ReviewHigh-flow nasal cannula: Mechanisms, evidence and recommendations
Introduction
Nasal continuous positive airway pressure (CPAP) is the most widely used ‘non-invasive’ respiratory support for preterm infants around the world. In 2013, more than 85% of very preterm infants [<32 weeks of gestational age (GA)] registered to the Australian and New Zealand Neonatal Network (ANZNN) were treated with CPAP during their hospital admission [1]. CPAP delivers a continuous distending pressure to the lungs, usually set at between 5 and 10 cm of water (cmH2O) when treating preterm infants. Gases are heated and humidified, and the delivered oxygen concentration may be altered with the use of a ‘blender’.
Whereas CPAP is a well-studied and efficacious modality in preterm infants, it has some drawbacks. The need for the prongs to completely fill the nostrils may result in damage to the nasal mucosa and septum [2], [3]. Excessive leak around the prongs or mask may lead to inadequate support, whereas too much pressure may cause air leak from the lung into the pleural space (pneumothorax), both of which may require intubation and mechanical ventilation [4]. CPAP may cause abdominal distension, sometimes called ‘CPAP belly’ [5], and the bulky interfaces used to maintain the prong position in the nose obscure the infant's face, which may interfere with bonding, suck feeding, and positioning. The effective application of CPAP requires skilled clinical care, and in smaller centers it may be difficult to acquire and maintain these skills.
In the last decade, an alternative form of non-invasive respiratory support known as high-flow nasal cannula (HF, Fig. 1) has become available. This form of respiratory support uses smaller binasal prongs than nasal CPAP, and a simpler interface. HF delivers gas flows >1 L/min [6]. This therapy has evolved from the practice of providing supplemental oxygen to preterm infants via small binasal prongs at flows <1 L/min using unheated and unhumidified gas, a practice thought to provide no respiratory support to the infant other than sensory stimulation that may contribute to reduction in apnea.
Commercially available HF systems that have been used in randomized trials of HF, such as the Vapotherm Precision Flow (Vapotherm, Inc., Exeter, New Hampshire, USA), Fisher & Paykel Optiflow™ Junior (Fisher & Paykel Healthcare, Auckland, New Zealand), and Comfort Flo® (Teleflex Medical, Research Triangle Park, NC, USA) systems, heat and humidify the delivered gas. Oxygen and air may also be blended with these systems to deliver a target fraction of inspired oxygen, similar to CPAP systems.
HF has become a popular mode of non-invasive respiratory support in the pediatric population. In older infants and children, there is increasing evidence of its use and efficacy, especially in treating those with viral respiratory tract infections [7], [8], [9]. In recent years, there have been more reports of the increasing use of HF to treat preterm infants. The ANZNN has recently reported 2013 data showing that 24% (2332 infants) of all tertiary neonatal intensive care unit (NICU) registrants had received HF, a marked increase from about 8% in 2009 [1]. HF use was predominantly in preterm infants born <30 weeks of GA: about 60% of these infants received HF during their hospital admission. Typical gas flows used ranged from 2–8 L/min.
Several published surveys have helped to quantify HF use in the preterm population around the world. Hochwald and Osiovich [10] distributed a questionnaire regarding HF use to all 97 ‘academic’ neonatal units in the USA: 69% of respondents reported using HF. Hough[11] surveyed the member NICUs of the ANZNN in 2011 and found that 63% were using HF. In 2009, Nath[12] undertook a telephone survey of all 214 neonatal units in the UK: 55% used HF. This survey was updated in 2011 by Ojha[13] for tertiary neonatal units in the UK: HF was used in 77% of responding units. Anecdotally, we are aware of several tertiary NICUs around the world that have replaced CPAP with HF as their preferred mode of respiratory support for preterm infants.
The increasing use of HF to treat preterm infants is due to its perceived benefits, as well as accumulating evidence of efficacy and safety. The simpler interface of HF is often described as easier to apply than CPAP, and there is evidence that HF is preferred by parents [14] and nurses [15]. Nursing staff in one center using HF for the first time as part of a randomized trial described HF as being easier to set-up and use, more comfortable and less likely to cause nasal trauma compared with CPAP [15]. Osman[16] measured pain scores and salivary cortisol concentrations, and found that preterm infants receiving HF were more comfortable than infants receiving nasal CPAP.
