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European-Consensus-Guidelines-on-the-Management-of-Respiratory-Distress-Syndrome-2019-Update
European-Consensus-Guidelines-on-the-Management-of-Respiratory-Distress-Syndrome-2019-Update
Henry L. Halliday n
a Regional Neonatal Unit, Royal Maternity Hospital, Belfast, UK; b Department of Neonatology, Polytechnic University
of Marche, and Azienda Ospedaliero-Universitaria Ospedali Riuniti Ancona, Ancona, Italy; c Department of
Neonatology, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark; d Department of Pediatrics and
Adolescence, Oulu University Hospital, and PEDEGO Research Unit, Medical Research Center, University of Oulu,
Oulu, Finland; e Department of Pediatrics, Marmara University Medical Faculty, Istanbul, Turkey; f Leiden University
Medical Centre, Leiden, The Netherlands; g Division of Neonatology, Department of Obstetrics and Gynecology,
General Faculty Hospital and 1st Faculty of Medicine, Charles University, Prague, Czech Republic; h Department
of Paediatrics, University of Oxford, Medical Sciences Division, Newborn Services, John Radcliffe Hospitals,
Oxford, UK; i Department of Pediatric Research, Oslo University Hospital Rikshospitalet, University of Oslo, Oslo,
Norway; j Division of Pediatrics, CHUV & University of Lausanne, Lausanne, Switzerland; k Department of Pediatrics,
University Children’s Hospital, Würzburg, Germany; l Department of Pediatrics and Neonatal Research Unit, Health
Research Institute La Fe, University and Polytechnic Hospital La Fe, Valencia, Spain; m Department of Obstetrics and
Gynecology, University Medical Centre, Utrecht, The Netherlands; n Department of Child Health, Queen’s University
Keywords Abstract
Antenatal steroids · Continuous positive airway As management of respiratory distress syndrome (RDS) ad-
pressure · Evidence-based practice · Hyaline membrane vances, clinicians must continually revise their current prac-
disease · Mechanical ventilation · Nutrition · Oxygen tice. We report the fourth update of “European Guidelines
supplementation · Patent ductus arteriosus · Preterm for the Management of RDS” by a European panel of experi-
infant · Respiratory distress syndrome · Surfactant therapy · enced neonatologists and an expert perinatal obstetrician
Thermoregulation based on available literature up to the end of 2018. Optimis-
ing outcome for babies with RDS includes prediction of risk
of preterm delivery, need for appropriate maternal transfer
These updated Guidelines contain new evidence from recent Co- to a perinatal centre and timely use of antenatal steroids.
chrane reviews and the medical literature since 2016. Strength of ev- Delivery room management has become more evidence-
idence supporting recommendations has been evaluated using the based, and protocols for lung protection including initiation
GRADE system. The prenatal care section has been updated by Prof.
Gerard H.A. Visser. There are also new recommendations covering of CPAP and titration of oxygen should be implemented im-
less invasive surfactant administration. This guideline has been en- mediately after birth. Surfactant replacement therapy is a
dorsed by the European Society for Paediatric Research (ESPR). crucial part of management of RDS, and newer protocols for
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Table 1. Representations of quality of evidence and strength of rec- follow-up data are broadly reassuring, albeit sketchy [24],
ommendations and given the potential for long-term side-effects, steroids
are not currently recommended for women in spontane-
Quality of evidence
High quality A ous preterm labour after 34 weeks [25]. When given be-
Moderate quality B fore elective Caesarean section (CS) up to 39 weeks, they
Low quality C reduce risk of admission to NICU, although the number
Very low quality D needed to treat is >20 and follow-up data on term babies
Strength of recommendation exposed to antenatal steroids are lacking [26]. The optimal
Strong recommendation for using intervention 1
Weak recommendation for using intervention 2 treatment to delivery interval is more than 24 h and less
than 7 days after the start of steroid treatment; beyond 14
days, benefits are diminished. Beneficial effects of the first
dose of antenatal steroid start within a few hours, so ad-
