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- Neonatology
- Intensive Care Units, Neonatal
- Intensive Care Units, Paediatric
- Paediatrics
- Paediatric Emergency Medicine
Introduction
National guidance on neonatal life support (NLS) is regulated by the Resuscitation Council UK, and the NLS guidelines were updated in May 2021. This process was led by systematic reviews by the International Liaison Committee on Resuscitation (ILCOR) in collaboration with the European Resuscitation Council and accredited by the National Institute for Health and Care Excellence. The NLS algorithm (figure 1) is the hallmark in guidance for newborn resuscitation. In this guideline review, we discuss the key changes made to practice, explore the current and ongoing controversies in neonatal resuscitation and review emerging evidence, which may shape future guidance.
Key issues addressed by this updated guideline
The 2021 NLS guideline has many updated changes (box 1), and below we address the key changes that will impact practice.
What is new?
In management of the umbilical cord, clamping after at least 60 s is recommended, but if this is not possible cord milking is an option in babies >28 weeks’ gestation.
In non-vigorous infants born through meconium, immediate laryngoscopy with or without suction after delivery is not recommended.
Laryngeal mask may be considered in infants of ≥34 weeks’ gestation (>~2000 g) if face mask ventilation or tracheal intubation is unsuccessful.
Initial delivered oxygen concentration depends on gestation:
≥32 weeks’ gestation: 21% oxygen
28–32 weeks: 21%–30% oxygen
<28 weeks: 30% oxygen
Both initial and subsequent intravenous/intraosseous epinephrine doses are 20 μg kg−1 (0.2 mL kg−1 of 1:10 000 epinephrine (1000 μg in 10 mL)); in the absence of a response to cardiopulmonary resuscitation (CPR), give repeat doses every 3–5 min.
Stopping resuscitation should be considered and discussed if there has been no response after 20 min and reversible problems have been excluded.
In management of the umbilical cord, delayed cord clamping after at least 60 s is recommended, but if this is not possible umbilical cord milking is an option in babies >28 weeks’ gestation.
Delayed cord clamping (DCC) is defined as the practice of delaying clamping the umbilical cord to allow for increased placental blood flow to the infant. The benefits have been well established: two meta-analyses looking at term infants and those born <34 weeks’ gestational age (GA) found DCC led to a more stable cardiovascular transition, improved early haematological indices and improved iron stores in infancy.1 2 Currently, 60 s is the recognised recommended time for DCC; however, future practice may change as more trials are required to give the ideal time of DCC.
DCC may not always be possible (box 2), and due to the paucity of evidence, it cannot be recommended that DCC delays infant resuscitation. In cases where DCC is not possible, umbilical cord milking (UCM) has been explored as a method of increasing placenta to infant blood transfusion, as blood is milked from the placenta towards the infant.
Contraindications to delayed cord clamping
Fetal compromise
Placental abruption
Cord prolapse
Bleeding placenta praevia
Bleeding vasa praevia
Antepartum haemorrhage
Umbilical cord avulsion
When comparing UCM to DCC, a systematic review found similar benefits, with no increase in critical outcome in infants >28 weeks.3 However, the committee is clear that UCM is not recommended for infants <28 weeks’ GA, as a large multicentre trial was terminated early due to increased incidence of intraventricular haemorrhage (IVH) with UCM in this group.4
In non-vigorous infants born through meconium, immediate laryngoscopy with or without suction after delivery is not recommended.
The ILCOR analysed several systematic reviews since 2015 that evaluated important outcomes including mortality, neurodevelopmental impairment, meconium aspiration syndrome and use of extracorporeal membrane oxygenation. None of these showed any benefit when performing immediate laryngoscopy with or without suctioning for non-vigorous newborn infants delivered through meconium. Discussion has highlighted the potential for delay in effective resuscitation as the team focuses on direct laryngoscopy rather than oxygenation and ventilation and the ILCOR places weight on the need for harm avoidance.
Laryngeal mask airway (LMA) may be considered in infants of ≥34 weeks’ gestation (>~2000g) if face mask ventilation or tracheal intubation is unsuccessful.
If a practitioner is unable to achieve chest movement through face mask ventilation or tracheal intubation, a Guedel or oropharyngeal airway was previously recommended. A systematic review of seven trials including 794 infants found a LMA is more effective than face mask ventilation in the short-term stabilisation. The ILCOR now recommend that a LMA be considered in infants >2000 g or who are over approximately 34 weeks’ gestation as a second-line airway adjunct.
