Noninvasive Ventilation
Executive Summary
- NIV is increasingly accepted as an alternative to endotracheal intubation (ETI) for the management of respiratory failure, both acute and chronic.
- Studies have shown that NIV is associated with lower rates of complications, such as infections and local injury, and shorter ICU stays and hospitalizations when compared to ETI.
- There is support in the literature for the use of NIV in asthma and bronchiolitis.
- Sepsis, abnormal RR for age, high IPAP, high EPAP, and high FiO2 at initiation of therapy were all characteristics of patients who failed NIV.
- Most authors recommend starting with lower pressures that are gradually increased to produce relief of symptoms. This is in contrast to starting with higher pressure settings with the goal of rapid symptom relief, then titrating the pressure down to the lowest tolerated level.
- Worsening respiratory distress, increasing RR, increasing HR, reduced breath sounds, hypoxemia, and deteriorating mental or hemodynamic status despite NIV are generally accepted reasons to abandon NIV and initiate ET intubation.
Noninvasive ventilation (NIV) is increasingly accepted as an alternative to endotracheal intubation (ETI) for the management of respiratory failure, both acute and chronic. While randomized controlled trials are generally lacking in the pediatric literature, progressively more research is addressing the implementation of NIV. Studies that focus on identifying predictors of NIV success or failure may help identify patients who will benefit from NIV.
— Ann M. Dietrich, MD, Editor
What Is Non-invasive Ventilation?
Definitions. NIV is a method of providing artificial respiratory support without placement of an endotracheal airway. In the literature, the terminology for NIV is broad and the terms noninvasive positive pressure ventilation (NPPV), noninvasive respiratory support (NRS), continuous positive airway pressure (CPAP), and bilevel positive airway pressure (BiPAP) are all common, despite the fact that their definitions may only overlap. In general, NIV refers to the application of both ventilatory and pressure support through the use of expiratory positive airway pressure (EPAP) and inspiratory positive airway pressure (IPAP). Oxygen and sometimes inhaled medications can also be delivered through the machine. Although it does not offer ventilatory support, CPAP is often mentioned and studied together with NIV, as they share patient interfaces, such as oronasal masks and nasal prongs, and are considered in similar clinical scenarios. BiPAP is the most accurate medical colloquialism for NIV; however, the term "BiPAP" itself is a trade name of a specific brand of portable ventilator and, therefore, should not be generalized to all forms of this modality.
NIV has been well studied in adult populations, particularly in the setting of acute respiratory failure (ARF) in patients with chronic obstructive pulmonary disease (COPD).1In pediatric populations, the literature on NIV is less abundant and what exists can be divided into two main categories: NIV application for acute respiratory failure and for chronic respiratory support. The latter has been better studied, especially in pediatric patients with neuromuscular disorders or upper airway abnormalities, and is gaining widespread acceptance as an in-home, chronic therapy.2,3This review, however, will focus on the application of NIV for pediatric patients in ARF.
Pathophysiology of Acute Respiratory Failure in Pediatrics
Compared to adults, newborns and infants have more compliant rib cages with relatively horizontal ribs, flatter diaphragms, and smaller diameter airways.9These physiologic principles are largely responsible for the differences between the presentation of an older child with a mild viral respiratory illness and an infant hospitalized for bronchiolitis. To facilitate passage through the birth canal, the rib cages of newborns contain relatively more cartilage. As they grow, the bones become progressively more ossified. In part due to the horizontal relationship of the ribs, infants are less efficient at the upward and outward movement of the chest wall and, therefore, expend more energy to overcome a relatively small amount of airway resistance.0Neonates are primarily nasal breathers, while infants are primarily mouth breathers.11Congestion of the upper airway in neonates can therefore lead to respiratory distress as the infant attempts to generate the inspiratory negative pressure needed to overcome resistance in their nasal airways. These factors together explain why they are more susceptible to acute respiratory distress and failure in the setting of mild viral illnesses.
