Surfactant For Respiratory Distress Syndrome

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Surfactant for Respiratory Distress Syndrome

Alan Jobe
Neoreviews 2014;15;e236
DOI: 10.1542/neo.15-6-e236

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Article pulmonology

Surfactant for Respiratory Distress Syndrome


Alan Jobe, MD, PhD* Educational Gaps
1. There is a lack of recognition of the limitations and confounders for the diagnosis of
Author Disclosure respiratory distress syndrome (RDS).
Dr Jobe has disclosed 2. Some practitioners lack experience with using continuous positive airway pressure
he is a consultant for (CPAP) in the delivery room to transition infants to spontaneous breathing.
Fisher & Paykel 3. There may be a lack of confidence to treat infants with surfactant other than by
Healthcare, Chiesi intubation.
Farmaceutici, AbbVie
Inc., and Sobi (Swedish Abstract
Orphan Biovitrum AB). Surfactant treatment is standard of care for infants who have respiratory distress syn-
drome (RDS). However, many practical questions remain about what RDS is, and who
This commentary does
should be treated and when. This review will attempt to answer these questions on the
contain a discussion of
basis of new clinical trials and a perspective on the goals of treatment. Clinical data now
an unapproved/ support an initial use of continuous positive airway pressure to stabilize most infants
investigative use of before treatment, but the optimal way to treat an infant is under intense investigation.
a commercial product/ The best treatment option for an infant ultimately depends on gestational age, clinical
device. status, and the experience of the clinician. The differences in surfactants are minor
given the low rates of complications with any surfactant treatment. The clinical man-
agement of RDS is the greatest success story in neonatology.

Objectives After completing this article, readers should be able to:


1. Recognize the limitations of the clinical diagnosis of respiratory distress syndrome
(RDS);
2. Decide how to best initially support preterm infants in the delivery room;
3. Assess an infant for the need for surfactant therapy; and
4. Anticipate the development of new approaches for surfactant treatments.

Introduction
Although surfactant for the treatment of respiratory distress syndrome (RDS) has been
widely available since 1990, the population of infants who have RDS has changed over
the last 24 years. Most infants now have been exposed to antenatal corticosteroids and
many are smaller and more immature. (1) Neonatologists also have changed their manage-
ment of infants who have RDS since the trials to validate surfactant treatments. Recent trials
have asked the following questions: Who should be treated? When should an infant be trea-
ted? How should the surfactant be given? Which surfactant should be used? I will answer
these questions from the perspective of the clinical trials,
clinical practice, and my perspective on information about
how surfactant works for the treatment of RDS. (2)
Abbreviations
BPD: bronchopulmonary dysplasia
CPAP: continuous positive airway pressure Who Should Be Treated With Surfactant?
INSURE: intubate, surfactant, and extubate Surfactants were developed specifically to replace surfactant
RDS: respiratory distress syndrome deficiency, which is the initiating abnormality resulting in
progressive respiratory failure in preterm infants. (2) As

*Neonatology/Pulmonary Biology, Cincinnati Children’s Hospital, University of Cincinnati, Cincinnati, OH.

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pulmonology surfactant for RDS