However, there have been complications when using HF in preterm infants. The most widely publicized was the Ralstonia contamination of the Vapotherm system that forced a temporary recall of this device in 2005 [17]. The Vapotherm system has since been subject to more stringent infection control measures and is back in widespread use. There has been a case report [18] of a preterm infant receiving humidified HF (2 L/min, device not reported) with concomitant subcutaneous scalp emphysema and pneumo-orbitis, which resolved after discontinuation of HF. A case series of pneumothoraces in older infants and children treated with HF was reported in 2013 [19].
This Chapter evaluates the evidence for the use of HF in preterm infants, including studies of physiological effects and its mechanisms of action, and randomized clinical trials of HF use in different clinical scenarios. Several study authors have kindly provided unpublished subgroup data, and/or clarified their trial methodology and results.
Section snippets
Heating and humidification of delivered gas
The human nasal air passages warm inspired air from the ambient temperature to 37°C, and humidify it to 100% relative humidity (RH) [20]. At flows >1 L/min, delivery of unheated, unhumidified gas has potential adverse consequences, including mucosal injury and infection [21], [22]. To this end, all commercially available HF systems deliver heated, humidified gas. Woodhead [23] demonstrated the clinical effectiveness of humidifying HF gas in a clinical crossover study of post-extubation support
Randomized studies of HF vs nasal CPAP as primary support
Three trials have compared HF with CPAP as primary support for preterm infants. No trial included extremely preterm infants born <28 weeks of GA.
Iranpour's single-centre study [44], published in Persian, enrolled 70 preterm infants born at 30–35 weeks' gestation who were receiving CPAP, and who had ongoing respiratory distress and supplemental oxygen requirement at 24 hours of age. The trial protocol allowed infants who met pre-specified criteria (before or after randomization) to receive
Randomized trials of HF vs CPAP to prevent extubation failure
There have been six randomized clinical trials that have compared HF with CPAP as post-extubation support, with the five largest trials all published in the last three years.
Campbell [49] performed a single-centre study that enrolled 40 intubated preterm infants of mean GA of 27 weeks and birth weight of 1.0 kg. They compared post-extubation humidified, unheated HF (mean gas flow 1.6 L/min) with variable flow CPAP at 5–6 cmH2O. Infants in the HF group were more likely to be re-intubated: HF
Using HF to aid CPAP weaning
HF therapy has been used to ‘wean’ or ‘step-down’ from CPAP treatment in convalescing preterm infants with evolving BPD. This practice stems from the belief that HF is a “milder” form of CPAP, and that infants requiring longer-term non-invasive support will benefit from the smaller nasal prongs and simpler interface, particularly by improving parental access, bonding, and establishment of suck feeding. To our knowledge, none of these potential effects has been studied in a published clinical
Summary of the evidence from randomized clinical trials of HF
Currently, the strongest evidence from randomised clinical trials for HF use in the neonatal population is as an alternative to CPAP for post-extubation support of preterm infants, although we recommend caution in extremely preterm infants where few data are available. Whereas treatment failure rates after extubation favor CPAP over HF, without reaching statistical significance, rates of actual re-intubation are no different due to several studies allowing ‘rescue’ CPAP/NIPPV when HF failed.
Acknowledgements
We sincerely thank Professor Bradley Yoder (University of Utah, USA) and Dr Clare Collins (Mercy Hospital for Women, Melbourne, Australia) for providing unpublished subgroup data. We also thank Dr Manizheh Mostafa-Gharehbaghi (Tabriz University of Medical Sciences, Tabriz, Iran), Dr Ramin Iranpour (Isfahan University of Medical Sciences, Isfahan, Iran) and Dr Ma Li for their assistance with translation and clarification of their trial methodology and results. A/Prof. Dominic Wilkinson
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