Respiratory Distress Syndrome in the first few days of life in Preterm Infants ( Neonatal ventilation guideline ) - Management of

Publication: 19/02/2014  --
Last review: 20/02/2017  
Next review: 01/02/2020  
Clinical Guideline
ID: 3678 
Approved By: Trust Clinical Guidelines Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2017  


This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Management of Respiratory Distress Syndrome in the first few days of life in Preterm Infants

Summary of Guideline

1. Delivery Room Care
2. Surfactant
3. Early Extubation In Babies Receiving Prophylactic Surfactant
4. Rescue Surfactant
5. Continuing Ventilation
6. Blood Gases
7. Sedation
8. Caffeine Citrate
9. Extubation
10. Reventilation

Appendix 1 - Volume Guarantee Flow Chart
Peer review

Summary of Guideline

This guideline has been put together to ensure consistency in ventilation practice with the Leeds neonatal service for preterm infants with respiratory distress syndrome. The guideline includes details on the initial delivery room management of these infants, initial ventilation strategy, extubation technique and medications associated with these procedures and treatments.

It should be read in conjunction with the surfactant and CPAP guideline already in circulation.

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a. Plastic bag

Remember hypothermia makes lung disease worse. All infants less then 30 weeks or those expected to be growth restricted should be initially placed in a plastic bag as part of their initial assessment.

b. All infants born at less than 26+6 weeks gestation should be electively intubated and given surfactant (Curosurf) immediately.

Curosurf has revolutionised neonatal care by reducing the risk of air leak and neonatal death. The European Consensus Statement recommends only giving prophylactic surfactant to those infants less than 26 weeks. As early extubation to Continuous Positive Airway Pressure (CPAP) is a major change of practice within the Leeds Neonatal Service we have decided to not be so bold and settled on 28 weeks. It may be this is reduced with time.

c. Infants born at 27-30 weeks gestation should have CPAP applied immediately after birth and maintained until settled and assessed on the neonatal unit (NNU).

This CPAP can be delivered via well fitting face mask applied by one operator creating a good seal. The PEEP pressure should be set at around 6cmH2O and this should be monitored during transfer. Losing the CPAP pressure will lead to loss of lung recruitment and therefore deterioration in the infant’s condition.

d. Infants born greater than 30 weeks gestation may be managed without CPAP in the delivery suite unless clinically indicated.

This means that the infant should have no oxygen requirement and no increased work of breathing

e. Saturation monitors should be used for all deliveries less than 32 weeks.

The use of the saturation monitor at preterm deliveries is probably more as a guide for the infants heart rate and when the infant is hyperoxic rather than hypoxic. Remember infants have low saturations at birth that only gradually increase over the first 10 minutes after birth (Resuscitation Council 2010). See table below:

2 minutes


3 minutes


4 minutes


5 minutes


10 minutes


If a preterm infant’s saturations are too high consider both reducing the FiO2 but also reducing the Peak Inspiratory Pressure (PIP) being used to ventilate them. Preterm infants look pink at a range of saturations so this is not a good guide to oxygenation. Equally the converse is true. If they remain hypoxic in-spite of an increase in FiO2 consider increasing the PIP used to ventilate.

For further information on delivery room management see: Guideline on Management of Preterm Infants Born Before 28 Weeks

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Guideline on Administration of Surfactant in Neonates

a. Curosurf remains the surfactant of choice

b. Surfactant prophylaxis should be given as soon as possible after delivery , within the first 15 minutes if infant stable, for all babies less than 26+6 weeks gestation 

The caveat to that is that it is not a drug of resuscitation. Only give it when the baby is stable and the ET tube is secured in a good position confirmed by Pedicap or NeoSTAT colour change and equal air entry bilaterally.