a general guideline, any preterm infant who has signifi- without RDS does not have RDS. The simple answer is
cant respiratory failure thought to be RDS should receive the miraculous potential of the human fetal lung for early
surfactant. The two key words are “significant” and gestational lung maturation as early as 23 to 24 weeks.
“RDS.” The clinical definitions of RDS are problematic (11) Although these very preterm saccular lungs are far
for both the individual infant and for population studies. from anatomically mature, they can have sufficient surfac-
(3) Traditionally, RDS was diagnosed for preterm infants tant and enough gas exchange surface to support adequate
who have clinical findings of retractions, grunting, and ventilation. Two clinically relevant mediators of this early
flaring who needed supplemental oxygen and had chest maturation are antenatal corticosteroid treatments and
radiographic findings of diffuse haziness and air broncho- chronic, often asymptomatic chorioamnionitis (Table 2).
grams. More recently, the diagnosis for epidemiologic Many infants have both these exposures. (12) It is safe
purposes has been simplified to be simply oxygen use to assume any pregnancy delivered before 30 weeks is
for ‡6 hours for the first 24 hours after birth, with or “stressed” and abnormal, but much remains to be learned
without ventilatory support and without the need for ra- about this remarkable early lung maturation (that promi-
diologic findings. (4) With this “permissive” diagnosis, nently includes increased amounts of surfactant).
approximately 95% of infants younger than 28 weeks’ The flip side of the question about why the infant does
gestational age will have RDS. Surfactant treatments at not have RDS is to ask if the infant who has respiratory
birth further complicate any definition of RDS. The failure really has RDS (Table 2). As noted, very preterm
change in management for low birthweight infants to al- infants are all “abnormal” in that delivery at early gesta-
low initial respiratory adaptation without intubation in tional ages are not normal. An increased percent of these
the delivery room has “uncovered” the previously known infants are growth restricted, which causes abnormal lung
fact that many very preterm infants initially do not have development in animal models and substantially increases
significant RDS. Earlier Scandinavian experiences and the the risks of bronchopulmonary dysplasia (BPD). (13) De-
transitioning of infants with continuous positive airway spite fetal growth restriction (and presumed severe stress)
pressure (CPAP) in the delivery room demonstrate that the incidence of RDS is not decreased. These infants may
many of these infants do not have surfactant deficiency have variable degrees of pulmonary hypoplasia or other
(Table 1). (5)(6)(7)(8) An extreme example of the ability lung structural abnormalities and not simply RDS. Sim-
to manage low birthweight infants was recently reported ilarly, pulmonary hypoplasia of variable severity can result
from South Africa. In an neonatal intensive care unit from decreased volumes of amniotic fluid and present as
(NICU) without the resources to ventilate infants less RDS, often with pulmonary hypertension.
than 1 kg, 69% of 309 infants were managed with nasal The greatest confounder to a “pure” diagnosis of RDS
CPAP alone, and 31% received surfactant followed by is chorioamnionitis. Although often clinically silent, more
CPAP with 75% surviving to discharge (Fig 1). (9) than 50% of infants delivered before 30 weeks’ gestational
These experiences demonstrate that many very low age will have been exposed to chorioamnionitis. (14) In
birthweight infants do not have RDS of sufficient severity animal models, intra-amniotic pro-inflammatory media-
to receive surfactant treatment. As the “normal fetus” tors cause lung inflammation. (15) That inflammation
would be expected to have RDS if delivered before can induce lung maturation and decrease RDS, but the
approximately 35 weeks’ gestational age, (10) the clini- inflammation also can be a diffuse pneumonia that can
cian should ask the question why a very preterm infant present as RDS. Surprisingly, a pure pneumonia syndrome

Incidence of Respiratory Distress Syndrome in Very Low


Table 1.

Birthweight Infants
Study Infants Reported % Treated With Surfactant Ref. No.
Danish Experience 27 – 2 weeks 30% 5
COIN Trial 950 g average 38% (CPAP arm) 6
NICHD–Support Trial 24–27 weeks 67% (CPAP arm) 7
Vermont-Oxford CPAP Trial 26–29 weeks 45% (CPAP arm) 8
CPAP¼continuous positive airway pressure; COIN¼continuous positive airway pressure or intubation at birth; NICHD¼National Institute of Child Health
and Human Development.

