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NIV and chronic respiratory failure in children

Article · November 2008

DOI: 10.1183/1025448x.00041019

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CHAPTER 19

NIV and chronic respiratory failure in

children

B. Fauroux*, G. Aubertin*, F. Lofaso#

*Paediatric Pulmonary Dept, Armand Trousseau Hospital, Paris, and #Physiology Dept, Raymond Poincaré
Hospital, Garches, France.

Correspondence: B. Fauroux, AP-HP, Hopital Armand Trousseau, Paediatric Pulmonary Dept, Research
Unit INSERM UMR S-893 Equipe 12, Université Pierre et Marie Curie-Paris 6, 28 Avenue du Docteur Arnold
Netter, Paris, F-75012 France. Fax: 33 144736174; E-mail: [email protected]

Introduction
A growing population of children have chronic respiratory failure, due to conditions,
such as muscle disease, abnormalities of the airways, the chest wall and/or the lungs, or
disorders of ventilatory control. Two factors explain the important development of
noninvasive positive pressure ventilation (NPPV) in this population group. First, most
of these disorders are fundamentally hypoventilation disorders. As such, oxygen therapy
alone is not only usually ineffective in relieving symptoms, but also has been shown to be
dangerous and may lead to a marked acceleration of carbon dioxide retention [1, 2].
Secondly, by definition, NPPV is a noninvasive technique that can be applied on
demand and preferentially at night, causing much less morbidity, discomfort and social
life and family disruption than a tracheostomy. But NPPV is not applicable to all
children. Noninvasive forms of mechanical ventilation are technically more difficult to
apply in infants and young children. Usually, NPPV is applied during the night and
during the daytime nap in young children. A minimal respiratory autonomy is thus an
absolute prerequisite for NPPV, even if the beneficial effects of NPPV can extend, after
a certain period, during periods of spontaneous breathing. NPPV is often used on an
empirical basis in children, with a gap between the expanding use and the lack of precise
knowledge on physiological effects. This makes it difficult to establish both the
appropriate timing of initiation of NPPV and the most pertinent therapeutic goals.
The present chapter focuses on long-term noninvasive ventilator management of
infants and children. The first section examines the diagnoses requiring ventilatory
assistance for infants and children. The second section deals with the (potential)
physiological benefits of long term NPPV in children. The third section focuses on
special considerations for infants and children concerning ventilation techniques,
equipment and practical use.

Disorders that may justify NPPV

The ability to sustain spontaneous ventilation can be viewed as a balance between
neurological mechanisms controlling ventilation, together with ventilatory muscle
power, on one side, and the respiratory load, determined by lung, thoracic and airway
mechanics, on the other (fig. 1). Significant dysfunction of any of these components of

Eur Respir Mon, 2008, 41, 272–286. Printed in UK - all rights reserved. Copyright ERS Journals Ltd 2008; European Respiratory Monograph;
ISSN 1025-448x.

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the respiratory system may impair the ability to spontaneously generate efficacious
breaths. In normal individuals, central respiratory drive and ventilatory muscle power
exceed the respiratory load and are, thus, able to sustain adequate spontaneous
ventilation. However, if the respiratory load is too high and/or ventilatory muscle power
or central respiratory drive is too low, ventilation may be inadequate, resulting in
hypercapnia. Chronic ventilatory failure, then, is the result of an imbalance in the
respiratory system, in which ventilatory muscle power and central respiratory drive are
inadequate to overcome the respiratory load. If this imbalance cannot be corrected with
medical treatment, the patient may benefit from long-term ventilatory support. Thus,
infants and children may require noninvasive long-term ventilatory support due to three
categories of respiratory system dysfunction: increased respiratory load (due to intrinsic
cardiopulmonary disorders, upper airway abnormalities, or skeletal deformities),
ventilatory muscle weakness (due to neuromuscular diseases or spinal cord injury) or
failure of neurological control of ventilation (with central hypoventilation syndrome
being the most common presentation; fig. 1).

