Respiratory failure is the most common indication for admission to a PICU, affecting more than half of all children in the PICU in a recent international study (1). In children, a common cause of respiratory failure is hypoxemic respiratory failure. There are several different terms for this disease process, including acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Recently, the new Berlin definition revised the classification of acute hypoxemic respiratory failure in adults and replaced the term acute lung injury with mild, moderate, and severe ARDS based on degree of hypoxemia (2). In this review, the new revised terminology will be used.
Noninvasive positive pressure ventilation (NPPV) is an attractive strategy for children with impending respiratory failure. Since ventilation is delivered noninvasively via mask or other interface, NPPV supports ventilation, can reduce atelectasis, and potentially unloads fatigued respiratory muscles while preserving the child’s natural airway and airway clearance mechanisms. In addition, NPPV potentially avoids some of the associated complications of more invasive therapies as well as the need for sedation or muscle relaxation to facilitate these therapies.
NPPV has been used to treat respiratory failure from a variety of etiologies in children, including pediatric ARDS (PARDS). A recent point prevalence study by Santschi et al (1), in collaboration with the Pediatric Acute Lung Injury and Sepsis Investigators network and the European Society of Pediatric and Neonatal Intensive Care, described the ventilatory strategies for ARDS in 52 PICUs in 12 countries. The authors found significant variability in the use of NPPV among PICUs but described an overall prevalence of 8.5% for the use of NPPV in PARDS.
The use of NPPV in children has increased significantly over the last decade. In one international cohort, investigators found that the use of NPPV increased from 0.5% to 12.2% between 1999 and 2008 (3). Additionally, in a survey of 353 U.S. physicians by Fanning et al (4), the investigators found that NPPV had been used by 99% of respondents, with 60% using noninvasive support as initial therapy more than 10% of the time. In this same survey, deterrents to use NPPV included lack of experience of staff, lack of appropriate equipment, and proper patient selection. Physicians also reported factors associated with less likelihood of use including severe defects in gas exchange, disease progression, and patient intolerability (4).
Despite the growing use of this therapy, there are few prospective controlled trials in pediatrics that might guide the clinician in determining indications and strategies for the use of NPPV (4, 5). Additionally, many studies of NPPV in children include all children with acute respiratory failure and do not differentiate between PARDS and other etiologies. A recent Cochrane review confirmed this assessment, stating that there was a lack of well-designed controlled experiments of NPPV in children with acute hypoxemic respiratory failure (5).
In this review, we will examine the literature to determine the utility of NPPV in this population and provide recommendations regarding the use of NPPV in children with PARDS. Of note, as the data specific to the use of NPPV in PARDS are limited, the recommendations in this section of the Pediatric Acute Lung Injury Consensus Conference (PALICC) proceedings, while still agreed upon, are less strongly so than in other PALICC topics where scientific literature is more plentiful. Therefore, we suggest that the use of NPPV in PARDS should be considered a crucial research priority in the near future.
PubMed, EMBASE, CINAHL, Web of Science, Cochrane Library, and Scopus were searched from inception until September 2013 using the following keywords in various combinations: noninvasive ventilation, continuous positive airway pressure, noninvasive positive pressure ventilation, high-flow nasal cannula, acute respiratory failure, and acute lung injury. No language restrictions were applied. References from identified articles were searched for additional publications.
Physiologic Rationale to Explain Potential Benefits of the Use of NPPV for the Treatment of PARDS
In PARDS, increased capillary permeability, damage to the capillary endothelium and alveolar epithelium, and impaired alveolar fluid removal partner to cause inflammation, surfactant dysfunction, and diffuse alveolar damage. These changes in turn lead to alterations in pulmonary mechanics that contribute to the hypoxemia and hypercapnea seen in ARDS. The lung disease of ARDS is a heterogeneous process, and hypoxemia develops in part as a result of alveolar hypoventilation and from perfusion (Q) to an area with low ventilation (Va). Alveolar hypoventilation and airspace derecruitment occur when transpulmonary pressure falls below the closing pressure. In addition, prolonged diaphragmatic pressure time products contribute to premature airway closure and increased air trapping. Inspiratory load is increased, since initiation of a breath requires a further increase in alveolar pressure (6, 7). This increased inspiratory load leads to increased work of breathing and an increase in oxygen consumption by the respiratory muscles, which can further increase hypoxemia. In children, lower lung and chest wall compliance and functional residual capacity only confound alveolar hypoventilation and derecruitment. These factors contribute to an increased risk of respiratory muscle fatigue and potential for respiratory failure in children with PARDS (Fig. 1).