Newborns and young infants exhibit a biphasic response in the setting of hypoxia. After 1-2 minutes of hyperventilation, immature brain centers develop hypoventilation when hypoxemia is sustained. Infants are therefore more likely to develop respiratory arrest in hypoxic states.10Bronchiolitis is a good condition to highlight how these physiologic differences change the clinical presentation in infants compared to adults and older children. In bronchiolitis, inflammation of the bronchioles causes a significant reduction in the radius of patent airway. As defined by Poiseuille’s law, resistance down a tube is inversely proportional to the radius taken to the fourth power. Therefore, as the airway radius decreases, the resistance down the airway increases. First, poor ventilation occurs, and then air trapping is seen. Because the rib cage is so compliant, the infant must contract the intercostal and accessory muscles vigorously to expand the rib cage and overcome small airway resistance. This can lead to "tiring out" of the infant and one common reason for transfer to a pediatric intensive care unit (ICU) for intubation.
Older children have more respiratory reserve. As children grow, they accumulate more alveoli, their diaphragms become more domed, and their rib cages ossify and become less compliant.9Children also become taller and have more total lung capacity. Alveoli also continue to develop after birth. A neonate possesses around 24 million alveoli. By 8 years of age, this number has increased to 300 million, and by adulthood there are between 300 and 500 million alveoli.9,12Asthma is the most common medical diagnosis for hospitalized children in the United States.13In the setting of status asthmaticus, respiratory failure stems from inflammatory mediated bronchoconstriction and airway collapse, leading to dynamic hyperinflation.14As airway narrowing worsens in the acute episode, the work of breathing against airway resistance greatly increases during both inspiration and expiration and can lead to fatigue. In asthma, the application of IPAP decreases work of breathing by unloading the inspiratory muscles. EPAP, on the other hand, works to open narrowed airways and ameliorate airway collapse during expiration.
ARF can be broadly separated into hypoxemic respiratory failure and hypercarbic respiratory failure.15Hypoxemic respiratory failure is the more common form and is characterized by an arterial oxygen tension (PaO2) lower than 60 mmHg with a low to normal arterial carbon dioxide tension (PaCO2). Examples of hypoxemic respiratory failure include etiologies that affect the parenchyma such as pneumonia, pulmonary edema, acute lung injury (ALI), and acute respiratory distress syndrome (ARDS), as well as airway obstruction such as bronchiolitis and status asthmaticus.16Hypercapnic respiratory failure, on the other hand, is characterized by a PaCO2 higher than 50 mmHg. Common etiologies include overdose, neuromuscular disease, chest wall abnormalities, and severe obstructive airway disease such as asthma and COPD. CPAP increases oxygenation and carbon dioxide (CO2) washout by recruiting atelectatic lung, reducing work of breathing, and preventing apnea by stenting upper airways and chest wall, which is especially important in former premature infants who may have components of bronchopulmonary dysplasia or laryngomalacia.16(See Table 1.) NPPV, on the other hand, allows for the benefits of CPAP with the additional benefit of better muscle unloading, alveolar recruitment, oxygenation, and CO2 washout, in addition to being able to augment the rate of ventilation.16
| Table 1.Mechanisms of Action |
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Why Implement Non-invasive Ventilation?
Benefits of Noninvasive Ventilation Compared to ET Intubation. NIV is increasingly considered as effective as and safer than ETI for managing ARF in pediatric populations. Studies have shown that NIV is associated with lower rates of complications, such as infections and local injury, and shorter ICU stays and hospitalizations when compared to ETI. This is important, as longer hospitalizations increase health care costs as well as opportunities for hospital-acquired infections and stress to families. Acute respiratory failure is the most common reason for admission to a pediatric ICU, accounting for about 20% of admissions.17Mechanical ventilation by ETI is required by 35% to 64% of pediatric ICU admissions.17,18Of those children who require intubation, many require only a short duration of treatment. In one study evaluating risk factors associated with prolonged intubation times, researchers found that less than 35% of pediatric patients requiring ventilation by ETI remained intubated for more than 12 hours, and less than 20% remained intubated for more than 24 hours.18Short-term ETI to bridge a period of ARF is therefore a common clinical situation seen in the pediatric ICU.
