Table of Contents
Respiratory disease is one of the most common causes of morbidity in pediatric patients, and noninvasive ventilation (NIV) has been used increasingly in the management of pediatric respiratory failure. High-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), and bilevel positive airway pressure (BPAP) are emerging as important modalities of respiratory support in the management of pediatric respiratory failure. This issue provides a review of the primary forms of NIV used in pediatric patients, indications for their use in the emergency department, and evidence-based recommendations for their use in the management of various disease processes. You will learn:
The mechanisms by which HFNC, CPAP, and BPAP provide respiratory support
The different types of interfaces that can be used for HFNC, CPAP, and BPAP
The indications for using HNFC and NIV in the emergency department, as well as contraindications to their use and complications that can result from their use
The benefits of using HNFC and NIV in the management of specific conditions, such as bronchiolitis and asthma
Clinical predictors and indicators of failure of HFNC and NIV
Recommendations for the use of HFNC and NIV for the management of acute respiratory failure in pediatric patients
The potential role of NIV in the management of pneumonia, acute respiratory distress syndrome (ARDS), and other disease processes
How the use of sedatives (eg, dexmedetomidine) can help overcome a common cause of failure of NIV
Considerations for using HFNC and NIV in patients with aerosolizing diseases
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Abstract
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Case Presentations
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Introduction
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Critical Appraisal of the Literature
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Physiology
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High-Flow Nasal Cannula
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Noninvasive Ventilation
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Continuous Positive Airway Pressure
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Bilevel Positive Airway Pressure
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Comparison of CPAP and BPAP
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Contraindications and Complications
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Contraindications
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Complications
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Prehospital Use
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Recommendations for Specific Conditions
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Bronchiolitis
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High-Flow Nasal Cannula
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Benefits of High-Flow Nasal Cannula for Bronchiolitis
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Indicators of Failure of High-Flow Nasal Cannula for Bronchiolitis
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Summary: High-Flow Nasal Cannula for Bronchiolitis
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Noninvasive Ventilation
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Benefits of Noninvasive Ventilation for Bronchiolitis
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Indicators of Failure of Noninvasive Ventilation for Bronchiolitis
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Heliox During Noninvasive Ventilation for Bronchiolitis
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Mask Styles
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Summary: Noninvasive Ventilation for Bronchiolitis
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Comparing HFNC and NIV for Treatment of Bronchiolitis
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Asthma
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Interfaces and Aerosol Delivery
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Evidence of Outcomes of High-Flow Nasal Cannula for Asthma
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Noninvasive Ventilation for Asthma
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Benefits of Noninvasive Ventilation for Asthma
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Complications of Noninvasive Ventilation for Asthma
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Predictors of Failure of Noninvasive Ventilation for Asthma
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Summary: Noninvasive Ventilation in Asthma
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Pneumonia
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High-Flow Nasal Cannula for Pneumonia
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Noninvasive Ventilation for Pneumonia
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Acute Respiratory Distress Syndrome
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Other Respiratory Conditions
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Acute Chest Syndrome
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Immunodeficiency
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Controversies and Cutting Edge
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Sedation
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High-Flow Nasal Cannula in Apneic Oxygenation
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Considerations for Noninvasive Ventilation With Aerosolizing Diseases
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Summary
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Time- and Cost-Effective Strategies
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Risk Management Pitfalls for High-Flow Nasal Cannula and Noninvasive Ventilation in Pediatric Patients
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Case Conclusions
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Clinical Pathway for the Use of HFNC and NIV in the Management of Acute Respiratory Failure in Pediatric Patients
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Table
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Table 1. Interfaces for High-Flow Nasal Cannula and Noninvasive Ventilation
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References
Abstract
The use of high-flow nasal cannula and noninvasive ventilation has become increasingly common in emergency medicine as a first-line treatment of pediatric patients with respiratory distress secondary to asthma and bronchiolitis. When implemented in clinical practice, close monitoring of vital signs and ventilation parameters is warranted to identify possible signs of respiratory failure. This issue provides evidence-based recommendations for the appropriate use of noninvasive ventilation modalities in pediatric patients including high-flow nasal cannula, continuous positive airway pressure, and bilevel positive airway pressure in the setting of acute respiratory distress. Contraindications and complications associated with these modalities are also discussed.
