|Year : 2018 | Volume
| Issue : 1 | Page : 2-6
Nasal high-flow therapy in infants and children
Donna Franklin, Andreas Schibler
Paediatric Intensive Care Unit, Lady Cilento Children's Hospital, Mater Research The University of Queensland, South Brisbane 4101 QLD, Australia
|Date of Web Publication||5-Apr-2018|
Paediatric Critical Care Research Group, Paediatric Intensive Care Unit, Lady Cilento Children's Hospital, Mater Research The University of Queensland, South Brisbane 4101 QLD
Source of Support: None, Conflict of Interest: None
This review highlights and summarizes the current evidence and knowledge of nasal high flow therapy management in infants and children. This review outlines the distinct differences in the use of NHF therapy between children and adults. A comprehensive literature review has been performed reviewing the relevant physiological studies and current evidence of support measures in these children. Despite the quick uptake of nasal high flow therapy in the clinical area there has been limited high-grade evidence, with new studies showing beneficial results with the use of nasal high flow therapy in acute respiratory disease and children.
Keywords: Acute respiratory distress, bronchiolitis, high flow, non-invasive respiratory support, pediatrics
|How to cite this article:|
Franklin D, Schibler A. Nasal high-flow therapy in infants and children. Pediatr Respirol Crit Care Med 2018;2:2-6
|How to cite this URL:|
Franklin D, Schibler A. Nasal high-flow therapy in infants and children. Pediatr Respirol Crit Care Med [serial online] 2018 [cited 2019 Jan 24];2:2-6. Available from: http://www.prccm.org/text.asp?2018/2/1/2/229318
| Introduction|| |
Of the 6.3 million children under the age of 5 years worldwide who died in 2013, over 1 million deaths were caused by respiratory infections. While the mortality of respiratory infections has decreased in high-income countries, acute hypoxic respiratory failure (AHRF) is the most frequent cause of hospital admission resulting in major consumption of health-care resources.,, Asthma, pneumonia, and bronchiolitis hospitalization in children in the USA are estimated to account for over US $3 billion/year., In contrast, children in under-resourced countries presenting to hospitals with severe hypoxemic respiratory failure have a mortality rate between 13% and 28%. There is an emerging trend to improve respiratory gas exchange with methods other than oxygen, particularly in the early stage of the disease process aiming to prevent the progression of the disease. 'Furthermore, to date, the provision of positive pressure ventilation has been restricted to intensive care, which remains costly and requires a high level of skill. In view of the global burden of respiratory disease, the development of low cost and low technology interventions is urgently needed, such as nasal high flow (NHF) therapy, that can reduce health-care costs,, both in the first world and assist in reducing the burden of this disease in under-resourced countries.
Current treatment options for acute hypoxic respiratory failure
The main goal of respiratory support in AHRF is the prevention of severe hypoxemia to protect cerebral function and reduce end-organ failure. Yet the danger of excessive use of oxygen (O2) has been recognized, with toxicity being related to the concentration and length of exposure.,, Oxygen causes tracheobronchial irritation and reduced mucociliary function (even in healthy volunteers exposed to 90% - 95% oxygen for 3 hours) and eventually, atelectasis, decreased vital capacity and changes similar to adult-type respiratory distress syndrome (RDS). For these reasons, other than emergency usage of 100% O2, it is recommended that inspired oxygen concentration (FiO2) should be carefully titrated against arterial hemoglobin saturation (SpO2 or if available SaO2). In neonates, use of 100% O2 during resuscitation increases mortality, myocardial injury and renal injury  and in newborn infants, following an asphyxiating perinatal event, it is thought to increase the risk of cerebral damage. A systematic review in children with chronic or recurrent hypoxia indicated that high level or prolonged use of O2 caused adverse effects on development, behavior, and academic achievement; however, most studies did not stratify by SaO2. Therefore, a more controlled application of O2 is desirable.