There are many well-known complications of ETI, including infection, vocal cord dysfunction, oropharyngeal injury, laryngeal injury, and the need for sedation.16,19Studies in adult populations have established that when compared to ETI, NIV is associated with shorter periods of ventilator assistance, shorter ICU stays, fewer infectious complications, and lower mortality both in the ICU setting and overall.17,20These studies in adults have especially looked at NIV used in the setting of acute exacerbations of COPD.21There is also evidence in adult populations that NIV can improve oxygenation and reduce the need for intubation in patients with hypoxemic ARF (such as ALI/ARDS) when instituted early.17
Literature on NIV for pediatric patients is less abundant, but increasingly in favor of NIV as an alternative to ETI for pediatric patients in ARF. What does exist is primarily from pediatric ICU literature and largely conducted in countries outside of the United States. One of the larger studies done in recent years was a prospective observational study that examined 278 children at a Malaysian university-based pediatric ICU being treated with NIV for a variety of conditions, including pneumonia, post-surgical respiratory support, upper airway obstruction, congestive heart failure, asthma, and bronchiolitis.21Of the 278 patients who received NIV in this study, 211 (75.9%) did not require any intubation. Additionally, pediatric ICU length of stay was reported to be statistically shorter for those who received NIV, especially the subgroup who never required intubation.
Many studies have examined disease-specific efficacy of NIV. Basnet et al showed in one randomized, controlled study that nine of 10 children admitted for treatment of status asthmaticus tolerated 24 hours of NIV without adverse effects and did not require any sedation.22Additionally, the NIV group had a more rapid and persistent improvement in clinical asthma score, less tachypnea, less tachycardia, lower supplemental oxygen requirement, and less need for adjunctive therapy.22Limitations of this study include small size. In a retrospective review of infants receiving mechanical ventilation for bronchiolitis, Lazner et al found that NIV was effective in 80% of infants receiving respiratory support for severe bronchiolitis.23Murase et al reported that at their institution, pediatric patients who received NIV following liver transplant had significantly lower rates of re-intubation and earlier discharge from the ICU.24They additionally found a benefit in decreasing atelectasis by applying NIV following extubation.
Complications of Noninvasive Ventilation
Poor patient interface, including improper fit and interface intolerance, is the root cause of the majority of NIV complications. Potential adverse effects include skin breakdown, inability to tolerate the interface, aspiration, and treatment failure leading to ETI. The location and types of local complications vary depending on the interface used. The most frequent complications reported in studies using oronasal masks are irritative dermatitis, mild erosion on the bridge of the nose, and irritative conjunctivitis.19,25Pressure sores are observed in 5.8% of children using the oronasal masks, and 7.2% develop a hospital-acquired pneumonia, although 75% of those who develop hospital-acquired pneumonia were previously intubated.21While in adult populations ineffective inspiratory efforts and double-triggering are the most common types of asynchrony leading to discomfort, in children auto-triggering is thought to be the primary cause of difficult patient-ventilator interaction.16Auto-triggering is defined as a cycle delivered by the ventilator in the absence of an inspiratory effort by the patient. Auto-triggering can be generated by cardiogenic oscillations (small variations in flow caused by heart beats) or leaks in the ventilator circuit, especially poor interface fit.
When to Use Noninvasive Ventilation
Selection of Candidates for Noninvasive Ventilation. While there are no consensus guidelines on selection criteria for NIV, many authors have suggested criteria for identifying patients who will benefit. Calderini et al suggest that NIV be initiated according to the presence of moderate to severe dyspnea, tachypnea, hypoxemia, and/or respiratory acidosis.16They also suggest that possible contraindications include life-threatening hypoxemia, upper airway obstruction, vomit, impaired cough, facial surgery, facial trauma, craniofacial abnormalities preventing a good mask interface, Glasgow Coma Scale (GCS) less than 10, hemodynamic instability, or congenital cyanotic heart disease that has not been corrected. NIV should also be avoided in severe ARF in the presence of clinical exhaustion, as these patients have a higher probability of failing NIV.16Institutional resources also factor greatly into the ability to initiate NIV, especially in the emergency department. (See Table 2.)