Implementation of NPPV (both continuous and bilevel) can be a theoretically efficient treatment for reducing work of breathing, facilitating airway opening and improving oxygenation (8). NPPV provides a continuous level of positive expiratory pressure that maintains small airway patency, may increase end-expiratory lung volumes, and improve pulmonary compliance, thereby reducing the change in alveolar pressure needed to initiate inspiration. With bilevel support, the additional inspiratory pressure can help raise tidal volumes and support fatigued respiratory muscles (8). This ventilatory support can improve work of breathing, dyspnea, and gas exchange until the underlying disease process improves.
Since the positive pressure is delivered noninvasively, another potential benefit of NPPV is the ability to avoid the complications associated with endotracheal intubation and invasive ventilation. Invasive ventilation can provide similar benefits to a patient’s pulmonary mechanics but can also be associated with significant adverse events compared with noninvasive ventilation, such as nosocomial pneumonia and an increased mortality rate in ICUs in one study (9). In addition, the procedure of endotracheal intubation, although potentially life-saving, is also inherently risky and can be associated with significant adverse events, including complication such as postextubation upper airway obstruction. Finally, since NPPV uses a noninvasive interface and requires less patient sedation, this therapy preserves spontaneous breathing and upper airway function, thereby allowing a patient to spontaneously provide their own airway clearance.
- The pathophysiology of the clinical conditions leading to hypoxemic respiratory failure in children provides a solid physiologic rationale for the use of NPPV in this population.
- NPPV can improve alveolar recruitment and ventilation and decrease work of breathing and respiratory muscle fatigue.
- NPPV has the potential for reducing intubation and thus avoiding associated comorbidities.
Indications for NPPV in Patients With PARDS
7.1.1 We recommend that NPPV be considered early in disease in children at risk for PARDS to improve gas exchange, decrease work of breathing, and potentially avoid complications of invasive ventilation. Weak agreement (88% agreement)
7.1.2 We recommend that selected populations of children, such as children with immunodeficiency who are at greater risk of complications from invasive mechanical ventilation, may benefit more from earlier NPPV in order to avoid invasive mechanical ventilation. Weak agreement (80% agreement)
7.4.2 NPPV is not recommended for children with severe disease. Strong agreement
There are relatively little data supporting the use of NPPV for the treatment of PARDS. Significant controversy exists concerning the indications and appropriate use of this therapy. In adults, randomized controlled trials have had conflicting results. In a large multicenter prospective study of adults with acute hypoxemic respiratory failure from a variety of etiologies by Antonelli et al (10), ARDS was independently associated with an increased risk of NPPV failure and need for intubation. However, in a recent multicenter randomized controlled trial in only those with ARDS, NPPV was associated with significant improvement in respiratory rate and oxygenation compared with standard oxygen therapy. In addition, the use of NPPV was also associated with significantly reduced frequency of intubation (11). This study has reopened the possibility of increased use of NPPV for the treatment of ARDS in adults.
In the pediatric population, there are several prospective and retrospective cohort studies that describe the use of NPPV for acute respiratory failure but most include a heterogeneous population that includes mild-to-severe ARDS (Table 1) (12–22). There has only been one randomized study in children by Yañez et al (23). In this study of 50 children with acute hypoxemia respiratory failure, NPPV was compared with standard care. The authors found that the frequency of intubation was significantly lower in the group that received NPPV (28% vs 60%; p = 0.045). Heart rate and respiratory rate also improved significantly in the NPPV group compared with controls. The authors concluded that the use of NPPV in children with acute hypoxemic respiratory failure can improve oxygenation, decrease respiratory effort, and potentially avoid the need for intubation in select children, particularly if used early in the disease process (23).
