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					Noninvasive Mechanical Ventilation
Rani Ganesan, MD, ⁎ Kim D. Watts, MD,y Steven Lestrud, MD ⁎z

                    Patients with respiratory distress and respiratory failure presenting to the emergency
                    department provide a diagnostic and therapeutic challenge. Developing technologies in
                    noninvasive positive pressure ventilation (NIPPV) have improved the ability to administer
                    significant respiratory support to these patients. Research and protocols for NIPPV are
                    expanding in adult medicine but are only slowly increasing in pediatrics. NIPPV has
                    successfully been used for obstructive sleep apnea, asthma, cystic fibrosis, and
                    neuromuscular disorders in both acute and chronic settings. Early administration of this
                    support may benefit patients presenting to emergency departments by improving
                    oxygenation, ventilation, and muscle fatigue; avoiding short- and long-term complications
                    of invasive mechanical ventilation; and improving patient outcomes.
                    Clin Ped Emerg Med 8:139-144 C 2007 Published by Elsevier Inc.

                    KEYWORDS mechanical ventilation, continuous positive airway pressure, obstructive sleep
                    apnea, bimodal positive airway pressure




R    espiratory distress and respiratory failure are common
     life-threatening conditions presenting to the pediatric
emergency department (ED) requiring prompt recognition
                                                                       intubation and ventilation while maintaining the physio-
                                                                       logic advantages of spontaneous respirations. We suggest
                                                                       NIPPV should be considered early in the course of
of symptoms and concurrent management. As diagnostic                   management of respiratory distress and even in some
testing is initiated, different modes of support are used to           forms of respiratory failure.
relieve symptoms. Modes of respiratory support range
from blow-by oxygen to mechanical ventilation via
endotracheal intubation. Symptoms of mild respiratory                  History of Modalities
insufficiency often respond to supplemental oxygen via                 During the 1930s, Poulton [1] reported the first usage of
nasal cannula or simple face mask. More severe disease                 continuous positive airway pressure (CPAP) in patients
may require positive pressure ventilation administered                 with pulmonary edema, asthma, and pneumonia [2]. The
through noninvasive modalities or endotracheal intuba-                 investigators used a household vacuum, which provided a
tion. Noninvasive positive pressure ventilation (NIPPV)                high inspiratory flow through an airtight mask. An Ambu
has been used in chronic and acute conditions in all age               valve close to the patient was used as an expiratory
groups. It provides respiratory support without the                    pressure-relief valve [1,2]. Because of the use of intubation
complications commonly associated with endotracheal                    during anesthesia in the 1930s, the use of CPAP was not
                                                                       common. However, in the 1960s, CPAP was found to be
                                                                       successful in the treatment of pediatric patients with
                                                                       postcardiac and neonatal hyaline membrane disease [2-4].
⁎Critical Care Medicine, Children's Memorial Hospital, Northwestern
   University Feinberg School of Medicine.
                                                                       Soon after, CPAP was being used in adult patients with
†Pulmonary Medicine, Children's Memorial Hospital, Northwestern        acute respiratory distress syndrome [5,6]. Today, CPAP is
   University Feinberg School of Medicine.                             used in all age groups in patients with chronic illnesses
‡Pulmonary and Critical Care Medicine, Children's Memorial Hospital,   such as obstructive sleep apnea (OSA) and chronic
   Northwestern University Feinberg School of Medicine.                obstructive pulmonary disease as well as acute illnesses
Reprint requests and correspondence: S. Lestrud, MD, Pulmonary and
   Critical Care Medicine, Children's Memorial Hospital, 2300
                                                                       such as pneumonia and pulmonary edema.
   Children's Plaza, Box 73, Chicago, IL 60614.                           In the 1980s, flow and pressure sensors were developed
   (E-mail: slestrud@childrensmemorial.org)                            to identify the commencement and cessation of a patient's

1522-8401/$ - see front matter C 2007 Published by Elsevier Inc.                                                                139
doi:10.1016/j.cpem.2007.08.013
140                                                                                                             R. Ganesan et al.

