Chronic Respiratory Disease 2007; 4: 167–177

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REVIEW ARTICLE

Mechanical ventilation in Duchenne patients with chronic

respiratory insufficiency: clinical implications of 20 years
published experience
M Toussaint1, M Chatwin2 and P Soudon1
1Inkendaal Rehabilitation Hospital, Neuromuscular Centre VUB-Inkendaal and Centre for Home Mechanical Ventilation, Inkendaalstraat, 1, B-1602
Vlezenbeek (Brussels) Belgium; and 2Sleep and Ventilation Unit, Royal Brompton Hospital, London, 6NP, UK

Chronic respiratory insufficiency is inevitable in the course of disease progression in patients with
Duchenne muscular dystrophy (DMD). Without mechanical ventilation (MV), morbidity and mor-
tality are highly likely towards the end of the second decade of life. The present review reports evi-
dence and clinical implications regarding DMD patients treated with MV. There is no doubt that
nocturnal hypercapnia precedes daytime hypercapnia. Historical comparisons have provided evi-
dence that non-invasive intermittent positive pressure ventilation (NIPPV) at night is effective and
improves quality of life and survival by 5–10 years. By contrast, the optimal criteria and timing for
initiation of NIPPV are inconsistent. A recent randomized study however demonstrated the benefits
of commencing NIPPV as soon as nocturnal hypoventilation is detected (Ward S, et al., Randomised
controlled trial of non-invasive ventilation (NIV) for nocturnal hypoventilation in neuromuscular and
chest wall disease patients with daytime normocapnia. Thorax 2005; 60: 1019–24). The respective
role of the three hypotheses of the indirect action of nocturnal NIPPV on daytime blood gases may
be complimentary; the main improvement may be due to improved ventilatory response to CO2. The
ultimate time to offer full time ventilation with the most advantageous interface is lacking in evi-
dence. Full time NIV is possible with a combination of a nasal mask during the night and a mouth-
piece during the day, however tracheostomy may be provided when mechanical techniques of
cough-assistance are useless to treat chronic cough insufficiency. Chronic Respiratory Disease
2007; 4: 167–177

Key words: Duchenne; hypercapnia; neuromuscular diseases; noninvasive ventilation; respiratory

failure

Introduction pending death within 12 months are highly pre-

dictable.2,6
Chronic respiratory insufficiency (CRI) is an inevitable In DMD patients, hypercapnic CRI typically
complication in the disease progression of patients evolves in four stages: Stage 1, sleep disordered
with Duchenne muscular dystrophy (DMD). Patients breathing (SDB) without hypercapnia; stage 2, SDB
with DMD who are not treated with mechanical venti- with hypercapnia during rapid eye movement (REM)
lation (MV) typically die between the age of 19–21.5 sleep; stage 3, SDB with hypercapnia during REM and
years old.1,2 The variability of respiratory progression non-REM sleep and stage 4, diurnal hypercapnia.7–11
can be assessed by regular vital capacity (VC) meas- At stage 4, mean survival is less than one year if no
urements. Pre-adolescents DMD patients with optimal ventilation is offered.12 At stages 2 and 3, intervention
respiratory muscle strength can have a VC plateau of with MV corrects hypercapnia, improves survival and
ⱖ2500 mL while the weaker patients reach a VC quality of life.9,12–22
plateau ⱕ1500 mL.3 During adolescence, VC The aim of this review is to evaluate 20 years of
decreases at a rate of 8–12%/year;2–5 when VC ⬍ 1 L, published literature on MV in DMD patients with
oxygen desaturations, uncontrolled hypercapnia and chronic respiratory failure; management of MV in
acute situation will not be discussed. This review
Correspondence: Michel Toussaint, ZH Inkendaal, Inkendaalstraat, 1, B-1602 includes available evidence supporting current opin-
Vlezenbeek, Belgium. ion. Consensuses and expert opinion are discussed
E-mail: michel.toussaint@inkendaal.be where evidence is unavailable. Priority is given to
© SAGE Publications 2007 Los Angeles, London, New Delhi and Singapore 10.1177/1479972307080697

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 Mechanical ventilation in Duchenne patients
M Toussaint et al.
168

specific studies with DMD patients, but non-specific
studies in the neuromuscular (NM) population includ-
ing DMD patients are used when specific studies are
deficient. In addition, this review includes recommen-
dations for further research when the matter is contro-
versial or unexplored.
not directly mediated by an effect on sleep quality.
This observation suggests that sleep deterioration may
trigger and complicate nocturnal hypoventilation
rather than inducing hypoventilation itself.27 An obvi-
ous question is to determine the role of sleep quality
monitoring (extensive polysomnography) in the proto-
col to detect hypercapnia in DMD patients.

The need for a protocol to detect CRI

The need for systematic detection of the risks for CRI
is evident.23 We know nocturnal hypoventilation
precedes daytime hypoventilation for some years in
disease progression of DMD patients (Figure 1).23
Hypoventilation during REM-sleep was first reported
in 1975 in generalized NM patients24 and in 1984
in DMD patients.10 After 1987, breathing disorders
during sleep were extensively documented.25,26
Interestingly, one study investigating daytime MV dur-
ing wakefulness was able to reverse nocturnal
hypoventilation with similar benefits as with ventila-
tion during sleep.27 This implies that respiratory
improvement obtained with daytime ventilation was
Extensive polysomnography
Many studies have reported sleep statistics in DMD
patients; alterations in sleep quality (arousals) and
architecture (sleep fragmentation).7,28–31 In adolescent
DMD patients, 60% of apnoeas are initially obstruc-
tive.11,32 With disease progression apnoeas are essen-
tially central29 or pseudo-central (inspiratory effort too
weak to be identified).32 The presence of macroglossia
was reported to exacerbate sleep apnoeas.29
Unfortunately, no studies concluded the impact of
sleep deterioration on the decision to initiate nocturnal
non-invasive positive pressure ventilation (NIPPV) in
DMD patients.33 The major reason is that sleep

Figure 1 This Figure demonstrates the impact of initiation time of non-invasive positive pressure ventilation (NIPPV) on survival of
Duchenne muscular dystrophy patients. Ages are given as indicative values; FVC: forced vital capacity; CRI: chronic respiratory
insufficiency; Prev. NIPPV: preventive NIPPV initiation (see text); early NIPPV: early NIPPV initiation (see text); late NIPPV: late NIPPV
initiation (see text); REM: rapid eye movement; Black vertical arrow: point of time of NIPPV intervention.