Case Presentations
A 2-month-old girl, born full-term without complications, presents to your ED in the middle of December. According to her mother, she has had 3 days of cough and congestion, as well as decreased feeding. The mother took her to the primary care physician’s office earlier in the day because she noticed that the girl's breathing had become extremely fast. On examination, the primary care physician noted wheezing and retractions, with an increased respiratory rate, and she recommended the mother take the child to the ED. The infant's initial vital signs are: temperature, 37.5°C (99.5°F); heart rate, 170 beats/min; respiratory rate, 74 breaths/min; blood pressure, 82/60 mm Hg; and oxygen saturation, 89% on room air. She weighs 5 kg. Her physical examination is notable for nasal congestion with grunting, tachypnea, and subcostal and supraclavicular retractions. She also has dry mucous membranes and a capillary refill of 3 seconds. Oxygen is provided by nonrebreather mask, and IV access is obtained. Nasal suctioning is performed without much change in her respiratory status. You make the decision to use high-flow nasal cannula as the initial form of respiratory support, with the following settings: FiO2, 40%; flow rate, 5 L/min. After about an hour on high-flow nasal cannula, the infant's vital signs are relatively unchanged. What are the signs of failure of high-flow nasal cannula? Is there a maximum flow rate above which this modality is not as effective, and how should it be titrated in pediatric patients? Are higher rates more likely to cause harm?
On a mid-spring day, a 5-year-old boy with a past medical history significant for asthma presents with audible wheezing and respiratory distress. His mother states that he had been playing in the backyard with his sister yesterday, and his symptoms have been persistent since then. Despite using his albuterol nebulizer every 4 hours at home, he has still been coughing and wheezing. When reviewing his history, you note that he has been admitted to the PICU for asthma exacerbations, with the most recent admission being 3 months ago. His vital signs are: temperature, 36.5°C (97.7°F); heart rate, 130 beats/min; respiratory rate, 44 breaths/min; blood pressure, 100/76 mm Hg; oxygen saturation, 93% on room air. He weighs 20 kg. On initial examination, the patient is awake and alert but in severe respiratory distress. He has diminished breath sounds throughout, with substernal and lower intercostal retractions. He cannot speak in full sentences. You immediately order 3 consecutive nebulized albuterol treatments with ipratropium, establish IV access, and administer methylprednisolone. Given the severity of his symptoms, you are considering bilevel positive airway pressure (BPAP) to prevent intubation. What are the optimal settings when initiating BPAP therapy? Can nebulized medications be given through the mask interface with BPAP, and are they still effective? What complications may arise while using BPAP, and is it an effective means of avoiding intubation?
Introduction
Respiratory disease is one of the most common causes of morbidity in pediatric patients, and acute or impending respiratory failure remains the leading diagnosis for admission to the pediatric intensive care unit (PICU).1 The mainstay of therapy for these patients has traditionally included mechanical ventilation. Inherent to endotracheal intubation and mechanical ventilation is the potential for iatrogenic complications, including upper airway trauma, laryngeal swelling, postextubation vocal cord dysfunction, prolonged sedation and hospitalization, and nosocomial infections.2 For more information on mechanical ventilation in pediatric patients, refer to the July 2020 issue of Pediatric Emergency Medicine Practice, “Mechanical Ventilation of Pediatric Patients in the Emergency Department.”
Noninvasive ventilation (NIV) has become an important tool in pediatric emergency medicine to delay or prevent endotracheal intubation. Initially introduced in the adult and neonatal population, NIV has been used increasingly in the management of pediatric respiratory failure.3,4 High-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), and bilevel positive airway pressure (BPAP) are the primary forms of NIV used in pediatric patients. Several different device interfaces for NIV exist, and emergency clinicians need to understand the options that are available in their particular clinical setting. While NIV has generally shown good results when used in the management of acute respiratory failure secondary to bronchiolitis and asthma, its role in the management of pneumonia, acute respiratory distress syndrome (ARDS), and other disease processes is less clear.
This issue of Pediatric Emergency Medicine Practice reviews the different types of NIV, cites the indications for their use in the emergency department (ED), and provides evidence-based recommendations for their use in patients with various disease processes.