Children with more severe PARDS, however, are significantly more likely to require intubation despite the use of NPPV. When reviewing studies of NPPV in children (Table 1), the median frequency of NPPV failure in those children with more mild PARDS was 21% (25–75%; interquartile range, 17–28%). However, in studies that included children with more severe hypoxemia and PARDS, a median of 57% progressed to intubation despite NPPV. There is no specific oxygenation threshold beyond which NPPV is contraindicated, but it is reasonable to conclude that children with severe hypoxemia and more severe PARDS on NPPV have a higher risk of progression to intubation.
- There are relatively little published data to support the routine use of NPPV for the treatment of PARDS.
- In select populations, such as children with mild PARDS, the addition of NPPV to standard medical therapy may prevent intubation and mechanical ventilation.
- The high level of NPPV failure in moderate and severe PARDS suggests that NPPV is not indicated in those populations.
The Use of NPPV in Immunocompromised Patients
Invasive ventilation is associated with a high risk of ventilator-associated pneumonia and mortality in immunocompromised patients. The use of noninvasive respiratory support is particularly appealing in this population because it avoids the complications of an invasive airway and potentially improves outcomes by preventing intubation. In adults, the usefulness of NPPV has been described in several studies of immunocompromised patients (24, 25). In children, there are no randomized trials, but several descriptive studies have been published that support the early use of NPPV in immunocompromised children with PARDS (26–28). Essouri et al (21) published a large descriptive cohort study of 114 children with hypoxemic respiratory failure, which included a subset of 12 immunocompromised children. All but one of these 12 were successfully managed with NPPV and avoided intubation. Piastra et al (28) conducted a prospective study of the use of NPPV for PARDS in 23 immunocompromised children; 13 of these 23 were successfully managed with NPPV and did not require intubation. And in a cohort of children with liver transplantations, Murase et al (26) reported that the use of NPPV for PARDS was associated with decreased frequency of intubation compared to those treated with oxygen alone (6.4% vs 23.4%). With the known risks of intubation in this population, these studies support the use of NPPV in the early treatment for PARDS in immunocompromised children.
- Immunocompromised patients have a very high risk of mortality when intubated with PARDS. Although data do not exist to confirm that the intubation itself increases this mortality risk, there is a physiologic basis that the risks of acquired infection may be higher with invasive versus noninvasive ventilation.
- Uncontrolled descriptive pediatric studies suggest that the early use of NPPV is beneficial in immunocompromised children with PARDS.
- Adult randomized studies have shown that NPPV is superior to medical therapy alone and that NPPV is associated with a reduction of ICU mortality.
- NPPV should be considered a first-line therapy in immunocompromised children with PARDS.
Hospital Location to Deliver NPPV
7.2.1 We recommend that, although noninvasive, NPPV should be delivered in a setting with trained experienced staff and where close monitoring is available to rapidly identify and treat deterioration. Strong agreement
Children with PARDS can deteriorate very quickly despite support with NPPV. Close monitoring and frequent reassessment are required to rapidly identify success or failure of NPPV and not to delay intubation if needed. Thus, when using NPPV for the treatment of PARDS, it should be initiated only in carefully monitored locations, such as an ICU (12, 29). There is a significant risk of progression of respiratory failure, even in children with milder disease. Clinicians need to be prepared to provide more invasive airway support, and therefore, patients should be in a setting where rapid intubation can be performed.
NPPV is a mode of ventilatory support that requires staff training and experience. Unit-specific factors should be assessed when choosing the location of initiation of NPPV therapy. In addition to availability of resources such as number of personnel, equipment, and monitoring capacity, the experience level and training of the staff need to be considered. An experienced staff, comfortable with the equipment and the process, will have greater success in the use of NPPV than a nonexperienced team.
In adult populations, some randomized controlled trials support the early use of NPPV in the emergency department (31–33). This strategy of early intervention may be beneficial in children as well as long as staff training and availability of resources are sufficient.
- NPPV should only be performed for children with PARDS in an acute care setting with continuous monitoring and where invasive ventilation is also available.
- An experienced staff, comfortable with the equipment and the process, will have greater success in the use of NPPV than a nonexperienced team.