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pulmonology surfactant for RDS

transient tachypnea of the newborn


includes low surfactant levels. (17)
Although essentially unstudied in
preterm infants, the delayed clear-
ance of fetal lung fluid from preterm
monkey lungs contributes to their
respiratory failure. (18) My inter-
pretation of RDS in preterm infants
is as follows: the surfactant pool
sizes will be small, even for infants
who may not have RDS. The pre-
term sheep with approximately 5
mg/kg surfactant in the airspaces
(an amount comparable with the
healthy adult human) has minimal
respiratory distress on CPAP. (19)
Lung inflammation, structural ab-
normalities, or excessive lung fluid
Figure 1. Outcomes of infants treated with continuous positive airway pressure (CPAP). A
will compromise the function of
clinical experience with infants of birthweight 500 to1,000 g and ‡25 weeks’ gestational
age in a low resource academic neonatal intensive care unit (NICU) in South Africa that a small amount of surfactant, and
did not support infants with mechanical ventilation. The majority of the infants were poor respiratory effort will promote
managed with CPAP alone, and some infants were intubated and given surfactant and atelectasis. Any mechanical ventila-
then extubated back to CPAP (intubate, surfactant, and extubate [INSURE]). Data from tion may be injurious and may fur-
Kirsten et al. (9) ther damage surfactant function.
BPD[bronchopulmonary dysplasia; GA[gestational age; NCPAP[nasal CPAP. (20) The infant with marginal sur-
factant amounts might escape
is seldom diagnosed soon after very preterm birth. (4) In- RDS if transitioned with CPAP. In contrast, the same in-
fants exposed to chorioamnionitis who have a fetal inflam- fant may end up with a preterm version of adult RDS if
matory response have a poor response to surfactant. (16) the lung is not stabilized or if ventilation is excessive.
Another confounder for a pure diagnosis of RDS is the Thus, many very preterm infants have RDS plus, and
amount of fetal lung fluid retained in the lung. Severe the plus is various combinations of the confounders listed
in Table 2. Nevertheless, any preterm infant with a diag-
nosis of significant respiratory failure, probably with
a RDS component, should be treated with surfactant.
There are no contraindications to surfactant treatment
Confounders of Diagnosis
Table 2. for suspected RDS.
of Respiratory Distress
Syndrome When to Treat?
The decision of when to treat an infant who has surfac-
Possible Explanations for No RDS
• Antenatal corticosteroids tant deficiency continues to evolve. The trials following
• Chorioamnionitis and induced lung maturation licensure of surfactant for general use strongly supported
• Presently unknown mechanisms the treatment of infants at high risk of RDS in the delivery
Alternative Causes or Contributors to RDS room after initial stabilization. (21) A trial of treatment at
• Pulmonary hypoplasia delivery and preferably before the infant breathing versus
• Pulmonary hypertension
• Lung inflammation/pneumonia after initially stabilization of the infant revealed more
• Retained fetal lung fluid BPD in the very early treatment group, presumably be-
• Failure of respiratory drive–apnea cause the surfactant treatment interfered with the initial
• Injury from mechanical ventilation care of the infant. (22) Many clinicians prefer a delayed
RDS¼respiratory distress syndrome. treatment, often after several hours of age. The Vermont-
Oxford group reported a quality improvement initiative

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pulmonology surfactant for RDS