Chronic Respiratory Disease

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apnoeas do not always lead to hypercapnia.11,24 As a
consequence, there is no need to know that sleep is dis-
rupted to initiate NIPPV. By contrast, there is a need to
measure hypercapnia to initiate NIPPV. One must be
aware that a full polysomnography is expensive and
hospital admissions are considered a major organiza-
tional event for DMD patients.34
Nocturnal monitoring
Carbon dioxide tension (PCO2) measurement during
the night should be considered every year once VC
declines,35 and ultimately when daytime PCO2 ⱖ
45 mmHg.8 Nocturnal measurement of PCO2 should
always be considered in symptomatic patients in
whom CRI is highly likely,36 however clinically this
does not always occur.
PCO2 measurement: invasive or non-invasive
technique?
There is no agreement regarding the technique to detect
hypercapnia in NM patients. One concern is to know
whether transcutaneous PCO2 (TcCO2) is sufficient
compared to the arterial PCO2 measurement (PaCO2).
PaCO2 has the disadvantage to be measured in the
morning during wakefulness therefore not reflecting
PCO2 during sleep. Despite slightly overestimating
PaCO2, TcCO2 has an excellent agreement with PaCO2
in stable patients with NIPPV (r: 0.97, P ⬍ 0.001)37
and in patients with critical illness.38,39 New technology
using earlobe sensor38 provides an excellent agreement
between TcCO2 and PaCO2 (r: 0.98, P ⬍ 0.0001).40
TcCO2 has the advantage of being non-invasive, and
easy to use. However, morning arterial or venous PCO2,
pH and base excess should be carried out to ensure
accurate baseline TcCO2. Overnight pulse oxymetry
can be effective but is considered as less sensitive in the
earlier stages of DMD disease.6,41
Detection of symptoms
CRI develops insidiously and symptoms of respiratory
failure may not be pronounced, especially in patients
with nocturnal hypercapnia with low mobility such as
in wheelchair bound DMD patients.20,42–44 The first
symptoms are related to a poor sleep quality with or
without hypercapnia,41,45 such as somnolence which is
the most common complaint,41 nightmares, morning
headaches and poor concentration have also been
reported.19,46,47 Pure respiratory-related symptoms
appear very late usually at the time of diurnal
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Mechanical ventilation in Duchenne patients
M Toussaint et al.
169
hypercapnia such as weariness, dyspnoea, orthopnoea,
chest oppression, hand sweating, swallowing distur-
bance, loss of appetite and moodiness.21,48,49 To date,
no validated symptom score is available.
Detection of CRI by daytime measurements
Undoubtedly, lung function best assess the degree of
respiratory muscle involvement in DMD patients.3
Indispensable lung function measurements include
VC,2,6,7 the maximal inspiratory and expiratory pres-
sures (MIP and MEP) at the mouth49–51 and the peak
expiratory flow during coughing (PCF).51–53 Sniff
nasal inspiratory pressure is reported as an accurate
estimate of maximal inspiratory strength. However, it
has been shown to underestimate inspiratory strength
in the DMD population.54 It is recommended that VC
in sitting and supine position, MIP and MEP, and PCF
measurements should be recorded twice a year in non-
ambulatory patients.45,55 In DMD patients, the age at
which VC falls below 1 L is a best predictor of age of
death than nocturnal oxygen saturation.6,9
Prediction of hypercapnia by the vital capacity
Few studies have addressed the unique needs of DMD
patients. Some authors failed to establish a relationship
between VC and hypercapnia20,56 while others demon-
strated the appropriateness of VC ⬍ 40%7,8,45,46,56,57
and MIP ⬍ 30 cm H2O7,49 in predicting nocturnal
hypercapnia. At a later stage of disease progression,
VC ⬍ 20% and MIP ⬍ 26 cm H2O accurately pre-
dicted daytime hypercapnia.31 The disability score
added to VC% provides a better indication of the need
for MV than VC% alone.45
Prediction of hypercapnia by the breathing pattern
During weaning procedure, the use of the rapid and
shallow breathing index (RSBI)58,59 and the tension
time index (TTI) calculated by Ti/Ttot x Pi/MIP59,60
provides prediction of the ability for NM patients to
self ventilate. However, additional investigations are
needed to detect whether hypercapnia is related to
those indexes in DMD patients.61 The TTI59,62 and the
endurance tests at constant inspiratory load63 are
promising indices to discriminate those DMD patients
at risks for respiratory muscle fatigue approaching the
need for full time-assisted ventilation.
Multidisciplinary team
There is a need for an integrated multidisciplinary
team in the care of DMD patients. Such a team should
include a key physician, particularly between
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 Mechanical ventilation in Duchenne patients
M Toussaint et al.
170
childhood and adult transition to assure continuity in
the detection of CRI.64 There should be compassionate
discussions with patients and family about respiratory
progression and prognosis and about MV before CRI
occurs;24,35 this should be with the most appropriate
member of the multidisciplinary team.
The optimum timing for initiation of MV:
four options
No ventilation
Assisted ventilation was seldom proposed to DMD
patients5 before the 1980’s. The option of no ventila-
tion is now universally judged as unethical in countries
where the technology is available. However, in rare
cases it may be ethical not to commence NIPPV where
this is in accordance with the profound wishes of some
well-informed patients.
Preventive use of NIPPV
The initial objective of preventive NIPPV is aimed at
lowering the inevitable worsening of VC with disease
progression in normocapnic and asymptomatic
patients.1,3 Rideau et al.18 showed preventive NIPPV
resulted in long-term stabilization of VC in 70% of
patients. In 1994 a French multicenter randomized
study conducted by Raphael et al.65 investigated the
impact of preventive NIPPV on survival in a DMD
population versus control without NIPPV. Survival
rates were significantly lower in the NIPPV group. As
a conclusion, prophylactic use of NIPPV in Duchenne
patients was not recommended for DMD patients with
VC ranging 20–50% predicted.65 Pure prophylactic
introduction of NIPPV was thereafter rejected.
However, this study has been criticized for the follow-
ing reasons: The families in both groups were aware
that if the individual in the control arm deteriorated
they would receive NIPPV, and the NIPPV arm, should
use their ventilator more liberally. This advice may
have caused the control arm to seek medical assistance
earlier than the NIPPV arm and this may have pre-
vented deaths. In this study, there were no recommen-
dations that the ventilator could be used to assist in
secretion clearance. Secondly, cardiac function was
significantly worse in the NIPPV arm with only 10
having normal echo versus 20 in the control group,
potentially biasing the results. Thirdly, Raphael et al.65
did not measure nocturnal PCO2 in patients with VC
ranging 20–50% although DMD patients with
VC ⬍ 40% are exposed at high risk of developing noc-
turnal hypercapnia.8,46,57 Consequently, Raphael
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et al.65 did not discriminate patients without nocturnal
hypercapnia from those with nocturnal hypercapnia,
although NIPPV should be considered as a treatment
of nocturnal hypercapnia (see below). All these
methodological shortcomings make interpretation of
the results of this study65 confusing.
‘Early’ initiation of NIPPV with nocturnal
hypercapnia alone
Early initiation of NIPPV is a growing approach
(Table 1): NIPPV is here proposed in nocturnal hyper-
capnia alone, even when sleep-related symptoms are
not present.22 At this stage of respiratory involvement,
DMD patients do not show severe O2 desaturation at
night.42 Soudon et al.15 proposed a very early approach
by starting MV as soon as REM sleep hypercapnia was
present, considering early MV as a curative treatment
of early CRI. These authors however, could not vali-
date their approach. Other groups suggested that a
‘semi-early’ approach was beneficial since hypercap-
nia was present either during 50%21 or 100%
sleep.22,55 Importantly, Ward et al.22 recently investi-
gated the initiation of NIPPV with patients with noc-
turnal hypercapnia alone in a randomized controlled
study; they demonstrated that these patients are likely
to deteriorate with the development of daytime hyper-
capnia within two years. Initiation of nocturnal NIPPV
before the development of daytime hypercapnia was
beneficial to the patient. Benefits included increased
quality of life, relief of the symptoms, reduction of
daytime hypercapnia and reduced risk of admission in
ICU for decompensated respiratory failure.22 Initiation
of NIPPV in the presence of nocturnal hypercapnia
alone can delay future daytime hypercapnia which
occurs 4–5 years after NIPPV initiation.48
‘Late’ initiation of NIPPV with diurnal
hypercapnia
In this approach, NIPPV is established when daytime
hypercapnia occurs, meaning that patients have raised
CO2 levels day and night. Most patients are very symp-
tomatic patients66 with VC ⬍ 20% predicted7 some-
times resulting in uncontrolled respiratory
decompensation.67 At this stage of disease progression,
DMD patients will show severe O2 desaturations at
night,11,19,42,68,69 with up to 30% sleeping time with
SpO2 ⬍ 90%.8
Published consensuses do not clearly guide clini-
cians on the correct time for NIPPV initiation. A
European consensus considers NIPPV initiation when
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Table 1 Patient group demographics of studies reporting initiation of non-invasive positive pressure ventilation (NIPPV) in DMD patients
Study Patients Conditions at
characteristics characteristics NIPPV initiation Results