Increase in respiratory load

Upper or lower airway obstruction or chest wall deformity are characterised by an
increase in respiratory load.
Obstructive sleep apnoea (OSA) is less common in children than in adults. The
pathophysiology is also different with the predominant role of enlarged tonsils and
adenoids [3]. If tonsillectomy and adenoidectomy are not able to relieve upper airway
obstruction, then noninvasive continuous positive airway pressure (CPAP) ventilation is
proposed as the first therapeutic option [4–6]. Indeed, the maintenance of airway
patency by means of a continuous positive pressure reduces the respiratory muscle

Decrease in respiratory muscles capacity

Neuromuscular disorders
Increase in respiratory load
Cystic fibrosis
Upper airway obstruction

Alveolar hypoventilation
Pa,O2 and Pa,CO2

Fig. 1. – Spontaneous ventilation is the result of a balance between neurological mechanisms controlling ventilation
together with ventilatory muscle power on one side, and the respiratory load, determined by lung, thoracic and airway
mechanics, on the other. If the respiratory load is too high and/or ventilatory muscle power or central respiratory
drive is too low, ventilation may be inadequate, resulting in alveolar hypoventilation with hypercapnia and
hypoxaemia.

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 B. FAUROUX ET AL.

output, which translates into an improvement in alveolar ventilation. Young children

are more exposed to these problems; their small lung volumes and the progressive
maturation of sleep stages may render them particularly susceptible to the
cardiovascular consequences of increased upper airway resistance during sleep.
In children and young adults with advanced pulmonary cystic fibrosis (CF), as lung
disease progresses, with a progressive fall in the forced expiratory volume in one second
(FEV1), there is an increase in the respiratory muscle load [7]. Indeed, as FEV1 falls,
indices reflecting the respiratory muscle output, such as the pressure/time product of the
oesophagus (PTPoes) and diaphragm (PTPdi) and the elastic work of breathing increase.
Indeed, in a group of children with CF, having a FEV1 of 30–50% of predicted value,
PTPoes and PTPdi were increased 3–5-fold [7]. As a result, the patients develop a
compensatory mechanism of a rapid, shallow breathing pattern in an attempt to reduce
the increase in load. Although this breathing strategy maintains the level of ventilation,
arterial carbon dioxide tension (Pa,CO2) rises. Thus, in CF, an imbalance between the
load imposed on the respiratory system and the capacity of the respiratory muscles,
explains the inability of the respiratory muscle pump to clear carbon dioxide. Short-term
physiological studies, during waking and sleep, have demonstrated that NPPV reduces
respiratory muscle load and work of breathing [8–10], increases minute ventilation [8,
10] and, thus, improves alveolar ventilation and gas exchange.
Restrictive parenchymal lung diseases are difficult to manage with long-term NPPV.
Experience of NPPV in this group of patients is poor. Infants with hypoplastic lungs
may be candidates for long-term mechanical ventilation but because of their age and the
poor prognosis, they are most-often ventilated with a tracheostomy.
Chest wall abnormalities such as severe scoliosis, kyphosis or thoracic dystrophy are
among the chest wall abnormalities that may cause restrictive disease, severe enough to
require long-term NPPV. The prognosis of these children depends upon the severity,
type and evolution of the disease. In some children, the chest wall abnormalities will
cause progressive restrictive pulmonary disease, ultimately resulting in death, even with
mechanical ventilation. Other children appear to improve clinically, even in the absence
of changes in the chest wall anomaly, due to certain degree of catch-up caused by the
physiological growth.

Respiratory muscle weakness

Respiratory muscles are rarely spared in neuromuscular diseases [11]. In general,
respiratory muscle weakness is associated with inspiratory muscle weakness, which
limits inspiration, resulting in atelectasis and expiratory muscle weakness, causing
inability to cough, predisposing to pulmonary infection and hypoventilation, resulting in
inadequate gas exchange. Respiratory muscle weakness, dysfunction, or paralysis can
occur because of neuromuscular disease, or as a result of spinal cord injury.
The most common neuromuscular diseases requiring NPPV during childhood are
Duchenne muscular dystrophy and spinal muscular atrophy. Duchenne muscular
dystrophy is a progressive disorder and ventilatory failure is inevitable in the course of
the disease, although the time course of progression to it varies between individuals.
Home NPPV counteracts the hypoventilation and can improve survival [12–14].
Respiratory failure is also common in children with spinal muscular atrophy (SMA).
The SMAs are inherited as autosomal recessive disorders. Severity is inversely
proportional to the amount of survival motor-neuron protein in the anterior horn cell.
SMAs range from total paralysis and need for ventilatory support from birth, to the
relatively mild muscle weakness presenting in the young adult. Diaphragmatic strength
is generally preserved and respiratory muscle weakness predominates on the other