Once the surfactant is administered close observation should be made of the infant’s oxygen requirement and overall lung compliance. It is quite likely that shortly after administration FiO2 can be reduced and the PIP may also be titrated down in line with the clinical response seen. This can be done by assessing the infant clinically and if ventilated looking at tidal volumes and pressures on the ventilator. Blood gases do not need to be taken for every change made if clinically the infant is felt to have coped with it.

c. Surfactant prophylaxis should be 200mg/kg

It may be rounded up /down to nearest whole vial ( either 120 or 240mg)  but if a dose of a whole vial results in >200mg/kg round DOWN to nearest whole vial.

Think sensibly: Surfactant is expensive and so part vials should never be used. It comes in 120mg and 240mg vials. Both should be available, use the most suitable.

Prophylactic surfactant has been shown to reduce the incidence of pneumothorax, PIE and mortality in infants of < 30 weeks gestation (Engle WA 2008). Please see link to surfactant guideline.

d. Rescue surfactant for babies over 26+6 weeks should be 200mg/kg.

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a. Clinical judgement must be used for each infant

b. Early extubation to CPAP should be considered in infants after transfer to NNU

Infants with an ongoing oxygen requirement after surfactant still have some degree of surfactant deficiency and so may need a further rescue dose of surfactant. It would be wrong to eagerly extubate to only have to re-intubate shortly after for a rescue dose.

c. Early extubation to flat CPAP should be considered in all other infants after transfer to the NNU BEFORE commencing on the ventilator if saturations and oxygen requirement allow.

It has been shown, in animal studies, that even short periods of ventilation cause damage to the fragile alveoli in the premature infants’ lungs. This damage has long lasting effects. In animal studies those kept on CPAP rather than ventilation had near normal lung architecture at 28 days. Infants who receive prophylactic surfactant and are immediately extubated to CPAP have a significantly reduced need for mechanical ventilation when compared to those who remain ventilated. In the study by Dani et al at 7 days none of the CPAP group had been re-ventilated but the other cohort remained stuck on the ventilator.

In such infants at less than 28 weeks gestation it is important to remember that they will still require a loading and then regular dose of caffeine. However in this situation extubation does not need to be delayed until the caffeine has been administered.

For a successful extubation to CPAP the technique used is key. See details in the CPAP section. The infant then needs to be left alone as much as possible.

This also confers the added benefit of not wasting a ventilator circuit that may only be used for 30 minutes.

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a. For any infant of any gestation rescue surfactant should be considered if the infant consistently requires >30% oxygen if they remain ventilated.

b. For any infant <30 weeks gestation rescue surfactant should be considered if they consistently require >30% oxygen on CPAP.

c. For any infant above 30 weeks gestation rescue surfactant should be considered if the infant consistently requires >40% oxygen on CPAP

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a. If any infant requires ongoing ventilation after admission to the neonatal unit the primary mode of choice is PC-AC (pressure control - assist control [previously SIPPV]) with Volume Guarantee (PC-AC + VG)

PC-AC means that EVERY breath the infant takes is pressure supported and then the back up rate is only there if they are apnoeic. Very few of our infants have complete lack of respiratory effort and so supporting their every breath is preferable to synchronised intermittent mandatory ventilation (SIMV) where only the rate of breaths set is supported meaning the additional breaths are taken by the infant through ET CPAP - a very tiring way to breathe. In either case there is no benefit in weaning the baby’s back up rate.

Volume guarantee has been shown in several trials and in Cochrane review to be preferable to the traditional pressure limited ventilation. Please read the references for more details. Briefly the cause of lung damage is volutrauma not barotrauma. It is seen that when infants are ventilated according to set PIPs they regularly have tidal volumes that are either too great or too little for the infant leading to damage and inadequate gas exchange. As gas exchange is dependent on tidal volume it makes more sense to keep the volume constant and the pressure varied accordingly to lung compliance.

b. Setting up ventilator correctly ensures successful use of volume guarantee :

When using volume guarantee the alarm that causes problems is the one highlighting a high PIP. To avoid this it is recommended that the Pmax is set at 30cmH2O. The reason being that the infant may need upwards of these pressures to achieve the tidal volumes set and if it is set too low the alarm will sound repeatedly. This could be reduced to 25cm H2O if the infant is very preterm. As the ventilator is delivering a set tidal volume and it is volutrauma that we are worried about the occasional need for a PIP of 30cm H2O is not of concern. Clearly if this is ringing off repeatedly the infant should be reviewed, as this would infer poor lung compliance and the possible need for further surfactant or High Frequency Oscillatory ventilation.