PCO2 PCO2
Length criterion measurement PCO2 PCO2 Survival
First author Year (months) n DMD VC (mL) Age (years) Option (mmHg) technique (mmHg) (mmHg) (Age/Years)

Mohr14 1990 39 8 616 22 L ⬎45* Art 63* 45 –

Soudon15 1991 30 14 517 19.9 L ⬎45** Tc 89** 35 –
Soudon15 1991 30 3 1383 16.1 E ⬎45** Tc 65** 47 –
Bach91 1993 72 38 305 19.3 L – End-tidal – – 26.4
Leger17 1994 36 16 700 21 L ⬎45* Art 52* 42 28
Raphael65 1994 52 35 1334 16 P ⬍45* Art 39* – 19
Vianello12 1994 24 5 670 19.8 L ⬎45* Art/Tc 48.8* 46 ⬎22
Rideau18 1995 45 14 1756 14.1 P – – – – –
Fanfulla62 1998 24 10 752.5 18.3 L * Art 44.3 – –
Simonds9 1998 60 23 306 20.3 L ⬎52.6* Art/Tc 77.1* 45 26.6
Baydur20 2000 22 15 600 20.3 L ⬎45* Art 49.7* 46.7 –
Hukins8 2000 11 8 910 – L * Art 54* 49.1 –
Eagle55 2002 24 ⬍1250 – E – – – – 25.3
Mellies21 2003 29 5 1200 16.6 E ⬎50.5** ART/Tc 45.9** 41.9 –
50% sleep
Konagaya108 2005 – 73 – – – – – – – 31
Ward22 2005 24 8 530 – L ⬎48.9* Art/Tc 56* – –
Ward22 2005 24 2 1010 – E ⬎48.9** Art/Tc 43.5* – –
Kohler68 2005 – 14 470 23.3 L ⬎50** Art/Tc 48.1* – –
Toussaint48 2006 – 42 1016 19.4 E ⬎45** Tc – – ⬎25

VC: vital capacity; L: late NIPPV initiation (see text), E: early NIPPV initiation (see text); P: preventive NIPPV initiation (see text); Art: arterial PCO2 meas-
urement; Tc: transcutaneous PCO2 measurement; *wakeful PCO2 measured during the day; **PCO2 measured during sleep.

a PaCO2 ⱖ 45 mmHg.70 The American consensus
statement23 considers two possible criteria; first one
should consider NIPPV with the presence of symp-
toms accompanied by paCO2 ⱖ 45 mmHg or noctur-
nal SpO2 ⱕ 88% for five consecutive minutes. The
second consideration may indicate onset of NIPPV
with the presence of symptoms, but accompanied here
by less severe criteria such as MIP ⬍ 60 cm H2O or
FVC ⬍ 50% predicted. As previously stated, Ward
et al.22 provided powerful arguments in favour of com-
mencing assisted ventilation in the presence of
PCO2 ⬎ 48.9 mmHg during the night.
Contraindications and precautions
for NIPPV
Contraindications are rare and include: lack of con-
sciousness, lack of cooperation from the patient,
inability to maintain the airway, presence of severe
bulbar impairment and a lack of nasal access.56,57,71
Patients should be taught airway clearance techniques
prior to the commencement of NIPPV.24,64,72,73–76
Education of caregivers and families on airway clear-
ance techniques during home NIPPV is an important
factor in the success of NIPPV.76,77
Choice of the ventilator and settings
Ventilator
Intermittent positive pressure ventilators supplanted
negative pressure ventilators previously used with
DMD patients.13,78 Two types of positive pressure ven-
tilators were used: volume ventilators and pressure
support ventilators. Both systems have similar effects
on alveolar hypoventilation,79,80 and on (partial) respi-
ratory muscles unloading.80–82 Recently, microproces-
sor-based ventilators were developed aiming at
combining the advantages of pressure and volume ven-
tilators.83–85 This new generation of ventilators pro-
vides leaks compensation, targeted volume86 and
sensitive triggering for optimal synchronization87 and
comfort.21,78,88,89 During the daytime, volume ventila-
tors are preferable48,77,90 for the benefits of air-stack-
ing16,74,90 and for the absence of leaks compensations
enabling mouthpiece ventilation on demand.48,90
Settings
Effective ventilation is easier achieved with low-inspi-
ratory positive airway pressures (IPAP) between