Critical Appraisal of the Literature
A literature search was performed in PubMed, Google Scholar, Ovid MEDLINE®, and the Cochrane Database of Systematic Reviews using the search terms: pediatric noninvasive ventilation, high-flow nasal cannula, HFNC, continuous positive airway pressure, CPAP, bilevel positive airway pressure, and BiPAP. A total of 363 abstracts were evaluated, and 177 full-text articles published between 1995 and 2019 were reviewed. Citations within articles were also cross-referenced.
The literature regarding NIV in pediatric patients is limited in the number of prospective studies and randomized controlled trials. Most of the strong evidence for its use comes from neonatal and adult literature. All pediatric-specific Cochrane reviews regarding this topic did not have sufficient evidence to make recommendations.
Physiology
High-Flow Nasal Cannula
The introduction of HFNC into pediatric emergency care has offered a less invasive means of improving respiratory distress. In its most basic form, the equipment necessary for HFNC is a source of pressurized oxygen or air, a sterile water reservoir, an insulated or heated circuit, and a nonocclusive cannula interface. The equipment remains an open system, meaning that the cannula interface does not fully obstruct the nostrils. This characteristic distinguishes HFNC from the closed systems used in other NIV modalities (CPAP and BPAP).5 In the existing literature, HFNC is not routinely considered to be NIV and will thus be referred to as HFNC, while other modalities will be referred to as NIV throughout this review. For information on HFNC setup, watch the video at: www.youtube.com/watch?v=BD79VxUlsis
There are several mechanisms by which HFNC is believed to provide respiratory support to pediatric patients. The air or oxygen in HFNC is heated and humidified. Normally, the initial temperature is 1°C to 2°C below body temperature and adjusted for patient comfort. Theoretically, by providing heated and humidified air, the HFNC system allows for greater clearance of secretions, reduced airway obstruction, and decreased energy expenditure. In addition, HFNC can be titrated to higher flow rates than simple nasal cannula. These flow rates can meet and exceed the inspiratory demands of the patient, thus decreasing the work of breathing. Because the patient is not inhaling as much room air through their own inspiratory forces, dilution of the oxygen support provided by nasal cannula is prevented.6 Finally, during rebreathing, HFNC can wash out CO2 that collects in the relatively larger nasopharyngeal dead space in children;7 this washout improves gas exchange and breathing efficiency.5,6
Because HFNC is an open system, it was not regarded initially as a form of positive pressure ventilation, as it was not believed to generate measurable airway pressures. It has now been shown that HFNC can generate some degree of positive end-expiratory pressure (PEEP), thus recruiting alveoli and increasing the functional residual capacity. Nonetheless, the measurement of pressure is highly variable and dependent on leakage around the nasal prongs.8,9 Reports in the literature have shown that there is 3 to 6 cm H2O of PEEP generated, which may help to explain some of the observed clinical benefit.10-12 Unlike CPAP and BPAP, however, this cannot be titrated precisely, so the clinical response of the patient will vary and must be monitored individually.
Flow rates for HFNC can be titrated to as high as 60 L/min to achieve the desired effect. However, the maximum benefit in the pediatric population appears to be at flow rates between 1.5 to 2 L/kg/min.13 When compared with patients treated with HFNC at 3 L/kg/min, there was no significant difference in failure rate, intubation rate, or duration of invasive ventilation or NIV. Additionally, patients with bronchiolitis who were treated with 3 L/kg/min of flow experienced greater discomfort and increased length of stay in the PICU.14
Noninvasive Ventilation
NIV, which includes CPAP and BPAP, consists of an external interface that delivers pressurized gas supplied by a pressure-targeted ventilator.3 There are several different interfaces that can be employed, which are shown in Table 1.15,16 The most important aspect of the equipment is an interface that fits the patient's face correctly. Generally, one should be able to pass a finger between the headgear and the face.17 Without an appropriately sized mask, air leaks around the mask can occur, which lead to patient-ventilator asynchrony that results in insufficient inspiratory flow and treatment failure.18,19 For information on how to set up a BPAP machine, watch the video at: www.youtube.com/watch?v=hXtx0nEoL9E
Risk Management Pitfalls for High-Flow Nasal Cannula and Noninvasive Ventilation in Pediatric Patients
1. “The patient was not improving on BPAP. I wanted to avoid endotracheal intubation and its associated complications, so I continued management with BPAP.”
Since its introduction in pediatric emergency care, NIV has helped avoid intubation in several patient populations. Despite this, ignoring the signs that indicate when escalation of therapy is necessary can be fatal. When a patient’s respiratory rate is worsening, the PaCO2 is climbing, or intolerance of the interface is preventing adequate ventilation, it may be necessary to perform endotracheal intubation.