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inspiratory muscles and the expiratory muscles [11]. Respiratory failure is less frequent
in other muscular dystrophies, such as Becker, limb-girdle and facioscapulohumeral
dystrophies. Congenital myopathies are often static [11]; however, the condition of
children may deteriorate functionally with growth because weakened muscles are unable
to cope with increasing body mass.
The importance of respiratory failure associated with spinal cord injury depends on
the level of the injury. High spinal cord injury, above C-3, causes diaphragm paralysis.
This almost always causes respiratory failure in infants and young children. NPPV can
be attempted in older children, who have a sufficient respiratory autonomy for at least
8–10 h?day-1. In patients with lower cervical cord injury, expiratory muscle function is
severely compromised, impairing cough and the clearance of bronchial secretions. As a
result, retention of secretions, leading to atelectasis and bronchopneumonia, frequently
occurs in such patients and may require short periods of NPPV during episodes of acute
respiratory failure. However, these children, with respiratory muscle weakness, often do
not have severe intrinsic or parenchymal lung disease, thus making them good
candidates for home NPPV.

Failure of the neurological control of ventilation

Disorders of neurological control of breathing, that are severe enough to cause
chronic respiratory failure, are uncommon to rare. Congenital central hypoventilation
syndrome (‘‘Ondine’s curse’’) is the most common presentation in childhood and is
characterised by the failure of autonomic control of breathing [15]. Hypoxia and
hypercapnia worsen during sleep. A tracheostomy is nearly always mandatory in infants
and young children but NPPV may be successful in older children, who sustain adequate
ventilation during waking but require ventilatory assistance during sleep [16, 17].

Benefits of NPPV
The benefits of NPPV vary according to the underlying disease. Some beneficial
effects, such as the correction of nocturnal alveolar hypoventilation are common to the
different diagnostic groups, whereas other effects, such as the increase in survival, may
be specific for a group of disorders (table 1).

Correction of nocturnal hypoventilation and gas exchange

The most obvious effect, in the paediatric population, is the correction of nocturnal
hypoventilation. Sleep is associated with changes in respiratory mechanics, such as an
increase in ventilation–perfusion mismatch, an increase in airflow resistance and a fall in
functional residual capacity (fig. 2). Although the activity of the diaphragm is preserved,
those of the intercostal and upper airway muscles are decreased significantly. Finally,
central drive and chemoreceptor sensitivity are less efficient during sleep than during
waking. All of these abnormalities explain a physiological degree of nocturnal
hypoventilation, even in normal subjects, causing a rise in Pa,CO2 of up 3 mmHg
(0.4 kPa) in adults [18]. This decrease in alveolar ventilation predominates during rapid
eye movement (REM) sleep and explains why patients with chronic respiratory failure
are vulnerable during this sleep stage. Nocturnal hypoventilation will also predominate
during REM sleep in children with OSA because of the physiological relaxation of the
upper airway muscles.

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 B. FAUROUX ET AL.

Table 1. – Potential benefits of long term noninvasive positive pressure ventilation in children according to the
underlying disease.

Neuromuscular disorders Obstructive sleep apnoea Cystic fibrosis

Improvement in nocturnal Yes Yes Yes
hypoventilation and gas
exchange
Increase in survival Yes (in patients with Duchenne Not applicable (tracheost- Not proven
muscular dystrophy) omy is an alternative)
Improvement in lung function Not proven Not applicable Limited data
Improvement in respiratory Not proven Not applicable Limited data
muscle performance
Improvement in exercise Not proven Not applicable Yes
tolerance
Preservation of normal Not proven Not applicable Not applicable
pulmonary mechanics and
lung growth
Improvement of quality of life Yes Yes (as an alternative to Not proven
tracheostomy)

The efficacy of NPPV in relieving nocturnal hypoventilation in children with OSA has
been demonstrated in several studies. Nasal CPAP has been used by some experienced
teams for several decades [4–6]. Therapy with nasal CPAP eliminated the signs of OSA
in 90% (of 80) children in whom this treatment was tried due to the persistence of the
symptoms after adenotonsillectomy [4].
Several studies have shown the efficacy of NPPV to correct or improve nocturnal
hypoventilation in patients with CF. These patients may experience periods of
oxyhaemoglobin desaturation, during sleep, that are most marked during REM sleep
[19, 20]. A study including seven adults with CF showed that, compared with a control
night without CPAP, nasal CPAP resulted in a significant improvement in arterial
oxygen saturation (Sa,O2) during both REM and non-REM sleep [19]. However,
transcutaneous carbon dioxide tension (Ptc,CO2) measurements were not significantly
different between the control and CPAP nights. Another interesting study compared gas
exchange and quality of sleep in adults with CF during three nights: a control night, a
night with oxygen and a night with NPPV [21]. Similar significant improvements of
Sa,O2 and time spent in REM sleep, were observed during the nights with oxygen and
NPPV. Most interestingly, the night with oxygen was associated with a significant
increase in Ptc,CO2, whereas NPPV resulted in a significant decrease in Ptc,CO2.