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 Mechanical ventilation in Duchenne patients
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10–15 cm H2O19,84,92 although pressures ⬎ 20 cmH2O
have been reported.93 In NM patients, adequate setting
for volume ventilators devices was found at high-res-
piratory rate (RR: 23/min⫺1) and low tidal volume
(VT: 14 mL/kg of actual weight).94 Parameters may
extremely vary among individuals.
Interfaces
Introduced in the 1980’s by Rideau et al.1 the nasal
mask still remains the first choice of interface for noc-
turnal ventilation;9,12,16–20,22,47,68,89,95–98 however, there
is no agreement concerning the choice of the diurnal
interface. Dr Alba introduced mouthpiece ventilation in
DMD patients;16 daytime mouthpiece ventilation
(Figure 2) has become a growing technique.90 A recent
Belgian cohort study reported use of 24 h nasal/mouth-
piece ventilation in 42 DMD patients over a period of
9.6 years.48 They concluded that it is a safe and effective
form of ventilation for patients requiring 24/24 h NIV;
the mean survival was 31 years. Some authors consider
tracheostomy as more effective and more secure than
non-invasive interfaces,14,20 although a similar risk of
death with both non-invasive and invasive ventilation
has been reported.99 Tracheostomy offers the possibility
for direct suctioning,100 with an additional risk for tra-
cheal erosion,93 mucus hypersecretion, granulation tis-
sue formation,101 tracheobronchomalacia93 and tracheal
haemorrhage.93,101,102 This morbidity may decrease the
quality of life of the patient and caregivers. Patients are
more likely to be cared for in an institution as opposed
to the family home,48 while families and caregivers are
exposed to greater demands for care.
Figure 2 This Figure demonstrates mouthpiece ventilation in a
patient with Duchenne muscular dystrophy. Nasal mask ventilation
is used at night.
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The appropriate time to offer tracheostomy for 24 h
MV remains controversial and depends on individual
experiences.76 Traditionally, early tracheostomy is
used more commonly in France compared to other
countries103 despite requiring more carer and financial
resources than NIPPV.100,103 Undoubtedly, tra-
cheostomy should be considered when non-invasive
techniques for airway clearance have become ineffec-
tive to treat chronic cough insufficiency.
PCO2 monitoring during MV
As suggested by many recent clinical stud-
ies,9,21,22,37,40,48,68 TcCO2 is considered as the first
choice of technique to monitor nocturnal blood CO2
tension in the follow-up of home MV.
Efficacy of MV
Quality of life and symptoms
DMD patients consider home MV beneficial for inde-
pendent living and enhancing their overall health104
and quality of life9,14,21,68 while health-related quality
of life further decreases without MV.105 Nocturnal
NIPPV reverses symptoms associated with poor sleep
quality22,47,66 and full time MV reverses symptoms
associated with daytime dyspnoea.48,55 Quality of life
may be perceived differently in function of the inter-
face. Tracheostomized patients express fewer positive
statements than those ventilated non-invasively.104,106
Blood gas improvement
A consensus report23 and a Meta-analysis107 validated
the short-term benefits of nocturnal MV on nocturnal
(direct effect) and diurnal (indirect effect) blood gases
in NM patients. Nevertheless, by contrast with other
NM disorders,17,20,105 PCO2 normalization is often
suboptimal in DMD patients as suggested by PCO2
ranging 45–50 mmHg during NIPPV (table
1).8,9,12,17,20 This phenomenon is not explained and
warrants further investigation in order to avoid biased
additional daytime ventilation to compensate for inef-
fective nocturnal NIPPV.
Survival
Cohorts of DMD patients receiving MV were com-
pared to patients refusing MV.12,15 Survival rates at 24
and 30 months were 100%12 and 80%,15 respectively,

while death occurred within 10 months without MV. In
two other studies, survival reached 25.3 years55 and 31
years108 with MV compared to 19.3 years55 and 20.4
years108 without MV. In DMD patients, MV is
generally considered to provide an additional life’s
expectancy of 5–10 years (Figure 1).9,48,55,108–110
To date, there is no data to support an enhanced
survival rate depending on timing of NIPPV
initiation.34
Ethical considerations
Quality of life is not estimated as lower by DMD
patients after MV initiation, suggesting that MV
itself does not adversely affect the perceived health
status.68 However, resistances to recommend MV are
reported in underinformed medical teams believing
that MV brings a new handicap in DMD patients’
life.111 Information given to patients and family is
never unbiased and often influences the choice for
MV institution and evolution, especially when full
time MV is required.106,111,112 The issue of euthana-
sia has never been reported in end-stage DMD
patients.
Indirect effect of nocturnal MV on
gas exchange during spontaneous
breath
Three hypotheses were developed to explain the indi-
rect mechanism of action of nocturnal MV in sustained
normocapnia during the spontaneous breathing during
wakefulness (SBW).113
Respiratory muscle rest
This hypothesis is controversial and not convinc-
ing.14 Undoubtedly, NIPPV has been shown to
unload inspiratory muscles,62,84,114 but the relation
between muscle fatigue and respiratory failure is not
evident.115
Improvement of respiratory system
compliance
In NM disorders, short sessions of 20 min per day of
insufflations with positive pressure did not change the
respiratory system compliance.116,117 The effects on
compliance of NIPPV during the night have been
reported as variable in DMD patients and require
further investigation.
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M Toussaint et al.
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Resetting of the central respiratory centre
sensitivity for CO2
In NM disorders, resetting of the central respiratory
centres may be the most important among the three
hypotheses.99,118,119 Many studies support the
hypothesis8,19,21,25,27,98,120,121–123 that nocturnal NIPPV
leads to an upward resetting of the central respiratory
centre CO2 sensitivity, indirectly reducing daytime
hypercapnia.27,80,119
Undoubtedly, future work is required to clarify the
role of these three hypotheses at different stages of
illness progression.119 Sessions of daytime ventilation
are deemed to offer interesting area of research.27,124,125
What to do when NIPPV fails?
All non-invasive techniques should be fully explored
before providing tracheostomy. Failure of NIPPV may
occur, due to technical issues, patient’s reluctance or
due to disease progression.126
Technical issues
Technical problems include mask discomfort, leaking
and gastro intestinal bloating. Mask discomfort126 is
easily solved by using another mask64 or a custom
made mask.95 Leaking around the mask and/or by the
mouth is associated with poor ventilation and sleep
disruption,88,127,128 and is often related to poor mask
fitting,126 to problems of timing of ventilation or to the
use of excessive IPAP.126 The strategy to reduce leak-
ing include increasing RR (ⱖ23/min),94 decreasing
IPAP (ⱕ15 cm H2O)129 or VT (ⱕ13 mL/kg),94 or
increasing the inspiratory/expiratory (I/E) ratio (from
1/1.5 to 1/1).126
Mouth leaking24 and asynchrony87 may be
improved by the use of microprocessor-based ventila-
tors, which compensate for leaks. An additional mouth
taping24 via a chin strap127,128 or a cervical collar126 is
very useful in reducing mouth leaking. Mouthpiece
with lip sealing or full face mask ventilation may be
used when uncontrolled leaks are present.16 Finally,
gastro-intestinal bloating may be a severe complica-
tion of NIPPV. Again, limiting IPAP is useful.126
Anxiety, lack of confidence, lack of intellectual
cooperation
Anxiety can be limited by educating the patient,
family and caregivers. Patients are often more afraid
about the idea of NIPPV than NIPPV itself. Anxiety
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 Mechanical ventilation in Duchenne patients
M Toussaint et al.
174
can easily be reduced by an informal trial during a con-
sultation to actually experience ventilation via a nasal
mask. A trial is also useful in patients with learning
difficulties, one must bear in mind severe learning dif-
ficulties is not a contra-indication to NIPPV, although
the process can be challenging.
Disease progression
Tracheostomy ventilation has become less common
within the disease progression management of DMD
patients.130 As previously said, DMD patients are
being managed safely with a series of non-invasive
techniques.16,48,74
Short-term physiological effects of MV
In non-NM patients receiving NIPPV, VT and Ti
increase, while RR, p0.1 and the tension-time index all
reduce during assisted ventilation.62 During intervals
of spontaneous breathing between periods of NIPPV,
RR remains constant131 or increases with increasing
p0.1.27 The impact on the short-term of MV on
spontaneous breathing has not been studied in DMD
patients.
Long-term physiological effects of MV
Long-term physiological outcomes of MV are conflict-
ing in DMD patients:75 VC have been shown to
increase,27,102 to stabilize,12,97,121 to decline at a slower
rate15,18,20 or to decline further similarly to that prior to
MV.8,21 One explanation for the inconsistent reports
may be related to the use of different types of ventila-
tors and settings. Hospitalization rates have been
reported as reduced17,132 or unchanged20,65 after
initiation of MV and therefore we would recommend
further investigation in this area.
Full time ventilation
When is full time MV required?
Extension of MV to daytime use is empirically
driven.14,45,76 The use of MV from 18 to 20/24 h has
been reported with VC ⱕ 400 mL14 to VC ⬍ 300 mL,
respectively.4,91 Ventilator free time was documented as
less than 15 min in patients with VC ⬍ 10% predicted.20
The ATS consensus statement for DMD patients
recommends daytime MV when PCO2 ⬎ 50 mmHg
Chronic Respiratory Disease
Downloaded from crd.sagepub.com at University of New England on June 9, 2015
and/or SpO2 ⬍ 92% while awake.133 Those criteria
were recently reported as difficult to reach in sympto-
matic patients in whom diurnal PCO2 ⬎ 45 mmHg
served as decisive factor to extend NIPPV into the
daytime.48,55 Worsening of the symptoms48 and dysp-
noea55 during the day suggest a high cost of energy
expenditure spent in maintaining normocapnia.
Reversal of the symptoms may be expected with a few
hours of daytime NIPPV,48,55 but this has not yet been
demonstrated. Controlled investigations should help
clinicians in deciding when and how to start daytime
ventilation,76 possibly by the use of a simple symptom
score.36,46,48
Outcome of 24 h MV
There is little information on the outcome of 24 h MV.
Three studies reported prolonged survival in DMD
patients with a combination of daytime mouthpiece
ventilation and nocturnal nasal NIPPV16,48,89 with
stabilization of VC over five years.48 Undoubtedly,
tracheostomy and intubations may be avoided on the
condition that cough-assistance techniques are
available.74 With mouthpiece ventilation, the challenge
of eating together with breathing via the mouth may
lead to the loss of weight and consequently to the
placement of enteral feeding.133
Conclusions
Undoubtedly, nocturnal ventilation is safe and effec-
tive to treatment in DMD patients with hypercapnia.
However, the ideal timing of when to initiate nocturnal
assisted ventilation remains debatable. The ultimate
timing to offer full time ventilation with the most
advantageous interface is also lacking in evidence.
Future investigations are required to enable clinicians
to refine the introduction and long-term follow-up of
both nocturnal and full time-assisted ventilation in
DMD patients.
References
1. Rideau Y, Gatin G, Bach J et al. Prolongation of life in Duchenne’s
muscular dystrophy. Acta Neurol 1983; 5: 118–124.
2. Phillips MF, Quinlivan RC, Edwards RH et al. Changes in spirometry
over time as a prognostic marker in patients with Duchenne muscular
dystrophy. Am J Respir Crit Care Med 2001; 164: 2191–4.
3. Rideau Y, Jankowski LW, Grellet J. Respiratory function in the muscu-
lar dystrophies. Muscle Nerve 1981; 4: 155–164.
4. Baydur A, Gilgoff I, Prentice W et al. Decline in respiratory function
and experience with long-term assisted ventilation in advanced
Duchenne’s muscular dystrophy. Chest 1990; 97: 884–9.