The back up rate should be set at 40/min. It should not need to be higher because the infants usually have a good respiratory drive and on PC-AC EVERY breath they take will be supported.

For flow chart on the setting up of volume guarantee please see Appendix 1

The following should be done within the first hour:

a. Blood gas – to ensure the infant is not over-ventilated as lung compliance improves

CXR – to ensure good ET position, especially if planning a second dose of surfactant.

Ensure NG tube inserted prior to CXR

b. If gases worsening- pH↓ or CO2↑

     i. Review infant

  1. colour, saturations, air entry etc
  2. Think DOPE
    1. Displacement – tube position?
    2. Obstruction – are there secretions – look at flow loops on ventilator graphs
    3. Pneumothorax – use cold light
    4. Equipment – is the ventilator working as you would expect

     ii. then consider if  tidal volume should be increased
     iii. consider change of mode of ventilation- HFOV- consultant decision

c. Weaning from initial ventilatory setting should be as follows:

     i. Consider decreasing tidal volume to 4ml/kg if CO2 low if baby unlikely to successfully extubate
     ii. The ventilator rate could be reduced to 30/min
     iii. PC-AC and VG allows “autoweaning” for infant providing consistent VT with decreasing pressure as lung compliance improves.
     iv. Remember to load with caffeine and stop morphine if not already done.

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a. Clinical judgement should always be exercised. There are not set rules regarding timing of the next blood gas. If you are going to do a blood gas ask yourself why you are doing it and what you will do with the result.

b. The blood gas of choice is arterial.

c. If an infant does not have arterial access a capillary sample is acceptable (sucrose analgesia should be used if appropriate) Guideline for Procedural Pain in the Newborn

d. Acceptable range of pH is 7.2-7.35.

This is not set in stone. Review each blood gas in the context of the clinical situation. Capillary samples can be misleading if perfusion is poor.

e. With each blood gas result

i. Review the infant
ii. Review the ventilator settings and measurements given
iii. Review nursing charts

f. PaCO2 should be allowed to rise as long as the pH is acceptable

This is known as permissive hypercapnia. It is important as a form of respiratory stimulant for the infant and does not cause any long term effects compared to increasing ventilator parameters simply chasing a PaCO2 result.  If the PaCO2 has risen do not automatically increase tidal volume, please review the infant as it may be due to a range of causes – recent handling, secretions, displaced ET tube.  Equally if an infant is on CPAP and is not displaying other respiratory signs – increased recession, increased oxygen requirement, increased desaturations / bradycardias and has a high PaCO2 do not re-ventilate just to make yourself feel better about the numbers.

g. Remember DOPE for high PaCO2

h. PaCO2 less than 4.5 should be acted upon as an emergency and suitable ventilatory adjustment made. A repeat gas should be available within 20 minutes.

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a. Elective intubation in delivery suite for prophylactic surfactant does not require pre-medication

b. Planned elective intubations for rescue surfactant, endotracheal tube (ETT) change etc should be considered for pre-medication.

c. Propofol is our drug of choice for sedation for intubation unless the baby is cardiovascularly unstable, has a cardiac condition (excluding PDA) or has already received 4mg/kg propofol in last 24 hours.

d. The use of propofol or suxamethonium, atropine and fentanyl does not preclude early extubation.