to decrease the interval from birth to treatment. (23) Al- 45% received surfactant. This trial suggests no benefit to early
though the educational intervention decreased the time surfactant even if the infant is not subsequently ventilated.
to treatment from 78 minutes to 21 minutes, there were The trials demonstrate that stabilization of spontaneous
no differences in any outcome, including BPD or death. breathing in the delivery room is marginally better than in-
Infants who have RDS often have a honeymoon period of tubation and surfactant treatment for very preterm infants.
relatively good lung function before progression toward The contentious point is how low can you go (in birth-
severe RDS. My interpretation is that delayed treatments weight/gestational age) with CPAP to support spontane-
reflect reasonable clinical decisions to avoid unnecessary ous ventilation. The experience from South Africa in
treatments. The practical advantage for delaying treat- a resource-limited environment was that most infants less
ment beyond the initial period of stabilization at delivery than 1,000 g did well on CPAP alone, although they did
is that treatment of the large number of infants without not support infants less than 500 g, and 38% of infants
RDS is avoided. There are no data to demonstrate any were growth restricted. (9) At Columbia University,
benefit of a surfactant treatment for an infant not des- 69% infants who have gestational ages of 23 to 25 weeks
tined to have RDS. Selective treatment of infants as they could be initially stabilized with CPAP, and 31% remained
progress toward RDS allows more controlled treat- on CPAP at 72 hours. (26) The Surfactant Positive Pres-
ments in the NICU rather than the delivery room. The sure and Pulse Oximetry Randomized Trial (SUPPORT)
counter argument is that any ventilation, even spontane- enrolled a large number of infants at 240 to 256 weeks’ ges-
ous breathing with RDS, will cause lung injury and result tational age. (7) Although there were no significant differ-
in a less favorable response to surfactant, more acute ences for outcomes for the overall trial that included more
complications such as pneumothorax, and increased risks mature infants, this very low gestational age group seemed
of poor outcomes (death and BPD). These risks of delay- to benefit from randomization to CPAP (Table 3).
ing treatments with surfactant are supported by the stud- The clinical message from these trials is that CPAP in
ies of animal models of RDS. the delivery room is a reasonable strategy for any preterm
From my perspective, this controversy has been re- infant who can be coaxed (quickly) to breathe, indepen-
solved by the series of randomized controlled trials that dent of size or gestational age. Unfortunately, the bene-
have recently been published and compiled into two fits of the CPAP/avoiding ventilation strategy are not as
meta-analyses. (24)(25) The trials were designed to ask great as might be anticipated from research with preterm
this question: Will initial stabilization of breathing with animals. The research emphasis is now on how best to re-
CPAP be better than early intubation and surfactant cruit lung gas volumes immediately after birth. Perhaps
treatment for very preterm infants? Although each of a CPAP plus strategy that might use higher pressures
the trials differ in patient population and choice of surfac- or supplemental long initial breaths (sighs) will improve
tant, the results of the four large trials including 2,782 outcomes. (27) A problem with converting information
patients compiled by Schmolzer et al (24) and the seven from the trials into practice guidelines is the clinical reality
trials evaluated by Fischer and Buhrer (25) that included that these very fragile infants are not uniform at birth
3,289 patients were similar. A CPAP strategy to avoid (Fig 3). Each infant needs the equivalent of a 10-second
early mechanical ventilation decreased death or BPD sig-
nificantly, odds ratio 0.83 (0.71–0.96), with a number
needed to treat of 35. (25) The meta-analysis that com-
pared CPAP with early intubation and surfactant treat-
ment revealed that the CPAP strategy decreased BPD
and death was decreased qualitatively from 12% to 11%
(Fig 2). (24) The combined outcome had a risk ratio
of 0.91 (0.84–0.99) that favored the CPAP strategy.
The Dunn et al (8) trial had three randomization arms
for infants of mean gestational age 28 weeks (early surfac-
tant treatment with ventilation, early surfactant with
Figure 2. Outcomes for infants randomly assigned to con-
rapid extubation to CPAP or CPAP alone). Although tinuous positive airway pressure (CPAP) initiated in the de-
the trial was underpowered, the two groups that did livery room or intubation and surfactant treatment in the
not receive more prolonged ventilation had lower mortal- delivery room. The combined outcome of death or broncho-
ity and BPD. Only 52% of the CPAP only group needed pulmonary dysplasia significantly favored the CPAP group.
mechanical ventilation during their hospitalization and Data from Schmölzer et al. (24)

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pulmonology surfactant for RDS