5. Inkley SR, Oldenburg FC, Vignos PJ Jr. Pulmonary function in
Duchenne muscular dystrophy related to stage of disease. Am J Med
1974; 56: 297–306.
6. Phillips MF, Smith PE, Carroll N et al. Nocturnal oxygenation and
prognosis in Duchenne muscular dystrophy. Am J Respir Crit Care
Med 1999; 160: 198–202.
7. Ragette R, Mellies U, Schwake C et al. Patterns and predictors of sleep
disordered breathing in primary myopathies. Thorax 2002; 57: 724–28.
8. Hukins CA, Hillman DR. Daytime predictors of sleep hypoventilation
in Duchenne muscular dystrophy. Am J Respir Crit Care Med 2000;
161: 166–170.
9. Simonds AK, Muntoni F, Heather S et al. Impact of nasal ventilation
on survival in hypercapnic Duchenne muscular dystrophy. Thorax
1998; 53: 949–52.
10. Soudon P, Wouters A, Kulakowski S. pO2-pCO2. Transcutaneous
monitoring during sleep and ventilatory function in X-linked progres-
sive muscular dystrophies. Cardiomyology 1984; 3: 21–38.
11. Suresh S, Wales P, Dakin C et al. Sleep-related breathing disorder in
Duchenne muscular dystrophy: disease spectrum in the paediatric pop-
ulation. J Paediatr Child Health 2005; 41: 500–3.
12. Vianello A, Bevilacqua M, Salvador V et al. Long-term nasal intermit-
tent positive pressure ventilation in advanced Duchenne’s muscular
dystrophy. Chest 1994; 105: 445–48.
13. Curran FJ. Night ventilation by body respirators for patients in chronic
respiratory failure due to late stage Duchenne muscular dystrophy.
Arch Phys Med Rehabil 1981; 62: 270–74.
14. Mohr CH, Hill NS. Long-term follow-up of nocturnal ventilatory
assistance in patients with respiratory failure due to Duchenne-type
muscular dystrophy. Chest 1990; 97: 91–96.
15. Soudon P, Steens M, Toussaint M et al. Ventilation assistée au long cours
dans les maladies neuro-musculaires. Louvain Med 1991; 110: 235–53.
16. Bach JR, O’Brien J, Krotenberg R, Alba AS. Management of end stage
respiratory failure in Duchenne muscular dystrophy. Muscle Nerve
1987; 10: 177–182.
17. Leger P, Bedicam JM, Cornette A et al. Nasal intermittent positive
pressure ventilation. Long-term follow-up in patients with severe
chronic respiratory insufficiency. Chest 1994; 105: 100–5.
18. Rideau Y, Delaubier A, Guillou C et al. Treatment of respiratory insuf-
ficiency in Duchenne’s muscular dystrophy: nasal ventilation in the
initial stages. Monaldi Arch Chest Dis 1995; 50: 235–38.
19. Fanfulla F, Berardinelli A, Gualtieri G et al. The efficacy of noninva-
sive mechanical ventilation on nocturnal hypoxaemia in Duchenne’s
muscular dystrophy. Monaldi Arch Chest Dis 1998; 53: 9–13.
20. Baydur A, Layne E, Aral H et al. Long term non-invasive ventilation in
the community for patients with musculoskeletal disorders: 46 year
experience and review. Thorax 2000; 55: 4–11.
21. Mellies U, Ragette R, Dohna Schwake C et al. Long-term noninvasive
ventilation in children and adolescents with neuromuscular disorders.
Eur Respir J 2003; 22: 631–36.
22. Ward S, Chatwin M, Heather S et al. Randomised controlled trial of
non-invasive ventilation (NIV) for nocturnal hypoventilation in neuro-
muscular and chest wall disease patients with daytime normocapnia.
Thorax 2005; 60: 1019–24.
23. Anonymous. Consensus conference. Clinical indications for noninva-
sive positive pressure ventilation in chronic respiratory failure due to
restrictive lung disease, COPD, and nocturnal hypoventilation: a con-
sensus conference report. Chest 1999; 116: 521–34.
24. Coccagna G, Mantovani M, Parchi C et al. Alveolar hypoventilation
and hypersomnia in myotonic dystrophy. J Neurol Neurosurg
Psychiatry 1975; 38: 977–84.
25. Ellis ER, Bye PT, Bruderer JW et al. Treatment of respiratory failure
during sleep in patients with neuromuscular disease. Positive-pressure
ventilation through a nose mask. Am Rev Respir Dis 1987; 135: 148–52.
26. Smith PE, Calverley PM, Edwards RH. Hypoxemia during sleep in
Duchenne muscular dystrophy. Am Rev Respir Dis 1988; 137: 884–88.
27. Schonhofer B, Geibel M, Sonneborn M et al. Daytime mechanical ven-
tilation in chronic respiratory insufficiency. Eur Respir J 1997; 10:
2840–46.
28. Carroll N, Bain RJ, Smith PE et al. Domiciliary investigation of sleep-
related hypoxaemia in Duchenne muscular dystrophy. Eur Respir J
1991; 4: 434–40.
Downloaded from crd.sagepub.com at University of New England on June 9, 2015
Mechanical ventilation in Duchenne patients
M Toussaint et al.
175
29. Barbe F, Quera-Salva MA, McCann C et al. Sleep-related respiratory
disturbances in patients with Duchenne muscular dystrophy. Eur
Respir J 1994; 7: 1403–8.
30. Hess DR. Noninvasive ventilation in neuromuscular disease: equip-
ment and application. Respir Care 2006; 51: 896–911.
31. Ragette R, Mellies U, Schwake C et al. Sleep-disordered breathing in
neuromuscular diseases. Pneumologie 2003; 57: 729–33.
32. Khan Y, Heckmatt JZ. Obstructive apnoeas in Duchenne muscular
dystrophy. Thorax 1994; 49: 157–61.
33. Bourke SC, Gibson GJ. Sleep and breathing in neuromuscular disease.
Eur Respir J 2002; 19: 1194–1201.
34. Lofaso F, Quera-Salva MA. Polysomnography for the management of
progressive neuromuscular disorders. Eur Respi J 2002; 19: 989–90.
35. Ramelli GP, Hammer J. Swiss physicians’ practices of long-term
mechanical ventilatory support of patients with Duchenne Muscular
Dystrophy. Swiss Med Wkly 2005; 135: 599–604.
36. Fauroux B, Lofaso F. Non-invasive mechanical ventilation: when to
start for what benefit? Thorax 2005; 60: 979–80.
37. Janssens JP, Howarth-Frey C, Chevrolet JC et al. Transcutaneous
PCO2 to monitor noninvasive mechanical ventilation in adults:
assessment of a new transcutaneous PCO2 device. Chest 1998; 133:
768–73.