| Table 2.Contraindications to NIV |
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As NIV is becoming a more widely accepted and applied modality of treating ARF, research is lacking on how individual patients will respond to therapy. NIV failure is generally considered to be the cessation of therapy due to major complications, poor tolerance, and/or inability to stabilize the progression of respiratory failure requiring tracheal intubation.25One major concern in the literature is that implementation of NIV may delay definitive treatment. Payen et al conducted a retrospective cohort study to identify risk factors associated with longer durations of mechanical ventilation in pediatric ICU patients.18Among the possible risk factors evaluated, they found NIV failure was associated with a high risk of prolonged mechanical ventilation. While Payen et al did not demonstrate a causative relationship, their group does highlight that a better understanding of risk factors for NIV failure could be immensely useful in preventing a delay to ETI in those patients who will eventually require it. Sepsis, abnormal RR for age, high IPAP, high EPAP, and high FiO2 at initiation of therapy were all characteristics of non-responders to NIV in another study.21
Identifying patients who will respond favorably to NIV is equally contentious in the literature. Evans et al identified oxygen requirement in the emergency department as the strongest single predictor of nasal prong CPAP requirement at their institution.26They also identified several other factors, including younger age at presentation, lower oxygen saturation, lower GCS, and younger gestational age. Muñoz-Bonet et al found young age and more severe underlying condition to be risk factors at their institution.25Cavari et al, in a retrospective study of NIV at their institution, separated patients with bronchiolitis and respiratory failure into "responders" (64%) and "non-responders" (36%) to NIV via nasal prong CPAP.27Their group failed to detect any physiologic or clinical markers to predict an individual patient’s response to NIV, including demographics or disease severity.27Their group recommends that any infant in impending respiratory failure without other organ failure be given a trial with NIV. When evaluating NIV failures in their pediatric ICU, Lum et al also found no significant difference in demographics, sedation use, onset of NIV post-operatively, or prior ET intubation requirement.21
Many predictive factors have been suggested, including Pediatric Risk of Mortality III (PRISM III) score. PRISM III is a tool designed to assess risk factors contributing to mortality in pediatric ICUs.28Lum et al found that patients with higher PRISM II scores (a predecessor to PRISM III) were less likely to avoid intubation despite NIV therapy.21Additionally, using a multivariate analysis, they showed that a higher PRISM II score, sepsis, and a higher fraction of inspired oxygen (FiO2) requirement at initiation of NIV were independent predictors of NIV failure. The two main causes of NIV failure in their study were worsening respiratory failure and septic shock. Muñoz-Bonet also found a higher PRISM III score, as well as requiring more hemodynamic support, were predictors of failure.19
When selecting patients for NIV, pediatric-specific risk factors should be taken into consideration in addition to those associated with NIV in adult populations. Patients with developmental or behavioral disorders, such as autism spectrum disorders or other developmental delays, may react poorly to the NIV interface, especially in conjunction with being in a new environment and acutely ill. This group may require significant sedation and ultimately may progress to ETI due to mask intolerance. Young children have a tendency to increase mouth breathing in the setting of nasal obstruction. This may induce air leaks and auto-triggering around nasal mask devices. Certain patient populations, such as those with cerebral palsy and former premature infants, may have intrinsic immaturity of their airway protective reflexes and be at high risk of aspiration with NIV. Lastly, gastroesophageal reflux is a physiologically normal process for infants from around 2 months to approximately 1 year of age.29Although rarely seen with the pressures used in NIV, barotrauma and air swallowing could theoretically worsen their gastroesophageal sphincter function and, thereby, their reflux.30
Some of the highest NIV failure rates are for patients with severe hypoxemic respiratory failure, especially ARDS. Muñoz-Bonet et al in a prospective non-controlled study searching for predictive factors of NIV failure found failure rates reach as high as 75% for pediatric patients with ARDS.25In their study, FiO2 greater than 0.57 was associated with nearly 80% of NIV failures. Other studies have subsequently used this number as a cut off for intubation.11Muñoz-Bonet et al also commented on an association between failure and worsening radiographic imaging between 24 hours and 48-72 hours after initiation of therapy. Mean arterial pressure (MAP) greater than 11.5 cm H2O also showed some predictive value, and was associated with nearly 90% of failures in their study. Patients in severe respiratory distress with high or rapidly increasing oxygen requirements may therefore be poor candidates for initiation of NIV.