Outcomes for Support Trial


Table 3.
evaluation of the infant involves a balanced clinical judg-
ment of the abnormalities. Significant apnea requires in-
Infants With Gestational Ages of tervention. The larger infant in 30% oxygen with
240 to 256 Weeks a normal PCO2 may be distressed with radiologic findings
of RDS, but the infant is compensating because of his
Relative Risk (95% ability to increase respiratory effort. The very small infant
Confidence Interval) P may have only modest distress, but elevated PCO2 values
BPD or death 0.96 (0.85–1.07) .45 and need surfactant treatment. Bahadue and Soll (28) re-
BPD 1.06 (0.91–1.25) .46 ported a benefit for early treatment within 1 to 2 hours
Death 0.68 (0.50–0.92) .01 relative to treatment at more than 2 hours with significant
Use of postnatal 0.66 (0.46–0.94) .02 risk ratios of 0.84 (0.72–0.95) for death, 0.61 (0.48–
steroids
0.78) for air leak, and 0.69 (0.55–0.86) for BPD. The
BPD¼bronchopulmonary dysplasia. Data from Finer et al. (7) European Consensus Guidelines for the management
of RDS are to treat infants younger than 26 weeks’ ges-
tation with RDS with surfactant early in the clinical
Apgar score (a physiologic assessment) for the clinician to course when oxygen requirements are more than 30%
decide what will be best for that infant. Severe depression and to use more than 40% oxygen for infants older than
requires assistance with positive pressure ventilation (PPV), 26 weeks’ gestation. (29) The recently published guide-
whereas the larger vigorous infant needs no ventilatory sup- lines from the American Academy of Pediatrics Commit-
port and the smaller infant may benefit from CPAP to assist tee on Fetus and Newborn are less specific, but suggest
with transition. The problem is the large number of in- early rather than later treatment on the basis of a recent
fants between these extremes. Units that routinely use meta-analysis. (30) Surfactant treatment can be avoided
CPAP in the delivery room can coax most of these infants in some infants by strategies such as the use of higher
to breathe and transition on CPAP. A standard of care for pressure for CPAP or noninvasive ventilation. Failure
delivery room management for all infants less than 1 kg is of CPAP increased as gestational age decreased and in-
problematic. Intubation may harm the vigorous infant. In creased for higher oxygen requirements in the first hours
contrast, a CPAP standard could harm the depressed in- after birth. (31) CPAP failure was associated with a higher
fant by delaying ventilation. risk of BPD and pneumothorax. If an infant has progres-
The next decision point for the clinician is the evalu- sive RDS, there is a specific therapy that should be given,
ation of the infant for RDS and surfactant treatment. The surfactant.

How Should Surfactant Be


Given?
Surfactant was the first drug approved
by the Food and Drug Administra-
tion (FDA) for direct instillation into
the lungs through an endotracheal
tube. All the early trials for testing
the value of surfactant treatment used
instillation via an endotracheal tube.
At the time the standard manage-
ment for RDS was mechanical venti-
lation of intubated infants. With the
interest in avoiding intubation at de-
livery and the management of RDS
Figure 3. A flow diagram for an action plan following a 10-second Apgar (physiologic
with CPAP or noninvasive ventila-
assessment of a very low birthweight infant). Based on appearance and breathing activity the tion, strategies to give surfactant
clinician must decide how to initially support respiratory transition. Subsequently, all infants without intubation with an endotra-
will need an evaluation for respiratory distress syndrome (RDS) and surfactant treatment. cheal tube have been developed. An-
CPAP[continuous positive airway pressure; PPV[positive pressure ventilation. other concern has been the acute

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pulmonology surfactant for RDS