38. Senn O, Clarenbach CF, Kaplan V et al. Monitoring carbon dioxide
tension and arterial oxygen saturation by a single earlobe sensor in
patients with critical illness or sleep apnea. Chest 2005; 128: 1291–96.
39. Herrejon A, Inchaurraga I, Palop J et al. Usefulness of transcutaneous
carbon dioxide pressure monitoring to measure blood gases in adults
hospitalized for respiratory disease. Arch Bronconeumol 2006; 42:
225–29.
40. Cox M, Kemp R, Anwar S et al. Non-invasive monitoring of CO2
levels in patients using NIV for AECOPD. Thorax 2006; 61: 363–64.
41. Laub M, Berg S, Midgren B. Symptoms, clinical and physiological
findings motivating home mechanical ventilation in patients with
neuromuscular diseases. J Rehabil Med 2006; 38: 250–54.
42. Manni R, Zucca C, Galimberti CA et al. Nocturnal sleep and oxygen
balance in Duchenne muscular dystrophy. A clinical and polygraphic
2-year follow-up study. Eur Arch Psychiatry Clin Neurosci 1991; 240:
255–57.
43. Lanini B, Misuri G, Gigliotti F et al. Perception of dyspnea in patients
with neuromuscular disease. Chest 2001; 120: 402–8.
44. Hours S, Lejaille M, Pozzi D et al. Perceived inspiratory difficulty in
neuromuscular patients with primary muscle disorders. Neuromuscul
Disord 2004; 14: 289–96.
45. Lyager S, Steffensen B, Juhl B. Indicators of need for mechanical ven-
tilation in Duchenne muscular dystrophy and spinal muscular atrophy.
Chest 1995; 108: 779–85.
46. Mellies U, Ragette R, Schwake C et al. Daytime predictors of sleep
disordered breathing in children and adolescents with neuromuscular
disorders. Neuromuscul Disord 2003; 13: 123–8.
47. Mellies U, Dohna-Schwake C, Ragette R et al. Nocturnal noninvasive
ventilation of children and adolescents with neuromuscular diseases:
effects on sleep and symptoms. Wien Klin Wochenschr 2003; 115:
855–59.
48. Toussaint M, Steens M, Wasteels G et al. Diurnal ventilation via
mouthpiece: survival in end-stage Duchenne patients. Eur Respir J
2006; 28: 549–55.
49. Yasuma F, Kato T, Matsuoka Y et al. Row-a-boat phenomenon: respi-
ratory compensation in advanced Duchenne muscular dystrophy. Chest
2001; 119: 1836–39.
50. Nicot F, Hart N, Forin V et al. Respiratory muscle testing: a valuable
tool for children with neuromuscular disorders. Am J Respir Crit Care
Med 2006; 174: 67–74.
51. Kang SW, Kang YS, Sohn HS et al. Respiratory muscle strength and
cough capacity in patients with Duchenne muscular dystrophy. Yonsei
Med J 2006; 47: 184–190.
52. Chaudri MB, Liu C, Hubbard R et al. Relationship between supramax-
imal flow during cough and mortality in motor neurone disease. Eur
Respir J 2002; 19: 434–38.
53. Gauld LM, Boynton A. Relationship between peak cough flow and
spirometry in Duchenne muscular dystrophy. Pediatr Pulmonol 2005;
39: 457–60.
http://crd.sagepub.com
 Mechanical ventilation in Duchenne patients
M Toussaint et al.
176
54. Iandelli I, Gorini M, Misuri G, Gigliotti F, Rosi E, Duranti R, Scano G.
Assessing inspiratory muscle strength in patients with neurologic and
neuromuscular disease. Chest 2001; 119: 1108–13.
55. Eagle M, Baudouin SV, Chandler C et al. Survival in Duchenne mus-
cular dystrophy: improvements in life expectancy since 1967 and the
impact of home nocturnal ventilation. Neuromuscul Disord 2002; 12:
926–29.
56. Canny GJ, Szeinberg A, Koreska J et al. Hypercapnia in relation to pul-
monary function in Duchenne muscular dystrophy. Pediatr Pulmonol
1989; 6: 169–171.
57. Braun NM, Arora NS, Rochester DF. Respiratory muscle and pul-
monary function in polymyositis and other proximal myopathies.
Thorax 1983; 38: 616–23.
58. Yang KL. Inspiratory pressure/maximal inspiratory pressure ratio: a
predictive index of weaning outcome. Intensive Care Med 1993; 19:
204–8.
59. Vassilakopoulos T, Zakynthinos S, Roussos C. The tension-time index
and the frequency/tidal volume ratio are the major pathophysiologic
determinants of weaning failure and success. Am J Respir Crit Care
Med 1998; 158: 378–85.
60. Koga T, Watanabe K, Sano M et al. Breathing intolerance index: a new
indicator for ventilator use. Am J Phys Med Rehabil 2006; 85: 24–30.
61. Misuri G, Lanini B, Gigliotti F et al. Mechanism of CO(2) retention in
patients with neuromuscular disease. Chest 2000; 117: 447–53.
62. Fanfulla F, Delmastro M, Berardinelli A et al. Effects of different ven-
tilator settings on sleep and inspiratory effort in patients with neuro-
muscular disease. Am J Respir Crit Care Med 2005; 172: 619–24.
63. Matecki S, Topin N, Hayot M et al. A standardized method for the
evaluation of respiratory muscle endurance in patients with Duchenne
muscular dystrophy. Neuromuscul Disord 2001; 11: 171–77.
64. Panitch HB. Respiratory issues in the management of children with
neuromuscular disease. Respir Care 2006; 51: 885–93.
65. Raphael JC, Chevret S, Chastang C et al. Randomised trial of preven-
tive nasal ventilation in Duchenne muscular dystrophy. French
Multicentre Cooperative Group on Home Mechanical Ventilation
Assistance in Duchenne de Boulogne Muscular Dystrophy. Lancet
1994; 343: 1600–4.
66. Howard RS, Davidson C. Long term ventilation in neurogenic respira-
tory failure. J Neurol Neurosurg Psychiatry 2003; 74: 24–30.
67. Simonds AK. Home ventilation. Eur Respir J Suppl 2003; 47: S38–46.
68. Kohler M, Clarenbach CM, Boni L et al. Quality of life, physical dis-
ability, and respiratory impairment in Duchenne muscular dystrophy.
Am J Respir Crit Care Med 2005; 172: 1032–36.
69. Ogata K, Kohno S, Komiya T et al. Different mechanism may under-
lie respiratory failure of myotonic and Duchenne muscular dystro-
phies: a pulseoxymetric and spirometric study. Rinsho Shinkeigaku
1996; 36: 850–53.
70. Robert D, Willig TN, Leger P et al. Long-term nasal ventilation in neu-
