Introduction
Our aim was to develop consensus recommendations from United Kingdom (UK) neonatal
specialists on the use of surfactant for the management of respiratory distress syndrome
RDS in preterm infants. RDS due to surfactant deficiency is common in preterm infants.
Signs, including tachypnoea, recessions, and grunting, usually commence shortly after
birth, and increase in severity during the first 12–48 h of postnatal life. Significant
RDS may require mechanical ventilation (MV) or noninvasive ventilatory support (NIV),
both of which have potential to cause lung injury via a number of mechanisms.
1
The aim of RDS management is to provide appropriate respiratory support whilst minimising
complications and, ultimately, bronchopulmonary dysplasia (BPD). Treatment with exogenous
surfactant reduces requirement for positive pressure ventilation, mitigates risk of
pulmonary air leak, and improves survival.
1
International consensus guidelines on management of RDS have been published;
1
however, recent developments in the field of less invasive surfactant administration
prompt the need for a UK national consensus on surfactant use in preterm infants with,
or at risk of, RDS.
Methods
For the purpose of this expert consensus, UK specialists in neonatal respiratory disease
and its management were selected based on their previous clinical and scientific experience
of RDS management. In a three-step modified Delphi process, seven recommendations
were debated and modified in a series of iterative reviews, with the goal of reaching
an expert panel consensus. The final stage of the Delphi process was a face-to-face
meeting to discuss the precise wording and hierarchy of the recommendations. The Delphi
process was supported by an unconditional grant from Chiesi UK Limited; however, the
authors maintain complete control over all content of the recommendations.
Key recommendations
Consensus recommendations for the management of RDS in preterm infants were developed;
this manuscript provides a narrative for these recommendations. The recommendations
are as follows:
1. All neonatal units should have an agreed policy for the management of early RDS.
Minimising unwarranted variation in care is an NHS (National Health Service) mandate
(www.england.nhs.uk/rightcare; www.1000livesplus.wales.nhs.uk), and European Standards
of Care for Newborn Health (www.newborn-health-standards.org) require that guidelines
for management of RDS should be available in individual units.
2. Early rescue surfactant rather than prophylaxis is recommended. In some situations,
this may include surfactant administration in the delivery suite.
Early rescue involves surfactant treatment for RDS early in the course of the disease
when additional oxygen requirement is still relatively low, usually within a few hours
after birth. Surfactant prophylaxis is traditionally defined as surfactant administration
solely on the basis of gestational age and/or expected high risk of RDS. In the modern
context of noninvasive ventilatory management, surfactant prophylaxis and unnecessary
intubation has potential for harm. A systematic review of studies comparing surfactant
administration through intubation as prophylaxis versus stabilisation on continuous
positive airway pressure (CPAP) with early rescue surfactant (if required) showed
that infants initiated on CPAP were at lower risk of chronic lung disease or death.
2
The potential benefit or harm of prophylactic surfactant administration using less
invasive surfactant administration (LISA) techniques is at present unknown.
Whilst advocating avoidance of routine prophylaxis, it is important to recognize that
in some situations, surfactant may need to be administered very soon after birth.
This would include infants who require intubation for stabilisation soon after birth,
or who have rapidly increasing oxygen requirements beyond initial stabilisation. Surfactant
should therefore always be available in the delivery suite, and this should be acknowledged
in local policies for early RDS management.
3. In babies with evolving RDS, rescue surfactant should be administered early in
the course of the disease. Inspired oxygen concentration above 30% in the first hours
of life is a reasonable predictor of CPAP failure.
The incidence of CPAP failure, defined as the need for MV following initiation of
CPAP, increases with lower gestational age at birth.
3
Infants who fail initial CPAP therapy have an increased incidence of adverse outcomes
including mortality, pneumothorax, intraventricular hemorrhage, and BPD, compared
with infants for whom CPAP is successful.
3
In infants with evolving RDS, rescue surfactant should be used in an effort to prevent
CPAP failure.
3
The inspired oxygen concentration required to achieve acceptable oxygen saturations
as measured by pulse oximetry is widely available to clinicians as a proxy to assess
the severity and progression of RDS. According to Dargaville et al., inspired oxygen
concentration above 30% for preterm infants in the first hours of life is strongly
predictive of CPAP failure, and is typically reached more rapidly by infants with
lower gestational ages.