physiologic effects of surfactant treatments on the cardiovas- based treatment resulted in less BPD than INSURE.
cular system of the infant. For example, Miedema et al (32) (40) The outcomes from these different approaches to get-
recently reported that infants treated with surfactant while ting surfactant into the lungs are highly operator and detail
supported on an oscillator had a 61% increase in lung gas dependent. For example, the use of sedatives or analgesics
volume within 4 minutes. Such changes probably explain for the laryngoscopy will change the responses of the infant
the increases in systemic blood flow as infants respond to to treatment. Infants treated by using the INSURE ap-
surfactant treatments. (33) The combined procedure of in- proach can be ventilated briefly while a catheter technique
tubation followed by surfactant treatment can alter brain requires vigorous spontaneous breathing. Ultimately, the
perfusion and suppress the normal electroencephalography. clinician must decide how much control of the airway will
(34) Further, surfactant treatments can obstruct the airways be needed for a safe surfactant treatment for each infant.
and cause hypoxia and increase the PCO2 unless sufficient Important variables are the respiratory effort of the infant,
pressures are used to distribute the surfactant into the distal the size of the infant, and the severity and progression of
lung. (35) the RDS.
Surfactant has been given into amniotic fluid in the The holy grail of surfactant treatment is to aerosolize
hope that the infant will aspirate the surfactant and be surfactant while supporting the infant with CPAP. Such
treated before birth. Surfactant has been instilled into an approach would avoid intubation and mechanical ven-
the nasopharynx before delivery of the shoulders with tilation and avoid the acute cardiovascular changes that oc-
the anticipation that the infant will aspirate the surfactant cur when an infant responds quickly to surfactant. The
with the initiation of breathing. (36) Another noninva- problems with a successful Aerosolization strategy are sub-
sive approach is to use a laryngeal mask airway to give sur- stantial: surfactant doses and volumes are large, aerosol-
factant. (37) A laryngeal mask airway small enough for izers could inactivate the surfactant, the surfactant tends
infants less than 1,200 g is not available. These ap- to deposit where the lung is being ventilated and not to
proaches have not been extensively tested. atelectatic or air trapped regions, and much of the aerosol
An effective approach to minimize mechanical ventila- will get deposited in the nose and pharynx. (41) A Co-
tion for surfactant treatment for an infant on CPAP is in- chrane Neonatal Review in 2012 concluded that there
tubate, surfactant, and extubate (INSURE) to CPAP. were insufficient data to evaluate aerosolized surfactant
This technique may decrease the
need for mechanical ventilation and
BPD in larger infants. (38) Very pre-
term infants may not have sufficient
respiratory reserve to cope with the
intubation and surfactant instillation
if quickly extubated to CPAP. The
European Consensus Guidelines sup-
port considering INSURE for larger
infants needing surfactant, whereas
the American Academy of Pediatrics
Guidance document makes no rec-
ommendation. (29)(30)
Another option is to avoid tradi-
tional intubation by passing a fine
catheter into the trachea of the infant
with direct visualization by laryngos-
copy while maintaining some CPAP
with high flow. Once the catheter is
positioned, the laryngoscope is re-
Figure 4. Decrease in death from respiratory distress syndrome (RDS) from 1970 to 2010.
moved and the infant is treated dur- Infant mortality has decreased by 95%, although the infants coded as having RDS have
ing spontaneous breathing while on gotten smaller and more immature. The years for introduction of the interventions into
CPAP. (39) This approach can re- clinical practice are indicated on the graph. Figure redrawn from data in Lee et al (49)
duce the need for mechanical venti- with additional data for 2010 to 2011 from Hamilton et al. (50)
lation, and in one trial the catheter CPAP[continuous positive airway pressure; PEEP[positive end-expiratory pressure.

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pulmonology surfactant for RDS