measurement possibly in combination with a biomarker vanced dilatation should not be a reason to refrain from
may determine which women are actually at risk of deliv- therapy and the same may hold for MgSO4 [27]. There is
ery within 7 days and allow more judicious use of antena- still debate as to whether steroids should be repeated 1 or
tal treatments [14]. Extremely preterm babies should, if 2 weeks after the first course for women with threatened
possible, be transported in utero to tertiary centres where preterm labour. A repeat course reduces the risk of respi-
appropriate skills are available; best outcomes are achieved ratory support. However, it decreases fetal growth, and
for babies born in centres with a high throughput of repeat doses do not reduce mortality or other serious
VLBW babies [15]. In cases of prenatal pre-labour rup- health outcomes. No effect on neurosensory disability in
ture of membranes (PPROM), antibiotics can delay pre- follow-up has been observed, but data on potential longer-
term delivery and reduce neonatal morbidity, although term adverse effects are lacking [28, 29]. WHO recom-
co-amoxiclav should be avoided because of its association mends that a single repeat course of steroids may be con-
with increased risk of necrotising enterocolitis (NEC) sidered if preterm birth does not occur within 7 days after
[16]. Magnesium sulphate (MgSO4) given to women with the initial course and there is a high risk of preterm birth
imminent preterm delivery reduces cerebral palsy at 2 in the next 7 days [30]. It is unlikely that repeat courses
years of age by about 30% [17], although longer-term given after 32 weeks’ gestation improve outcome [31].
benefits are less clear [18]. Tocolytic drugs can be used in Steroids are potent drugs with many side effects, but
the short-term to delay birth, permit safe transfer to a when given appropriately they improve outcome. If not,
perinatal centre and allow prenatal corticosteroids time then side effects, such as impaired fetal and placental
to take effect, although tocolytics have no direct beneficial growth, apoptosis in the brain and increased infection,
effect on the fetus [19]. Given their limited value, only may prevail. Use of steroids should be reduced by ade-
drugs that are safe for the mother should be considered, quate preterm birth risk assessment and avoidance of un-
that is oxytocin antagonists or Ca-channel blockers [20]. necessary early elective CS. In some cases when an early
A single course of prenatal corticosteroids given to CS is needed, establishment of fetal lung maturity may be
mothers with anticipated preterm delivery improves sur- better than giving steroids to all women [32]. There is
vival, reduces RDS, NEC and intraventricular haemor- little evidence that delivering preterm infants by CS rath-
rhage and does not appear to be associated with any sig- er than allowing vaginal delivery improves outcome.
nificant maternal or short-term fetal adverse effects [21].
Prenatal corticosteroid therapy is recommended in all Recommendations
pregnancies with threatened preterm birth before 34 1 Mothers at high risk of preterm birth <28–30 weeks’ gesta-
weeks’ gestation where active care of the newborn is an- tion should be transferred to perinatal centres with experi-
ence in management of RDS (C1).
ticipated. Although there are limited RCT data in babies 2 Clinicians should offer a single course of prenatal corticoste-
at <25 weeks’ gestation, observational studies suggest that roids to all women at risk of preterm delivery from when
antenatal corticosteroids, together with other active man- pregnancy is considered potentially viable until 34 weeks’
agement practices, reduce mortality at gestations as low as gestation ideally at least 24 h before birth (A1).
22 weeks [22]. In pregnancies between 34 and 36 weeks’ 3 A single repeat course of steroids may be given in threatened
preterm birth before 32 weeks’ gestation if the first course
gestation, prenatal steroids also reduce risk of short-term was administered at least 1–2 weeks earlier (A2).
respiratory morbidity but not mortality, and there is in- 4 MgSO4 should be administered to women in imminent la-
creased risk of neonatal hypoglycaemia [23]. Long-term bour before 32 weeks’ gestation (A2).
