Noninvasive home ventilation for chronic obstructive pulmonarydisease: indications, utility and outcomeStephan Budweiser, Rudolf A. Jo¨rresand Michael
aCenter for Pneumology, Hospital Donaustauf,
Donaustauf, bInstitute and Outpatient Clinic for
Despite its widespread use, the role of noninvasive home mechanical ventilation for the
Occupational, Social and Environmental Medicine,Ludwig-Maximilians-University, Munich and
management of severe chronic obstructive pulmonary disease and chronic hypercapnic
cDepartment of Internal Medicine II, Division of
respiratory failure is still controversial. The majority of randomized controlled trials show
Respirology, University of Regensburg, Regensburg,Germany
methodological weaknesses, including issues of patient selection, insufficient pressuresupport and poor adherence to therapy. Data from short-term trials, while assuring
Correspondence to Dr med. Stephan Budweiser,Klinik Donaustauf, Zentrum fu¨r Pneumologie,
effective ventilation, are encouraging by demonstrating physiological improvements, in
Ludwigstraße 68, 93093 Donaustauf, Germany
line with benefits regarding symptoms and quality of life. The role of home mechanical
Tel: +49 9403 80 715; fax: +49 9403 80 211;e-mail:
ventilation for long-term survival is, however, still unclear. Recent findings
Current Opinion in Pulmonary Medicine 2008,
Possible indications of home mechanical ventilation, physiological concepts underlying
the effects of noninvasive ventilation and their impact on clinically important long-termoutcomes are reported. SummaryDue to systemic involvement, the decision to undertake home mechanical ventilationshould probably not be based on symptomatic chronic hypercapnia alone, but on abroader spectrum of factors. In particular, patients with repeated hypercapnicdecompensation are at high risk for death and obvious candidates for home mechanicalventilation. Beyond restoration of chemosensitivity, changes in breathing pattern and areduction of mechanical load are likely mechanisms of home mechanical ventilation,inducing symptom relief and improving functional reserve. To fully utilize its potential,high pressure levels are required. Future prospective controlled studies should take intoaccount these experiences.
Keywordschronic hypercapnic respiratory failure, chronic obstructive pulmonary disease,noninvasive ventilation
Curr Opin Pulm Med 14:128–134ß 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins
Chronic obstructive pulmonary disease (COPD) is one of
COPD with chronic hypercapnic respiratory failure
the leading causes of death worldwide While phar-
(CHRF) has grown to be one of the major indications
macotherapy has not yet consistently demonstrated
for HMV in Europe, as demonstrated by a survey of
21 526 patients from 329 centers This might imply a
(LTOT) is capable of reducing mortality in advanced,
high conviction among clinicians regarding the clinical
hypoxemic COPD Noninvasive positive-pressure
benefit from HMV in COPD, including the view that
ventilation (NPPV) is established in the management
withholding this therapy could be life-threatening; how-
of acute hypercapnic respiratory failure after severe
ever, clear-cut evidence that supports this view is still
exacerbation whereas the evidence in support of
scarce. The survey did not provide details of the criteria
domiciliary, long-term NPPV in chronic hypercapnic
of HMV, but significant differences between institutions
COPD is equivocal. The review aims to integrate current
and countries with regard to these and the willingness to
clinical and pathophysiological concepts, indications
for and the utility of noninvasive home mechanicalventilation (HMV), highlighting its impact on long-term
According to the definition of CHRF elevated daytime
arterial carbon dioxide tension (PaCO2) is considered as a
1070-5287 ß 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins
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Noninvasive home ventilation Budweiser et al.
key indicator of alveolar hypoventilation and constitutes a
adequately described by (chronic) hypercapnia alone.
major criterion for the decision to undertake HMV. Its use
Probably more important long-term determinants are
in COPD is often based on recommendations of an Inter-
the reductions in functional reserves including airway
national Consensus Conference According to this,
HMV should be considered after optimization of therapy
including maximal bronchodilation and LTOT if typicalsymptoms are present and PaCO2 levels are 55 mmHg or
These risk factors, and their combination, imply a high
above, or if levels are lower (50–54 mmHg) but nocturnal
susceptibility for exacerbations and instability, associated
oxygen desaturation of 88% or below occurs for 5 min or
with a high risk of uncompensated respiratory failure and
more consecutively despite continuous administration of
death . Noninvasive HMV can reduce the work of
2 l/min or more of oxygen. This statement was derived
breathing and evoke beneficial changes in the ventilatory
from data demonstrating clinical effects from HMV on
pattern thus probably bolstering functional
blood gases and sleep quality or quality of life in patients
reserves and counteracting life-threatening events,
presenting with pronounced nocturnal hypoventilation
including those originating during an exacerbation.