Sleep

Ventilatory Respiratory Respiratory

drive muscles mechanics

Central drive Preservation of the activity Ventilation/perfusion mismatch

Chemoreceptor sensitivity of the diaphragms Airflow resistance
Activity of the upper Functional residual capacity
airway muscles

Fig. 2. – Physiological alterations during sleep explaining the worsening of respiratory failure during sleep.

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 NIV IN CHILDREN

Sleep-related respiratory disturbances are frequent in teenagers and adults with

Duchenne muscular dystrophy patients, especially when diurnal arterial hypoxaemia is
present [22]. NPPV has been shown to be associated with a substantial improvement in
alveolar hypoventilation during both night and day, in children with various
neuromuscular diseases [23]. The benefits of NPPV may be due to combined effects
of several interrelated processes. The increase in respiratory drive is probably due to a
reduction in cerebrospinal fluid bicarbonate concentration which resets the ventilatory
response to carbon dioxide, and to an improvement in sleep quality which influences the
ventilatory response to carbon dioxide and respiratory muscle endurance [24]. In
addition, NPPV may decrease the work of breathing during spontaneous ventilation as a
result of an increase in chest wall and lung compliance due to the increase in respiratory
movements during NPPV.

Increase in survival
The improvement in survival represents a major expectation of NPPV in patients with
progressive neuromuscular or lung disease. But this benefit has only been demonstrated
in patients with neuromuscular diseases in a case series [13] and in one nation-wide
study. Indeed, the benefit of NPPV on the survival of patients with Duchenne muscular
dystrophy in Denmark was evaluated between 1977 and 2001 [14]. While overall
incidence remained stable at 2.0 per 100,000 people, prevalence rose from 3.1 to 5.5 per
100,000 people, mortality fell from 4.7 to 2.6 per 100 yrs at risk and the prevalence of
ventilator users rose from 0.9 to 43.4 per 100. Ventilator use is probably the main reason
of this dramatic increase in survival.
An increase in survival has not been demonstrated in patients with CF. In other
diseases, such as OSA, survival is not an issue, because a tracheostomy may constitute
an alternative to NPPV.

Improvement in lung function, respiratory muscle performance and exercise

tolerance
The stabilisation or slowing of the decline in lung function, by NPPV, in patients
whose disease course is characterised by a decline in lung function, such as patients with
neuromuscular disease or CF, represents a major expectation of long-term NPPV. No
data are presently available to support this hypothesis for patients with neuromuscular
disease. Recent data from the French Cystic Fibrosis Observatory have shown that
NPPV was associated with a stabilisation of the decline in lung function in patients with
advanced lung disease [25]. Indeed, 44 patients (NPPV group) were compared with
matched controls (control group), 1 yr prior to the initiation of NPPV, during the year
of NPPV initiation, and after 1 yr of NPPV treatment. Each patient of the NPPV group
was matched for a control patient for sex, CFTR genotype, age¡1 yr, weight¡2 kg,
FEV1¡10% predicted and follow up at the same centre. During the year prior to
initiation of NPPV, the two groups were comparable but at the year of initiation, the
NPPV group had a significantly greater decline in vital capacity (VC) and FEV1. After
1 yr, the decline in VC and FEV1 was similar in the two groups, demonstrating a
stabilisation of lung function decline in the NPPV group.
NPPV has been associated with an improvement in respiratory muscle performance in
patients with CF. PIPER et al. [26] reported an increase in maximal expiratory (PE,max)
and inspiratory pressure (PI,max) in four adults with CF after 1 month of NPPV.
However, improvement due to a learning effect or better motivation could not be
excluded because of the volitional nature of these tests. Significant decreases have been