5. “The patient was still breathing fast after 5 minutes of BPAP therapy, so I decided it was time to intubate him.”
Troubleshooting for reasons for deterioration after placement of NIV should be systematic. Evaluation of the mask and how well it fits is important. Observe the patient for asynchrony with the machine and the possible etiologies. Examine the patient for complications secondary to initiation. Finally, evaluate the equipment for possible failure. After troubleshooting and evaluating for complications, if NIV still appears to be failing, then intubation may be necessary.
9. “My trauma patient with a Glasgow Coma Scale score of 6 and several pulmonary contusions needed respiratory support. I initiated CPAP since his oxygen saturation was 100%.”
Alteration in mental status (eg, a low Glasgow Coma Scale score) when the patient is not protect-ing his airway requires intubation. This is a contraindication for NIV. Other contraindications to its use include severe craniofacial abnormalities, severe ARDS, untreated pneumothorax, or severe hemodynamic instability.
References
Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.
To help the reader judge the strength of each reference, pertinent information about the study is included in bold type following the reference, where available. In addition, the most informative references cited in this paper, as determined by the author, are highlighted.
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Conti G, Piastra M. Mechanical ventilation for children. Curr Opin Crit Care. 2016;22(1):60-66. (Review)
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Najaf-Zadeh A, Leclerc F. Noninvasive positive pressure ventilation for acute respiratory failure in children: a concise review. Ann Intensive Care. 2011;1(1):15. (Review)
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Deis JN, Abramo TJ, Crawley L. Noninvasive respiratory support. Pediatr Emerg Care. 2008;24(5):331-338. (Review)
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Benckert M, Morris M, Wilson P. 752: Non-invasive ventilation usage and adverse events in an academic PICU. Crit Care Med. 2015;43(12):189. (Prospective observational study; 58 patients)
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Slain KN, Shein SL, Rotta AT. The use of high-flow nasal cannula in the pediatric emergency department. J Pediatr (Rio J). 2017;93 Suppl 1:36-45. (Literature review)
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Lodeserto FJ, Lettich TM, Rezaie SR. High-flow nasal cannula: mechanisms of action and adult and pediatric indications. Cureus. 2018;10(11):e3639. (Review)
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Shein SL, Slain KN, Rotta AT. High flow nasal cannula flow rates: new data worth the weight. J Pediatr. 2017;189:9-10. (Editorial)
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Viscusi CD, Pacheco GS. Pediatric emergency noninvasive ventilation. Emerg Med Clin North Am. 2018;36(2):387-400. (Review)
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Hasan RA, Habib RH. Effects of flow rate and airleak at the nares and mouth opening on positive distending pressure delivery using commercially available high-flow nasal cannula systems: a lung model study. Pediatr Crit Care Med. 2011;12(1):e29-e33. (Lung model study)
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Arora B, Mahajan P, Zidan MA, et al. Nasopharyngeal airway pressures in bronchiolitis patients treated with high-flow nasal cannula oxygen therapy. Pediatr Emerg Care. 2012;28(11):1179-1184. (Prospective observational study; 25 patients)
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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(1):82-88. (Prospective observational study; 27 patients)
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Nielsen KR, Ellington LE, Gray AJ, et al. Effect of high-flow nasal cannula on expiratory pressure and ventilation in infant, pediatric, and adult models. Respir Care. 2018;63(2):147-157. (Lung model study)
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Weiler T, Kamerkar A, Hotz J, et al. The relationship between high flow nasal cannula flow rate and effort of breathing in children. J Pediatr. 2017;189:66-71.E3. (Prospective cohort trial; 21 patients)
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Milesi C, Pierre AF, Deho A, et al. A multicenter randomized controlled trial of a 3-L/kg/min versus 2-L/kg/min high-flow nasal cannula flow rate in young infants with severe viral bronchiolitis (TRAMONTANE 2). Intensive Care Med. 2018;44(11):1870-1878. (Randomized controlled trial; 286 patients)
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Mortamet G, Amaddeo A, Essouri S, et al. Interfaces for noninvasive ventilation in the acute setting in children. Paediatr Respir Rev. 2017;23:84-88. (Literature review)
