy
include very rapid weaning and extubationto
CPAP (grade B evidence).”
Dr Ajay Agade
Ventilatory strategy-INSURE
Dr Ajay Agade
WHAT ARE THE RISKS OF EXOGENOUS SURFACTANT
THERAPY?
Dr Ajay Agade
The short-term risks of surfactant replacement therapy
•Bradycardiaand hypoxemia during instillation,
•Blockage of the endotrachealtube
•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
Is Surfactant
beyond the
reach of the
common
man?
Dr Ajay Agade
Cost implications
•Surfactant is expensive
•22% reduction in hospital charges per
survivor
•52 % Reduction in ancillary charges
Dr Ajay Agade
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