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observed in PE,max and PI,max, in 19 children with CF, after a 20-min physiotherapy
session [27]. When the physiotherapy session was performed with pressure-support
ventilation (PSV) administered by a nasal mask, a significant increase of these
parameters was observed. The improvement of PI,max after the PSV session suggests that
pressure support may ‘‘rest’’ the inspiratory muscles during chest physiotherapy. The
improvement of PE,max after the PSV session could be explained by the increase in tidal
volume (VT) during PSV. During PSV, the VT tends to the total lung capacity. This
allows a larger amount of energy to accumulate, thereby facilitating expiration and
decreasing the work of the expiratory muscles.
Noninvasive CPAP ventilation has been associated with an improvement in exercise
tolerance in 33 patients with CF [28]. Indeed, 5 cmH2O CPAP ventilation resulted in a
decrease in oxygen consumption, respiratory effort, assessed by the transdiaphragmatic
pressure (Pdi) and dyspnoea score. These beneficial effects during exercise were the most
important in the patients with severe lung disease in whom the presence of intrinsic
positive end-expiratory pressure (PEEP) may be favourably counteracted by CPAP.

Preservation of normal pulmonary mechanics and lung growth

The physiological changes in the compliance of the lungs and the chest wall play a
crucial role in the normal development of the lung. In infancy, the chest wall is nearly
three times as compliant as the lung [29]. By the end of the second year of life, chest wall
stiffness increases to the point that the chest wall and lung are nearly equally compliant,
as in adulthood. Stiffening of the chest wall plays a major role in developmental changes
in respiratory system function such as the ability to passively maintain resting lung
volume and improved ventilatory efficiency afforded by reduced rib cage distorsion. An
important point would be to know if long-term NPPV in infants and young children can
preserve a near to normal chest wall compliance, in both children with a too stiff chest,
due to chest deformity for example, or those with neuromuscular disease, exposed to
ankylosis in the costosternal and costovertebral joints and to gradual stiffening of the
rib cage because of a breathing at smaller VT and greater respiratory frequency.
Chronic hypoventilation can alter the dynamic or static compliance of the lung. The
majority of observations in patients with neuromuscular disease have shown a
significant reduction in pulmonary compliance [11]. The measurements of these patients
were of dynamic compliance reflecting abnormalities in airways rather than a true
change in the elastic properties of the lungs. Specific compliance, relating static
expiratory compliance to total lung capacity, is normal in patients with respiratory
muscle weakness. Atelectasis could explain the hypoxaemia, due to the ventilation–
perfusion mismatching.
A major concern in paediatric patients is the effect of chronic hypoventilation on lung
growth, and, as a logical consequence, the effect of NPPV in promoting or preserving
physiological lung and chest wall growth in the developing child. To the present authors’
knowledge, this has not been studied in children; however, animal models have shown
that the congenital absence of the diaphragm or the intercostals muscles is associated
with both lung hypoplasia and a lack of lung differentiation [30, 31].

Improvement of quality of life

Studies are scarce, but NPPV has not been shown to be associated with deterioration
in quality of life in children with neuromuscular disease. In a small group of children
with SMA and other neuromuscular diseases, NPPV was associated in an improvement
in symptoms of nocturnal hypoventilation, and the maintenance of the different

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modules of quality of life measures, except the physical module, which reflects the
progression of the underlying neuromuscular disease [32]. NPPV was also associated with
an improvement in quality of life in boys with Duchenne muscular dystrophy [13]. Such a
benefit has not been demonstrated in patients with CF. In patients with OSA, the
alternative for NPPV is tracheostomy, which clearly puts the balance in favour of NPPV.

