Background: Heated humidified high-flow nasal cannula (HHHFNC) therapy has been widely used in preterm infants. However, evidence to support its use as a continuous positive airway pressure (CPAP) weaning method is still controversial. Objectives: We aimed to compare time to wean directly off CPAP vs. weaning by using HHHFNC. Methods: Infants with a gestational age (GA) of <32 weeks who met the predefined criteria for weaning off CPAP, i.e. with a CPAP of ≤6 cm H2O and a fraction of inspired oxygen (FiO2) of ≤0.3 for at least 24 h, were randomly assigned to wean by using HHHFNC or wean directly from CPAP. In the HHHFNC group, flow rate was reduced by 1 liter/min every 24 h to 2-3 liters/min depending on body weight (i.e. < or ≥1,000 g), and then HHHFNC was discontinued. In the CPAP group, pressure was reduced by 1 cm H2O every 24 h until stable on CPAP 4 cm H2O and then discontinued. The primary outcome was the time it took to wean off the use of the CPAP or HHHFNC devices. Results: One-hundred and one infants were enrolled, 51 in the HHHFNC and 50 in the CPAP group. Both groups had similar demographics and respiratory conditions before enrollment. There was no difference in time to successfully wean between the 2 groups [median (IQR): 11 (4-21) days in the HHHFNC group vs. 11 (4-29) days in the CPAP group; p = 0.12]. There were no differences in morbidities or related complications. Infants in the HHHFNC group had significantly less nasal trauma (20 vs. 42%; p = 0.01). Conclusions: In our study, the time to wean off CPAP using HHHFNC was not different from when weaning directly from CPAP.

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