Noninvasive and invasive mechanical ventilation
Noninvasive ventilation (NIV) and mechanical ventilation (MV) deliver both an O2/air mix and positive pressure through a face-mask or endotracheal tube. Both improve lung function and gas exchange.,, Children require high levels of sedation to tolerate NIV or MV, which have been shown to carry inherent risks for long-term neurodevelopment, and which often prolong hospital stay due to related side effects.,,, Systems for NIV/MV are expensive, only applicable in Intensive Care Units (ICUs), and require high levels of expertise.
Nasal high-flow therapy
Historically, NHF therapy has been first introduced by a paper published in 1986 in the lancet by Klein and Reynolds. In this study, children with severe upper airway obstruction were exposed to continuous fresh gas flow, which was humidified and heated. The authors showed a significant reduction in the work of breathing of these children while on NHF therapy. Others have shown that high fresh gas flow delivered through nasal cannula generates some positive airway pressure. In preterm infants, NHF therapy rapidly became a common respiratory support mechanism, particularly in the postextubation phase. In pediatric critical care, high flow has first been used in infants with bronchiolitis and children with AHRF to prevent invasive ventilation. This review highlights the current evidence to use NHF therapy in children and explore some distinct differences in the use of NHF therapy between children and adults.
| Neonatal High Flow|| |
Preterm infants are at risk to develop respiratory distress resulting from surfactant deficiency, which is often required immediately after delivery intubation and MV. Exposure to endotracheal positive pressure ventilation is a risk factor for bronchopulmonary dysplasia, an important morbidity in preterm infants with potentially serious sequelae. This has led clinicians to explore alternative and less invasive respiratory support methods such as nasal continuous positive airway pressure (CPAP). NHF therapy was first introduced in neonatal nurseries in 2002 as an alternative to nasal CPAP, and its main indication was for apnea of prematurity and then later for respiratory support postextubation in preterm infants with RDS. NHF systems have since increased in popularity, as they are less bulky and less cumbersome to be placed on an infant's face than standard nasal CPAP systems. Since the introduction of NHF therapy, several well-performed physiological studies were completed, and many randomized controlled trials were performed comparing NHF therapy with standard nasal CPAP.
Physiological evidence of high flow in neonates
Early studies in preterm infants showed that relatively small flow rates of 2 L/min can generate positive distending pressure of 4–5 cm H2O and produced distending pressure showed to be dependent on both the flow and weight for the infant in addition to the size of the nasal cannula applied. With the mouth open the effect of distending pressure can get lost and have no effect. Aside from the physiological effect, it is the infant's tolerance level and the high acceptance of high flow by the staff and parents that makes high flow in many neonatal units the preferred option for “CPAP” treatment. Despite the good tolerance, there remains from a clinical point of view some concerns regarding the risk of pneumothorax and gastric distension.
Evidence-based efficacy of nasal high-flow therapy in premature infants
A recently published large randomized controlled trial (RCT) in premature infants with RDS showed that NHF therapy can be successfully used as a primary respiratory support mode but CPAP remains the gold standard in these patients in regards to efficacy, particularly in very young preterm babies. NHF therapy was used successfully in several large RCTs in premature infants postextubation and the failure rate (measured in reintubation rate) was similar to conventional nasal CPAP., The weaning of respiratory support is a less well-investigated topic in preterm infants. Following the introduction of NHF therapy, clinicians soon began to explore the option to use it as a weaning therapy to come off nasal CPAP. The question still remains as to whether this practice is associated with increased length of oxygen therapy and respiratory support. The safety aspect of NHF therapy in premature infants remains a topic of debate because delivered airway pressures cannot be measured and there are concerns for potential excessive airway pressures. With more than 1000 studied infants on NHF therapy in large RCTs there is no obvious trend toward any specific side effect. There is also no evidence that NHF treatment is associated with any of the significant outcomes such as death or bipulmonary dysplasia. For safety measures the use of NHF therapy requires a selection of appropriate nasal cannula-to-nares ratio to enable adequate gas leak (approximately 50% of the area of the aperture of the nares). The flow rates used in preterm infants is relatively high compared to adults. The currently accepted and well-tolerated flow range is 2–8 L/min (translated in flow rates up to 8 L/kg/min).