Criteria to initiate NPPV

Validated criteria for beginning long term NPPV are lacking in children [33]. Several
consensus conferences agree on the value of daytime hypercapnia and an acute
exacerbation to initiate NPPV because these criteria are the signature of established
ventilatory failure [34–36]. But these two classical criteria are preceded by a variable
period of nocturnal hypoventilation, during which, treatable symptoms, such as
frequent arousals, severe orthopnea, daytime fatigue and alterations in cognitive
function, may deteriorate the daily life of the patient. There is also a wide agreement to
consider that clinical symptoms attributable to nocturnal hypoventilation are most
important for the decision of NPPV. Initiation of NPPV before overt daytime
hypercapnia may thus be beneficial, not only on quality of sleep but also, according to
the underlying disease, on survival, lung growth and lung function and respiratory
muscle performance.
A major problem is thus to optimally schedule a polysomnographic sleep study in order
to document nocturnal hypoventilation. A polysomnography should be realised without
delay when the patient recognises symptoms related to sleep disordered breathing but
patients with neuromuscular disorders tend to underestimate symptoms, such as fatigue,
before using mechanical ventilation. Sleep disordered breathing may be difficult to
establish in children because of reliance on parents and second-hand caregivers, who have
a different perception of the child’s disease. Lung function parameters are poor indicators
of nocturnal hypoventilation. Thus, further studies are mandatory to establish, for every
diagnostic group, first, the most pertinent criteria which should ask for a sleep study, and
second, those which may require the initiation of NPPV.
A recent study showed that the initiation of NPPV at the stage of nocturnal
hypercapnia without daytime hypercapnia in children and adults with neuromuscular
disorders and chest wall disease was associated with an improvement in nocturnal gas
exchange [37]. Larger prospective studies, in homogeneous groups of patients, are
warranted in order to confirm the benefit of this ‘‘early’’ initiation of NPPV.

Ventilation techniques, ventilation equipment and use in children

Ventilation techniques
The type of equipment and the specific ventilator settings that should be chosen
remain a matter of debate. The specific equipment available for therapy evolves more
rapidly with industry capability rather than with clear indications available from
scientific trials.
Nasal CPAP is the treatment of choice for obstructive events during sleep [6, 38].
Upper airway patency is maintained with nasal CPAP by a pneumatic splinting effect. In
addition, it has been demonstrated that CPAP reduces the work of breathing in patients
with flow limitation [39, 40]. In such patients, CPAP overcomes the inspiratory
threshold imposed by auto-PEEP, and pneumatically splints the airways to prevent

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dynamic collapse during exhalation. Thus, if the main indication of CPAP is OSA, it is
also advocated in obstructive lung disease, when intrinsic PEEP increases the work of
breathing; however, because upper airway loading with complete or partial obstruction
and intrinsic PEEP are not the sole mechanisms of hypoventilation, CPAP should be
insufficient in patients with respiratory function abnormalities.
Volume-targeted ventilation is characterised by the delivery of a fixed, predetermined
VT. The main advantage of this mode is that a guaranteed minimal VT is delivered, but
this can result in detrimentally high inspiratory airway pressures causing discomfort and
poor tolerability. Despite many of the volume-targeted ventilators having no leak
compensation mechanisms, this mode is suited to patients with neuromuscular diseases,
where the ventilator acts as a substitute for the weakened respiratory muscles, which are
unable to trigger the ventilator. However, a relatively high back up rate (2–3 breaths
lower than the spontaneous respiratory rate of the patient) is required to avoid
nocturnal desaturations, and, as a consequence, many patients adopt a controlled mode
without triggering the ventilator. Also, the inspiratory triggers of these ventilators are
not very sensitive, which is another factor justifying the use of a relatively high back up
rate [9, 41]. Initial studies with long term NPPV in children with neuromuscular disease
and CF have used volume-targeted devices [42, 43]. These ventilators designed for home
use are relatively portable. They are not as technologically sophisticated as hospital
ventilators. Furthermore, few of them are capable to operate within certain limits (i.e.
VT ,50–100 mL).
PSV is pressure-targeted, during which each breath is triggered and terminated by the
patient and supported by the ventilator; the patient can control their respiratory rate,
inspiratory duration and VT [44]. This explains the relative ease in adapting to, and the
greater comfort and synchrony of this mode. In contrast to volume-targeted ventilation,
VT is not predetermined but depends on the level of PSV, the inspiratory effort of the
patient and the mechanical properties of the patient’s respiratory system. During this
mode, since there are no mandatory breaths present, an in-built low-frequency back-up
rate is used to prevent episodes of apnoea. Furthermore, because the breaths are
triggered by the patient, the sensitivity of the trigger is crucial. The sensitivity of the
inspiratory triggers of the different ventilators designed for the home is variable but
some are as sensitive as those of intensive care devices [41, 45]. Because, during PSV,
inspiratory muscle activity may influence respiratory frequency and VT, this ventilatory
mode is generally proposed in patients who can breathe spontaneously for substantial
periods of time and require mainly nocturnal ventilation.
Bi-level PPV is the combination of PSV and PEEP, permitting an independent
adjustment of expiratory positive airway pressure (EPAP) and inspiratory positive
airway pressure (IPAP). In this condition upper airway obstruction and/or work of
breathing induced by intrinsic PEEP are prevented by EPAP and thus PS can be
triggered easily by the patient. This ventilatory mode has been used in children with
OSA, CF [46, 47] and neuromuscular disease [46, 48, 49].
For all ventilatory modes, alarms must be correctly set. When positive pressure
ventilators are used, low pressure or disconnect alarms are classically present. Alarms for
high pressure, incorrect timing and power failure are also frequently present. The alarm of
a minimal VT is very useful in children. A back-up frequency is generally set on the
ventilator. All these alarms must be carefully checked before the discharge of the patient.

