Comparison of Humidified High Flow Nasal Cannula to Nasal CPAP in Neonates

Respiratory failure remains a common problem in the neonatal ICU. Among premature infants
with respiratory failure the use of mechanical ventilation has been associated with
increased risk for secondary lung injury and subsequent development of bronchopulmonary
dysplasia (BPD). As reported by Avery et al and Van Marter et al, early application of nasal
continuous positive airway pressure (nCPAP) has been shown as an effective non-invasive mode
of respiratory support in this population.(1, 2) Additionally, in the premature sheep and
baboon models of BPD, the early use of nCPAP is accompanied by significant improvement in
subsequent lung development and alveolization.(3) In light of these findings, there has been
a concerted effort in most NICU's to avoid prolonged ventilator support through the early
application of nCPAP.

Unfortunately, nCPAP systems are not always easily applied or tolerated in the preterm
population.

Difficulties with the application of nCPAP include bulky head wraps, positional problems,
compression of the nose, marked dilation and tissue breakdown of the nares, and apparent
agitation, often leading to the use of potentially neurotoxic medications.(4) Previous
studies have suggested that NC flows at 1-2 lpm may also generate a positive pressure in the
airway of preterm infants.(5) The use of NC flow to generate positive airway pressure would
minimize many of the application issues of nCPAP. However, standard NC systems used in
neonates routinely employ gas that is inadequately warmed and humidified, limiting the use
of such flows due to increased risk of nasal mucosa injury, and possibly increasing the risk
for nosocomial infection.(4, 6) The development of humidified high flow via nasal cannulas
(HHFNC) systems may obviate these problems and provide a safe, effective alternative to
nCPAP in the preterm infant. Unfortunately, HHFNC does not allow the measurement of
distending pressure without an invasive process such as an esophageal pressure catheter. Two
recent reports have suggested that HHFNC does not provide excessive distending pressure.(7,
8) The study by Saslow and colleagues found that work of breathing and lung compliance were
improved in preterm infants on HHFNC up to a maximum of 5 lpm compared to nCPAP at 6 cm
H2O.(7) In comparison to nCPAP, the maximum positive distending pressure measured was 4.8
cm H2O and was not significantly increased with HHFNC flows up to 5 lpm. Kubicka and
colleagues also demonstrated that the maximum distending pressure measured during support
with HHFNC up to 8 lpm was < 5 cm H2O.(8)

A recent publication has suggested that HHFNC can safely and effectively be applied in the
non-invasive respiratory management of premature infants with respiratory dysfunction.(9) In
this retrospective analysis evaluating over 1000 infants, Shoemaker et al reported a
significant decrease in ventilator days among the group of infants managed with HHFNC
compared to infants previously managed with nCPAP. Additionally, they found no increased
adverse effects noted such as air leak, intraventricular hemorrhage, nosocomial infection or
BPD. In a smaller prospective study, Campbell et al did not find a benefit from high-flow NC
among a group 40 infants < 1250 grams.(10) However, they did not use adequate humidification
and the maximum "high-flow" applied was < 2 lpm. The previously noted study by Woodhead et
al demonstrated that HHFNC decreased respiratory work effort and was more effective at
preventing reintubation than high-flow from a standard, non-heated, non-humidified nasal
cannula.(4)

Thus HHFNC, with flow rates as high as 8 lpm, is being used clinically in a large number of
NICU's, including all of the units participating in this study, for management of a variety
of neonatal respiratory problems. The introduction of HHFNC into clinical practice has not
been accompanied by apparent changes in neonatal outcome, but this has not been
systematically studied in a randomized, controlled approach.

The purpose of this randomized controlled trial is to evaluate the clinical impact of
applying HHFNC to that of nCPAP among a group of infants requiring continuing non-invasive
respiratory support in the NICU.