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Nasal High-Flow Therapy during Neonatal Endotracheal Intubation

@katehodg18. NEJM 2022;386:1627-1637; DOI: 10.1056/NEJMoa2116735

Clinical Question

  • In neonates undergoing elective endotracheal intubation, does nasal high-flow therapy compared with standard care, improve 1st pass success without physiological instability?

Background

  • A multicentre, international registry reported that 1st pass success in neonatal intubation was only 50%
  • Neonates have a lower functional residual capacity and a greater metabolic demand than older children and adults. This can contribute to physiological instability during intubation attempts. The same registry reported that in ~half of the intubations performed, the neonates SpO2 dropped by ≥20%
  • High flow nasal oxygen has been used in adults to aid intubation and prolong apnoea time

Design

  • Randomised controlled trial
    • Computer-generated random-assignment sequence based on permuted blocks with varying block sizes
    • Stratified according to trial centre, post-menstrual age (≤28 or >28 weeks), and the use of premedication for intubation
  • Non-blinded
  • Intubation attempt defined as insertion of laryngoscope blade beyond the lips until its removal from the mouth
  • Physiological instability defined as decrease in SpO2 of 20% from baseline or HR <100
  • All intubations were recorded, including recording of oxygen saturation monitor
  • Primary outcome assessed by independent assessment of video
  • Sample size calculation
    • 246 intubations would give 90% power to detect an increase in the primary outcome from 30% to 50% with a 2 sided alpha level of 0.05
  • Modified intention to treat analysis (excluded patients that had exclusion criteria)
  • Primary outcome adjusted for randomisation stratification factors
  • Registered on Australian New Zealand Clinical Trials Registry

Setting

  • Two tertiary neonatal intensive care units in Melbourne, Australia
  • Data collected: 2018 – 2021

Population

  • Inclusion criteria:
    • Infants undergoing oral endotracheal intubation in the delivery room or neonatal intensive care unit
  • Exclusion:
    • Nasal intubation
    • Urgent intubation as determined by the treating clinician
    • HR <120 beats
    • Contraindication to high-flow therapy (e.g., congenital nasal anomaly, congenital diaphragmatic hernia, or abdominal wall defect)
    • Cyanotic congenital heart disease
    • Suspected or proven severe COVID infection in the infant or mother
  • 462 intubations were eligible for randomisation. 258 intubations randomised. 7 excluded post randomisation
  • Comparing baseline characteristics of intervention vs. control group
    • Median gestational age: 27 vs 27 weeks
    • Median birth weight: 893 vs 841g
    • Median Apgar score at 5 min: 8 vs 7.5
    • Median age at intubation: 7 vs 13 hours
    • Median weight at intubation: 976g vs 907g
    • Location of intubation
      • Delivery room: 25% vs 27%
      • Neonatal intensive care unit: 75% vs 73%
    • FiO2 before intubation: 0.62 vs 0.62
    • Primary indication for intubation
      • Hypoxia: 59% vs 58%
      • Apnoea: 21% vs 20%
      • Resuscitation: 2.4% vs 5.5%
    • Operator experience
      • <20 previous intubations: 49% vs 40%
      • >20 previous intubations: 51% vs 60%
    • Use of videolaryngoscopy
      • 9.7% vs 7.1%

Intervention

  • High flow nasal oxygen
    • Applied immediately before laryngoscopy, set at 8l/min
    • FiO2 was set at the concentration delivered before laryngoscopy and was increased to 100% oxygen if SpO2 <90%
    • Discontinued after 1st intubation attempt

Control

  • Standard care
    • Laryngoscopy performed without high-flow nasal oxygen or supplemental oxygen

Management common to both groups

  • The pre-intubation FiO2, the use of VL and the duration of intubation attempt was at the discretion of the treating clinician
  • Pre-medication with atropine, fentanyl and suxamethonium was standard practice for intubations that occurred outside the delivery room

Outcome

  • Primary outcome: Successful intubation on the 1st attempt without physiological instability – significantly greater in the intervention group
    • 50% vs 31.5%
    • Adjusted risk difference 17.6% (95% CI 6-29.2)
    • NNT 6 (95% CI 4-17)
  • Primary outcome component analysis:
  • Comparing intervention vs. control group
    • Significantly greater in intervention group
      • Successful intubation on 1st attempt
        • 68.5% vs 54.3%
        • Adjusted risk difference: 15.8 (95% CI 4.3-27.3)
      • No physiological instability
        • 63.7% vs 50.4%
        • Adjusted risk difference: 13.4% (95% CI 1.3-25.5)
  • Secondary outcomes:
  • Comparing intervention vs. control group
    • Median SpO2
      • 94% vs 89%
      • Difference: 5 (95% CI 1.1-8.9)
      • Time to desaturation
        • 44.3 vs 35.5s
    • Significantly less in intervention group
      • Intubations in which desaturation occurred
        • 28.2% vs 39.4%
    • No significant difference in
      • Median duration of 1st intubation attempt
        • 124 vs 127 seconds
      • Oesophageal intubation
        • 14.5% vs 15.7%
    • Median time to apply nasal prongs in intervention group: 9.9s
  • Adverse events, comparing intervention vs control group
    • CPR or adrenaline within 1 hour of intubation attempt
      • 0% vs 1.6%
    • Pneumothorax within 72 hours post randomisation
      • 1.6% vs 4.7%
    • Death within 72 hours post randomisation
      • 0.8% vs 2.4%
  • Sub-group analysis for primary outcome, comparing intervention vs standard group
    • Operator experience
      • <20 intubations: 49.2% vs 15.7%
        • Adjusted risk difference 33.3% (95% CI 18.3-48.2)
      • ≥20 intubations: 50.8% vs 42.1%
        • Adjusted risk difference 7.5% (-9.4 to 24.3)

Authors’ Conclusions

  • In neonates the use of high-flow therapy during oral endotracheal intubation led to greater likelihood of successful intubation without physiological instability

Strengths

  • Randomised controlled trial
  • Multi-centre
  • Video recording of intubation attempt and SpO2 monitor, with independent review of video to assess primary outcome
  • Stratified according to operator experience

Weaknesses

  • Clinicians were not blinded but impossible to do, and use of sham high flow may have affected standard care as may have prolonged intubation attempt
  • Only conducted in 2 tertiary centres in 1 country, limiting external validity

The Bottom Line

  • For neonates undergoing intubation, the first pass success rate without physiological instability is low
  • The application of high flow nasal oxygen immediately prior to laryngoscopy significantly increased the rate of successful intubation on the 1st attempt without physiological instability – this is particularly pronounced for operators with limited experience

External Links

Metadata

Summary author: David Slessor
Summary date: 28th April 2022
Peer-review editor:Segun Olusanya

Image by: Image by RitaE from Pixabay

 

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