| Pediatric High Flow|| |
Definition of high flow in pediatric respiratory disease
The definition of high flow remains vague and is commonly described as flow rates delivered of equal or more than 1 L/kg/min in infants with bronchiolitis. A more precise (and the authors' preferred definition) could be: NHF therapy is an accurate oxygen delivery and estimate of the required inspired oxygen fraction (FiO2) with fresh gas flow rates that exceed the inspiratory demand of the patient through nasal cannula using heated, humidified, and blended gas with a mixture of oxygen and air.
The physiological effects of high flow are based on the CO2 washout effect of the nasopharyngeal dead space and on the support of the inspiratory and expiratory effort. During the expiratory phase, there is positive airway pressures while exhaling against the flow into the nasopharynx. This positive end-expiratory pressure effect is commonly described in the range of 4–6 cm H2O. During the inspiratory phase, the inspiratory demand of the patient ideally should be matched by the delivered high flow. If the correct flow rate is applied, patients are experiencing a facilitated inspiration (inspiratory aid). If the inspiratory demand increases such as during respiratory distress, the high flow rate applied needs to be increased to prevent room air entrapment around the nasal cannula and hence reducing the inspired oxygen fraction (FiO2) [Figure 1].
Physiological effects of nasal high flow
The physiological effects of NHF therapy in children are summarized as follows:
- Washout of nasopharyngeal dead space resulting in increased fraction of oxygen and decreased carbon dioxide for the following inspiration and the alveoli ,
- Reduction of inspiratory resistance (mainly upper airway) and work of breathing by providing adequate flow if matched with inspiratory demand ,
- Improvement of airway conductance and pulmonary compliance by reducing the effect of cold air; an in vitro study has shown that inspired gas with low humidity even for short periods may result in worsened function of human airway epithelial cells inflammatory indices ,
- Reduction of the metabolic cost of gas conditions by providing air with 100% relative humidity 
- Providing an end-distending pressure to the lungs.,
In comparison to adults, infants break the expiratory phase using active innervation of the diaphragm to prevent the lung from partial collapse as infants are breathing near the closing volume of the lung. In the presence of respiratory distress, the expiratory phase can become active with the use of auxiliary, abdominal and intercostal muscles. To overcome and compensate for increased expiratory resistance, children and infants tend to increase their functional residual capacity. This not only allows distension of the airways but also provides a higher recoil pressure to work against airway resistance. Most of the studies investigating the physiological impact of NHF therapy were completed in infants with bronchiolitis. The estimated positive airway pressure using 2 L/kg/min in infants <12 months is approximately 4–6 cm H2O. In the absence of robust measurement techniques, the work of breathing is commonly assessed with clinical scoring systems, which are subjective and based on the clinical experience of the observer. Using the directly measured electrical signal of the diaphragm muscle it has been shown that the workload of the diaphragm is significantly reduced in infants with bronchiolitis who are treated with high flow [Figure 2].
|Figure 2: Diaphragmatic electrical activity off and on nasal high flow therapy in an infant with bronchiolitis.|
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Clinical evidence in pediatric respiratory disease
Despite the current widespread use of NHF therapy in children, the current pediatric clinical evidence for NHF therapy has been obtained mostly from infants with bronchiolitis. Two recent retrospective studies showed that after the introduction of NHF therapy as the standard approach for oxygen therapy in infants admitted to intensive care for bronchiolitis the intubation rates decreased to <10% from originally >30%., With the introduction of NHF therapy in the emergency department (ED) a significant reduction in the odds of intubation in ED occurred suggesting the early use of NHF therapy may prevent escalation of therapy. Similarly, an improved effectiveness of NHF therapy was demonstrated once introduced across the hospital and in the general pediatric ward. The use of NHF therapy during pediatric transportation of children <2 years of age of which approximately 51%–57% were infants with bronchiolitis showed a high safety profile of NHF therapy and no impact on intubation rates subsequently after admission to pediatric ICU.