for clinical use. (42) One trial concluded only that aerosol- with synchronization to spontaneous breathing by using
ized surfactant for infants on CPAP appeared to be safe. techniques such as neural adjusted ventilator assist with
(43) However, there are new innovations in nebulizer de- triggering from the electrical signal of the diaphragm are
sign that greatly improve efficiency of aerosol delivery. being evaluated. (48) Surfactant treatment strategies are
(44) Recent reports in animal models also support the fea- being integrated into these respiratory support strategies.
sibility of aerosol strategies. (45) Aerosolization of surfac- Aerosols of surfactant may be another approach to improv-
tant is being actively developed for infants with RDS. ing treatment strategies and outcomes. In 2014, we must
recognize that the multifaceted treatments for preterm in-
Which Surfactant Should Be Used? fants with RDS are the major success story in neonatology.
In the United States, three surfactants sourced from an- Mortality from RDS decreased by 95% from 1970 to 2011
imal lungs (beractant, calfactant, and poractant) and one (Fig 4). (49)(50) Over this period the infants diagnosed
synthetic containing a surfactant protein analog (lucinactant) with RDS are more immature, such that infants who have
are available for clinical use. Elsewhere in the world, lo- RDS who died with RDS in 1970 no longer die. The in-
cally produced surfactants, often of unvalidated quality, fants who die of RDS now are the most immature infants
are available at lower cost. The choice of a surfactant who have multiple other complications of prematurity.
by the physician is likely to be influenced by advertising Improved neonatal care plus surfactant has essentially
claims that may not be relevant to the primary outcomes eliminated mortality from RDS for infants more than 1
of interest, which should be major complications of pre- kg unless they have other complicating problems.
maturity that can be improved with surfactant therapy.
Those outcomes are death and pneumothorax. Contrary
to popular belief, surfactant treatments have not de-
creased the incidence of BPD, rather the increased sur- American Board of Pediatrics Neonatal-Perinatal
vival results in more very preterm infants at risk for Content Specifications
BPD. Surfactant and better ventilation support strategies • Know the pathophysiology and risk factors
have decreased the severity of BPD. Trembath et al (46) for respiratory distress syndrome (RDS).
reported the comparative effectiveness for the animal lung • Know the clinical strategies and therapies
used to decrease the risk and severity of
derived surfactants in 51,282 infants. There were no con- RDS.
sistent differences for pneumothorax, BPD, or death be- • Know the management of RDS, including
tween the surfactants. surfactant replacement.
New synthetic surfactants that contain full length Sur-
factant Protein C and analogs of Surfactant Protein B are
being developed for treatment of RDS. (47) These sur- References
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the advantages of more quality control for manufacture Neonatal Research Network. Association of antenatal corticosteroids
and they have no risk of animal derived disease (although with mortality and neurodevelopmental outcomes among infants
born at 22 to 25 weeks’ gestation. JAMA. 2011;306(21):2348–2358
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NeoReviews Quiz Requirements


To successfully complete 2014 NeoReviews articles for AMA PRA Category 1 CreditTM, learners must demonstrate a minimum performance level of
60% or higher on this assessment, which measures achievement of the educational purpose and/or objectives of this activity. If you score less than
60% on the assessment, you will be given additional opportunities to answer questions until an overall 60% or greater score is achieved. NOTE:
Learners can take NeoReviews quizzes and claim credit online only at: http://neoreviews.org.

1. A female infant is born at 27 weeks’ gestational age and is admitted to the neonatal intensive care unit (NICU).
The mother received antenatal steroids 3 days before delivery. The infant is brought to the unit on continuous
positive airway pressure (CPAP) and has increasing oxygen requirement, worsening signs of respiratory distress,
and is placed on mechanical ventilation and given surfactant by endotracheal tube. She remains on the
ventilator for 24 hours and is then extubated. Which of the following descriptions best matches this clinical
scenario and respiratory distress syndrome (RDS)?
A. Considering the clinical course, this patient cannot be considered to have RDS by standard definitions.
B. Although antenatal steroids may have assisted in alveolar development, all infants at this gestational age
have surfactant deficiency, which would ultimately benefit from replacement.
C. The presence of chorioamnionitis, even when asymptomatic, can potentially lead to early maturation of the
lungs, including increased surfactant.
D. As the infant was initially maintained on continuous positive airway pressure, the diagnoses of pulmonary
hypoplasia or problems of anatomic lung development can be excluded.
E. Recent studies indicate that optimal management for patients in this clinical situation should have
included nitric oxide treatment starting in the delivery room.