and/or hypercapnia . Conversely, in those randomized
Following this argument, it seems adequate to base
controlled trials which did not observe benefits, patients
the decision for HMV on an individual picture covering
showed a lower degree of hypercapnia In line with
a broad range of risk factors. Such multidimensional
this, the Global Initiative on Obstructive Lung Disease
approaches are already customary in decisions about
(GOLD) proposed long-term HMV particularly in patients
lung volume reduction surgery or lung transplantation
A further indication for HMV is thought to be given at a
In accordance with this, a recent controlled, although not
lower degree of hypercapnia (PaCO2 50–54 mmHg) if
randomized, study provided further evidence that
two or more episodes of hypercapnic respiratory decom-
patients showing a profile of known risk factors especially
pensation occur per year This basically relied on
benefit from HMV which has to be corroborated in
reported benefits of HMV in COPD, diffuse bronchiec-
randomized controlled trials. Patients who experience a
tasis and cystic fibrosis, as reflected in a lower number of
severe acute exacerbation requiring the use of NPPV
hospitalizations in the year after HMV compared to
in the hospital show a high risk for subsequent life-
preceding years suggesting a role for HMV
threatening events and the continuation of venti-
beyond the reversal of chronic hypercapnia.
latory support at home might help to stabilize theirclinical state Correspondingly, a lower frequency
The critical limits of hypercapnia are not tightly defined
of hospital admissions and lower healthcare
or verified in prospective randomized controlled trials.
costs after initiation of HMV have been reported.
Even more intriguing, some authors argue that the
Moreover, in a recent observational study, maintenance
development of chronic hypercapnia might represent
HMV after a prolonged period of weaning implied
a natural wisdom preventing respiratory muscle fatigue
improved long-term survival, compared to patients dis-
This view obviously interferes with the rationale
charged without NIV, independent of the patient’s age
underlying HMV In fact, large observational
and duration of hospital stay As these data were also
studies performed prior to the widespread application
derived from a retrospective analysis, they need to be
of HMV found similar or even lower mortality
confirmed. At least they suggest an indication for
in moderately hypercapnic compared to normocapnic
HMV after difficult weaning, although possibly only in
patients. The prognostic value of chronic hypercapnia
selected groups of patients and a certain time window.
is thus not clear and base excess might constitute a
more reliable parameter, reflecting the long-termmetabolic response Nonetheless, extreme hyper-
Table 1 Possible and apparently most appropriate indications
capnia or persistent hypercapnia following an acute
for the initiation of noninvasive HMV as derived from clinical
exacerbation seem to predict a poor long-term
trials that favored the use of noninvasive HMV in patients withchronic obstructive pulmonary disease and chronic hypercapnic
Although PaCO2 remains a hallmark of CHRF and itsreduction a goal of HMV, none of the currently available
recommendations defines a more detailed profile of
Unstable course of the disease with recurrent respiratory
decompensation and/or repeated hospital admissions
patients eligible for HMV. This seems surprising in a
Patients at high risk for death or severe exacerbation,
systemic, multidimensional disease such as COPD.
Particularly in most severe COPD, the risk of death or
Status after prolonged mechanical ventilation
severe exacerbations does not appear to be
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Obstructive, occupational and environmental diseases
not only underlie the sustained reduction of PaCO
but also the positive effects on respiratory muscle
A large number of investigations have elucidated the
long-term utility of ventilatory support in COPD, using
but these results need to be proven in long-term
a wide range of clinical outcome measures. Not surpris-
prospective controlled trials. In view of the pathophysio-
ingly, in this multifaceted disease some issues remain
logy of dyspnea it seems plausible that these
controversial, but a recent review of 466 patients from six
functional improvements correspond to the reduction
randomized and nine nonrandomized controlled trials
of dyspnea sensation – a consistent result of randomized
argued that HMV could well have an adjunctive role
controlled clinical trials as exemplified by
in the management of COPD through improve-
the correlation between the physiological improvements
ment of health-related outcomes or respiratory function.