Immunocompromised patients, such as those with immunodeficiency disorders, oncology patients, or those on immunosuppressive therapy, require special consideration. As a population, they are especially susceptible to ventilator-related infections and do poorly with mechanical ventilation. In adult populations, current evidence supports using NIV as a first-line approach for managing mild to moderate ARF in patients immunocompromised with cancer or HIV.20Bello et al reported that the risk of airway management complicated by infection with NIV to be less than that of ETI.20
A final consideration is provider familiarity and comfort with the modality. In a cross-sectional study evaluating the attitudes of pediatric critical care attending physicians concerning NIV, Fanning et al found that factors such as severe defects in oxygenation and ventilation, disease progression, and patient intolerability decrease the likelihood of a provider deciding to initiate NIV.17Age was not a factor in decision making. Providers were more comfortable initiating NIV for lower airway diseases, such as bronchiolitis or pneumonia, than with upper airway obstructions such as croup, with 27% of providers answering that they would avoid using NIV. The authors speculate that this stems from a provider belief that fighting the NIV interface reduces laminar flow in the upper airways and worsens respiratory distress. Overall, their qualitative study showed that the decision to initiate NIV has much to do with provider gestalt on the severity of respiratory distress and comfort with the modality.
Monitoring Response to NIV
Several groups have commented on objective measurements, such as vital signs or arterial blood gas findings, following implementation of NIV that may be useful in predicting a favorable response to therapy. Decrease in respiratory rate (RR) to age-appropriate limits and lack of need for increasing amount of sedation could be used to predict NIV success.27(See Table 3.) An increasing need for sedation may be a sign of asynchrony with the ventilator or discomfort with the interface and may serve as a marker of impending NIV failure. Lum et al measured RR, heart rate (HR), and FiO2 at the start of therapy, then six hours and 24 hours following implementation.21They found that both RR and FiO2 were significantly different at all three time points, while HR did not change significantly until the six-hour mark. All three metrics exhibited a downtrend toward age-adjusted norms in patients who tolerated therapy well. Bernet et al did not find improvement in blood gas to predict failure of NIV.31
| Table 3.Signs of Favorable Response to NIV (within 1-2 hours of application) |
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— Improved pH — Improved PaO2/FiO2 — Reduction in PaCO2
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How to Use Noninvasive Ventilation
Interfaces. Interfaces for delivering NIV to the pediatric patient come in a wide variety of shapes and sizes. The choice of a particular interface will depend on patient age, clinical presentation, presence of craniofacial abnormalities, and, most importantly for pediatric patients, tolerance of the device. Dead space is also a consideration, and many of the devices that are the best tolerated, such as a soft plastic helmet, may not be the ideal choice in the setting of hypercarbic respiratory failure. Proper fit is important for minimizing air leaks and thereby lowering the frequency of auto-triggering and improving patient comfort. There is little comparative data for different kinds of NIV interfaces.
Oronasal Mask. The most common interface is an oronasal mask that covers both the nose and the mouth. Properly fitted, it should extend from the bridge of the nose to just below the lower lip. While the oronasal mask allows for a tight fit and limits dead space, claustrophobia is commonly encountered. Pediatric populations often tolerate this modality poorly for this reason. When dealing with long-term therapy, the oronasal mask can cause breakdown of the skin around the nose as well as an irritative conjunctivitis. Many authors suggest having multiple sizes and models of masks available and to change masks from time to time to avoid local complications such as skin breakdown.19Infants are primarily mouth breathers, and for these patients a mask that covers the mouth is usually the best choice.