7.3.2 We recommend the use of an oronasal or full facial mask to provide the most efficient patient-ventilator synchronization for children with PARDS. Weak agreement (84% agreement)
7.3.3 We recommend that children using NPPV should be closely monitored for potential problems, such as skin breakdown, gastric distention, barotrauma, and conjunctivitis. Strong agreement
7.3.4 Heated humidification is strongly recommended for NPPV in children. Strong agreement
The choice of patient-ventilator interface is crucial for success of NPPV, but choosing an appropriate size and type of mask can be challenging in the pediatric population (34, 35). A properly fitted mask must seal securely, not leak with inspiration and not cover the child’s eyes. Finding a mask that fits can be more difficult in children, as they have wider variations in the size and shape their facial structure compared with adults. Therefore, in a specific child, finding a properly fitting mask can often be challenging.
In addition to assessing fit, the provider must also choose the appropriate type of interface. NPPV is most commonly delivered using facial masks, oronasal masks, nasal masks, and helmet interfaces. Compared with oronasal masks, nasal masks may be better tolerated in some children due to fears about covering both the mouth and nose in some children. However, since children will frequently breathe through their mouth to bypass nasal resistance, these nasal interfaces are associated with significant air leaks and patient-ventilator asynchrony (36, 37). Oronasal masks and facial masks will provide superior levels of support and synchrony. The helmet interface has been used in patients unable to tolerate oronasal or nasal masks (38, 39). However, although theoretically this interface is appealing, studies in adults have found this interface to be less efficient at unloading respiratory muscles and to be associated with higher asynchrony (13, 34, 38).
Dryness of the airway epithelium will release inflammatory mediators and increase local edema. This, in turn, leads to increased airway resistance in children due to their small upper airways. Humidification and heating of the inspiratory air will help to prevent these complications. Inadequate airway gas conditioning has been associated with anatomical and functional deterioration of nasal mucosa, increased work of breathing, and decreased compliance with NPPV (40). The preferred method of providing this condition is heated humidification rather than heat and moisture exchangers. In two studies that compared the physiologic effects of heated humidifiers versus heat and moisture exchangers, heat and moisture exchangers were found to be associated with higher dead space and significantly increased work of breathing to maintain the same level of alveolar ventilation (41, 42).
Children using NPPV should be closely monitored for potential complications associated with this therapy. Frequent assessment of a child’s skin is important since abrasions and ulcerations can develop from the mask and the pressure required securing the mask to the child’s face. The use of protective barriers prophylactically may diminish or prevent this from occurring. Irritation to the eyes and conjunctivitis can also occur due to air leaks around the mask. This can be a source of significant discomfort for a patient. Minimizing these leaks reduces this complication and may improve compliance with NPPV. Gastric distention can occur with NPPV and puts the child at risk for vomiting and potential aspiration. In children, this risk is more significant than in adults since an immature gastroesophageal sphincter makes children more likely to vomit. Oronasal mask interfaces may increase the likelihood of gastric distention and vomiting, and thus, they deserve close monitoring.
- The efficacy of NPPV is associated with a good patient-ventilator interface. Appropriate fitting masks will improve tolerance of NPPV therapy.
- Facial or oronasal masks provide superior support over nasal and helmet interfaces in children with PARDS due to reduced airleaks and increased patient-ventilator synchrony.
- Humidification with a heated humidifier is strongly recommended for NPPV in children.
- Children using NPPV should be closely monitored for potential problems, such as skin breakdown, conjunctivitis, and gastric distention.
Mode of Ventilation to Use in PARDS
7.3.6 To reduce inspiratory muscle effort and improve oxygenation, we recommend noninvasive pressure support ventilation combined with positive end-expiratory pressure in patients with PARDS. Continuous positive airway pressure alone may be suitable for those children who are unable to attain patient-ventilator synchrony or when using nasal interface. Weak agreement (92% agreement)
Physiologic and clinical experience suggests that the use of bilevel positive airway pressure is superior to continuous positive airway pressure (6, 7). Continuous airway pressure alone will improve oxygenation and alveolar recruitment. However, bilevel positive airway pressure provides additional support during inspiration, which improves both oxygenation and ventilation and by unloading respiratory muscles reduces the potentially significant increased work of breathing in children.
Although there are no randomized trials comparing continuous positive airway pressure with bilevel positive airway pressure in children with PARDS, there are studies in adults and children that support the benefit of adding an inspiratory pressure. L’Her et al (7) found that both continuous positive airway pressure and bilevel pressure improved gas exchange and dyspnea; however, there was a greater reduction of esophageal and diaphragmatic pressure time products in those who received inspiratory and expiratory support. Although not specifically designed to compare these modes, trials of adults and children with ARDS by Yañez et al (23) and Zhan et al (11) both found that bilevel support was superior to continuous positive pressure. These data together support the superiority of the combined use of inspiratory and expiratory pressure in children with PARDS.