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Nava S, Navalesi P, Gregoretti C. Interfaces and humidification for noninvasive mechanical ventilation. Respir Care. 2009;54(1):71-84. (Review)
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Hostetler MA. Use of noninvasive positive-pressure ventilation in the emergency department. Emerg Med Clin North Am. 2008;26(4):929-939. (Review)
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Oto J, Chenelle CT, Marchese AD, et al. A comparison of leak compensation during pediatric noninvasive ventilation: a lung model study. Respir Care. 2014;59(2):241-251. (Lung model study)
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Fedor KL. Noninvasive respiratory support in infants and children. Respir Care. 2017;62(6):699-717. (Review)
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Sinha IP, McBride AKS, Smith R, et al. CPAP and high-flow nasal cannula oxygen in bronchiolitis. CHEST. 2015;148(3):810-823. (Review)
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Teague WG. Noninvasive ventilation in the pediatric intensive care unit for children with acute respiratory failure. Pediatr Pulmonol. 2003;35(6):418-426. (Review)
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Mastropietro CW. Bubble CPAP: not all bubbling is good bubbling. Respir Care. 2013;58(11):1990-1991. (Editorial)
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Calderini E, Chidini G, Pelosi P. What are the current indications for noninvasive ventilation in children? Curr Opin Anaesthesiol. 2010;23(3):368-374. (Review)
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Rehder KJ. Adjunct therapies for refractory status asthmaticus in children. Respir Care. 2017;62(6):849-865. (Review)
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Marohn K, Panisello JM. Noninvasive ventilation in pediatric intensive care. Curr Opin Pediatr. 2013;25(3):290-296. (Review)
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Akingbola OA, Hopkins RL. Pediatric noninvasive positive pressure ventilation. Pediatr Crit Care Med. 2001;2(2):164-169. (Review)
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Baudin F, Gagnon S, Crulli B, et al. Modalities and complications associated with the use of high-flow nasal cannula: experience in a pediatric ICU. Respir Care. 2016;61(10):1305-1310. (Retrospective study; 177 patients)
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Thia LP, McKenzie SA, Blyth TP, et al. Randomised controlled trial of nasal continuous positive airways pressure (CPAP) in bronchiolitis. Arch Dis Child. 2008;93(1):45-47. (Prospective randomized crossover controlled trial; 29 patients)
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Lum LC, Abdel-Latif ME, de Bruyne JA, et al. Noninvasive ventilation in a tertiary pediatric intensive care unit in a middle-income country. Pediatr Crit Care Med. 2011;12(1):e7-e13. (Prospective observational study; 278 patients)
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Munoz-Bonet JI, Flor-Macian EM, Brines J, et al. Predictive factors for the outcome of noninvasive ventilation in pediatric acute respiratory failure. Pediatr Crit Care Med. 2010;11(6):675-680. (Prospective noncontrolled observational study; 47 patients)
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Chidini G, Calderini E, Cesana BM, et al. Noninvasive continuous positive airway pressure in acute respiratory failure: helmet versus facial mask. Pediatrics. 2010;126(2):e330-e336. (Randomized controlled crossover study; 20 patients)
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Chidini G, Piastra M, Marchesi T, et al. Continuous positive airway pressure with helmet versus mask in infants with bronchiolitis: an RCT. Pediatrics. 2015;135(4):e868-e875. (Randomized controlled trial; 30 patients)
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Velasco Arnaiz E, Cambra Lasaosa FJ, Hernandez Platero L, et al. Is a nasopharyngeal tube effective as interface to provide bi-level noninvasive ventilation? Respir Care. 2014;59(4):510-517. (Prospective observational study; 151 patients)
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Yaman A, Kendirli T, Odek C, et al. Efficacy of noninvasive mechanical ventilation in prevention of intubation and reintubation in the pediatric intensive care unit. J Crit Care. 2016;32:175-181. (Prospective observational study; 160 patients)
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Mayordomo-Colunga J, Medina A, Rey C, et al. Predictive factors of non invasive ventilation failure in critically ill children: a prospective epidemiological study. Intensive Care Med. 2009;35(3):527-536. (Prospective noncontrolled observational study; 116 patients)
