Review question
Does high flow nasal cannula oxygen therapy improve the health outcomes of critically ill newborn infants requiring support for their breathing?
Background
When newborn infants have difficulty breathing, they may need external support to help move air in and out of their lungs (ventilation). There are various methods used to provide this breathing support. Invasive ventilation delivers air via a breathing tube placed in the baby's windpipe. Non-invasive ventilation delivers air via a mask that can be applied over the mouth or face, or small tubes positioned just inside the nostrils. These methods are often preferred since they may help avoid some of the complications associated with invasive ventilation.
What is high flow nasal cannula (HFNC) oxygen therapy?
HFNC oxygen therapy is one form of non-invasive respiratory support. It delivers heated, humidified oxygen gas at flow rates greater than 2 litres per minute via tubes positioned just inside the nostrils and is proposed to provide advantages over alternative oxygen therapies. However, in term infants (babies born after 37 weeks of pregnancy are completed) during their first month of life (the neonatal period) the evidence regarding the safety and effectiveness of HFNC is limited, and there is no consensus of opinion regarding its use in this population.
What did we want to find out?
We wanted to find out if high flow nasal cannula oxygen therapy improves the health outcomes of critically ill, term infants requiring respiratory support in their first month of life, when compared with other methods of non-invasive support. We also wanted to find out if it was associated with any unwanted effects.
What did we do?
In a search conducted to December 2022, we identified eight studies that investigated HFNC therapy across a total of 654 term infants. Six of these studies (625 participants) contributed data to our primary analysis. This involved comparing and summarising the results of the studies, and rating our confidence in the evidence based on factors such as study size and any limitations in the methods they used. Four of the studies compared HFNC with an alternative method of non-invasive support known as continuous positive airway pressure (CPAP) (where air is pressurised by a machine to a constant pressure and delivered into the airway via a mask placed over the face/mouth or tubes positioned just inside the nostrils). Two studies compared HFNC with low flow nasal cannula (LFNC) (oxygen therapy up to a maximum gas flow rate of 2 L/min).
Key results
The first results are from the comparison of HFNC and CPAP. Zero deaths were recorded by the studies. HFNC may have little to no effect on treatment failure, but the evidence is very uncertain. One study investigated chronic lung disease (the need for oxygen support at 28 days of life) but no infants in the study met these criteria. HFNC may have little to no effect on the duration of respiratory support (length of time infants receive any form of extra breathing support with or without the addition of oxygen), but the evidence is very uncertain. HFNC likely results in little to no difference in the length of stay at the intensive care unit (ICU). HFNC may reduce the incidence of nasal trauma (damage to the nasal tissue) and abdominal overdistension (where air accumulates in the abdomen and causes excessive expansion), but the evidence is very uncertain.
Our second results are from the comparison of HFNC and LFNC. Zero deaths were recorded by the studies. The evidence suggests HFNC may reduce treatment failure slightly. Neither study investigated chronic lung disease. HFNC may have little to no effect on the duration of respiratory support, length of stay at the ICU, or hospital length of stay, but the evidence is very uncertain. Both studies recorded zero adverse events.
What are the limitations of the evidence?
Our confidence in the evidence is moderate to very low. Three main factors reduced our confidence in the evidence. Firstly, some studies used methods likely to introduce errors in their results. Secondly, the results across the different studies were moderately inconsistent. Finally, some studies were very small.
Conclusions
When compared with CPAP, HFNC may result in little to no difference in treatment failure. HFNC may have little to no effect on the duration of respiratory support, but the evidence is very uncertain. HFNC likely results in little to no difference in the length of stay at the intensive care unit. HFNC may reduce the incidence of nasal trauma and abdominal overdistension, but the evidence is very uncertain.
When compared with LFNC, HFNC may reduce treatment failure slightly. HFNC may have little to no effect on the duration of respiratory support, length of stay at the ICU, or hospital length of stay, but the evidence is very uncertain.
There is insufficient evidence to enable the formulation of evidence-based guidelines on the use of HFNC for respiratory support in term infants. Larger, methodologically robust trials are required to further evaluate the possible health benefits or harms of HFNC in this patient population.
When compared with CPAP, HFNC may result in little to no difference in treatment failure. HFNC may have little to no effect on the duration of respiratory support, but the evidence is very uncertain. HFNC likely results in little to no difference in the length of stay at the intensive care unit. HFNC may reduce the incidence of nasal trauma and abdominal overdistension, but the evidence is very uncertain.
When compared with LFNC, HFNC may reduce treatment failure slightly. HFNC may have little to no effect on the duration of respiratory support, length of stay at the ICU, or hospital length of stay, but the evidence is very uncertain.