Neurally adjusted ventilatory assist (NAVA) is a mode of ventilation that uses diaphragmatic signals to attempt to improve patient synchrony. In adults, NAVA is associated with significantly decreased asynchrony compared with simple bilevel support (43). However, children have a greater prevalence of air leaks compared with adults, which adversely affect patient-ventilator interaction with this mode. In addition, clinical studies of NAVA for PARDS in children are lacking.
- In PARDS, bilevel ventilation that provides an increased level of support during inspiration will provide a superior level of support than continuous positive pressure alone.
Identification of NPPV Failure and Timing of NPPV
7.3.1 We recommend that intubation should be considered in patients receiving NPPV who do not show clinical improvement or have signs and symptoms of worsening disease, including increased respiratory rate, increased work of breathing, worsening gas exchange, or an altered level of consciousness. Strong agreement
7.3.5 We recommend that to allow the most efficient patient-ventilator synchronization and tolerance, sedation should be used only with caution in children receiving NPPV for PARDS. Weak agreement (88% agreement)
The severity of the underlying disease is the key determinant of NPPV success or failure. In a study by Piastra et al (29) of 61 children with PARDS who received NPPV, the number of organs in failure and elevated severity of illness score at admission were associated with the need for intubation despite NPPV. Bernet et al (12) also found that a lower oxygen requirement was associated with success. Muñoz-Bonet et al (19) found that children who had improved heart rates and PaCO2 within 4 hours of initiation of NPPV were more likely to have success with NPPV.
Early initiation of NPPV may influence the course of PARDS in some patients by reversing the evolution of the pathology (11). In adults, there is evidence that use of NPPV early in the hospital course can improve outcomes and reduce intubation (31, 33). However, the need for intubation remains quite high compared with other etiologies of acute respiratory failure, and close monitoring for progression of disease is required. Although no specific sign or symptom is predictive, factors that indicate worsening disease despite NPPV include an increased respiratory rate, increased oxygen requirement, a decreased PaO2/FIO2 ratio, an increased of PaCO2, or an altered level of consciousness (10, 15, 18).
NPPV can also be used following extubation in children to prevent recurrence of respiratory failure requiring invasive mechanical ventilation. Several authors have described the use of NPPV as a bridge to extubation in certain populations, including children with ARDS (16, 17). However, clinicians need to monitor these children carefully due to their high risk of developing the need for reintubation.
Sedation may be helpful in improving the tolerance to NPPV in some children. Noncooperative children can dislodge a carefully placed mask, increasing air leaking and reducing the level of support provided. However, sedation should be used cautiously in children receiving NPPV for PARDS, since sedatives can also depress the respiratory drive and level of consciousness of the child, potentially contributing to the need for invasive ventilation.
- Severe hypoxemia in PARDS is an identified factor of NPPV failure; thus, children with severe gas exchange alterations within the first hours of NPPV are likely to require intubation.
- Factors that indicate worsening disease despite NPPV include an increased respiratory rate, increased oxygen requirement, a decreased PaO2/FIO2 ratio, an increased PaCO2, or an altered level of consciousness.
- Sedation should be used with caution in children receiving NPPV for PARDS. Although sedation can sometimes facilitate tolerance of NPPV therapy, sedation medications can also depress the respiratory drive and level of consciousness of the child, thus contributing to the need for invasive ventilation.
The Role of High-Flow Nasal Cannula
7.4.1 We recommend that further studies are needed to identify clinical indications for high-flow nasal cannula (HFNC) in patients at risk of PARDS. HFNC has not been demonstrated to be equivalent to NPPV. Strong agreement
The use of HFNC has exploded in popularity due to ease of application and perceived improved patient tolerance. However, there are few studies examining the use of this therapy in children, and the pathophysiologic mechanism is unknown (44–47). Additionally, the efficacy of HFNC compared with NPPV is also unknown.