Interfaces
The necessity of interfaces, specifically designed for children, represents an important
technical limitation of NPPV in paediatric patients. In adults, four different types of

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interfaces are used: full face masks (enclose mouth and nose); nasal masks; nasal
pillows or plugs (insert directly into the nostrils); and mouthpieces. Nasal pillows and
plugs are too large for children and mouthpieces require a good co-operation and are
difficult to use in neuromuscular patients. In young children, nasal masks are preferred
because they have less static dead space, are less claustrophobic and allow
communication and expectoration more easily than full face masks. Nasal masks
allow also the use of a pacifier in infants, which contributes to the better acceptance of
NPPV and the reduction of mouth leaks; however, few industrial masks are available
for children. This shortcoming is even more important for infants. Most often, NPPV
is thus restrained to some highly specialised paediatric centres which have the
possibility of manufacturing custom-made masks for infants and children who can not
use industrial masks [50].
The nasal interface represents a crucial determinant of the success of NPPV. The
patient will be unable to tolerate and accept NPPV in case of facial discomfort, skin
injury or significant air leaks. The evaluation of the short term tolerance of the nasal
mask is thus an essential component of NPPV [50]. NPPV is generally used during sleep,
which can represent the major part of the day in young infants. In these young patients,
there is a potential risk of skin injury and facial deformity, such as facial flattening and
maxilla retrusion, caused by the pressure applied by the mask on growing facial
structures. These potential side effects justify the systematic follow up of children
receiving NPPV by a paediatric maxillo-facial specialist.

Additional therapies
Oxygen therapy at home must be justified on the basis of an individual-based medical
necessity, as determined by appropriate physiologic monitoring, such as Sa,O2 during
periods of sleep, wakefulness, feeding and physical activity and arterial blood gases. CO2
should be minimised first by ventilator use before considering oxygen therapy, especially
for patients with neuromuscular disorders and OSA. It is important to remember that
supplemental oxygen is not a replacement for assisted ventilation in patients who
hypoventilate.
Systematic humidification of the ventilator gas is not necessary for NPPV because of
the respect of the upper airway. However, nasal intolerance, due to excessive dryness can
resolve after humidification of the ventilator gas.
The maintenance of an optimal nutritional status is of major importance. Chronic
respiratory insufficiency is associated with an increased energy demand, feeding
difficulties and poor caloric intake. Swallowing problems may occur in patients with
neuromuscular disease [51]. In some patients, gastrostomy may be a useful adjunct
therapy to NPPV and contribute to postponing the time of a tracheostomy [51, 52].
It is essential that the child, if the age permits it, and the parents should have the
opportunity to discuss NPPV therapy in advance. Discussion should start long enough
before the anticipated need, to allow the child and the family to evaluate options
thoroughly and to discuss their feelings. NPPV, here, has an essential first place as a
noninvasive therapy but still represents an objective element reflecting a further step in
the severity of a disease. It is crucial to determine short- and intermediate-term goals of
NPPV with the child and the family and to explain the principles of NPPV. A wide
range of ventilators and masks are available and great care will be taken to choose the
most appropriate equipment and settings. The final objective is that NPPV translates
into well-being and a better quality of life with a total adherence of the child and their
family.