Nasal Cannula. Positive pressure delivery through nasal prongs is beneficial when little respiratory support is needed. They are generally easy to use and keep in place, but highly flow-resistive and problematic if nasal obstruction is part of the underlying ARF process, such as in bronchiolitis.
Nasal Mask. Nasal masks possess the advantage of being less anxiety-inducing for smaller children. A nasal mask should rest between the bridge of the nose to just above the upper lip. Nasal masks are generally easy to use and keep in place, but are associated with air leaks caused by mouth opening. Chin straps designed to keep the mouth closed have been made to address this issue. In general, the smaller the nasal mask, the better the fit and the less dead space.
Full Face Masks. Full face masks are infrequently used. They cover the entire face, including the eyes, and are made of a clear plastic. While they limit oral leaks and can reduce claustrophobia, they carry a relatively large amount of dead space compared to other interfaces, and patients may have difficulty eliminating CO2. Craniofacial abnormalities may be of less concern with this interface.
Helmet. Transparent, soft plastic helmets are gaining more attention as a possible alternative to masks, especially in younger infants. Chidini et al found that CPAP delivered by a helmet was associated with a lower number of trial failures, less patient intolerance, longer tolerated application time, and reduced need for sedation in infants with ARF when compared with a mask.11In general, helmets tend to be well tolerated and associated with little air leakage and a lower risk of pressure sores. They also allow for speaking and coughing, which are of immense psychological and therapeutic value.16Craniofacial abnormalities become less of an issue with the helmets, as the interface is fit at the level of the shoulders and does not take into account the contours of the face. The main downsides to helmet-mediated NIV include CO2 rebreathing, although this can be overcome by using a high-flow helmet system.11,16Ventilator settings are different with this interface, especially IPAP, to account for the compliance of the helmet itself. It is also better suited for application of CPAP alone and less well adapted to ventilation.
Initiating Noninvasive Ventilation
As a general rule, NIV settings are adequate when the work of breathing and respiratory rate have improved. Early initiation is especially important in patients with hypoxemic ARF, as discussed above.17,19When initiating NIV, it is important to consider interface fit and, if possible, have options at hand for interface types and sizes. Mild sedation may improve patient-ventilator synchrony, especially in infants.27As discussed above, good patient-ventilator synchrony is a positive predictor of NIV success.27Most authors recommend starting with lower pressures that are gradually increased to produce relief of symptoms. This is in contrast to starting with higher-pressure settings with the goal of rapid symptom relief, then titrating the pressure down to the lowest tolerated level. In this low-to-high approach, EPAP can be started at 5-8 cm H2O and titrated to a maximum of 8-12 cm H2O. IPAP can be started at 6-8 cm H2O and titrated to a maximum of 20 cm H2O. FiO2 can be started at 0.4 and titrated up to 0.6 as needed.21IPAP should be adjusted and increased until optimal chest rise is seen and chest retractions are minimized. Once the patient is breathing comfortably, the IPAP can then be reduced in small increments (roughly 2 cm H2O) until the normal range is met. Worsening respiratory distress, increasing RR, increasing HR, reduced breath sounds, hypoxemia, and deteriorating mental or hemodynamic status despite NIV are generally accepted reasons to abandon NIV and initiate ET intubation.
Nasal CPAP pressures 4-8 cm H2O are generally safe.16Aerophagia and gastric distension are a concern with NIV, especially as the regurgitation of gastric contents can lead to aspiration. The risk of gastric distension increases with higher pressures. The need for gastric decompression is unlikely under 25 cm H2O and, therefore, placement of a nasogastric tube for decompression is unnecessary in most cases.19
Summary
NIV is increasingly considered as effective as and safer than ETI for managing ARF in pediatric populations.
References
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- Lazner MR, Basu AP, Klonin H. Non-invasive ventilation for severe bronchiolitis: Analysis and evidence. Pediatric Pulmonology 2012;47(9):909-916.
- 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 Transplantation 2012;18(10):
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