Through the use of heated and humidified gas, HFNC provides support that may meet or exceed a child’s spontaneous inspiratory flow rate. Standard nasal cannula generally delivers support below the child’s spontaneous inspiratory requirement. In neonates, flows more than 1 L/min are generally considered high flow, whereas in infants or children, flows more than 6 L/min are considered high flow (46).
There are several theorized pathophysiologic mechanisms that have been proposed to explain the beneficial effects of HFNC. One is that HFNC provides improved oxygenation and reduced dead space by “washing out” of nasopharyngeal CO2, thereby increasing effective ventilation. Another is that HFNC generates a modest degree of positive pressure, thereby reducing upper airways resistance and reducing work of breathing. Unfortunately, the level of positive pressure generated by currently available HFNC systems is unknown, but it is thought to be less than that provided by NPPV (45).
- HFNC is a promising therapy for treatment of respiratory disease, including PARDS, in children. However, at this time, the efficacy of HFNC compared with NPPV is unknown.
The use of NPPV can be beneficial in children with PARDS. Despite the paucity of randomized controlled studies in this population, physiologic rationales and data from cohort studies support the use of NPPV for PARDS in children to improve gas exchange and potentially avoid intubation. In particular, children with milder disease and children at greater risk for complications from invasive intubation may be more likely to benefit from this therapy. The choice of interface, environment, and trained providers are crucial for the success of NPPV. Additionally, children receiving NPPV for PARDS deserve close monitoring for progression of their disease and need for intubation.
1. Santschi M, Jouvet P, Leclerc F, et al.PALIVE Investigators; Pediatric Acute Lung Injury
and Sepsis Investigators Network (PALISI); European Society of Pediatric and Neonatal Intensive Care (ESPNIC). Acute lung injury
in children: Therapeutic practice and feasibility of international clinical trials. Pediatr Crit Care Med. 2010;11:681–689
2. Ranieri VM, Rubenfeld GD, Thompson BT, et al. Acute respiratory distress syndrome
: The Berlin Definition. JAMA. 2012;307:2526–2533
3. Fernandez A, Monteverde E, Farias J:. Changes in the practice of mechanical ventilation that took place in cohorts between 1999 and 2008 in PICUs: A multicenter study. Pediatr Crit Care. 2012;13:620
4. Fanning JJ, Lee KJ, Bragg DS, et al. U.S. attitudes and perceived practice for noninvasive ventilation
in pediatric acute respiratory failure. Pediatr Crit Care Med. 2011;12:e187–e194
5. Shah PS, Ohlsson A, Shah JP. Continuous negative extrathoracic pressure or continuous positive airway pressure for acute hypoxemic respiratory failure in children. Cochrane Database Syst Rev. 2005;3:CD003699
6. Essouri S, Durand P, Chevret L, et al. Physiological effects of noninvasive positive ventilation during acute moderate hypercapnic respiratory insufficiency in children. Intensive Care Med. 2008;34:2248–2255
7. L’Her E, Deye N, Lellouche F, et al. Physiologic effects of noninvasive ventilation
during acute lung injury
. Am J Respir Crit Care Med. 2005;172:1112–1118
8. . Organized jointly by the American Thoracic Society, the European Respiratory Society, the European Society of Intensive Care Medicine, and the Société de Réanimation de Langue Française, and approved by ATS Board of Directors, December 2000: International Consensus Conferences in Intensive Care Medicine: Noninvasive positive pressure ventilation in acute respiratory failure. Am J Respir Crit Care Med. 2001;163:283–291
9. Girou E, Schortgen F, Delclaux C, et al. Association of noninvasive ventilation
with nosocomial infections and survival in critically ill patients. JAMA. 2000;284:2361–2367
10. Antonelli M, Conti G, Moro ML, et al. Predictors of failure of noninvasive positive pressure ventilation in patients with acute hypoxemic respiratory failure: A multi-center study. Intensive Care Med. 2001;27:1718–1728