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Contraindications, side effects and limits of NPPV

The general point-of-view is that NPPV is preferred over invasive mechanical
ventilation as the first therapy of chronic respiratory failure. However NPPV is
contraindicated in some circumstances (table 2) [53]. NPPV is also contraindicated in
case of recent pneumothorax, which can occur in patients with advanced CF lung
disease. Pneumothorax can also occur as a side effect of NPPV in patients with
neuromuscular disorders [54]. In patients with CF, nasal polyps are common and should
be treated before the initiating of NPPV.
Side effects are common; they are caused by the interface and the delivery of a positive
pressure. In the present authors’ experience, skin injury, from transient erythema to
permanent skin necrosis, due to the nasal mask, has been observed in 53% of the 40
patients during their routine 6-months follow-up [50]. In young children, there is also a
potential risk of facial deformity, such as facial flattening and maxilla retrusion, caused
by the pressure applied by the mask on growing facial structures. These potential side
effects justify the systematic evaluation before the initiation and during the follow up of
children receiving NPPV by a paediatric maxillo-facial specialist. Abdominal distension
is an uncommon problem which can be lessened by switching to a PSV or decreasing the
VT on a volume-targeted ventilator [53].
NPPV is not always successful in adequately relieving hypoventilation. Air leaks have
been shown to be an important cause of persistent hypercapnia in both invasively and
noninvasively ventilated neuromuscular patients [55]. In these patients, simple practical
measures such as changing the mask, using a chin strap, increasing minute ventilation
and changing the type of the ventilator, were able to reduce the volume of air leaks and
improve the efficacy of ventilation [55].
In patients with neuromuscular disease, cough assisted techniques are useful when
ventilatory dependence is increasing. Several techniques are available such as manual
physiotherapy, intermittent positive pressure breathing, and mechanical insufflation-
exsufflation [56-59]. These techniques, associated with daytime ventilation by means of a
mouthpiece [60], extend the use of NPPV in patients having increasing ventilatory
dependency. However, despite these measures, in progressive diseases such as some
neuromuscular diseases, a tracheotomy will become necessary at a certain moment.
Close monitoring of the patient’s physiological status and disease progression, together
with clear information of the family are essential. Technical problems, especially with
regards to the nasal mask and the ventilator equipment, frequently limit the use of
NPPV in infants. Because noninvasive ventilation leaves airway protection, those with
copious secretions or severe swallowing dysfunction may respond poorly, requiring the
discussion of a tracheostomy with the patient and their family.

Table 2. – Contraindications for noninvasive positive pressure ventilation (NPPV). Adapted from [53]

Relative contraindications
Severe swallowing impairment
Inadequate family/caregiver support
Need for full-time ventilatory assistance
Absolute contraindications
Complete persistent upper airway obstruction during NPPV
Uncontrollable secretion retention
Inability to co-operate
Inability to achieve adequate peak cough flow, even with assistance
Inadequate financial resource
Inability to fit an interface

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In conclusion, noninvasive positive pressure ventilation is increasingly used in

children and infants. Unfortunately, in this age group, this therapy is generally initiated
on an empirical basis. Further studies are urgently needed to determine the most
pertinent criteria to initiate noninvasive positive pressure ventilation according to the
disease and the age of the patient; to evaluate the long term benefits, with regard to the
increase in survival, stabilisation in the decline in lung function and respiratory muscle
performance; to promote lung growth and respiratory mechanics; and, most
importantly, to improve the quality of life of the child and their family.

Summary
Domiciliary noninvasive positive pressure ventilation (NPPV) is increasingly used in
children. Three categories of respiratory system dysfunction can justify long term
NPPV: an increase in respiratory load (due to intrinsic cardiopulmonary disorders or
skeletal deformities); respiratory muscle weakness (due to neuromuscular diseases or
spinal cord injury); or failure of neurologic control of ventilation (such as the central
hypoventilation syndrome). In these different diseases, the role of NPPV will be to
respectively unload the respiratory muscles, to replace the respiratory muscles or to
replace central drive, in order to correct alveolar hypoventilation. The benefit of
NPPV on nocturnal and daytime gas exchange has been demonstrated in children.
Other effects, such as an improvement of lung function, respiratory muscle
performance or respiratory mechanics, are less well documented. The effect of
NPPV on lung growth is an important point that needs to be investigated. The type of
equipment and the specific ventilator settings that should be chosen remain a matter
of debate and evolve more rapidly with industry capability than with clear indications
available from scientific trials. The major advantage of NPPV is that it can be applied
at home, combining greater potential for psychosocial development and family
function, at a lesser cost. The use of home NPPV requires appropriate diagnostic
procedures, appropriate titration of the ventilator, co-operative and educated families
and a careful, well-organised follow up. NPPV represents a challenge for the future
whose objective is to improve the well-being of a child with chronic respiratory
insufficiency and his or her family.

Keywords: Alveolar hypoventilation, children, chronic respiratory insufficiency, home

care, noninvasive mechanical ventilation.

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