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Bernet V, Hug MI, Frey B. Predictive factors for the success of noninvasive mask ventilation in infants and children with acute respiratory failure. Pediatr Crit Care Med. 2005;6(6):660-664. (Prospective noncontrolled observational study; 42 patients)
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Schlapbach LJ, Schaefer J, Brady AM, et al. High-flow nasal cannula (HFNC) support in interhospital transport of critically ill children. Intensive Care Med. 2014;40(4):592-599. (Retrospective study; 793 patients)
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Baird JS, Spiegelman JB, Prianti R, et al. Noninvasive ventilation during pediatric interhospital ground transport. Prehosp Emerg Care. 2009;13(2):198-202. (Retrospective review; 31 transports)
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Cheema B, Welzel T, Rossouw B. Noninvasive ventilation during pediatric and neonatal critical care transport: a systematic review. Pediatr Crit Care Med. 2019;20(1):9-18. (Systematic review; 8 observational studies, 858 patients)
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Millan N, Alejandre C, Martinez-Planas A, et al. Noninvasive respiratory support during pediatric ground transport: implementation of a safe and feasible procedure. Respir Care. 2017;62(5):558-565. (Prospective observational study; 288 patients)
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Baird JS, Ravindranath TM. Out-of-hospital noninvasive ventilation: epidemiology, technology and equipment. Pediatr Rep. 2012;4(2):e17. (Review)
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Clayton JA, McKee B, Slain KN, et al. Outcomes of children with bronchiolitis treated with high-flow nasal cannula or noninvasive positive pressure ventilation. Pediatr Crit Care Med. 2019;20(2):128-135. (Multicenter retrospective study; 92 centers, 6496 patients)
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Bradshaw ML, Deragon A, Puligandla P, et al. Treatment of severe bronchiolitis: a survey of Canadian pediatric intensivists. Pediatr Pulmonol. 2018;53(5):613-618. (Cross-sectional survey; 57 intensivists)
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Schibler A, Pham TM, Dunster KR, et al. Reduced intubation rates for infants after introduction of high-flow nasal prong oxygen delivery. Intensive Care Med. 2011;37(5):847-852. (Retrospective chart review; 298 patients)
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Pham TM, O’Malley L, Mayfield S, et al. The effect of high flow nasal cannula therapy on the work of breathing in infants with bronchiolitis. Pediatr Pulmonol. 2015;50(7):713-720. (Prospective observational study; 14 patients)
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McKiernan C, Chua LC, Visintainer PF, et al. High flow nasal cannulae therapy in infants with bronchiolitis. J Pediatr. 2010;156(4):634-638. (Retrospective cohort study; 115 patients)
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Goh CT, Kirby LJ, Schell DN, et al. Humidified high-flow nasal cannula oxygen in bronchiolitis reduces need for invasive ventilation but not intensive care admission. J Paediatr Child Health. 2017;53(9):897-902. (Retrospective cohort study; 166 patients)
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Kepreotes E, Whitehead B, Attia J, 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(10072):930-939. (Randomized controlled trial; 202 patients)
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Franklin D, Babl FE, Schlapbach LJ, et al. A randomized trial of high-flow oxygen therapy in infants with bronchiolitis. N Engl J Med. 2018;378(12):1121-1131. (Randomized controlled trial; 1472 patients)
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Milani GP, Plebani AM, Arturi E, et al. Using a high-flow nasal cannula provided superior results to low-flow oxygen delivery in moderate to severe bronchiolitis. Acta Paediatr. 2016;105(8):e368-e372. (Prospective observational study; 36 patients)
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Hilliard TN, Archer N, Laura H, et al. Pilot study of vapotherm oxygen delivery in moderately severe bronchiolitis. Arch Dis Child. 2012;97(2):182-183. (Randomized controlled trial; 19 patients)
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Valencia-Ramos J, Miras A, Cilla A, et al. Incorporating a nebulizer system into high-flow nasal cannula improves comfort in infants with bronchiolitis. Respir Care. 2018;63(7):886-893. (Randomized crossover study; 113 nebulizations)
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Mayfield S, Bogossian F, O’Malley L, et al. High-flow nasal cannula oxygen therapy for infants with bronchiolitis: pilot study. J Paediatr Child Health. 2014;50(5):373-378. (Prospective pilot study; 94 patients)
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Bueno Campana M, Olivares Ortiz J, Notario Munoz C, et al. High flow therapy versus hypertonic saline in bronchiolitis: randomised controlled trial. Arch Dis Child. 2014;99(6):511-515. (Randomized controlled trial; 74 patients)