Initial delivered oxygen concentration depends on gestation:
≥32 weeks’ gestation: 21% oxygen
28–32 weeks: 21%–30% oxygen
<28 weeks: 30% oxygen
The initial concentration of oxygen given to infants who require supported transition has been a long-debated topic, particularly because initial oxygen concentrations can have a final determinant on critical outcomes including bronchopulmonary dysplasia and retinopathy of prematurity. Conversely, practitioners recognise the consequences of hypoxia and bradycardia with mortality and IVH in extremely preterm infants.5 Further to this, subsequent analysis by the ILCOR recognised that significant numbers of infants born <28 weeks’ gestation required between 30% and 40% oxygen to maintain adequate oxygenation, giving the justification of starting in 30% oxygen. However, it is still emphasised that oxygen delivery should be titrated to reach optimal target saturations as highlighted in the algorithm (figure 1).
Yet, the debate for the ideal concentration of oxygen for resuscitation for preterm infants continues, particularly because the recommendation of target oxygen saturations in the transitioning preterm neonate is taken from term infants.6 Those in favour of using air to initiate stabilisation argue that the low-oxygen state of the fetus can tolerate transient hypoxia better than the damage caused by hyperoxia. However, some authors demonstrate better outcomes with resuscitating in higher oxygen in animal studies and the TORPEDO trial showed that using room air to initiate resuscitation was associated with an increased risk of death in infants <28 weeks’ gestation, but it was underpowered to address this post hoc hypothesis reliably.7 8 Most authors agree that a large multicentre randomised controlled trial (RCT) is required to look at the outcomes of premature infants stabilised in 30% oxygen.
Both initial and subsequent IV/IO epinephrine doses are 20 μg kg−1 (0.2 mL kg−1 of 1:10 000 epinephrine (1000 μg in 10 mL), in the absence of a response to CPR give repeat doses every 3–5 min.
The previous intravenous epinephrine dose recommendation of 0.1–0.3 mL/kg of 1:10 000 was derived from indirect evidence from animal studies. Currently there are no large-scale human studies demonstrating the exact epinephrine dosage during neonatal resuscitation, therefore they have now removed ambiguity and recommend a specific dose of 20 μg kg−1 (0.2 mL/kg). However, this may well be changed in the future as Sankaran et al, published after the taskforce review, report that 0.3 mL/kg of epinephrine with 3 mL/kg flush is most effective in obtaining ROSC in term newborn lambs.9
Stopping resuscitation should be considered and discussed if there has been no response after 20 min and exclusion of reversible problems.
The decision to cease CPR is critical, as the length of resuscitation cannot predict death or moderate to severe neurodevelopmental outcome. The NLS Task Force reviewed the most recent evidence of 13 studies involving 277 infants and found that 11% of infants who had an APGAR of 0 or 1 at 10 min survived without moderate to severe neurodevelopmental impairment. However, this recommendation is of low certainty of evidence, with variables including quality of resuscitation and low cohort numbers effecting the data. The committee recognised that excluding all reversible factors and completing all the steps involved in advanced neonatal resuscitation can take a considerable amount of time. This alongside including the family and senior members of staff in the decision to stop CPR provides the justification of extending this timeframe to 20 min.
Sustained inflation: an ongoing controversy in neonatal resuscitation
In infants who have ineffective or no spontaneous breathing, the primary goal of resuscitation is to successfully aerate and recruit lung tissue to establish functional residual capacity (FRC). Currently, NLS guidance recommends practitioners use five inflation breathes of 2–3 s followed by 1 s intermittent positive pressure ventilation (IPPV) to achieve this. However, with sustained inflation (SI) the practitioner uses prolonged inflation times to establish FRC. Currently the length of time is undefined; however, the ILCOR reviewed evidence from studies that compared the use of SI in times >1 s to >15 s in different subcategories and in either <20 cm H2O and >20 cm H2O.
The debate to use SI has intensified, and many units across Europe are already using this practice, with the potential of its success being underpinned by animal studies demonstrating improved short-term respiratory outcomes when intubated.10 11 However, these animal models must be examined with caution due to significant differences in anatomy and lung maturity. Furthermore, the larynx closes in hypoxia, making studies which have used intubated models difficult to compare to face mask ventilation. Difficulties also arise when analysing the use of SI; many trials involving human models use variable duration of SI and pressures, making it difficult to make specific recommendations.