2. Upon examination of the placenta of the patient in the above question, there is evidence of histologic
chorioamnionitis. Which of the following is true regarding the relationship between chorioamnionitis and
respiratory development in the premature infant?
A. Although there may be evidence on pathologic examination, chorioamnionitis is a clinical diagnosis and
unless the mother exhibited symptoms such as fever and tachycardia, there would be no consequence to
the newborn infant.
B. Chorioamnionitis can induce lung maturation and decrease RDS, but may also lead to symptoms of diffuse
pneumonia presenting as respiratory distress.
C. Premature infants exposed to chorioamnionitis tend to have a particularly positive response to surfactant.
D. The majority of premature infants born after chorioamnionitis will present with a classic pneumonia
syndrome, but with negative radiographic findings.
E. In growth restricted infants, the incidence of RDS and respiratory distress in general is approximately 25%
of that of similar gestational age infants.

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pulmonology surfactant for RDS

3. A male infant is born at 33 weeks’ gestational age and has symptoms of respiratory distress including
tachypnea, subcostal retractions, and nasal flaring. Chest radiograph reveals what appears to be retained lung
fluid. Which of the following considerations is appropriate regarding the further evaluation and treatment of
this patient?
A. This may be a presentation of severe transient tachypnea of the newborn with retained lung fluid, which
may be associated with low surfactant levels.
B. Mechanical ventilation by itself without surfactant replacement in primate and human studies has been
shown to be a potent stimulator of endogenous surfactant function.
C. Recent studies have demonstrated that preterm infants at this gestational age are unlikely to benefit from
surfactant, and should be treated with supportive care until lung maturation occurs in the first few days.
D. Because infants at this gestational age do not typically have surfactant deficiency, the treatment plan
should not include surfactant therapy unless the infant is growth restricted.
E. The main problem in infants with respiratory distress at this gestational age is a lack of lung fluid leading to
a decreased activation of surfactant, rather than the amount of surfactant available.

4. Your team is preparing for an infant who will be delivered at 27 weeks’ gestational age because of severe
maternal preeclampsia. The mother has received antenatal steroids, magnesium sulfate, and antibiotics. Which
of the following is correct regarding current understanding of appropriate treatment for the infant after birth?
A. Although previous studies have revealed that continuous positive airway pressure is sufficient for care for
most infants at this gestational age, recent studies reveal that prophylactic surfactant leads to reduced
incidence of bronchopulmonary dysplasia.
B. Quality improvement projects aimed at reducing the time to surfactant therapy have demonstrated
a reduction in mortality, bronchopulmonary dysplasia, and length of hospital stay.
C. Because RDS occurs in 100% of infants at this age, surfactant should be given unless the infant is able to
breathe in room air.
D. The decision of when to treat an infant at this gestational age is not amenable to one approach, because
treatment for patients who do not have RDS is not beneficial, but a delay in treatment for a patient with
RDS could lead to complications.
E. The most recent studies have not revealed any difference in the incidence of bronchopulmonary dysplasia,
regardless of initial treatments in the delivery room or first several hours in the neonatal intensive care
unit.

5. Which of the following statements is correct regarding the delivery of surfactant to premature infants?
A. Although surfactant has been shown in clinical trials to have efficacy for RDS, it is not officially approved
by the Food and Drug Administration (FDA) for premature infants.
B. Studies have demonstrated that the optimal use of surfactant is facilitated by at least 6 hours of
subsequent mechanical ventilation.
C. Intubation followed by surfactant treatment has been shown to alter cerebral perfusion and
electroencephalography activity.
D. The most promising alternative to intubation for surfactant is delivery by laryngeal mask airway,
particularly for infants more than 500 g who may be difficult to intubate.
E. Synthetic surfactant mimics the phospholipid component of natural surfactant, lacks protein, and has
proven to be ineffective in animal models.

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Surfactant for Respiratory Distress Syndrome
Alan Jobe
Neoreviews 2014;15;e236
DOI: 10.1542/neo.15-6-e236

Updated Information & including high resolution figures, can be found at:
Services http://neoreviews.aappublications.org/content/15/6/e236
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