11. Zhan Q, Sun B, Liang L, et al. Early use of noninvasive positive pressure ventilation for acute lung injury
: A multicenter randomized controlled trial. Crit Care Med. 2012;40:455–460
12. 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;6:660–664
13. Chidini G, Calderini E, Cesana BM, et al. Noninvasive continuous positive airway pressure in acute respiratory failure: Helmet versus facial mask. Pediatrics
14. Dohna-Schwake C, Stehling F, Tschiedel E, et al. Non-invasive ventilation on a pediatric intensive care unit: Feasibility, efficacy, and predictors of success. Pediatr Pulmonol. 2011;46:1114–1120
15. Essouri S, Nicot F, Clément A, et al. Noninvasive positive pressure ventilation in infants with upper airway obstruction: Comparison of continuous and bilevel positive pressure. Intensive Care Med. 2005;31:574–580
16. Fortenberry JD, Del Toro J, Jefferson LS, et al. Management of pediatric acute hypoxemic respiratory insufficiency with bilevel positive pressure (BiPAP) nasal mask ventilation. Chest. 1995;108:1059–1064
17. Joshi G, Tobias JD. A five-year experience with the use of BiPAP in a pediatric intensive care unit population. J Intensive Care Med. 2007;22:38–43
18. 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;35:527–536
19. Muñoz-Bonet JI, Flor-Macián EM, Brines J, et al. Predictive factors for the outcome of noninvasive ventilation
in pediatric acute respiratory failure. Pediatr Crit Care Med. 2010;11:675–680
20. Padman R, Lawless ST, Kettrick RG. Noninvasive ventilation
via bilevel positive airway pressure support in pediatric practice. Crit Care Med. 1998;26:169–173
21. Essouri S, Chevret L, Durand P, et al. Noninvasive positive pressure ventilation: Five years of experience in a pediatric intensive care unit. Pediatr Crit Care Med. 2006;7:329–334
22. Muñoz-Bonet JI, Flor-Macián EM, Roselló PM, et al. Noninvasive ventilation
in pediatric acute respiratory failure by means of a conventional volumetric ventilator. World J Pediatr. 2010;6:323–330
23. Yañez LJ, Yunge M, Emilfork M, et al. A prospective, randomized, controlled trial of noninvasive ventilation
in pediatric acute respiratory failure. Pediatr Crit Care Med. 2008;9:484–489
24. Antonelli M, Conti G, Bufi M, et al. Noninvasive ventilation
for treatment of acute respiratory failure in patients undergoing solid organ transplantation: A randomized trial. JAMA. 2000;283:235–241
25. Hilbert G, Gruson D, Vargas F, et al. Noninvasive ventilation
in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure. N Engl J Med. 2001;344:481–487
26. Murase K, Chihara Y, Takahashi K, et al. Use of noninvasive ventilation
for pediatric patients after liver transplantation: Decrease in the need for reintubation. Liver Transpl. 2012;18:1217–1225
27. Piastra M, Antonelli M, Chiaretti A, et al. Treatment of acute respiratory failure by helmet-delivered non-invasive pressure support ventilation in children with acute leukemia: A pilot study. Intensive Care Med. 2004;30:472–476
28. Piastra M, De Luca D, Pietrini D, et al. Noninvasive pressure-support ventilation in immunocompromised children with ARDS: A feasibility study. Intensive Care Med. 2009;35:1420–1427
29. Piastra M, De Luca D, Marzano L, et al. The number of failing organs predicts non-invasive ventilation failure in children with ALI/ARDS. Intensive Care Med. 2011;37:1510–1516
30. Ottonello G, Villa G, Moscatelli A, et al. Noninvasive ventilation
in a child affected by achondroplasia respiratory difficulty syndrome. Paediatr Anaesth. 2007;17:75–79
31. Kramer N, Meyer TJ, Meharg J, et al. Randomized, prospective trial of noninvasive positive pressure ventilation in acute respiratory failure. Am J Respir Crit Care Med. 1995;151:1799–1806
32. Poponick JM, Renston JP, Bennett RP, et al. Use of a ventilatory support system (BiPAP) for acute respiratory failure in the emergency department. Chest. 1999;116:166–171
33. Wysocki M, Tric L, Wolff MA, et al. Noninvasive pressure support ventilation in patients with acute respiratory failure. A randomized comparison with conventional therapy. Chest. 1995;107:761–768
34. Nava S, Navalesi P, Gregoretti C. Interfaces and humidification for noninvasive mechanical ventilation. Respir Care. 2009;54:71–84