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bining these data in a meta-analysis with other trials [33]. Heated, humidified oxygen delivered by high-flow
shows a significant reduction in in-hospital mortality for nasal cannula (HFNC) has also been studied as a primary
preterm infants in whom cord clamping was delayed [38]. mode of respiratory support but was inferior to CPAP in
Specialist resuscitation equipment designed to maintain terms of failure, with babies randomised to HFNC often
body temperature makes it feasible to provide advanced needing rescue with CPAP to prevent intubation [54].
resuscitation with the umbilical cord intact [39]. Umbili- Heart rate assessment is important in determining in-
cal cord milking may be an alternative to delayed cord fant well-being during transition. Heart rate <100/min for
clamping in emergency situations [40]. Two randomised >2 min in the first 5 min after birth is associated with 4.5-
trials including 255 babies <33 weeks’ gestation offered fold increase in mortality [55]. Monitoring heart rate can be
broad reassurance that short-term outcomes are broadly done by stethoscope, electrocardiography, pulse oximetry
equivalent [41], and one follow-up study suggested better or photoplethysmography. Pulse oximetry signals are often
cognitive and language scores in those randomised to delayed for up to a minute. Auscultation with a stethoscope
cord milking [42]. However, animal studies show that may not be as accurate as ECG in determining heart rate
cord milking causes considerable haemodynamic distur- during transition; however, for most units at present ECG
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is not universally available [56]. Provided heart rate is sat- 6 Plastic bags or occlusive wrapping under radiant warmers
isfactory, the aim is, where possible, to mimic normal tran- should be used during stabilisation in the delivery suite for ba-
bies < 28 weeks’ gestation to reduce the risk of hypothermia
sitional saturations measured at the right wrist by pulse ox- (A1).
imetry with saturations gradually rising from about 60–
90% over the first 10 min after birth. Blended air/oxygen
should therefore be available. For term babies requiring re-
suscitation, there is reduced mortality when using fraction Surfactant Therapy
of inspired oxygen (FiO2) 0.21 rather than 1.0 [57]. There is
evidence of increased oxidative stress when starting pre- Surfactant therapy plays an essential role in manage-
term infants in 100% oxygen; however, there is still uncer- ment of RDS as it reduces pneumothorax and improves
tainty about the longer-term effects of high or low oxygen survival. However, intratracheal administration requires
exposure at birth in preterm infants [58]. Observational skill and may cause harm, particularly if uncontrolled pos-
studies have raised concerns about starting extremely pre- itive pressure is applied to the newborn lung. Prior to
term infants in air because of poorer recovery from brady- 2013, prophylactic surfactant was recommended for the
cardia and increased mortality in the smallest babies [59]. smallest babies as it improved survival in clinical trials
Moreover, the combination of bradycardia (<100/min) and from the pre-CPAP era [63]. After 2013, with increased
lower SpO2 (<80%) in the first 5 min is associated with use of antenatal steroids and early initiation of CPAP, out-
death or intracranial haemorrhage [60]. Further trials are comes are best if surfactant is reserved for infants showing
underway to resolve this issue. Presently, it is known that clinical signs of RDS, and for the smallest infants early
when titrating oxygen, most infants end up in about 30– initiation of CPAP may avoid the harmful effects of intu-
40% oxygen by 10 min, so we believe it is reasonable to start bation and mechanical ventilation (MV) during the tran-
preterm infants <28 weeks in about 30% oxygen until more sitional phase. The overall aim is to avoid invasive MV if
evidence is available [61]. For those between 28 and 31 possible whilst endeavouring to give surfactant as early as
weeks’ gestation, 21–30% oxygen is recommended [62]. possible in the course of RDS once it is deemed necessary.
Only a minority of babies should require intubation
for stabilisation. If intubation is required, the correct Surfactant Administration Methods
placement of the endotracheal tube can be quickly veri- Surfactant administration requires an experienced prac-
fied clinically by auscultation and using a colorimetric titioner with intubation skills and ability to provide MV if
CO2 detection device before administering surfactant required. Most surfactant clinical trials to date have used
which in most circumstances can be done prior to radio- tracheal intubation, bolus administration with distribution
graphic confirmation of RDS. of surfactant using intermittent positive pressure ventila-
tion, either manually or with a ventilator, followed by a pe-
Recommendations riod of weaning from MV as lung compliance improves.