romuscular disorders: report of a consensus conference. Eur Respir J
1993; 6: 599–606.
71. Hahn A, Bach JR, Delaubier A et al. Clinical implications of maximal
respiratory pressure determinations for individuals with Duchenne
muscular dystrophy. Arch Phys Med Rehabil 1997; 78: 1–6.
72. Servera E, Sancho J, Zafra MJ et al. Alternatives to endotracheal intu-
bation for patients with neuromuscular diseases. Am J Phys Med
Rehabil 2005; 84: 851–57.
73. Tzeng AC, Bach JR. Prevention of pulmonary morbidity for patients
with neuromuscular disease. Chest 2000; 118: 1390–96.
74. Gomez-Merino E, Bach JR. Duchenne muscular dystrophy: prolonga-
tion of life by noninvasive ventilation and mechanically assisted
coughing. Am J Phys Med Rehabil 2002; 81: 411–15.
75. Benditt JO. Full-time noninvasive ventilation: possible and desirable.
Respir Care 2006; 51: 1005–12.
76. Hill NS. Neuromuscular disease in respiratory and critical care medi-
cine. Respir Care 2006; 51: 1065–71.
77. Leger P, Paulus J. Summary: Recommendations of HAS: Practical
issues in home non-invasive ventilation in patients with neuromuscular
disease. Rev Mal Respir Suppl 2006; 23: S141–43.
78. Parker AE, Robb SA, Chambers J et al. Analysis of an adult Duchenne
muscular dystrophy population. QJM 2005; 98: 729–36.
79. Schonhofer B, Sonneborn M, Haidl P et al. Comparison of two
different modes for noninvasive mechanical ventilation in chronic
Chronic Respiratory Disease
Downloaded from crd.sagepub.com at University of New England on June 9, 2015
respiratory failure: volume versus pressure controlled device. Eur
Respir J 1997; 10: 184–191.
80. Chadda K, Clair B, Orlikowski D et al. Pressure support versus
assisted controlled noninvasive ventilation in neuromuscular disease.
Neurocrit Care 2004; 1: 429–34.
81. Kreit JW, Capper MW, Eschenbacher WL. Patient work of breathing
during pressure support and volume-cycled mechanical ventilation.
Am J Respir Crit Care Med 1994; 149: 1085–91.
82. Girault C, Richard JC, Chevron V et al. Comparative physiologic
effects of noninvasive assist-control and pressure support ventilation
in acute hypercapnic respiratory failure. Chest 1997; 111: 1639–48.
83. Branson RD, Davis K Jr. Dual control modes: combining volume and
pressure breaths. Respir Care Clin N Am 2001; 7: 397–408.
84. Keszler M. Volume-targeted ventilation. Early Hum Dev 2006; 82:
811–18.
85. Storre JH, Seuthe B, Fiechter R et al. Average volume-assured pres-
sure support in obesity hypoventilation: A randomized crossover trial.
Chest 2006; 130: 815–21.
86. Nava S, Ceriana P. Patient-ventilator interaction during noninvasive
positive pressure ventilation. Respir Care Clin N Am 2005; 11:
281–93.
87. Sassoon CS, Foster GT. Patient-ventilator asynchrony. Curr Opin
Crit Care 2001; 7: 28–33.
88. Meyer TJ, Pressman MR, Benditt J et al. Air leaking through the
mouth during nocturnal nasal ventilation: effects on sleep quality.
Sleep 1997; 20: 561–69.
89. Guilleminault C, Philip P, Robinson A. Sleep and neuromuscular
disease: bilevel positive airway pressure by nasal mask as a treatment
for sleep disordered breathing in patients with neuromuscular disease.
J Neurol Neurosurg Psychiatry 1998; 65: 225–32.
90. Boitano LJ, Benditt JO. An evaluation of home volume ventilators
that support open-circuit mouthpiece ventilation. Respir Care 2005;
50: 1457–61.
91. Bach JR, Alba AS, Saporito LR. Intermittent positive pressure venti-
lation via de mouth as an alternative to tracheostomy for 257 ventila-
tor users. Chest 1993; 103: 174–182.
92. Parreira VF, Jounieaux V, Aubert G et al. Nasal two-level positive-
pressure ventilation in normal subjects. Effects of the glottis and ven-
tilation. Am J Respir Crit Care Med 1996; 153: 1616–23.
93. Baydur A, Kanel G. Tracheobronchomalacia and tracheal hemor-
rhage in patients with Duchenne muscular dystrophy receiving long-
term ventilation with uncuffed tracheostomies. Chest 2003; 123:
1307–11.
94. Parreira VF, Jounieaux V, Delguste P et al. Determinants of effective
ventilation during nasal intermittent positive pressure ventilation. Eur
Respir J 1997; 10: 1975–82.
95. Leger P, Jennequin J, Gerard M et al. Home positive pressure venti-
lation via nasal mask for patients with neuromuscular weakness or
restrictive lung or chest-wall disease. Respir Care 1989; 34: 73–77.
96. Piper AJ, Sullivan CE. Effects of long-term nocturnal nasal ventila-
tion on spontaneous breathing during sleep in neuromuscular and
chest wall disorders. Eur Respir J 1996; 9: 1515–22.
97. Barbe F, Quera-Salva MA, de Lattre J et al. Long-term effects of
nasal intermittent positive-pressure ventilation on pulmonary func-
tion and sleep architecture in patients with neuromuscular diseases.
Chest 1996; 110: 1179–83.
98. Janssens JP, Derivaz S, Breitenstein E et al. Changing patterns in
long-term noninvasive ventilation: a 7-year prospective study in the
Geneva Lake area. Chest 2003; 123: 67–79.
99. Chailleux E, Fauroux B, Binet F et al. Predictors of survival in
patients receiving domiciliary oxygen therapy or mechanical ventila-
tion. A 10-year analysis of ANTADIR Observatory. Chest 1996; 109:
741–19.
100. Lofaso F, Orlikowski D, Raphael J-C. Ventilatory assistance in
patients with Duchenne muscular dystrophy. Eur Respir J 2006; 28:
468–69.
101. Soudon P. Mechanical ventilation by tracheostomy in neuromuscular
diseases: experience and evaluation. Eur Respir Rev 1993; 3: 300–4.
102. Gatin G. The value of assisted ventilation in muscular dystrophies.
Ann Med Phys 1983; 26: 111–28.
103. Shneerson JM, Simonds AK. Noninvasive ventilation for chest wall
and neuromuscular disorders. Eur Respir J 2002; 20: 480–87.