Guideline for Sedation and Analgesia for Non-Emergency Neonatal Intubation

e. Routine morphine infusion is not indicated but should be prescribed on an individual basis. Guideline for Sedation of Mechanically Ventilated Newborn Infants

There is much evidence showing that morphine infusions in these infants does not improve outcome and actually has some deleterious effects. It is well documented that morphine infusion leads to an increased need for inotropic support, prolongation of time spent on a ventilator with all the complications of infection, volutrauma, subglotic stenosis and also delays the time of achievement of full feeds (Menon G 2008) (Bhandari V 2005) (Hall R 2005).

f. Routine morphine infusions should only be given to an infant if he/she is distressed.

      i.    Consider why the infant is distressed
      ii.    Is the ventilator set as it should be?
     iii.    Signs of distress include – asynchrony with ventilator, tachycardia, brow furrowing,
     iv.    Can the infant be extubated?

g. Morphine infusions should be run at a maximum of 10micrograms/kg/hr unless clinically indicated.

Preterm infants are especially slow at metabolising morphine and so it quickly accumulates in their system. Giving them a high infusion dose will necessitate a longer time to wean off the ventilator prior to extubation thus prolonging the time spent on the ventilator and increased rate of extubation failure.

h. If more sedation is deemed necessary it is essential to evaluate first whether the infant needs to remain ventilated or whether their activity is a sign of the preparedness for extubation. If necessary morphine may be increased and then midazolam may be added. This should be a consultant decision.

i. If muscle relaxation is required pancuronium can be used as required or an infusion of atracurium started. This again should be a consultant decision.

j. If an infant is muscle relaxed adequate sedation should be given

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a. Infants less than 30 weeks gestation should be routinely prescribed caffeine citrate as a respiratory stimulant regardless of need for ventilatory support. Babies 30 -34 weeks may require caffeine citrate but it should be prescribed on clinical need rather than routine (Schmidt 2006).

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Immediate extubation on arrival at NNU

a. If on arrival to NNU, the infant has good respiratory effort and oxygen requirement using the T piece is less than 30% immediate extubation to flat CPAP. High flow may be used also although not initially in infants under 27 weeks

b. Remember to load with caffeine if less than 30 weeks gestation.

Planned extubation after ventilation

a. Infants less than 34 weeks should be extubated onto flat CPAP, high flow therapy (HFT) air or low flow oxygen. Note babies under 28 weeks should have CPAP initially rather than HFT.

b. Infants greater than 34 weeks may be extubated into air/low flow oxygen

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a. The decision to re-ventilate should be well considered.

Clearly if an infant is having repeated apnoeas on CPAP / High Flow they need additional support and evaluation for the cause of those apnoeas. The decision should not be made on the basis of a blood gas alone. The infant should be reviewed and the following should be thought about.

i. Is the gas venous / capillary or arterial as this can have a bearing on the results

ii. What is the infant’s work of breathing like?

iii. What is their oxygen requirement - has this changed significantly?

iv. Is CPAP being delivered effectively (see CPAP guideline)?

v. Why do you think the infant has deteriorated?

vi. What do you hope to achieve with re-ventilation?

This guideline should be read in conjunction with Surfactant, CPAP and High Flow guideline.

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Record: 3678

To establish consistent evidence based respiratory care
To establish consistent evidence based ventilatory support practice
To reduce the number of ventilator days within the NNU
To reduce the use of morphine within the NNU
To reduce the need for blood gases within the NNU
To decrease the incidence of broncho-pulmonary dysplasia

To provide evidence-based recommendations for appropriate management of respiratory distress syndrome in the preterm infant in the neonatal unit.

Clinical condition:

Respiratory distress syndrome

Target patient group: Pre term infants
Target professional group(s): Secondary Care Doctors
Secondary Care Nurses
Adapted from:

Evidence base

  1. Sweet DG, Carnielli V, Greisen G, Hallman M, Ozek E, Plavka R, Saugstad OD, Simeoni U, Speer CP, Vento M, Visser GHA,  Halliday HL; European Association of Perinatal Medicine. Neonatology. 2017;111:107-125 DOI:10.1159/000448985.
    European consensus guidelines on the management of respiratory distress syndrome - 2016 update.
  2. Resuscitation Council Guidelines 2010
  3. Engle WA; American Academy of Pediatrics Committee on Fetus and Newborn.
    Pediatrics. 2008 Feb;121(2):419-32. doi: 10.1542/peds.2007-3283.
    Surfactant-replacement therapy for respiratory distress in the preterm and term neonate.
  4. Thomson MA, Yoder BA, Winter VT, Martin H, Catland D, Siler-Khodr TM, Coalson JJ.
    Am J Respir Crit Care Med. 2004 May 1;169(9):1054-62. Epub 2004 Feb 12.
    Treatment of immature baboons for 28 days with early nasal continuous positive airway pressure.
  5. Dani C, Bertini G, Pezzati M, Cecchi A, Caviglioli C, Rubaltelli FF.
    Pediatrics. 2004 Jun;113(6):e560-3.
    Early extubation and nasal continuous positive airway pressure after surfactant treatment for respiratory distress syndrome among preterm infants <30 weeks' gestation.
  6. Davis PG, Morley CJ, Owen LS.
    Semin Fetal Neonatal Med. 2009 Feb;14(1):14-20. doi: 10.1016/j.siny.2008.08.003. Epub 2008 Oct 4.
    Non-invasive respiratory support of preterm neonates with respiratory distress: continuous positive airway pressure and nasal intermittent positive pressure ventilation.
  7. Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, Solimano A, Tin W; Caffeine for Apnea of Prematurity Trial Group.
    N Engl J Med. 2006 May 18;354(20):2112-21.
    Caffeine therapy for apnea of prematurity.
  8. Wheeler KI, Klingenberg C, Morley CJ, Davis PG.
    Neonatology. 2011;100(3):219-27. doi: 10.1159/000326080. Epub 2011 Jun 22. Review.
    Volume-targeted versus pressure-limited ventilation for preterm infants: a systematic review and meta-analysis.
  9. McCallion N, Lau R, Morley CJ, Dargaville PA.
    Arch Dis Child Fetal Neonatal Ed. 2008 Jan;93(1):F36-9. Epub 2007 Aug 8.
    Neonatal volume guarantee ventilation: effects of spontaneous breathing, triggered and untriggered inflations.
  10. Klingenberg C, Wheeler KI, Davis PG, Morley CJ.
    J Perinatol. 2011 Sep;31(9):575-85. doi: 10.1038/jp.2011.98. Epub 2011 Jul 14.
    A practical guide to neonatal volume guarantee ventilation.
  11. Hermeto F, Bottino MN, Vaillancourt K, Sant'Anna GM.
    Pediatrics. 2009 May;123(5):e907-16. doi: 10.1542/peds.2008-1647. Epub 2009 Apr 20.
    Implementation of a respiratory therapist-driven protocol for neonatal ventilation: impact on the premature population.

Approved By

Trust Clinical Guidelines Group

Document history

LHP version 1.0

Related information

Appendix 1 - Volume Guarantee Flow Chart

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Audit and Monitoring Compliance

There are various parts of this guidelines that shall be audited by the department once implemented in line with our aims stated at the beginning:

To establish consistent evidence based respiratory care
To establish consistent evidence based ventilatory support practice
To reduce the number of ventilator days within the NNU
To reduce the use of morphine within the NNU
To reduce the need for blood gases within the NNU
To decrease the incidence of broncho-pulmonary dysplasia

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Peer review

This guideline has been put together after extensive review of the literature. There has also been discussion within the consultant and nursing team both via email and also in open meetings. Feedback from all stakeholders has been taken on board and the guideline amended accordingly

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The principles of this guideline have already been implemented within the neonatal unit so ensure that the guidance is realistic and achievable. This has ben done through extensive education programs – new doctors induction, simulation training along with notice board displays to raise awareness of the proposals and information in the ward communication file.

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Equity and Diversity

The Leeds Teaching Hospitals NHS Trust is committed to ensuring that the way that we provide services and the way we recruit and treat staff reflects individual needs, promotes equality and does not discriminate unfairly against any particular individual or group.