respiratory efforts. Pressure support ventilation proved to      maintain alveolar ventilation and oxygenation. Muscle
be beneficial in invasive mechanical ventilation by Kac-         fatigue from increased work of breathing leads to inability
marek [7]. These technological advances were then applied        to augment minute ventilation and adjust for increasing
to noninvasive mechanical ventilation modalities. The use        carbon dioxide.
of flow-triggered inspiratory support with continuous               The combination of increased airway resistance and
positive airway pressure has proven beneficial.                  decreased lung compliance lead to a decrease in functional
   More recently, bimodal positive airway pressure (BiPAP)       residual capacity (FRC). When the FRC drops below the
provides inspiratory positive airway pressure (IPAP) and         critical closing volume, alveolar collapse occurs [9]. Critical
expiratory positive airway pressure (EPAP). This mode of         closing volume is altered by age, disease, and position [9].
ventilation is similar to the combination of CPAP and            With exhalation, intrathoracic pressure changes will result
pressure support ventilation. IPAP delivers positive pres-       in airway closure. This occurs first in dependent areas of the
sure during the inspiratory phase of the respiratory cycle.      lungs around the level of residual volume. During disease
EPAP delivers end-expiratory positive pressure during the        states, increased transpleural pressures result in increased
expiratory phase. This differs from CPAP, as CPAP provides       closing volumes. These closing volumes may occur at the
end expiratory positive pressure during the entire respira-      level of FRC, which result in atelectasis, subsequent
tory cycle.                                                      ventilation/perfusion (V/Q) mismatch, and eventual
   Modern-day CPAP/BiPAP machines (Respironics Inc,              hypoxemia and hypercarbia [9].
Murrysville, PA) are electrically controlled, pneumatically         Noninvasive positive-pressure ventilation has been
powered, low-pressure ventilators [8]. These machines are        shown to improve oxygenation, alveolar ventilation, and
designed to augment the patient's respiratory effort. Flow       work of breathing [10,11]. The flow provided by NIPPV
transducers in the patient's circuit are used to sense the       bypasses upper airway obstruction. The increase in upper
patient's effort. The data collected by the flow transducer is   airway pressure leads to a drop in airway resistance.
analyzed to determine the amount of pressure needed to           NIPPV also promotes recruitment of collapsed alveoli.
generate the tidal volume or pressure preset by the clinician.   When effective alveolar recruitment is achieved, FRC
The machine continuously recalibrates to adjust for leaks        increases and surpasses the critical closing volume [9].
and changes in lung compliance and airway resistance.            This leads to alveolar patency, alveolar stability, increase
   In recent years, systems developed to provide high-flow,      in lung compliance, and improvement in V/Q mismatch.
high-humidity nasal cannula supplemental gas has sup-            To recruit alveoli effectively, the pressure delivered must
planted the use of CPAP. These systems deliver 1 to 40           be higher than the critical opening pressure of the alveoli
L/min of flow rate, producing positive pressure support          [9]. The delivery of fixed FIO2 through a closed circuit
as well as supplemental oxygen. This mode of                     improves patient oxygenation. The increase in open
noninvasive positive pressure supplementation has                alveoli leads to redistribution of pulmonary blood flow
been used more typically in newborns and infants but             to these areas of improved ventilation. This also improves
likely will find increased usage in all patients with            patient ventilation and oxygenation. The addition of
respiratory distress.                                            CPAP/BiPAP may decrease work of breathing by several
                                                                 mechanisms including relief of upper airway obstruction,
                                                                 alteration of thoracic closing volumes, and decrease
                                                                 in diaphragmatic work. All of these factors together
Physiology of Modalities                                         improve oxygenation, ventilation, and overall systemic
Respiratory disease may involve the upper airway, lower          and cellular acidosis.