A recent Australian single-center RCT in infants with bronchiolitis compared standard stand oxygen therapy with NHF therapy and showed no difference in the length of oxygen therapy (primary outcome) but showed a significantly reduced failure rate defined as intensive care admission in the NHF therapy group. This study suggested that early use of NHF therapy does not modify the underlying disease process in moderately severe bronchiolitis, but NHF therapy may have a role as a rescue therapy to reduce the proportion of children requiring high-cost intensive care. The investigators used flow rates of 1 L/kg/min, which may be for some of these infants inadequate flow rates to fully support the inspiratory demand. A similar large RCT is currently completed in Australia and New Zealand and awaiting the outcome results. A recent well-conducted French multi-center study conducted in intensive care compared the use of NHF therapy and CPAP in infants with bronchiolitis. The authors showed that NHF therapy had a proportionally greater failure rate than CPAP (NHF failure was rescued with CPAP), however, infants in both intervention groups had a similar intubation rate. A recent trial in limited resource settings compared Standard oxygen therapy (SOT), NHF therapy and bubble CPAP. This study enrolled children up to 5 years of age with acute respiratory failure, of which approximately 10%–15% had bronchiolitis. The authors showed that the use of bubble CPAP reduced the mortality in comparison to SOT, but no difference between NHF therapy and bubble CPAP could be found.
A recent large RCT investigating the efficacy of NHF therapy in 1400 infants <12 months of age with bronchiolitis has been completed, and the results are currently pending and eagerly awaited to inform clinical practice. The safety and quality aspect of this trial was high (personal communication). The trial used 2 L/kg/min of NHF in a general pediatric ward setting with a standard nursing ratio of 1:4. We have recently completed a pilot study in 460 children with AHRF and have demonstrated that NHF therapy is safe and likely superior to standard oxygen therapy (unpublished own data). The following flow rates (based on the age and weight adjusted minute ventilation) were tested in this pilot trial in [Table 1]. The use of NHF therapy however in this age group >1 year still needs to be further investigated.
|Table 1: Nasal high flow rates as part of the clinical guidelines used at the Lady Cilento Children's Hospital, Brisbane, Queensland, Australia|
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| Conclusion|| |
The use of NHF therapy in infants with bronchiolitis has been well accepted in intensive care settings as well as in general pediatric wards. More detailed evidence, however, is needed to fully establish its use in these settings. The use of NHF therapy in older children with hypoxic respiratory failure seems a plausible therapy based on evidence obtained in adults and infants, but high-grade evidence is still required.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Liu L, Oza S, Hogan D, Perin J, Rudan I, Lawn JE, et al.
Global, regional, and national causes of child mortality in 2000-13, with projections to inform post-2015 priorities: An updated systematic analysis. Lancet 2015;385:430-40.
Nair H, Simões EA, Rudan I, Gessner BD, Azziz-Baumgartner E, Zhang JS, et al.
Global and regional burden of hospital admissions for severe acute lower respiratory infections in young children in 2010: A systematic analysis. Lancet 2013;381:1380-90.
Walker CL, Rudan I, Liu L, Nair H, Theodoratou E, Bhutta ZA, et al.
Global burden of childhood pneumonia and diarrhoea. Lancet 2013;381:1405-16.
Hasegawa K, Tsugawa Y, Brown DF, Mansbach JM, Camargo CA Jr. Trends in bronchiolitis hospitalizations in the United States, 2000-2009. Pediatrics 2013;132:28-36.
Schlapbach LJ, Straney L, Gelbart B, Alexander J, Franklin D, Beca J, et al.
Burden of disease and change in practice in critically ill infants with bronchiolitis. Eur Respir J 2017;49.pii:1601648.
Rambaud-Althaus C, Althaus F, Genton B, D'Acremont V. Clinical features for diagnosis of pneumonia in children younger than 5 years: A systematic review and meta-analysis. Lancet Infect Dis 2015;15:439-50.