and the Transition Dyspnea Index (TDI) The
Again this conclusion, although cautious and not covering
observed effects on breathing pattern and/or respiratory
patient eligibility, pointed towards a role for HMV
mechanics also imply a greater ventilatory reserve which
beyond the relief of chronic hypercapnia, in contrast to
could be advantageous during both physical exercise and
a previous meta-analysis of four randomized controlled
As yet, however, exercise capacity as quantified by 6-min
Defining the role of HMV precisely is, however, difficult
walk distance did not show changes after initiation of
in view of the fact that the contributions of the mech-
NPPV in most studies addressing this issue
anisms underlying noninvasive HMV are not clear .
it was found to be improved in only two short-term
The hypothesis that the resting of respiratory muscles
randomized controlled trials Dynamic hyperinfla-
allows them to restore their capacity is now being
tion during exercise probably poses a mechanical limiting
questioned as the leading factor in COPD
factor not amenable to nocturnal HMV Irrespective of
Although the activity of the diaphragm can be reduced by
this it seems a promising observation that high-intensity
ventilatory support this does not appear to
NPPV administered during walking can result in improved
translate into an increase of inspiratory muscle strength,
oxygenation, decreased dyspnea and increased walking
according to most of the controlled studies
Other effects such as restoration of chemosensitivity,with subsequent improvements in PaCO2 and alveolar
Of utmost importance for achieving these effects are
hypoventilation, have been suggested as being more
sufficient levels of inspiratory pressure, including a low
important Thus, the amelioration of blood gases,
positive end-expiratory pressure, to assure effective venti-
particularly hypercapnia, during noninvasive ventilation
lation. While the controlled studies with unfavorable out-
and spontaneous breathing is now considered as a major
come predominantly used low inspiratory pressures
target of long-term HMV and has been defined as a
, a 3-month randomized cross-over trial using
therapeutic goal in a current multicenter trial Not
levels of 18/2 mbar demonstrated salutary effects on
surprisingly, early randomized controlled studies in
daytime blood gases. It might be reassuring in this respect
which this goal was not reached, mainly due to insuffi-
that in clinical short- and long-term investigations
cient ventilation pressures or patient noncompliance, also
the observed changes in ventilatory pattern
showed no clinical effect Conversely, the
and PaCO2 were related to inspiratory pressure levels.
improvement of daytime blood gases by HMV was
In recent noncontrolled studies the improvement in
PaCO2 consistently occurred at inspiratory pressures up
and quality of life in a randomized controlled trial
to 28 mbar which were still tolerated by the patients
It has also been demonstrated that, despite theleakage at higher pressure, the increase in pressure still
Valuable insight into the potential of HMV has been
gained from short-term controlled or cross-over trials. Byapplying NPPV during close supervision, ascertaining
Moreover, the potential of HMV can only be fully
utilized when the mental attitude of the patient is
strated to be capable of raising tidal volume or minute
adequate and compliance sufficient. Clinical practice
indicates that this requires experience and familiarization
frequency and effective respiratory impedance
with the technique on the patients’ side, plus modern
These benefits occurred during both ventilatory support
ventilator technique. This is underlined by the obser-
vation that particularly in the early years of HMV high
were correlated with the reduction of PaCO2 levels
rates of nonacceptance and a lack of beneficial effects
Ameliorations of the ventilatory pattern could
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Noninvasive home ventilation Budweiser et al.
Figure 1 Possible effects and utility of noninvasive home ventilation according to short- and long-term trials with positive outcome
Randomized controlled trials are marked in bold. At 3 months. PaCO2, arterial carbon dioxide tension; PaO2, arterial oxygen tension; NPPV,noninvasive positive-pressure ventilation; HMV, home mechanical ventilation; HRQL, health-related quality of life.
In view of pathophysiological interactions it seems
reasonable to consider those patients as potentially suited
Although the improvement of physiological indices is
for HMV who show a high risk of hypercapnic failure or
desirable, it has to be kept in mind that these effects
death (see Indications) or present the greatest functional
should additionally translate into a substantial clinical
deficits and/or symptoms. This approach might be cross-
benefit. Long-term survival and health-related quality of
checked against conditions for which positive effects
life (HRQL) are probably most important in this respect,
have been reported. Apart from pronounced chronic
as in other chronic diseases. The question for a long-term
hypercapnia, the presence of marked clinical symptoms
benefit is also inevitable in view of the considerable
should encourage the initiation of noninvasive HMV.