airway, or both. Regardless of location of disease in the
respiratory tract, airway resistance and lung compliance
can be affected. Increased inflammation, debris, and
bronchospasm associated with respiratory disease result
                                                                 Administration and Monitoring of
in a higher transpulmonary pressure (difference between          Modalities
proximal airway pressure and alveolar pressure) required         Modern NIPPV ventilators provide different modes to
to produce a unit flow of gas through the airways of the         accommodate different patient physiology. The sponta-
lung. This is demonstrated by an increased airflow               neous mode can provide IPAP, EPAP or both, but only in
resistance [8]. As the properties of the alveoli may change      response to the patient's respiratory effort. In the
during disease, the amount of unit lung volume change            spontaneous/timed mode, pressure delivery is also con-
decreases for unit change in transalveolar pressure (the         trolled by patient effort. However, if no effort is detected
difference between alveolar pressure and pleural pressure).      within a set time, a breath is delivered to the patient. In
This is defined as a decrease in lung compliance [8]. The        timed mode, a breath is delivered at a set interval regardless
resultant decrease in lung compliance and increase in            of patient effort.
airway resistance in respiratory disease also require the           The decision to use BiPAP, CPAP, or high-flow nasal
patient to generate higher intrathoracic pressures to            cannula is dependent on the patient, specific disease, and
Noninvasive mechanical ventilation                                                                                          141

clinical expertise. NIPPV may be delivered via nasal or full-     in acute care hospitals in the United States [14]. This
face mask. Both modes of administration can deliver               survey showed great variation in use among hospitals
adequate support. However, full-face masks provide more           within the same region. In this study, use of NIPPV for
constant and reliable pressure delivery. Nasal masks are best     acute respiratory failure varied from less than 5% to greater
suited for patients who are able to comfortably keep their        than 50% of patients. Of those who used this modality in
mouths closed. These masks are considered more comfor-            less than 15% of the patients, lack of physician knowledge
table by patients. Infants, who are obligate nose breathers,      and equipment availability were cited as the top reasons for
generally benefit more from nasal prong CPAP or high-flow         this practice pattern. The site of initiation of NIPPV was
nasal cannula.                                                    most often the ICU (55%) followed by the ED (26%).
   Patients requiring NIPPV are generally critically ill.         Other studies have shown ED use to be higher [15]. In
These patients need to be closely monitored for worsening         these facilities, protocol-driven application and monitoring
respiratory failure. Patients should be monitored with            were associated with better success.
serial lung exams, continuous pulse oximetry, and                    Factors that influenced success of noninvasive ventila-
transcutaneous carbon dioxide monitoring. If a patient's          tion were also examined in a 2005 article by Merlani et al
status worsens or does not improve, endotracheal intuba-          [16]. In this retrospective analysis, patients admitted to the
tion with mechanical ventilation is warranted.                    ED for acute respiratory failure and treated with NIPPV
                                                                  were studied. Failure of NIPPV was defined as the need to
                                                                  undergo endotracheal intubation. In this study, 31% failed
                                                                  NIPPV. Factors associated with failure included a pH less
Clinical Uses of NIPPV                                            than 7.35 and a respiratory rate greater than 20 after 1 hour
Noninvasive positive pressure ventilation is used in the          of NIPPV. In adult ED patients, NIPPV is most often
pediatric population to address both acute and chronic            instituted for cardiogenic pulmonary edema, acute asthma,
respiratory compromise. It is important for the ED physician      chronic obstructive pulmonary disease, immunocompro-
to be knowledgeable about the uses of NIPPV. Under-               mised states, and pneumonia [14,17,18].