1 Delay clamping the umbilical cord for at least 60 s to pro- The IN-SUR-E technique allows surfactant to be given
mote placento-fetal transfusion (A1).
2 In spontaneously breathing babies, stabilise with CPAP of at without ongoing MV and was endorsed previously as it may
least 6 cm H2O via mask or nasal prongs (B1). Do not use SI reduce BPD [64]. In the last decade, new methods for ad-
as there is no long-term benefit (B1). Gentle positive pres- ministering surfactant using a fine catheter placed in the
sure lung inflations with 20–25 cm H2O peak inspiratory trachea under direct or video-laryngoscopy, with the infant
pressure (PIP) should be used for persistently apnoeic or spontaneously breathing on CPAP, have been described,
bradycardic infants.
3 Oxygen for resuscitation should be controlled using a blend- thereby avoiding exposure to positive pressure ventilation.
er. Use an initial FiO2 of 0.30 for babies <28 weeks’ gestation Specialised catheters designed for this method, known as
and 0.21–0.30 for those 28–31 weeks, 0.21 for 32 weeks’ ges- less invasive surfactant administration (LISA), are com-
tation and above. FiO2 adjustments up or down should be mercially available. Since the 2016 Guideline, there have
guided by pulse oximetry (B2). been further randomised trials and meta-analyses compar-
4 For infants <32 weeks’ gestation, SpO2 of 80% or more (and
heart rate >100/min) should be achieved within 5 min (C2). ing these methods. These suggest that LISA is superior in
5 Intubation should be reserved for babies not responding to terms of reducing need for MV and the combined outcome
positive pressure ventilation via face mask or nasal prongs of death or BPD [65]. However, these meta-analyses in-
(A1). Babies who require intubation for stabilisation should clude some studies that are open to bias and might not be
be given surfactant (B1). suitable for inclusion in a more rigorous systematic review.
Nevertheless, studies of higher quality, such as those from
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Table 2. Surfactant preparations (animal-derived) licensed in Europe in 2018
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dotracheal tube and use this information to apply limits to avoided by regular or continuous assessment of CO2. VTV
the amount of support delivered in order to prevent lung mode enables automatic weaning of PIP in real-time as
over-distension. Volume-targeted ventilation (VTV) en- compliance improves. Some babies will only require ven-
ables clinicians to ventilate with less variable tidal volumes tilation for a very short period of time, particularly those
and real-time weaning of pressure as lung compliance im- with RDS following surfactant therapy who can be rapidly
proves. VTV compared with time-cycled pressure ventila- weaned to low ventilator settings. Early extubation of even
tion results in less time on the ventilator, fewer air leaks and the smallest babies is encouraged provided it is judged clin-
less BPD [107]. An initial set tidal volume of about 5 mL/ ically safe [118]. Infant’s size, absence of growth restriction,
kg and an estimated maximum PIP according to observa- FiO2 and blood gases are all determinants of extubation
tion of chest movement may need to be adjusted according success [106]. Keeping small babies on low-rate MV for
to the baby’s own respiratory efforts and gas exchange as- longer does not improve chance of extubation success
sessment. The required set tidal volume may need to be [119]. Extubation may be successful from 7 to 8 cm H2O
increased with increasing postnatal age if the baby remains MAP on conventional modes and from 8 to 9 cm H2O CDP
ventilated [108]. Maintaining an “open lung” is achieved by on HFOV. Spontaneous breathing tests to predict extuba-
adjusting PEEP with optimal level for a given baby being tion readiness are sometimes used but there is little evi-
defined as that at which FiO2 is at its lowest with acceptable dence to show they are effective [120]. Extubating to a rel-
blood gases and haemodynamic stability [109]. Supporting atively higher CPAP pressure of 7–9 cm H2O or NIPPV
the infants’ own respiratory efforts with modes such as will improve chance of success [121]. Several other strate-
pressure support rather than synchronised intermittent gies have been used specifically to shorten duration of MV
mandatory ventilation also seems sensible even though no including permissive hypercarbia, caffeine therapy, post-
differences in clinical outcomes have been shown [110]. natal steroid treatment and avoiding over-use of sedation.