3
Although the above mentioned study was concerned with identifying predictors of CPAP
failure, the group of experts believes that this oxygen threshold may be considered
appropriate for NIV generally. Inspired oxygen concentration should also be interpreted
in combination with clinical assessment of work of breathing, direction of improvement
or worsening, and the general clinical condition of the infant.
4.(a)For rescue therapy using natural surfactants, poractant alfa at an initial dose
of 200
mg/kg reduces mortality and the need for redosing compared to 100
mg/kg of surfactant.
4
There is an absence of data on other natural surfactants at doses
>
100
mg/kg.
This recommendation is based on currently available evidence regarding natural surfactants
and their dosing via an endotracheal tube for the treatment of RDS in preterm infants.
Natural surfactants vary in their origin, composition, and recommended dosing, and
studies have shown differences in clinical effect. Poractant alfa (Curosurf®, Chiesi
Farmaceutici S.p.A., Parma, Italy) and beractant (Survanta®, AbbVie Inc., North Chicago,
USA) are the only surfactants currently licensed for the use in the UK. An initial
dose of 200 mg/kg of poractant alfa appears more effective than 100 mg/kg of poractant
alfa or beractant in reducing the need for repeat dosing.
4
Currently, poractant alfa is the only surfactant that is licensed at a 200 mg/kg initial
dose. There are no comparative dosing data for surfactants administered using less
invasive techniques.
4.(b)The surfactant dose should be calculated and administered based on the baby’s
weight. If surfactant is required before the baby’s birth weight is known, it is reasonable
to use whole vial dosing based on an estimated weight.
This recommendation supports accurate dosing of surfactant, which should be calculated
based on the infant's weight. Weight-based dosing applies to both early rescue administration
and treatment of established RDS. For some surfactant preparations of lesser volume
(e.g. poractant alfa), whole-vial dosing, based on estimated weight, is reasonable,
for example when administered for early rescue in the delivery suite.
4.(c)A second and sometimes a third dose of surfactant can be considered in ongoing
RDS.
On occasions, it may be necessary to administer a second, and sometimes a third dose
of surfactant in ongoing RDS (lack of improvement, persistent high oxygen requirement,
increased work of breathing on noninvasive support, or continuing need for MV).
1
Other causes of respiratory failure, which may require different treatments, should
be considered. Clinical trials comparing single versus multiple doses of surfactant
administered via endotracheal intubation showed better outcomes if multiple doses
were allowed.
1
Subsequent dosage should be guided by the manufacturer’s maximum cumulative dosage
recommendations.
5. There is emerging evidence that the LISA technique may be the preferred method
for spontaneously breathing preterm infants kept on NIV, as an alternative to the
intubation-surfactant-extubation (INSURE) technique.
INSURE describes surfactant administration after endotracheal intubation, followed
by brief ventilation, timely extubation (within 60 min) and reinstitution of NIV.
1
However, the implementation of INSURE is variable, particularly with regard to the
length of MV following surfactant administration; in some instances, MV may be prolonged
for different reasons, including physician’s preference. The LISA technique, also
referred to as minimally invasive surfactant therapy (MIST), is a method for administering
surfactant via an endotracheally placed catheter to infants spontaneously breathing
on NIV.
1
A soft-tipped, semi-rigid, fine bore surfactant administration catheter is placed
under direct laryngoscopy, with or without the use of Magill forceps; equipment specifically
designed for this use is available. Surfactant is then given slowly whilst the infant
continues to breathe. Vital signs are continuously monitored and patient comfort ensured
throughout the procedure, during which NIV is uninterrupted. Moderate desaturation,
with or without bradycardia, may occur, in which case surfactant administration should
pause without removal of the catheter. The catheter is removed once the surfactant
delivery is complete.
Current evidence from several randomised controlled trials of variable quality synthesised
in meta-analyses shows that in preterm infants on NIV, the LISA procedure reduces
need for MV and risk of death and BPD, compared with endotracheal intubation, surfactant
application, and MV.
5
The neonatal workforce applying LISA should be appropriately trained. Up-to-date education
on theory, mannequin simulations, and the use of video laryngoscopy is advisable.
Clear guidelines and local audits should be in place to identify local strengths and
challenges for LISA implementation.