standing the indications for NIPPV will facilitate its use as a      Studies evaluating treatment failure of NIPPV in the
treatment modality in the acute setting. By understanding         pediatric population have been conducted primarily in the
the limitations of NIPPV, better care can also be given to        pediatric intensive care setting. A small prospective study
those children with chronic respiratory conditions requiring      of infants and children in the ICU undergoing NIPPV for
mask ventilation who present to the ED with a change in           respiratory failure demonstrated that inspired oxygen
clinical status. The use of home ventilation is therefore an      (FIO2) after 1 hour of NIPPV may be a predictor for
important part of patient history taking in the ED setting.       outcome, with a requirement for an FIO2 greater than 80%
   In the acute setting, the benefits of NIPPV over               being associated with NIPPV failure [19]. A larger study of
endotracheal intubation include reduced risk of nosoco-           NIPPV in PICUs found that acute respiratory distress
mial infection, shorter intensive care unit (ICU) and             syndrome and a high pediatric logistic organ dysfunction
hospital stay, and decreased mortality [12]. It is important      (PELOD) score were independent predictive variables of
to note that NIPPV is not a replacement for endotracheal          NIPPV failure [11]. This study noted that there was
intubation in patients who require airway protection and          improvement in breathing pattern and in gas exchange in
have hypercarbia or life-threatening hypoxemia (PAO2              some patients on NIPPV in the first few hours. Most of the
b60 mm Hg on rebreathing facemask). NIPPV should                  patients who failed did so within the first 48 hours. These
not be attempted in patients who are rapidly deteriorating        findings support the need for close monitoring of patients
or who are somnolent or confused. It should also be               on NIPPV and the need to consider discontinuation if
avoided in patients who are hypotensive or have cardiac           improvement is not noted in the short term.
dysrhythmias [13]. Previous studies have demonstrated                A similar study of predictive factors for success of
that BiPAP will lead to improvement of symptoms within            NIPPV in the pediatric ED does not exist to our knowledge
hours, so trials of NIPPV should remain short in nature and       beyond small disease-specific cohorts. Therefore, it is
intubation with subsequent mechanical ventilation should          important to understand the specific indications for NIPPV
be instituted if indicated for the clinical situation.            in pediatrics and the literature that supports its use in
   Literature supporting the use of NIPPV in the pediatric        certain disease states.
population primarily emanates from either the pediatric
intensive care unit (PICU) as a treatment of respiratory          Asthma
distress or from the home setting as a management for             Noninvasive mechanical ventilation functions to bridge the
chronic respiratory conditions such as OSA and neuro-             gap between maximal medical management and mechanical
muscular disorders. Studies of NIPPV use in the ED are            ventilation in asthma. By avoiding intubation in an
mostly confined to the adult literature.                          asthmatic, complications such as bronchospasm, baro-
   A 2006 article by Maheshwari et al [14] sought to              trauma, ventilator-induced lung injury, cardiovascular
investigate the use of noninvasive mechanical ventilation         instability, and nosocomial infection can be reduced. The
142                                                                                                             R. Ganesan et al.

use of NIPPV in asthmatic patients works by applying                A prospective, randomized, placebo-controlled trial of
positive pressure, which decreases the workload of fatigued      BiPAP in an adult ED patient population with acute asthma
muscles used for inspiration including the diaphragm and         has been reported. It was found that in these adult patients,
accessory muscles. The positive pressure relieves the need       the use of BiPAP for 3 hours improved lung function,
for the patient to “auto-positive end expiratory pressure”       alleviated symptoms of the asthma attack more quickly than
(PEEP) to keep airways open during exhalation. This allows       in the control group, and reduced the rate of admission [24].
for improvement in V/Q mismatch by a direct bronchodilator
effect and recruitment of smaller airways and collapsed          Neuromuscular Disorders
alveoli. Noninvasive ventilation may also improve delivery of    A variety of studies and case reports have supported the use of
bronchodilators to smaller lung airways. This modality can       NIPPV in neuromuscular diseases such as spinal muscular
be a reasonable alternative for the 5% to 10% of patients with   atrophy, myasthenia gravis, congenital myopathies, and
acute asthma who fail conventional therapy.                      muscular dystrophies [25-28]. In neuromuscular disorders,
   There are some studies to support the use of BiPAP            the discussion regarding ventilation, invasive or noninvasive,
for acute asthma exacerbations in the pediatric popula-          should ideally be made at a nonemergent time. This scenario,
tion [20,21]. In a descriptive, 1-year, retrospective chart      however, is not always possible. It is important to recognize
review of ED patients with acute asthma refractory to            the role that NIPPV can serve in patients with respiratory
conventional treatment subsequently treated with BiPAP,          failure and neuromuscular disorders. NIPPV works in
safety, tolerance, and benefit were studied. Nasal BiPAP         neuromuscular patients by improving ventilatory mechanics,
and continuous albuterol were applied to these other-            resting fatigued respiratory muscles, enhancing ventilatory
wise healthy pediatric asthma patients. Most of the              sensitivity to carbon dioxide, and improving sleep stage
patients tolerated the device; more than 70% had                 disturbances [28]. The initiation of NIPPV in these patients
improvement in respiratory rate and almost 90%                   has been found to reduce symptoms, such as sleepiness and
improved their oxygen saturation. Most patients were             headaches, hospitalizations, and health care costs in those
subsequently transferred to the PICU; however, almost            who use the device [26]. In patients with neuromuscular
25% were weaned off BiPAP in the ED and transferred to           disorders, care should be given when initiating NIPPV. BiPAP,
the pediatric general ward without any complications,            rather than CPAP, is the mode of choice because high
adverse events, or deaths.                                       continuous pressure may be difficult for weak muscles to
   These patients were started at an inspired positive           overcome to generate a breath.