104. Brooks D, King A, Tonack M et al. User perspectives on issues that
influence the quality of daily life of ventilator-assisted individuals
with neuromuscular disorders. Can Respir J 2004; 11: 547–54.
105. Dellborg C, Olofson J, Midgren B et al. Quality of life in patients
with chronic alveolar hypoventilation. Eur Respir J 2002; 19:
113–20.
106. Goldstein RS, Psek JA, Gort EH. Home mechanical ventilation.
Demographics and user perspectives. Chest 1995; 108: 1581–16.
107. Annane D, Chevrolet JC, Chevret S et al. Nocturnal mechanical ven-
tilation for chronic hypoventilation in patients with neuromuscular
and chest wall disorders. Cochrane Database Syst Rev 2000;
CD001941.
108. Konagaya M, Sakai M, Wakayama T et al. Effect of intermittent
positive pressure ventilation on life-span and causes of death in
Duchenne muscular dystrophy. Rinsho Shinkeigaku 2005; 45: 643–46.
109. Yasuma F, Sakai M, Matsuoka Y. Effects of noninvasive ventilation
on survival in patients with Duchenne’s muscular dystrophy. Chest
1996; 109: 590.
110. Jeppesen J, Green A, Steffensen BF et al. The Duchenne muscular
dystrophy population in Denmark, 1977–2001: prevalence, incidence
and survival in relation to the introduction of ventilator use.
Neuromuscul Disord 2003; 13: 804–12.
111. Gibson B. Long-term ventilation for patients with Duchenne muscu-
lar dystrophy: physician’s beliefs and practices. Chest 2001; 119:
940–46.
112. Simonds AK. Living ad dying with respiratory failure: facilitating
decision making. Chron Respir Dis 2004; 1: 56–59.
113. Hill NS. Noninvasive ventilation. Does it work, for whom, and how?
Am Rev Respir Dis 1993; 147: 1050–5.
114. Carrey Z, Gottfried SB, Levy RD. Ventilatory muscle support in res-
piratory failure with nasal positive pressure ventilation. Chest 1990;
97: 150–58.
115. Vassilakopoulos T, Zakynthinos S, Roussos C. Bench-to-bedside
review: Weaning failure: should we rest the respiratory muscles with
controlled mechanical ventilation? Crit Care 2006; 10: 204.
116. McCool FD, Mayewski RF, Shayne DS et al. Intermittent positive
pressure breathing in patients with respiratory muscle weakness.
Alterations in total respiratory system compliance. Chest 1986; 90:
546–52.
117. De Troyer A, Deisser P. The effects of intermittent positive pressure
breathing on patients with respiratory muscle weakness. Am Rev
Respir Dis 1981; 124: 132–27.
118. Turkington PM, Elliott MW. Rationale for the use of non-invasive
ventilation in chronic ventilatory failure. Thorax 2000; 55: 417–23.
Downloaded from crd.sagepub.com at University of New England on June 9, 2015
Mechanical ventilation in Duchenne patients
M Toussaint et al.
177
119. Meyer TJ, Hill NS. Noninvasive positive pressure ventilation to treat
respiratory failure. Ann Intern Med 1994; 120: 760–70.
120. Goldstein RS, Molotiu N, Skrastins R et al. Reversal of sleep-induced
hypoventilation and chronic respiratory failure by nocturnal negative
pressure ventilation in patients with restrictive ventilatory impair-
ment. Am Rev Respir Dis 1987; 135: 1049–55.
121. Annane D, Quera-salva MA, Lofaso F et al. Mechanisms underlying
effects of nocturnal ventilation on daytime blood gases in neuromus-
cular diseases. Eur Respir J 1999; 13: 157–62.
122. Dellborg C, Olofson J, Hamnegard CH et al. Ventilatory response to
CO2 re-breathing before and after nocturnal nasal intermittent posi-
tive pressure ventilation in patients with chronic alveolar hypoventi-
lation. Respir Med 2000; 94: 1154–60.
123. Nickol AH, Hart N, Hopkinson NS et al. Mechanisms of improve-
ment of respiratory failure in patients with restrictive thoracic disease
treated with non-invasive ventilation. Thorax 2005; 60: 754–60.
124. Ergun P, Aydin G, Turay UY et al. Short-term effect of nasal intermit-
tent positive-pressure ventilation in patients with restrictive thoracic
disease. Respiration 2002; 69: 303–8.
125. Diaz O, Begin P, Andresen M et al. Physiological and clinical effects
of diurnal noninvasive ventilation in hypercapnic COPD. Eur Respir
J 2005; 26: 1016–23.
126. Leger P, Langevin B, Guez A et al. What to do when nasal ventilation
fails for neuromuscular patients. Eur Respir Rev 1993; 3: 279–83.
127. Teschler H, Stampa J, Ragette R et al. Effects of mouth leak on effec-
tiveness of nasal bilevel ventilatory assistance and sleep architecture.
Eur Respir J 1999; 14: 1251–57.
128. Gonzales J, Sharshar T, Hart N et al. Air leaks during mechanical
ventilation as a cause of persistent hypercapnia in neuromuscular
disorders. Intensive Care Med 2003; 29: 596–602.
129. Parreira VF, Delguste P, Jounieaux V et al. Effectiveness of controlled
and spontaneous modes in nasal two-level positive pressure ventilation
in awake and asleep normal subjects. Chest 1997; 112: 1267–77.
130. Leger P. Long-term ventilation in restrictive ventilatory disorders.
Respir Care Clin N Am 2002; 8: 507–32.
131. Windisch W, Dreher M, Storre JH et al. Nocturnal non-invasive pos-
itive pressure ventilation: physiological effects on spontaneous
breathing. Respir Physiol Neurobiol 2006; 150: 251–60.
132. Katz S, Selvadurai H, Keilty K et al. Outcome of non-invasive posi-
tive pressure ventilation in paediatric neuromuscular disease. Arch
Dis Child 2004; 89: 121–24.
133. Finder JD, Birnkrant D, Carl J et al. American Thoracic Society.
Respiratory care of the patient with Duchenne muscular dystrophy:
ATS consensus statement. Am J Respir Care Med 2004; 170: 456–65.
http://crd.sagepub.com