Indeed, dyspnea or sleep quality are improved byHMV according to noncontrolled and controlledtrials
Some of the available reports covered an observationperiod of sufficient length to address long-term HRQL
The nonnegligible costs associated with this sophisti-
or survival, but most of them in a small number of patients
cated therapy call for regular assessment of therapeutic
effectiveness including patient willingness to continue
ging that the majority of controlled and noncon-
HMV Some data indicate a benefit from HMV
trolled studies on the long-term effects of HMV
even in the case of not being used every day or only for a
reported positive findings irrespective of the choice of
generic or disease-specific questionnaires. It seems
usage has positive effects Thus, it seems
important to note that improvements in HRQL also
questionable to retract the ventilator only because it is
occurred in measures specifically designed for patients
not used daily, as it might be helpful in periods of
with ventilatory failure, such as the Maugeri Foundation
deterioration, provided that the patient has learnt its
Respiratory Failure Questionnaire (MRF-28) and the
Severe Respiratory Insufficiency (SRI) questionnaire
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Obstructive, occupational and environmental diseases
which was recently also validated specifically for COPD
In view of the potential of domiciliary noninvasive venti-
lation to reduce overall healthcare costs, at least inpatients with recurrent exacerbations HMV should
Contrary to the predominantly favorable findings regard-
thus be further evaluated in randomized controlled trials
ing HRQL, the two randomized clinical trials on long-term
and samples of adequate size. As suggested factors
mortality which comprised samples of acceptable size and
in favor of an improved long-term outcome are the
observation periods of 1 and 2 years, respectively, found no
selective inclusion of patients with severe COPD and
difference in survival rate between patients with HMV
high risk for exacerbation or death, sustained adaptation
compared to LTOT alone Treatment efficiency
to HMV, high pressure levels, and familiarization with
and inspiratory pressure levels might, however, have been
the technique. Naturally, HMV can only be part of a
too low Although changes in overall treatment
comprehensive management strategy in COPD and
associated with HMV should be taken into account, it
should be noted that survival rates of patients treated with
pharmacological therapy and LTOT Even in the
noninvasive efficient HMV were higher than those of
terminal stage of the disease noninvasive ventilation can
historical controls In a further observational
alleviate symptoms without the undesirable side-
study comprising the as yet largest population and longest
effect of prolonging the process of dying.
observation period, patients with noninvasive HMVpresented with better long-term survival compared topatients who were not successfully adapted to this therapy
. Of course, as the control group was not
In patients with COPD and CHRF, studies that used
chosen at random, these data also show weaknesses.
high pressure levels and ensured adequate compliance
Nonetheless, a detailed analysis which took into account
have shown beneficial effects on physiological measures
the (minor) differences at baseline between the study and
and health-related outcomes such as dyspnea and quality
control group unequivocally indicated a benefit from
of life. Data on long-term survival are currently weak, but
HMV. These results are encouraging and fit well into
promising. From recent findings it seems inappropriate to
base the decision to undertake HMV on PaCO2 alone. Inparticular, patients with unstable disease, recurrenthypercapnic decompensations, life-threatening events
Figure 2 Survival rates of patients with COPD and high adher-
or high risk for death should be considered for long-term
ence (89%) to HMV (n U 99) as compared to patients not suc-cessfully adapted to HMV (n U 41) according to the data from a
HMV. These patients should be part of prospective
controlled, although not randomized, design
controlled trials to define the role of noninvasive HMVin severe hypercapnic COPD more precisely.
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ment strategy for patients with most severe COPD.
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Introduction GOLD 2006 PRESENTATION Tertiary bis-phosphines of the form R P-(CH ) -PR (n = 1 – 4 and R = Me, Et, t-Bu and Ph) and cis-R PCH=CHPR (R = Ph) are often used as chelating ligands for a wide range of transition metals.[1-4] These ligands have shown wider applications in metal complexation reactions and have attracted much attention, especially in the fields of medicine and cat
DISKUSSIONSFORUM Samstag, 15.02.2014 15:00 - 18:00 Uhr NIG, Hörsaal 3 Universitätsstraße 7, 1010 Wien DIE GRENZEN DER MEINUNGSFREIHEIT Über die Grauzone zwischen Recht und Unrecht Bei dieser Podiumsdiskussion werden Experten und Betroffene anhand konkreter Beispiele über die Verfolgung politischer und gesellschaftskritischer Aktivitäten