airway pressure of 10 cm H2O and an expired positive
airway pressure at 5 cm H2O with inspiratory pressure            Obstructive Sleep Apnea/Airway Obstruction
adjusted to achieve an exhaled tidal volume of 6 to              Obstructive sleep apnea is the major indication for NIPPV
9 mL/kg. A nasal mask was used to reduce the risk of             in airway obstruction. It is estimated that OSA syndrome
gastric insufflation, vomiting, and aspiration. Albuterol        affects about 2% of children. This can be secondary to
was placed in the circuit between the whisper valve and          neuromuscular airway control or from anatomic narrow-
nasal mask. This study was limited, however, because of its      ing of the airway. In most children, obstruction is caused
retrospective nature, differences in administration of           by enlarged tonsils and adenoids, and surgical intervention
magnesium and terbutaline, and the lack of an objective          generally improves the condition. However, with increas-
measure on when to start BiPAP therapy [22].                     ing rates among children, obesity is playing a greater role in
   In 2004, a prospective crossover study was performed          pediatric OSA.
involving 20 children in the PICU randomized to either              If pediatric OSA is not alleviated by tonsillectomy and
2 hours of nasal BiPAP (10cm/5cm) followed by 2 hours of         adenoidectomy, CPAP or BiPAP can be used. A review
standard therapy or the reverse. A clinical asthma score         article from Guilleminault et al [29] in 2005 gives an
was used to evaluate patients. All patients were on              overview of the symptoms of OSA associated with different
continuous albuterol and intravenous steroids but other          age groups. These clinical symptoms along with findings on
therapies were at the treating physician's discretion. This      polysomnography confirm the diagnosis of sleep-disor-
study found that there were decreased signs of work of           dered breathing. The use of nasal CPAP for OSA in children
breathing and dyspnea in the BiPAP group as compared             has been studied, and the training of parents and patients,
with the standard therapy group. Discontinuation of BiPAP        frequent reevaluation and fitting, and attention to midface
after 2 hours in the group who initially received it was         growth are important. A recent study investigating
associated with an increase in respiratory rate and the          adherence and effectiveness of these modalities in children
clinical asthma score. In the group receiving conventional       with OSA found poor compliance even with intensive home
therapy first, only 2 children showed improvements in            support by health care professionals. They also found that
respiratory rate and clinical asthma score, and only with a      of those who do use the equipment, the duration was less
BiPAP trial. BiPAP was not associated with significant           than prescribed. This study did show that NIPPV was
differences in oxygen saturation and transcutaneous              effective in improving clinical symptoms of OSA and was
carbon dioxide monitoring [23].                                  associated with improved polysomnographic findings [30].
Noninvasive mechanical ventilation                                                                                            143

   There are case reports and studies that investigate the      mass. This type of obstruction, resulting in compression of
use of NIPPV in children with laryngomalacia, tracheoma-        the bronchi, may cause wheezing that could be mis-
lacia, and bronchomalacia [31-33]. NIPPV was found to           interpreted as asthma. It is important to note that
relieve the load on respiratory muscles caused by severe        wheezing caused by a fixed obstruction is monophonic,
laryngomalacia and was associated with clinical improve-        rather than polyphonic. A chest x-ray could help to
ment in sleep and growth when upper airway obstruction          differentiate if needed. Currently, there is no indication for
is associated with alveolar hypoventilation [31].               NIPPV in this setting.