The task force conducted a new systematic review of 10 RCTs enrolling 1502 preterm infants and found neither benefit nor harm when using SI for >1 s rather than IPPV of <1 s in all critical outcomes. However, the SAIL Trial, the largest multicentre trial to date, defined SI as a maximum of 25 cm H2O for 15 s using a T-piece and mask and compared this with standard delivery room IPPV with a positive end-expiratory pressure of 5–7 cm H2O. This trial was stopped early due to potential harm in using SI, with increased rates of death at less than 48 hours in preterm infants (7.4% vs 1.4%, p=0.002).12 However, a large proportion of the extremely premature infants were allocated to the intervention group, increasing the risk of early death.
With so many variables impacting individual infant tidal volumes, technology has been developed that allows real-time tidal volume feedback on mannequin simulations, with the view to be used in delivery rooms.13 Furthermore a recent study demonstrated the feasibility of measuring tidal volumes via the endotracheal tube for preterm neonatal ventilation in the delivery room.14 The ILCOR does not recommend the use of SI, but these developments allow the potential for future changes in the way we initiate ventilation in infants, and without a large multicentre trial examining the optimal duration and pressure of SI, the benefits of this intervention have yet to be established.
A final word
We have highlighted the main changes and the implications for practice in boxes 3 and 4. There are many areas of the NLS recommendations that are consensus statements, and we must recognise that some of the recommendations are based on low quality or low certainty evidence. However, having this clear protocol aims to allow all practitioners to perform neonatal resuscitation with uniformity based on the current best evidence available. Yet, we should be mindful of the evidence behind such recommendations and the scope for changes to practice in the future. Box 5 lists the relevant resources for this 2021 update.
What should I stop doing?
Using a Guedel airway as a first-line airway adjunct (they should still be available, but an LMA should be used in preference).
Resuscitating/stabilising preterm infants <28 weeks in air.
Immediately suctioning under direct vision in a floppy non-vigorous infant born through meconium.
Administering epinephrine if needed at 0.1 or 0.3 mL/kg of 1:10 000.
What should I do differently?
Prior to resuscitation:
All obstetric and neonatal staff should remember that delayed clamping of at least 60 s is recommended, and all units should have a guideline in place for this.
Greater emphasis on preventing hypothermia in neonates with importance on delivery room temperature preparation and use of heat prevention strategies.
Airway/breathing changes to the algorithm:
When attending the delivery of a non-vigorous infant born through meconium, immediate laryngoscopy with or without suction after delivery is not recommended.
If you are unable to intubate or face mask ventilate, then a laryngeal mask may be considered in infants of ≥34 weeks’ gestation (>~2000 g) and therefore neonatal doctors will need to be trained in how to insert this.
Start in either oxygen or air depending on gestation: ≥32 weeks’ gestation: 21% oxygen, 28–32 weeks: 21%–30% oxygen, <28 weeks: 30% oxygen.
In babies <32 weeks, delivered oxygen concentration should be titrated to achieve saturations of >80% at 5 min.
Cardiovascular changes to the algorithm:
Intraosseous (IO) access can be used an alternative method of emergency vascular access if umbilical access is not possible.
Both initial and subsequent intravenous/IO epinephrine doses are 20 μg kg−1 (0.2 mL kg−1 of 1:10 000 epinephrine (1000 μg in 10 mL); in the absence of a response to CPR, give repeat doses every 3–5 min.
Practitioners should consider stopping resuscitation if there has been no response after 20 min and reversible problems have been excluded.
Resources
Link to full guideline—Newborn resuscitation and support of transition of infants at birth guidelines: https://www.resus.org.uk/library/2021-resuscitation-guidelines/newborn-resuscitation-and-support-transition-infants-birth%23key-points
European Resuscitation Council Guidelines 2021: Newborn resuscitation and support of transition of infants at birth: https://www.resuscitationjournal.com/article/S0300-9572(21)00067-8/fulltext
Neonatal Life Support 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency cardiovascular care science with treatment recommendations: https://www.ahajournals.org/doi/pdf/10.1161/CIR.0000000000000895
Link to NLS course provided by Resus Council UK: https://www.resus.org.uk/training-courses/newborn-life-support/nls-newborn-life-support
Ethics statements
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Ethics approval
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References
Footnotes
Contributors CP wrote and edited the manuscript. CH edited the manucript. Both authors approved the final draft.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Commissioned; externally peer reviewed.