Intensive Care Med (2020) 46:2436–2449

https://doi.org/10.1007/s00134-020-06291-0

REVIEW

How to ventilate obstructive and asthmatic

patients
Alexandre Demoule1,2*  , Laurent Brochard3,4, Martin Dres1,2, Leo Heunks5, Amal Jubran6, Franco Laghi6,
Armand Mekontso‑Dessap7,8, Stefano Nava9, Lamia Ouanes‑Besbes10,11, Oscar Peñuelas12,13, Lise Piquilloud14,
Theodoros Vassilakopoulos15,16 and Jordi Mancebo17

© 2020 Springer-Verlag GmbH Germany, part of Springer Nature

Abstract 
Exacerbations are part of the natural history of chronic obstructive pulmonary disease and asthma. Severe exacerba‑
tions can cause acute respiratory failure, which may ultimately require mechanical ventilation. This review summarizes
practical ventilator strategies for the management of patients with obstructive airway disease. Such strategies include
non-invasive mechanical ventilation to prevent intubation, invasive mechanical ventilation, from the time of intuba‑
tion to weaning, and strategies intended to prevent post-extubation acute respiratory failure. The role of tracheos‑
tomy, the long-term prognosis, and potential future adjunctive strategies are also discussed. Finally, the physiological
background that underlies these strategies is detailed.
Keywords:  Mechanical ventilation, Chronic obstructive pulmonary disease, Asthma, Intrisic positive end-expiratory
pressure (PEEP), Non-invasive ventilation, Weaning

Introduction management of the two conditions is similar in various

respects.
Respiratory failure from acute exacerbations of chronic
obstructive pulmonary disease (COPD) or severe asthma Acute respiratory failure in COPD and asthma: the
is characterized by acute worsening of respiratory symp- magnitude of the problem
toms associated with the development of severe airflow COPD exacerbations are common and have impor-
limitation, gas trapping, dynamic hyperinflation and tant clinical consequences, including an acute decline
intrinsic positive end-expiratory pressure (PEEPi). In the in quality of life, temporary or permanent reduction in
most severe cases, these exacerbations may cause acute lung function and exercise capacity, hospitalization, and
respiratory failure, which may require mechanical ven- increased mortality. They also have a major economic
tilation. This review focuses on strategies for ventilation impact. According to cohort studies that enrolled unse-
and describes the physiological background that under- lected critically ill patients receiving mechanical ventila-
lies them. Even though the pathogenesis and clinical tion (invasive or non-invasive) for more than 12 h [1], the
course of asthma and COPD differ, ventilator support proportion of patients managed for COPD exacerbation
decreased from 10% in 1998 to 7% in 2016 (Fig. 1). This
trend paralleled an increased rate of non-invasive ven-
tilation (NIV) use as first ventilatory support following
*Correspondence: [email protected]
1
intensive care unit (ICU) admission (from 16% in 1998 to
Service de Pneumologie, Médecine Intensive—Réanimation
(Département “R3S”), Hôpital Pitié‑Salpêtrière, AP-HP, Sorbonne Université,
51% in 2017). Simultaneously, overall mortality decreased
75013 Paris, France (Fig. 1).
Full author information is available at the end of the article
 2437

Severe asthma exacerbation causing respiratory fail-

ure may lead to major mechanical ventilation-associated Take‑home message 
complications (e.g., barotrauma, cardiovascular collapse,
This review summarizes practical ventilator strategies to manage
atelectasis, and pneumonia) that can impact on morbid- patients with asthma and chronic obstructive pulmonary disease
ity and mortality. Severe asthma exacerbation accounts (COPD). The causes, impact and management of dynamic hyperin‑
for approximately 1% of mechanically ventilated patients flation are discussed, as well as heart–lung interaction. We underline
the importance of non-invasive ventilation to prevent intubation.
admitted to the ICU [1]. NIV use in these patients We provide key messages regarding ventilator settings in intubated
increased from 3% in 1998 to 34% in 2016 [2]. patients. Future adjunctive strategies are discussed.

