Efficacy and Safety of Two Different Flow Rates of Nasal High-Flow Therapy in Preterm Neonates ≥28 Weeks of Gestation: A Randomized Controlled Trial

Abstract

Objective The study aimed to compare the efficacy and safety of two different nasal high-flow rates for primary respiratory support in preterm neonates Study Design In this single-center, double-blinded randomized controlled trial, preterm neonates ≥28 weeks of gestation with respiratory distress from birth were randomized to treatment with either increased nasal flow therapy (8–10 L/min) or standard nasal flow therapy (5–7 L/min). The primary outcome of nasal high-flow therapy failure was a composite outcome defined as the need for higher respiratory support (continuous positive airway pressure [CPAP] or mechanical ventilation) or surfactant therapy. Results A total of 212 neonates were enrolled. Nasal high-flow failure rate in the increased flow group was similar to the standard flow group (22 vs. 29%, relative risk = 0.81 [95% confidence interval: 0.57–1.15]). However, nasal flow rate escalation was significantly more common in the standard flow group (64 vs. 43%, p = 0.004). None of the infants in the increased flow group developed air leak syndromes. Conclusion Higher nasal flow rate (8–10 L/min) when compared with lower nasal flow rate of 5 to 7 L/min did not reduce the need for higher respiratory support (CPAP/mechanical ventilation) or surfactant therapy in moderately and late preterm neonates. However, initial flow rates of 5 L/min were not optimal for most preterm infants receiving primary nasal flow therapy. Key Points

The effects of flow settings during high-flow nasal cannula oxygen therapy for neonates and young children

“…Consequently, 44 studies were included: 15 were in vitro studies [ 12 – 26 ], two combined in vitro and in vivo studies were conducted on neonates [ 27 , 28 ] and 27 were clinical studies [ 6 – 8 , 29 – 52 ]. In the clinical studies ( supplementary table S1 ), 14 were conducted on neonates [ 29 – 41 , 51 ] including preterm infants with [ 29 , 31 , 34 , 35 , 37 , 38 , 51 ] or without [ 30 , 32 , 33 , 36 , 39 – 41 ] lung disease, while 13 focused on paediatric patients with bronchiolitis [ 6 – 8 , 44 , 46 – 48 , 50 , 52 ] or requiring HFNC for various reasons [ 42 , 43 , 45 , 49 ], with most the patients younger than 2 years. Four of these studies were RCTs [ 48 – 51 ], and ten were randomised crossover studies [ 31 , 33 , 34 , 37 , 39 – 41 , 43 , 45 , 46 ].…”

“…Consequently, 44 studies were included: 15 were in vitro studies [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26], two combined in vitro and in vivo studies were conducted on neonates [27,28] and 27 were clinical studies [6-8, 29 -52]. In the clinical studies (supplementary table S1), 14 were conducted on neonates [29][30][31][32][33][34][35][36][37][38][39][40][41]51] including preterm infants with [29,31,34,35,37,38,51] or without [30,32,33,36,[39][40][41] lung disease, while 13 focused on paediatric patients with bronchiolitis [6-8, 44, 46-48, 50, 52] or requiring HFNC for various reasons…”

“…In the clinical studies (supplementary table S1), 14 were conducted on neonates [29][30][31][32][33][34][35][36][37][38][39][40][41]51] including preterm infants with [29,31,34,35,37,38,51] or without [30,32,33,36,[39][40][41] lung disease, while 13 focused on paediatric patients with bronchiolitis [6-8, 44, 46-48, 50, 52] or requiring HFNC for various reasons [42,43,45,49], with most the patients younger than 2 years. Four of these studies were RCTs [48][49][50][51], and ten were randomised crossover studies [31, 33, 34, 37, 39-41, 43, 45, 46].…”

“…NIV, invasive ventilation). Promising results from physiological studies and a subgroup analysis from the RCT conducted by B alasubramanian et al [ 51 ] suggest a flow of 3–4 L·kg −1 ·min −1 may be beneficial for some neonates. However, further RCTs are required to more definitively evaluate this higher flow strategy relative to patient outcomes.…”

“…In a RCT involving 212 preterm neonates with a gestational age of ≥28 weeks, B alasubramanian et al [ 51 ] compared HFNC therapy under two different flows (5 versus 8 L·min −1 ) and found no significant difference in treatment failure rates between the two groups (29% in the 5 L·min −1 group versus 22% in the 8 L·min −1 group, p=0.22) ( table 1 ). Treatment failure was defined as the need for higher respiratory support (CPAP or invasive ventilation) or surfactant therapy.…”