A Randomized Trial of High-Flow Oxygen Therapy in Infants with Bronchiolitis

Abstract

BACKGROUNDHigh-flow oxygen therapy through a nasal cannula has been increasingly used in infants with bronchiolitis, despite limited high-quality evidence of its efficacy. The efficacy of high-flow oxygen therapy through a nasal cannula in settings other than intensive care units (ICUs) is unclear. METHODSIn this multicenter, randomized, controlled trial, we assigned infants younger than 12 months of age who had bronchiolitis and a need for supplemental oxygen therapy to receive either high-flow oxygen therapy (high-flow group) or standard oxygen therapy (standard-therapy group). Infants in the standard-therapy group could receive rescue high-flow oxygen therapy if their condition met criteria for treatment failure. The primary outcome was escalation of care due to treatment failure (defined as meeting ≥3 of 4 clinical criteria: persistent tachycardia, tachypnea, hypoxemia, and medical review triggered by a hospital early-warning tool). Secondary outcomes included duration of hospital stay, duration of oxygen therapy, and rates of transfer to a tertiary hospital, ICU admission, intubation, and adverse events. RESULTSThe analyses included 1472 patients. The percentage of infants receiving escalation of care was 12% (87 of 739 infants) in the high-flow group, as compared with 23% (167 of 733) in the standard-therapy group (risk difference, −11 percentage points; 95% confidence interval, −15 to −7; P<0.001). No significant differences were observed in the duration of hospital stay or the duration of oxygen therapy. In each group, one case of pneumothorax (<1% of infants) occurred. Among the 167 infants in the standard-therapy group who had treatment failure, 102 (61%) had a response to high-flow rescue therapy. CONCLUSIONSAmong infants with bronchiolitis who were treated outside an ICU, those who received high-flow oxygen therapy had significantly lower rates of escalation of care due to treatment failure than those in the group that received standard oxygen therapy. Original ArticleThe New England Journal of Medicine 1122T h e ne w e ngl a nd jou r na l o f m e dicine B ronchiolitis, an acute lower airway lung disease that is generally caused by respiratory viruses, is the most common reason worldwide for nonelective hospital admission in infants. In the United States, bronchiolitis is responsible for $1.7 billion in hospitalization costs annually.1,2 In Australia and New Zealand, there has been a population-based increase in admissions to the intensive care unit (ICU) for bronchiolitis, with associated increases in hospital costs. 3Numerous studies have investigated the role of medical therapies 4 in infants with bronchiolitis; none of these interventions have shown efficacy. 5The American Academy of Pediatrics guidelines recommend only supportive therapy that includes oxygen therapy for hypoxemia, respiratory support, and the maintenance of hydration. 5,6 Respiratory support as provided in emergency and ward settings has been limited to oxygen delivered through a standard nasal cannula, at a rate of up to 2 li...

‘Rational use of high‐flow therapy in infants with bronchiolitis. What do the latest trials tell us?’ A Paediatric Research in Emergency Departments International Collaborative perspective

“…In our subsequent systematic literature search, three further RCTs have been identified involving 1816 participants. Thus, there have now been four RCTs, including 1891 participants, of HFNC in infants with bronchiolitis: three of these studies involved infants treated in EDs and inpatient paediatric wards in Spain, Australia and New Zealand, and one study involved infants treated in paediatric ICUs in France (Table ).…”

“…The three studies conducted outside the ICU differed in important areas, and of concern, there was significant variation in the amount of supplemental oxygen entrained with the HFNC as highlighted in Table . Franklin et al . enrolled patients with oxygen saturations <92–94% (depending on individual institution cut‐offs for hypoxia) and used flow rates of 2 L/kg/min.…”

“…The primary outcomes and the definition of treatment failure itself also differed between the three studies. Franklin et al . used treatment failure as the primary outcome, defined as escalation of care and ≥ 3 of 4 pre‐specified physiological end‐points (persistent or increased tachycardia; persistent or increased tachypnoea; hypoxemia (FiO 2 of ≥0.4 if on HFNC or >2 L/min if on nasal cannula, to maintain SpO 2 ≥92–94%); medical review triggered by a hospital early‐warning tool).…”

“…As such, Guideline recommendations regarding the use of HFNC for bronchiolitis were as follows: (i) in non‐hypoxic infants, its use should be confined to randomised controlled trials (RCTs); and (ii) in hypoxic infants (oxygen saturations less than 92%), there is a low‐level recommendation (NHMRC: C, GRADE: Conditional) to consider HFNC. Subsequent to the 2015 systematic literature search for the Australasian bronchiolitis guidelines, a number of RCTs published their results, particularly three major studies . This paper updates the systematic literature review regarding HFNC use in bronchiolitis used for the Australian bronchiolitis guideline, summarises and critiques the new RCTs and provides evidence‐based recommendations for the use of HFNC to manage bronchiolitis in the ED and ward settings.…”

BET 1: High-flow nasal oxygen therapy in bronchiolitis

“…Franklin et al 1 demonstrated that in patients under the age of 12 months, high-flow oxygen reduced the need for escalation of care compared with those receiving low-flow oxygen and that it has a role as rescue therapy for those not responsive to standard oxygen therapy. This was a large, randomised and multicentre trial involving both tertiary hospital and regional hospitals.…”