   In the ED, it is important to recognize severe upper
airway obstruction, especially in infants, as an etiology for   Ingestion/Toxin
respiratory distress and failure to thrive. Prompt interven-    Ingestion and poisoning causing respiratory failure are not
tion with NIPPV can provide acute relief until further          indications for NIPPV. A full face mask device puts patients
studies and possible surgical interventions can be applied.     at a high risk for aspiration if vomiting occurs. If
                                                                consciousness is impaired, NIPPV is of little use unless
Bronchiolitis                                                   BiPAP with a physiological back-up rate is applied. However,
Bronchiolitis is a common diagnosis in the ED with only a       if this is needed, conventional ventilation with protection of
small percentage of children worsening into respiratory         the airway with an endotracheal tube is indicated.
failure. Little research has been done to investigate the use
of NIPPV in bronchiolitis in the ED. A randomized               Foreign Body Aspiration
crossover trial comparing CPAP to standard therapy              The size and location of an aspirated foreign body dictate
found that CPAP decreased hypercarbia in infants with           treatment. However, if a foreign body is producing
bronchiolitis compared to standard therapy [34]. A study        significant respiratory distress with concern of impending
by Martinon-Torres et al [35] found that there was an           respiratory failure, NIPPV is not indicated and will not
improvement in clinical score, tachypnea and hypercarbia        provide significant relief past a fixed tracheal obstruction.
in patients with refractory bronchiolitis treated with heliox
and CPAP.
                                                                Summary
Postoperative                                                   Patients presenting to pediatric EDs with respiratory
A retrospective study of patients undergoing tonsillectomy      distress represent an array of diagnostic and therapeutic
and adenoidectomy found that BiPAP was safe and effective       challenges. With the development of NIPPV, there is an
in patients that were predisposed to postoperative post-        effective tool in our armamentarium to provide significant
obstructive airway complications. These factors include         respiratory support. NIPPV has demonstrated benefits in
obesity, young age, asthma, and neurologic compromise           decreasing work of breathing, relieving fatigued muscles of
[36]. It was also found that the use of NIPPV in pediatric      respiration, improving oxygenation, and possibly avoiding
patients after liver transplantation helped resolve atelec-     common complications of endotracheal intubation. There
tasis and improved outcomes [37]. NIPPV has also been           are clear clinical scenarios in which NIPPV is contra-
found to be useful postoperatively in patients with spinal      indicated, such as an obtunded patient, certain post-
cord surgery and laryngotracheal reconstruction proce-          operative patients, patients with vomiting, and patients in
dures [38,39].                                                  which mask ventilation is not tolerated. More frequently, it
                                                                is the patient with pulmonary disease resulting in
Cystic Fibrosis                                                 respiratory distress that is amenable to this therapy. It is
The use of NIPPV in cystic fibrosis has been found to be        important to obtain any history of NIPPV usage in the ED.
beneficial not only in those patients with end-stage            Increasing numbers of children are on nocturnal settings
disease awaiting lung transplant but also earlier in the        for OSA and support settings for chronic respiratory
course of the disease to improve nocturnal oxygenation          insufficiency with diseases such as myopathies, cystic
and sleep quality and rest respiratory muscles [40,41].         fibrosis, and bronchiectasis. Advancements in the knowl-
These findings suggest that there may be a short-term           edge of NIPPV management strategies for respiratory
benefit of NIPPV in cystic fibrosis. In the ED setting, in      distress and early initiation of mask ventilation in the ED
the case of severe respiratory distress not necessitating       will enable the emergency physician to approach respira-
intubation, it may be reasonable to try NIPPV as a means        tory distress in a similar manner as sepsis; using goal-
of improving oxygenation as well as improving work of           directed therapies to improve oxygenation, ventilation, and
breathing [42].                                                 comfort of breathing.
Mediastinal Mass
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