High-Flow Nasal Cannulae in Very Preterm Infants after Extubation

February 2014

N Engl J Med 2013; 369:1425-1433 October 10, 2013DOI: 10.1056/NEJMoa1300071

High-Flow Nasal Cannulae in Very Preterm Infants after Extubation Brett J. Manley, M.B., B.S., Louise S. Owen, M.D., Lex W. Doyle, M.D., Chad C. Andersen, M.B., B.S., David W. Cartwright, M.B., B.S., Margo A. Pritchard, Ph.D., Susan M. Donath, M.A., and Peter G. Davis, M.D.



The use of high-flow nasal cannulae is an increasingly popular alternative to nasal continuous positive airway pressure (CPAP) for noninvasive respiratory support of very preterm infants (gestational age, <32 weeks) after extubation. However, data on the efficacy or safety of such cannulae in this population are lacking.


In this multicenter, randomized, noninferiority trial, we assigned 303 very preterm infants to receive treatment with either high-flow nasal cannulae (5 to 6 liters per minute) or nasal CPAP (7 cm of water) after extubation. The primary outcome was treatment failure within 7 days. Noninferiority was determined by calculating the absolute difference in the risk of the primary outcome; the margin of noninferiority was 20 percentage points. Infants in whom treatment with high-flow nasal cannulae failed could be treated with nasal CPAP; infants in whom nasal CPAP failed were reintubated.


The use of high-flow nasal cannulae was noninferior to the use of nasal CPAP, with treatment failure occurring in 52 of 152 infants (34.2%) in the nasal-cannulae group and in 39 of 151 infants (25.8%) in the CPAP group (risk difference, 8.4 percentage points; 95% confidence interval, −1.9 to 18.7). Almost half the infants in whom treatment with high-flow nasal cannulae failed were successfully treated with CPAP without reintubation. The incidence of nasal trauma was significantly lower in the nasal-cannulae group than in the CPAP group (P=0.01), but there were no significant differences in rates of serious adverse events or other complications.


Although the result for the primary outcome was close to the margin of noninferiority, the efficacy of high-flow nasal cannulae was similar to that of CPAP as respiratory support for very preterm infants after extubation. (Funded by the National Health and Medical Research Council; Australian New Zealand Clinical Trials Network number, ACTRN12610000166077.)

Increased exposure to PB is associated with worse neurodevelopmental outcomes than LEV. Prospective studies of outcomes of neonatal exposure to AEDs are essential.


The authors conclude that when comparing high-flow nasal cannula vs. nasal CPAP for extubation of infants less than 32 weeks, high-flow nasal cannula is non-inferior to nasal CPAP. However, the “non-inferiority margin” is ample and the calculated NNT is 5.

Half of the infants that failed on high-flow nasal cannula were successfully treated with nasal CPAP and did not require intubation. So, theoretically if all patients in this study were started on high-flow nasal cannula with failures switched to nasal CPAP the total number of failed extubations would be less.  Go figure!

Roberto Sosa, M.D.

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