HFOV is an alternative strategy to conventional MV al-
lowing gas exchange to be achieved using very small tidal Permissive Hypercarbia
volumes delivered at very fast rates with the lung held open Targeting arterial CO2 levels in the moderately hyper-
at optimal inflation using a continuous distending pres- carbic range is an accepted strategy to reduce time on MV
sure (CDP). The optimal CDP on HFOV is determined [122]. The PHELBI trial explored tolerating even higher
clinically by finding the pressure at which oxygenation de- PaCO2 up to about 10 kPa compared to 8 kPa in preterm
teriorates during stepwise reduction from full inflation and babies <29 weeks for the first 14 days. Analysis was per-
aiming for 1–2 cm H2O above this [111]. Studies compar- formed on 359 of a planned 1,534 infants after the study
ing HFOV to conventional MV show modest reductions was stopped early, and there was no difference in the pri-
in BPD favouring HFOV, although there is a relative pau- mary outcome of death or BPD but trends to worse out-
city of trials where volume targeting is used in the conven- comes in the higher target group [123]. Follow-up of this
tional MV arm [112]. Volume targeting in HFOV may re- cohort and others suggests no long-term adverse sequelae
duce CO2 variability and allow even lower tidal volumes to of permissive hypercarbia and it is therefore reasonable
be used [113]. Neurally adjusted ventilator assistance ven- to allow moderate elevation of PaCO2 during weaning
tilation offers the potential for better synchronisation of provided the pH is acceptable [124].
ventilator support with infants’ own respiratory needs in
real time, but further research on effectiveness of this mode Caffeine Therapy
is required before it can be recommended [114]. Modern Optimising success of non-invasive support involves
ventilators now also have the option of servo-controlled use of caffeine therapy as a respiratory stimulant. Most in-
oxygen delivery. This increases time spent in the desired formation about the clinical effects of caffeine comes from
saturation range and reduces hyperoxia, but there are no the Caffeine for Apnea of Prematurity (CAP) study cohort
trials to show this improves outcomes [115, 116]. What- where 2,006 babies <1,251 g coming off ventilation or with
ever ventilation mode is used within an individual unit, it apnoeic episodes were randomised to caffeine or placebo.
is important that all staff are familiar with its use. Caffeine facilitated earlier extubation with reduction in
Once stabilised on MV and spontaneous breathing is BPD and better neurodevelopmental outcomes at 18
present, clinicians should immediately consider strategies months [125, 126]. In this cohort, at age 11 years the caf-
for weaning. There is no evidence favouring any particular feine-treated children had better respiratory function [127]
weaning protocol [117]. Hypocarbia and severe hypercar- and reduced risk of motor impairment [128]. Caffeine pro-
bia are associated with worse outcomes and should be phylaxis soon after admission has become standard based
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able in the delivery room and in the NICU. Pulse oximetry as maternal chorioamnionitis or early signs of septicae-
from birth provides information of response to stabilisa- mia to ensure that antibiotics are only prescribed for
tion. In the NICU, there should be access to continuous those at greatest risk [159]. It is reasonable not to use rou-
pulse oximetry, ECG monitoring and monitoring of tine antibiotics in preterm babies with RDS at low risk
PaCO2 levels. Detection of exhaled CO2 can ensure correct such as following planned delivery by elective CS. If
placement of endotracheal tubes, and continuous mea- screening is necessary, then antibiotics are started em-
surement of end-tidal CO2 also gives useful information pirically whilst waiting for test results. For those who have
showing trends in gas exchange. Umbilical arterial can- been started empirically on antibiotics, the shortest pos-
nulation is indicated if it is anticipated there will be need sible course should be used and stopping after 36 h is
for regular blood gas analyses. Transcutaneous oxygen achievable and considered good practice [160].