There is insufficient evidence to enable the formulation of evidence-based guidelines on the use of HFNC for respiratory support in term infants. Larger, methodologically robust trials are required to further evaluate the possible health benefits or harms of HFNC in this patient population.
Respiratory failure or respiratory distress in infants is the most common reason for non-elective admission to hospitals and neonatal intensive care units. Non-invasive methods of respiratory support have become the preferred mode of treating respiratory problems as they avoid some of the complications associated with intubation and mechanical ventilation. High flow nasal cannula (HFNC) therapy is increasingly being used as a method of non-invasive respiratory support. However, the evidence pertaining to its use in term infants (defined as infants ≥ 37 weeks gestational age to the end of the neonatal period (up to one month postnatal age)) is limited and there is no consensus of opinion regarding the safety and efficacy HFNC in this population.
To assess the safety and efficacy of high flow nasal cannula oxygen therapy for respiratory support in term infants when compared with other forms of non-invasive respiratory support.
We searched the following databases in December 2022: Cochrane CENTRAL; PubMed; Embase; CINAHL; LILACS; Web of Science; Scopus. We also searched the reference lists of retrieved studies and performed a supplementary search of Google Scholar.
We included randomised controlled trials (RCTs) that investigated the use of high flow nasal cannula oxygen therapy in infants ≥ 37 weeks gestational age up to one month postnatal age (the end of the neonatal period).
Two review authors independently assessed trial eligibility, performed data extraction, and assessed risk of bias in the included studies. Where studies were sufficiently similar, we performed a meta‐analysis using mean differences (MD) for continuous data and risk ratios (RR) for dichotomous data, with their respective 95% confidence intervals (CIs). For statistically significant RRs, we calculated the number needed to treat for an additional beneficial outcome (NNTB). We used the GRADE approach to evaluate the certainty of the evidence for clinically important outcomes.
We included eight studies (654 participants) in this review. Six of these studies (625 participants) contributed data to our primary analyses.
Four studies contributed to our comparison of high flow nasal cannula (HFNC) oxygen therapy versus continuous positive airway pressure (CPAP) for respiratory support in term infants. The outcome of death was reported in two studies (439 infants) but there were no events in either group. HFNC may have little to no effect on treatment failure, but the evidence is very uncertain (RR 0.98, 95% CI 0.47 to 2.04; 3 trials, 452 infants; very low-certainty evidence). The outcome of chronic lung disease (need for supplemental oxygen at 28 days of life) was reported in one study (375 participants) but there were no events in either group. HFNC may have little to no effect on the duration of respiratory support (any form of non-invasive respiratory support with or without supplemental oxygen), but the evidence is very uncertain (MD 0.17 days, 95% CI -0.28 to 0.61; 4 trials, 530 infants; very low-certainty evidence). HFNC likely results in little to no difference in the length of stay at the intensive care unit (ICU) (MD 0.90 days, 95% CI -0.31 to 2.12; 3 trials, 452 infants; moderate-certainty evidence). HFNC may reduce the incidence of nasal trauma (RR 0.16, 95% CI 0.04 to 0.66; 1 trial, 78 infants; very low-certainty evidence) and abdominal overdistension (RR 0.22, 95% CI 0.07 to 0.71; 1 trial, 78 infants; very low-certainty evidence), but the evidence is very uncertain.
Two studies contributed to our analysis of HFNC versus low flow nasal cannula oxygen therapy (LFNC) (supplemental oxygen up to a maximum flow rate of 2 L/min). The outcome of death was reported in both studies (95 infants) but there were no events in either group. The evidence suggests that HFNC may reduce treatment failure slightly (RR 0.44, 95% CI 0.21 to 0.92; 2 trials, 95 infants; low-certainty evidence). Neither study reported results for the outcome of chronic lung disease (need for supplemental oxygen at 28 days of life). HFNC may have little to no effect on the duration of respiratory support (MD -0.07 days, 95% CI -0.83 to 0.69; 1 trial, 74 infants; very low-certainty evidence), length of stay at the ICU (MD 0.49 days, 95% CI -0.83 to 1.81; 1 trial, 74 infants; very low-certainty evidence), or hospital length of stay (MD -0.60 days, 95% CI -2.07 to 0.86; 2 trials, 95 infants; very low-certainty evidence), but the evidence is very uncertain. Adverse events was an outcome reported in both studies (95 infants) but there were no events in either group.
The risk of bias across outcomes was generally low, although there were some concerns of bias. The certainty of evidence across outcomes ranged from moderate to very low, downgraded due to risk of bias, imprecision, indirectness, and inconsistency.