MoyaDonn 7/8/08 03:25 Page 73
Neonatal Medicine
Lucinactant—A Novel Synthetic Surfactant for the
Prevention of Respiratory Distress Syndrome
a report by
Fernando R Moya, MD
1
and Steven M Donn, MD
2
1. Director of Neonatology, New Hanover Regional Medical Center, and Professor of Pediatrics, University of North Carolina Medical School; 2. Professor, Department
of Pediatrics, University of Michigan Health System, and Chief, Division of Neonatal–Perinatal Medicine, CS Mott Children’s Hospital, University of Michigan
Respiratory distress syndrome (RDS) is the leading cause of morbidity and may contribute to the pathogenesis of BPD.
5
The first-generation synthetic
mortality in pre-term infants. Its incidence is inversely related to gestational surfactant colfosceril palmitate is no longer available in North America. It did
age and results from morphological and biochemical immaturity of the not contain any of the necessary surfactant-associated proteins A, B, C, and
lungs. As the lungs are in the saccular or canalicular phases of D (SP-A, SP-B, SP-C, and SP-D). Both SP-B and SP-C are essential to the
development, there is interruption of normal alveolarization and spreading and stabilization of the surfactant monolayer, whereas SP-A and
diminished pulmonary surface area. Furthermore, absent or inadequate SP-D play a role in host defense. Thus, a synthetic compound that contains
production of pulmonary surfactant, a naturally occurring compound synthetic SP-B or a synthetic ingredient that acts just like human SP-B would
comprising primarily phospholipids and associated proteins, results in high be a welcome addition. Lucinactant (Surfaxin
®
) is one such compound.
alveolar surface tension and a tendency toward progressive atelectasis,
with alterations in pulmonary gas exchange and lung mechanics. Lucinactant
Surfactant is produced by the type II pneumocytes, is secreted into the Lucinactant is a bio-engineered synthetic surfactant containing a mixture of
alveolar spaces, and confers foam stability at the air–liquid interface.
1
phospholipids and a unique peptide, sinapultide (KL
4
), which functions as
human SP-B, interacting with the phospholipids to lower surface tension in
Antenatal administration of corticosteroids has become the standard of care the alveolar space. It is a 21-amino acid peptide composed of sequenced
in most countries for reducing the incidence and severity of RDS in pre-term lysine and leucine segments chosen because they resemble the amphipathic
infants who have reached 26–34 weeks of gestation.
2
This therapy works in domains of SP-B.
6
KL
4
is more resistant to inactivation by protein and lipid
part by inducing surfactant production. The use of exogenous surfactant mediators as well as oxidants compared with exogenous surfactants that
replacement therapy (SRT) began in the late 1980s, and has now become contain animal-derived surfactant proteins. The total phospholipid
routine care for these infants. Early surfactants were either synthetic but concentration of lucinactant is 30mg/ml (dipalmitoyl phosphatidylcholine
devoid of the associated proteins, or derived from lung minces or washes 22.5mg/ml; palmitoyl-oleyl phosphatidylglycerol 7.5mg/ml). Lucinactant
from bovine or porcine sources.
3
Although SRT has dramatically improved
the survival of pre-term infants, it has not reduced the incidence of
Fernando R Moya, MD, is Director of Neonatology at New
bronchopulmonary dysplasia (BPD), a potentially disabling condition that
Hanover Regional Medical Center and South East Area Health
now affects 30–40% of infants <1,500g at birth. However, rather than this Education Center in Wilmington, and a Professor of Pediatrics
being a failure of SRT, it more likely represents the extension of survival to a
at the University of North Carolina Medical School, Chapel
Hill. He was the Richard Mithoff Professor of Pediatrics and
population of infants with less developed lungs. The pathogenesis of BPD
Director of the Division of Neonatal–Perinatal Medicine at The
remains incompletely understood but appears to be multifactorial. University of Texas-Houston from 1997 to 2005. Professor
Currently, antenatal steroid treatment, SRT, and mechanical ventilatory
Moya has published over 65 peer-reviewed publications, 13
invited articles, and 18 book chapters. In addition, he has
support are the main treatments for pre-term infants with RDS.
given over 120 guest lectures in 25 countries. He obtained his MD and completed his
residency in pediatrics at the Catholic University of Chile and his neonatal-perinatal medicine
Surfactant is one of the most carefully studied pharmaceuticals, with more
training in the Division of Perinatal Medicine, Yale School of Medicine.
than 40 published clinical trials enrolling over 20,000 subjects. Early or
E:
fernando.moya@seahec.net
‘prophylactic’ administration appears to be better than late or ‘rescue’
administration once RDS is established, with decreased mortality and Steven M Donn, MD, is a Professor of Pediatrics at the
pulmonary air leaks.
4 University of Michigan Medical School in Ann Arbor and Chief
of the Division of Neonatal–Perinatal Medicine at CS Mott
Children’s Hospital at the University of Michigan Health
There are about 300,000 infants born prematurely in the US each year, System. He is actively involved in teaching, research, and
representing about 10% of all births. About one-quarter of these will
patient care activities. He is certified by the American Board
of Pediatrics and its Sub-board of Neonatal–Perinatal
require SRT. Globally, there may be as many as 600,000–800,000 affected
Medicine. Professor Donn is a member of numerous
newborns. All currently available preparations in the US contain professional societies, including elected memberships in the
animal-derived material. They have several real and potential disadvantages,
Society for Pediatric Research and the American Pediatric Society. He has been chosen as one
of the ‘Best Doctors in America’ since 1994, and is internationally known for his expertise in
including lot-to-lot inconsistency, potential risk for transmitting infectious
the management of respiratory failure in newborns.
agents from their animal source, and later sensitization to foreign proteins.
They have also been shown to contain pro-inflammatory mediators, which
© TOUCH BRIEFINGS 2008
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