and CO2 monitoring can also be used to access continuous
information for trending but can cause skin injury espe- Early Fluids and Nutritional Support
cially in the most immature infants [152]. Methods of The smallest infants have very high initial transcutaneous
monitoring cerebral oxygenation are also available with losses of water, and water and sodium move from the inter-
potential to assess cerebral saturation, but no clear clinical stitial to the intravascular compartments making fluid bal-
benefit has been identified [153]. Close monitoring of se- ance challenging. Typically, fluids are initiated at about 70–80
rum electrolytes and haematological values is necessary mL/kg/day and adjustments individualised according to fluid
ideally using micro-sampling techniques. Blood pressure balance, weight change and serum electrolyte levels. A mod-
should be recorded by indwelling arterial lines or inter- est early postnatal weight loss is normal. Regimens with more
mittently using approved oscillometric devices. Around- restricted fluids have better outcomes with reductions in
the-clock access to radiology services and portable ultra- PDA, NEC and BPD [161]. Delaying introduction of sodium
sound is also essential as these are often used to confirm supplementation until beyond the third day or 5% weight loss
RDS diagnosis, exclude air leaks and confirm correct will also improve outcome [162]. Parenteral nutrition should
placement of endotracheal tubes and central lines. be started immediately as enteral feeding is initially limited.
Early initiation of higher levels of parenteral amino acids re-
Temperature Control sults in less postnatal growth failure and an increase in posi-
Maintaining body temperature between 36.5 and 37.5 ° C tive protein balance [163]. At least 1.5 g/kg intravenous pro-
at all times is recommended [33] as hypothermia is associ- tein [164] and 1–2 g/kg lipids should be started from day one
ated with worse outcome, although it is unclear if this is di- and increased to a maximum of 3.5 g/kg amino acid [165].
rect cause and effect [154]. After birth, immediate wrapping For stable infants, a small amount (0.5–1 mL/kg/h) of breast
in a polythene bag under a radiant warmer reduces heat loss milk can be started early to initiate enteral feeding [166].
[53]. Servo-controlled incubators with skin temperature set There is no evidence of increased NEC with advancing feeds
at 36.5 ° C decrease neonatal mortality [155]. Following sta-
fairly rapidly up to 30 mL/kg/day in stable VLBW babies
bilisation, infants should be nursed in incubators with high [167]. Mother’s milk is the preferred option for initiation of
relative humidity to reduce insensible water losses. For the feeding; however, if not available then pasteurised donor
smallest babies, humidity of 60–80% should be used initial- breast milk is better than formula for reducing risk of NEC
ly and reduced as skin integrity improves. Kangaroo Moth- but will result in slower postnatal growth [168].
er Care (KMC) is an effective means of maintaining tem- Recommendations
perature and improving outcomes in lower income settings 1 Core temperature should be maintained between 36.5 and
and is increasingly being used in NICU to maximise mater- 37.5 ° C at all times (C1).
nal-infant bonding even in ventilated babies with the poten- 2 Most babies should be started on intravenous fluids of 70–80
tial for benefits beyond hospital discharge [156, 157]. mL/kg/day in a humidified incubator, although some very
immature babies may need more (C2). Fluids must be tai-
lored individually according to serum sodium levels, urine
Antibiotics output and weight loss (D1).
Antibiotics are often started in babies with RDS until 3 Parenteral nutrition should be started from birth. Amino ac-
sepsis has been ruled out but policies should be in place ids 1–2 g/kg/day should be started from day one and quickly
to narrow the spectrum and minimise unnecessary expo- built up to 2.5–3.5 g/kg/day (C2). Lipids should be started
from day one and built up to a maximum of 4.0 g/kg/day if
sure. Routine antibiotic prophylaxis may do more harm tolerated (C2).
than good [158]. Guidelines usually offer advice on when 4 Enteral feeding with mother’s milk should be started from
to screen for sepsis based on additional risk factors such the first day if the baby is haemodynamically stable (B2).
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a case by case basis and treatment stopped quickly if there Disclosure Statement
is no obvious response.