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Kelly GS, Simon HK, Sturm JJ. High-flow nasal cannula use in children with respiratory distress in the emergency department: predicting the need for subsequent intubation. Pediatr Emerg Care. 2013;29(8):888-892. (Retrospective cohort review; 498 patients)
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Wing R, James C, Maranda LS, et al. 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(11):1117-1123. (Retrospective chart review; 848 patients)
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Ebraheem M, Shekerdemian L, Graf J, et al. 763: High flow nasal cannula in critically ill infants and children with bronchiolitis and pneumonia. Crit Care Med. 2014;42(12):A1544. (Retrospective cohort study; 650 patients)
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Milesi C, Baleine J, Matecki S, et al. Is treatment with a high flow nasal cannula effective in acute viral bronchiolitis? A physiologic study. Intensive Care Med. 2013;39(6):1088-1094. (Prospective observational study; 21 patients)
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Slain KN, Martinez-Schlurmann N, Shein SL, et al. Nutrition and high-flow nasal cannula respiratory support in children with bronchiolitis. Hosp Pediatr. 2017;7(5):256-262. (Retrospective cohort study; 70 patients)
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Heikkila P, Forma L, Korppi M. High-flow oxygen therapy is more cost-effective for bronchiolitis than standard treatment-A decision-tree analysis. Pediatr Pulmonol. 2016;51(12):1393-1402. (Decision-tree analysis of prior retrospective studies)
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Abboud PA, Roth PJ, Skiles CL, et al. Predictors of failure in infants with viral bronchiolitis treated with high-flow, high-humidity nasal cannula therapy. Pediatr Crit Care Med. 2012;13(6):e343-e349. (Retrospective review; 113 patients)
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Beggs S, Wong ZH, Kaul S, et al. High-flow nasal cannula therapy for infants with bronchiolitis. Cochrane Database Syst Rev. 2014(1):CD009609. (Cochrane review; 1 study, 19 patients)
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Cambonie G, Milesi C, Jaber S, et al. Nasal continuous positive airway pressure decreases respiratory muscles overload in young infants with severe acute viral bronchiolitis. Intensive Care Med. 2008;34(10):1865-1872. (Prospective observational study; 12 patients)
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Lazner MR, Basu AP, Klonin H. Non-invasive ventilation for severe bronchiolitis: analysis and evidence. Pediatr Pulmonol. 2012;47(9):909-916. (Retrospective review; 61 patients)
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Campion A, Huvenne H, Leteurtre S, et al. [Non-invasive ventilation in infants with severe infection presumably due to respiratory syncytial virus: feasibility and failure criteria]. Arch Pediatr. 2006;13(11):1404-1409. (Prospective noncontrolled trial; 101 patients)
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Javouhey E, Barats A, Richard N, et al. Non-invasive ventilation as primary ventilatory support for infants with severe bronchiolitis. Intensive Care Med. 2008;34(9):1608-1614. (Retrospective review; 80 patients)
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Essouri S, Laurent M, Chevret L, et al. Improved clinical and economic outcomes in severe bronchiolitis with pre-emptive nCPAP ventilatory strategy. Intensive Care Med. 2014;40(1):84-91. (Retrospective cohort review; 525 patients)
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Ganu SS, Gautam A, Wilkins B, et al. Increase in use of non-invasive ventilation for infants with severe bronchiolitis is associated with decline in intubation rates over a decade. Intensive Care Med. 2012;38(7):1177-1183. (Retrospective review; 399 patients)
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Nizarali Z, Cabral M, Silvestre C, et al. Noninvasive ventilation in acute respiratory failure from respiratory syncytial virus bronchiolitis. Rev Bras Ter Intensiva. 2012;24(4):375-380. (Retrospective cohort study; 162 patients)
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Milesi C, Matecki S, Jaber S, et al. 6 cmH2O continuous positive airway pressure versus conventional oxygen therapy in severe viral bronchiolitis: a randomized trial. Pediatr Pulmonol. 2013;48(1):45-51. (Randomized controlled trial; 19 patients)
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Lal SN, Kaur J, Anthwal P, et al. Nasal continuous positive airway pressure in bronchiolitis: a randomized controlled trial. Indian Pediatr. 2018;55(1):27-30. (Randomized controlled trial; 72 patients)
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