Thill PJ, McGuire JK, Baden HP, Green TP, Checchia PA. Noninvasive positive-pressure ventilation in children with lower airway obstruction. Pediatr Crit Care Med 2004;5:337-42.
Chisti MJ, Salam MA, Smith JH, Ahmed T, Pietroni MA, Shahunja KM, et al.
Bubble continuous positive airway pressure for children with severe pneumonia and hypoxaemia in Bangladesh: An open, randomised controlled trial. Lancet 2015;386:1057-65.
Askie LM, Henderson-Smart DJ, Irwig L, Simpson JM. Oxygen-saturation targets and outcomes in extremely preterm infants. N
Engl J Med 2003;349:959-67.
Jackson RM. Pulmonary oxygen toxicity. Chest 1985;88:900-5.
Davis WB, Rennard SI, Bitterman PB, Crystal RG. Pulmonary oxygen toxicity. Early reversible changes in human alveolar structures induced by hyperoxia. N
Engl J Med 1983;309:878-83.
Davis WB, Rennard SI, Bitterman PB, Gadek JE, Sun XH, Wewers M, et al.
Pulmonary oxygen toxicity. Bronchoalveolar lavage demonstration of early parameters of alveolitis. Chest 1983;83:35S.
Davis PG, Tan A, O'Donnell CP, Schulze A. Resuscitation of newborn infants with 100% oxygen or air: A systematic review and meta-analysis. Lancet 2004;364:1329-33.
Munkeby BH, Børke WB, Bjørnland K, Sikkeland LI, Borge GI, Halvorsen B, et al.
Resuscitation with 100% O2 increases cerebral injury in hypoxemic piglets. Pediatr Res 2004;56:783-90.
Bass JL, Corwin M, Gozal D, Moore C, Nishida H, Parker S, et al.
The effect of chronic or intermittent hypoxia on cognition in childhood: A review of the evidence. Pediatrics 2004;114:805-16.
Carrey Z, Gottfried SB, Levy RD. Ventilatory muscle support in respiratory failure with nasal positive pressure ventilation. Chest 1990;97:150-8.
Beers SL, Abramo TJ, Bracken A, Wiebe RA. Bilevel positive airway pressure in the treatment of status asthmaticus in pediatrics. Am J Emerg Med 2007;25:6-9.
Istaphanous GK, Loepke AW. General anesthetics and the developing brain. Curr Opin Anaesthesiol 2009;22:368-73.
Young C, Jevtovic-Todorovic V, Qin YQ, Tenkova T, Wang H, Labruyere J, et al.
Potential of ketamine and midazolam, individually or in combination, to induce apoptotic neurodegeneration in the infant mouse brain. Br J Pharmacol 2005;146:189-97.
Erickson S, Schibler A, Numa A, Nuthall G, Yung M, Pascoe E, et al.
Acute lung injury in pediatric intensive care in Australia and New Zealand: A prospective, multicenter, observational study. Pediatr Crit Care Med 2007;8:317-23.
Frat JP, Thille AW, Mercat A, Girault C, Ragot S, Perbet S, et al.
High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N
Engl J Med 2015;372:2185-96.
Klein M, Reynolds LG. Relief of sleep-related oropharyngeal airway obstruction by continuous insufflation of the pharynx. Lancet 1986;1:935-9.
Milési C, Baleine J, Matecki S, Durand S, Combes C, Novais AR, et al.
Is treatment with a high flow nasal cannula effective in acute viral bronchiolitis? A physiologic study. Intensive Care Med 2013;39:1088-94.
Sreenan C, Lemke RP, Hudson-Mason A, Osiovich H. High-flow nasal cannulae in the management of apnea of prematurity: A comparison with conventional nasal continuous positive airway pressure. Pediatrics 2001;107:1081-3.
Kubicka ZJ, Limauro J, Darnall RA. Heated, humidified high-flow nasal cannula therapy: Yet another way to deliver continuous positive airway pressure? Pediatrics 2008;121:82-8.
Roberts CT, Owen LS, Manley BJ, Frøisland DH, Donath SM, Dalziel KM, et al.