A European panel of experts was convened under the auspices of
Recommendations the European Society of Paediatric Research (ESPR) to update evi-
1 Surfactant can be used for RDS complicated by congenital dence-based guidelines on the management of RDS. The guidelines
pneumonia (C2). were prepared using evidence-based methods as summarised in Ta-
2 Surfactant therapy can be used to improve oxygenation fol- ble 1. Henry Halliday and Christian Speer are or have been consul-
lowing pulmonary haemorrhage (C1). tants to Chiesi Farmaceutici, Parma, the manufacturer of a leading
3 Use of iNO in preterm babies should be used with caution animal-derived surfactant preparation used to treat RDS and a caf-
and limited to those in clinical studies or as a therapeutic feine product for treatment of apnoea of prematurity. Virgilio Car-
trial when there is severe documented pulmonary hyperten- nielli is a member of the Chiesi Farmaceutici Advisory Board. Henry
sion (D2). Halliday and Christian Speer are joint Chief Editors of Neonatology.
Appendix
Summary of Recommendations
Prenatal care • Preterm babies at risk of RDS should be born in centres where appropriate care including MV is available.
• Judicious antenatal assessment should include risk of preterm delivery and need for maternal
corticosteroids if risk is moderate or high. Tocolytics can be used to allow time for steroids to take effect or
for safe transfer where appropriate.
• Magnesium sulphate should be given to mothers with impending preterm delivery.
Delivery room • Aim to delay cord clamping at birth by at least 1 min
stabilisation • Stabilise preterm babies (<28 weeks’ GA) in a plastic bag under a radiant warmer to prevent heat loss.
• Gently support breathing using CPAP if possible, and if inflations are needed avoid excessive tidal volumes.
Pulse oximetry can help guide heart rate response to stabilisation. Start with 21–30% oxygen for 28–31
weeks’ GA and 30% oxygen for <28 weeks’ GA and titrate up or down as needed according to SpO2 targets.
Aim at SpO2 of 80% or more within 5 min.
• Intubation at birth should be considered only for those not responding to the above, although early
intubation and surfactant may be required for babies who demonstrate early signs of severe RDS such as
chest retractions and high oxygen requirements.
Respiratory • An animal-derived surfactant should be used and given as early as possible in the course of RDS. A
support and treatment threshold of FiO2 0.30 on CPAP pressure of 6 cm H2O seems reasonable. Repeat doses of
surfactant surfactant may be required if there is ongoing evidence of RDS.
• If possible, administer surfactant using the LISA method but only if the baby is clinically stable on CPAP
with worsening signs of RDS and the clinician is experienced in the technique.
• If intubated, babies can often be extubated to CPAP, HFNC or NIPPV immediately following surfactant,
and judgement needs to be made if an individual baby will tolerate this.
• For those who require MV, aim to ventilate for as short a time as possible avoiding hyperoxia, hypocarbia
and volutrauma. This may be best achieved with volume-targeted ventilation and saturation alarm limits set
at 89 and 95%.
• Caffeine therapy should be used routinely to minimise need for ventilation. Babies should be maintained on
non-invasive respiratory support in preference to MV if possible. After 1–2 weeks, systemic steroids should
be considered to facilitate extubation if the baby remains ventilated.
• In preterm babies receiving oxygen, the saturation target should be between 90 and 94%. To achieve this,
suggested alarm limits should be 89 and 95%.
Supportive • Maintain body temperature at 36.5–37.5° C at all times.
care • Start parenteral nutrition immediately with amino acids and lipids in initial fluid volumes about 70–80 mL/
kg/day for most babies and restrict sodium during the early transitional period.
• Enteral feeding with mothers’ milk should also be started on day one if the baby is stable.
• Antibiotics should be used judiciously and stopped early when sepsis is ruled out.
• Blood pressure should be monitored regularly aiming to maintain normal tissue perfusion, if necessary
using inotropes. Haemoglobin should be maintained at acceptable levels.
• Protocols should be in place for monitoring pain and discomfort and consideration given for
non-pharmacologic methods of minimising procedural pain and judicious use of opiates for more invasive
procedures.
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