Ventilatory response to nitrogen multiple-breath washout in infants

Pediatr Pulmonol. 2014 Apr;49(4):342-7. doi: 10.1002/ppul.22841. Epub 2013 Jul 12.


Background: Nitrogen multiple-breath washout (N2 MBW) using 100% oxygen (O2) has regained interest to assess efficiency of tracer gas clearance in, for example, children with Cystic Fibrosis (CF). However, the influence of hyperoxia on the infants' respiratory control is unclear. We assessed safety and impact on breathing pattern from hyperoxia, and if exposure to 40% O2 first induces tolerance to subsequent 100% O2 for N2 MBW.

Methods: We prospectively enrolled 39 infants aged 3-57 weeks: 15 infants with CF (8 sedated for testing) and 24 healthy controls. Infants were consecutively allocated to the protocols comprising of 100% O2 or 40/100% O2 administered for 30 breaths. Lung function was measured using an ultrasonic flowmeter setup. Primary outcome was tidal volume (VT).

Results: None of the infants experienced apnea, desaturation, or bradycardia. Both protocols initially induced hypoventilation. VT temporarily declined in 33/39 infants across 10-25 breaths. Hypoventilation occurred independent of age, disease, and sedation. In the new 40/100% O2 protocol, VT returned to baseline during 40% O2 and remained stable during 100% O2 exposure. End-tidal carbon dioxide monitored online did not change.

Conclusion: The classical N2 MBW protocol with 100% O2 may change breathing patterns of the infants. The new protocol with 40% O2 induces hyperoxia-tolerance and does not lead to changes in breathing patterns during later N2 washout using 100% O2. Both protocols are safe, the new protocol seems an attractive option for N2 MBW in infants.

Keywords: cystic fibrosis; inert gases; lung function tests; respiratory physiology.

MeSH terms

  • Cystic Fibrosis / diagnosis*
  • Cystic Fibrosis / physiopathology*
  • Female
  • Humans
  • Infant
  • Male
  • Nitrogen* / pharmacology
  • Oxygen / administration & dosage
  • Oxygen / pharmacology
  • Prospective Studies
  • Respiratory Function Tests / methods
  • Tidal Volume* / drug effects


  • Nitrogen
  • Oxygen