Nasal high-flow therapy for primary respiratory support in preterm infants. N
Engl J Med 2016;375:1142-51.
Manley BJ, Owen LS, Doyle LW, Andersen CC, Cartwright DW, Pritchard MA, et al.
High-flow nasal cannulae in very preterm infants after extubation. N
Engl J Med 2013;369:1425-33.
Yoder BA, Stoddard RA, Li M, King J, Dirnberger DR, Abbasi S, et al.
Heated, humidified high-flow nasal cannula versus nasal CPAP for respiratory support in neonates. Pediatrics 2013;131:e1482-90.
Dysart K, Miller TL, Wolfson MR, Shaffer TH. Research in high flow therapy: Mechanisms of action. Respir Med 2009;103:1400-5.
Frizzola M, Miller TL, Rodriguez ME, Zhu Y, Rojas J, Hesek A, et al.
High-flow nasal cannula: Impact on oxygenation and ventilation in an acute lung injury model. Pediatr Pulmonol 2011;46:67-74.
Pham TM, O'Malley L, Mayfield S, Martin S, Schibler A. The effect of high flow nasal cannula therapy on the work of breathing in infants with bronchiolitis. Pediatr Pulmonol 2015;50:713-20.
Chidekel A, Zhu Y, Wang J, Mosko JJ, Rodriguez E, Shaffer TH, et al.
The effects of gas humidification with high-flow nasal cannula on cultured human airway epithelial cells. Pulm Med 2012;2012:380686.
Hough JL, Pham TM, Schibler A. Physiologic effect of high-flow nasal cannula in infants with bronchiolitis. Pediatr Crit Care Med 2014;15:e214-9.
Hammer J, Numa A, Newth CJ. Acute respiratory distress syndrome caused by respiratory syncytial virus. Pediatr Pulmonol 1997;23:176-83.
McKiernan C, Chua LC, Visintainer PF, Allen H. High flow nasal cannulae therapy in infants with bronchiolitis. J Pediatr 2010;156:634-8.
Schibler A, Pham TM, Dunster KR, Foster K, Barlow A, Gibbons K, et al.
Reduced intubation rates for infants after introduction of high-flow nasal prong oxygen delivery. Intensive Care Med 2011;37:847-52.
Wing R, James C, Maranda LS, Armsby CC. Use of high-flow nasal cannula support in the emergency department reduces the need for intubation in pediatric acute respiratory insufficiency. Pediatr Emerg Care 2012;28:1117-23.
Riese J, Fierce J, Riese A, Alverson BK. Effect of a hospital-wide high-flow nasal cannula protocol on clinical outcomes and resource utilization of bronchiolitis patients admitted to the PICU. Hosp Pediatr 2015;5:613-8.
Schlapbach LJ, Schaefer J, Brady AM, Mayfield S, Schibler A. High-flow nasal cannula (HFNC) support in interhospital transport of critically ill children. Intensive Care Med 2014;40:592-9.
Kepreotes E, Whitehead B, Attia J, Oldmeadow C, Collison A, Searles A, et al.
High-flow warm humidified oxygen versus standard low-flow nasal cannula oxygen for moderate bronchiolitis (HFWHO RCT): An open, phase 4, randomised controlled trial. Lancet 2017;389:930-9.
Milési C, Essouri S, Pouyau R, Liet JM, Afanetti M, Portefaix A, et al.
High flow nasal cannula (HFNC) versus nasal continuous positive airway pressure (nCPAP) for the initial respiratory management of acute viral bronchiolitis in young infants: A multicenter randomized controlled trial (TRAMONTANE study). Intensive Care Med 2017;43:209-16.
Franklin D, Dalziel S, Schlapbach LJ, Babl FE, Oakley E, Craig SS, et al.
Early high flow nasal cannula therapy in bronchiolitis, a prospective randomised control trial (protocol): A paediatric acute respiratory intervention study (PARIS). BMC Pediatr 2015;15:183.
[Figure 1], [Figure 2]