35. Schönhofer B, Sortor-Leger S. Equipment needs for noninvasive mechanical ventilation. Eur Respir J. 2002;20:1029–1036
36. Meduri GU. Noninvasive positive-pressure ventilation in patients with acute respiratory failure. Clin Chest Med. 1996;17:513–553
37. Mehta S, Hill NS. Noninvasive ventilation
. Am J Respir Crit Care Med. 2001;163:540–577
38. Navalesi P, Costa R, Ceriana P, et al. Non-invasive ventilation in chronic obstructive pulmonary disease patients: Helmet versus facial mask. Intensive Care Med. 2007;33:74–81
39. Chidini G, Calderini E, Pelosi P. Treatment of acute hypoxemic respiratory failure with continuous positive airway pressure delivered by a new pediatric helmet in comparison with a standard full face mask: A prospective pilot study. Pediatr Crit Care Med. 2010;11:502–508
40. Williams R, Rankin N, Smith T, et al. Relationship between the humidity and temperature of inspired gas and the function of the airway mucosa. Crit Care Med. 1996;24:1920–1929
41. Jaber S, Chanques G, Matecki S, et al. Comparison of the effects of heat and moisture exchangers and heated humidifiers on ventilation and gas exchange during non-invasive ventilation. Intensive Care Med. 2002;28:1590–1594
42. Lellouche F, Maggiore SM, Deye N, et al. Effect of the humidification device on the work of breathing during noninvasive ventilation
. Intensive Care Med. 2002;28:1582–1589
43. Schmidt M, Dres M, Raux M, et al. Neurally adjusted ventilatory assist improves patient-ventilator interaction during postextubation prophylactic noninvasive ventilation
. Crit Care Med. 2012;40:1738–1744
44. 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:e343–e349
45. ten Brink F, Duke T, Evans J. High-flow nasal prong oxygen therapy or nasopharyngeal continuous positive airway pressure for children with moderate-to-severe respiratory distress? Pediatr Crit Care Med. 2013;14:e326–e331
46. Lee JH, Rehder KJ, Williford L, et al. Use of high flow nasal cannula in critically ill infants, children, and adults: A critical review of the literature. Intensive Care Med. 2013;39:247–257
47. Yoder BA, Stoddard RA, Li M, et al. Heated, humidified high-flow nasal cannula versus nasal CPAP for respiratory support in neonates. Pediatrics
Appendix 1. Pediatric Acute Lung Injury Consensus Conference Group
Organizing Committee: Philippe Jouvet, University of Montreal, Canada; Neal J. Thomas, Pennsylvania State University; Douglas F. Willson, Medical College of Virginia
Section 1, Definition, incidence, and epidemiology: Simon Erickson, Princess Margaret Hospital for Children, Australia; Robinder Khemani, University of Southern California; Lincoln Smith, University of Washington; Jerry Zimmerman, University of Washington
Section 2, Pathophysiology, comorbidities, and severity: Mary Dahmer, University of Michigan; Heidi Flori, Children’s Hospital & Research Center Oakland; Michael Quasney, University of Michigan; Anil Sapru, University of California San Francisco
Section 3, Ventilatory support: Ira M. Cheifetz, Duke University; Peter C. Rimensberger, University Hospital of Geneva, Switzerland
Section 4, Pulmonary-specific ancillary treatment: Martin Kneyber, University Medical Center Groningen, The Netherlands; Robert F. Tamburro, Pennsylvania State University
Section 5, Nonpulmonary treatment: Martha A. Q. Curley, University of Pennsylvania; Vinay Nadkarni, University of Pennsylvania; Stacey Valentine, Harvard University
Section 6, Monitoring: Guillaume Emeriaud, University of Montreal, Canada; Christopher Newth, University of Southern California
Section 7, Noninvasive support and ventilation: Christopher L. Carroll, University of Connecticut; Sandrine Essouri, Université Pierre et Marie Curie, France
Section 8, Extracorporeal support: Heidi Dalton, University of Arizona; Duncan Macrae, Royal Brompton Hospital, United Kingdom
Section 9, Morbidity and long-term outcomes: Yolanda Lopez, Cruces University Hospital, Spain; Michael Quasney, University of Michigan; Miriam Santschi, Université de Sherbrooke, Canada; R. Scott Watson, University of Pittsburgh
Literature Search Methodology: Melania Bembea, Johns Hopkins University