Indian Pediatr 2011;48:
Surfactant, Mechanical Ventilation or CPAP for
Treatment of Early Respiratory Failure in Preterm Infants: A
Professor of Pediatrics, University of Durham and James
Cook University Hospital, Middlesbrough, United Kingdom.
xogenous surfactant replacement
therapy and mechanical ventilation (MV) still remain the ‘standard of
care’ while treating preterm infants with respiratory failure. However,
this requires endotracheal intubation - an invasive procedure associated
with complications. Moreover, the skills required to intubate very small
babies are not universally available and may vary among the health care
professionals. This has led to increasing interest in the use of
non-invasive form of respiratory support which do not require placement of
an endotracheal tube. These non-invasive respiratory support methods
include: Continuous Positive Airway Pressure (CPAP), Nasal Intermittent
Positive Pressure Ventilation (NIPPV) and High Flow Nasal Cannulae (HFNC).
The application of CPAP helps keep the upper airway
open during both inspiration and expiration, and improve the functional
residual capacity. Two large randomised controlled trials comparing CPAP
with traditional intubation and ventilation have recently been published.
In the first trial, 610 infants of between 25 to 28 weeks gestation were
randomized to receive either early CPAP or Intubation and Ventilation
without surfactant (CPAP or Intubation (COIN Trial)) . Although
appearing to be better in short term, when assessed at 36 weeks gestation,
CPAP did not show any advantage in terms of survival or chronic lung
disease (CLD) at the time of discharge. Moreover, babies in CPAP group had
somewhat higher incidence of pneumothorax as compared to ventilation
group. Another recently published trial, Surfactant Positive Pressure and
Pulse Oximetry Randomised Trial (SUPPORT Trial) , enrolled 1316 infants
born between 24 to 27 weeks gestation to receive either early CPAP in the
delivery room without any surfactant (CPAP group) or intubation and
surfactant treatment within one hour after birth (ventilation group). The
primary outcome of death or chronic lung disease at 36 weeks did not
differ between the two groups (47% in CPAP group vs 51.0% in
ventilation group). There was also no difference in the incidence of
pneumothorax. These two trials have recruited 1926 infants between them
and showed that almost half of them could be successfully managed on early
CPAP who otherwise might have been candidate for mechanical ventilation.
The downside of the story is that half of the infants enrolled in these
studies particularly of those between 24-28 weeks’ gestation failed CPAP
treatment. It can be argued that such babies might have been disadvantaged
because of delay in the ‘standard care’ of treatment and this has prompted
some investigators to assess the effect of early surfactant through
intubation followed by quick extubation to nasal CPAP (INSURE) technique.
The data on this approach has been limited. Recently, the results of a
large randomised trial (VON Trial)  become available in abstract form.
In this trial, 648 infants between 26-29 weeks’ gestation were randomized
in three groups: prophylactic surfactant and mechanical ventilation,
INSURE, and CPAP with selective intubation. The trial reported no
difference in death or chronic lung disease at 36 weeks between the three
groups and similarly, there were no differences in the incidence of
pneumothorax. The results from another study just prior to this also
reported no difference in need for mechanical ventilation, BPD or
pneumothorax among infants born at 24-28 weeks gestation and randomized to
receive prophylactic or early selective surfactant with nasal CPAP,
suggesting early rescue surfactant is as good as prophylactic surfactant
. Thus, the results are confusing and evidence so far does not tell us
the full story. The onus is on the clinicians to improve their skills in
selecting the right mode of treatment for individual infants, optimising
different modes of treatment and collecting long term safety and clinical
outcome data. In this issue of the journal, Tsakildis, et al. 
describe the advantages of surfactant administration followed by brief
ventilation and extubation (Intubation–Surfactant-Extubation-Insure).
Their findings are in line with previous published studies but do not
provide any new information. Further research is still needed to answer
many questions, both in the short and long terms, related to the efficacy
and safety of various forms of respiratory support currently being
practiced in neonatal units.
Competing interests: None stated.
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For COIN Trial investigators. Nasal CPAP or intubation at birth for very
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2. SUPPORT Study Group of the Eunice Kennedy Shriver
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Porpodi M, Nikolaidis N. Early rescue administration of surfactant and
nasal continuous positive airway pressure in preterm infants <32 weeks
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