Respiratory system mechanics and gas exchange

In terms of respiratory system mechanics, asthma barotrauma and hemodynamic compromise. Hypox-
and COPD are characterized by the development of emia in asthma is characterized by the presence of low
dynamic hyperinflation, defined as increased relaxa- V/Q units; hypoxemia is usually attenuated by compen-
tion volume of the respiratory system at the end of a satory redistribution of blood flow mediated by hypoxic
tidal expiration. In healthy subjects, the end-expiratory vasoconstriction and changes in cardiac output [9, 11]. It
alveolar and airway pressures are zero relative to the has been described that in asthma patients, hypercapnia
atmosphere, and pleural pressure is negative. In the is mainly due to increased dead space ventilation caused
presence of dynamic hyperinflation, the alveolar pres- by alveolar overdistension [11, 12]. However, this mecha-
sure remains positive throughout expiration, leading to nism has not been proved [9].
the development of auto-positive end-expiratory pres-
sure (auto-PEEP), also termed intrinsic PEEP or PEEPi Heart–lung interactions in the mechanically
[3] (Fig. 2). ventilated COPD patient
In COPD, PEEPi is primarily caused by expiratory The pathophysiological changes in the pulmonary system
flow limitation, a complex phenomenon that is due to may have adverse effects on cardiac function.
reduced lung recoil pressure (emphysema) leading to COPD is associated with pulmonary hypertension,
small airway collapse that increases airway resistance increased pulmonary vascular resistance, right ventri-
(see [4] for an extensive description). It is exacerbated cle dilatation, and right ventricle hypertrophy. Both left
by shortened expiratory time, due to increased respira- ventricle systolic and left ventricle diastolic functions are
tory rate, and increased tidal volume, the latter being, in often impaired in COPD patients. Among 148 patients
general, a consequence of an augmentation of respira- admitted to the ICU for severe COPD exacerbation, 31%
tory drive (and therefore a higher volume to exhale) [5]. had an exacerbation that was definitely associated with
The consequences of dynamic hyperinflation depend on left-heart dysfunction [13]. These cardiac alterations are
whether patients are passively ventilated or triggering caused by dynamic hyperinflation and the large swings
their ventilator. In passively ventilated patients, dynamic in negative intrathoracic pressure developed by the res-
hyperinflation increases delivered mechanical power [6] piratory muscles to overcome the inspiratory elastic
with its associated risk of barotrauma and hemodynamic threshold caused by PEEPi and increased airway resist-
compromise [7]. In patients triggering their ventilator, ance. Dynamic hyperinflation is more detrimental to left
initiation of inspiratory flow requires inspiratory force ventricle hemodynamics than large swings in negative
to overcome PEEPi [8], which translates into increased intrathoracic pressure [14]. Direct ventricular interac-
inspiratory effort during the triggering phase. Ultimately, tion and significant septal flattening appear to be respon-
this increased effort may fail to trigger the ventilator, sible for reduced left ventricle end-diastolic volume and
leading to ineffective triggering, one of the most frequent stroke volume [15]. Dynamic hyperinflation worsens
dyssynchronies [5]. In terms of gas exchange, patients the increase in right ventricular impedance (afterload
with COPD have complex patterns of V/Q distributions: effect), while large negative intrathoracic pressure swings
low V/Q regions that remain perfused, high V/Q regions, increase the venous return to the right ventricle (preload
and mixed patterns. COPD patients often exhibit small effect). Both favor direct ventricular interaction with left-
amounts of shunt (typically less than 10% of cardiac out- ward shift of the septum.
put) [9]. Application of external PEEP up to values approaching
Severe asthma exacerbation is characterized by a PEEPi does not result in hemodynamic impairment in
major increase in airway resistance due to bronchos- COPD [4]. Higher PEEP levels reduce cardiac index [16].
pasm, airway inflammation, and mucus. Expiratory flow However, the effects of external PEEP on lung mechan-
is dramatically reduced with resultant major dynamic ics and hemodynamics depend on many factors, such
hyperinflation [10]. This leads to an increased risk of as airway characteristics, lung volumes, intravascular
2438

In patients with severe asthma, similar heart–lung

interactions are observed. Because of the presence of an
extremely severe hyperinflation, they may develop severe
hypotension [21].

Non‑invasive ventilation in COPD over the decades

Delivering mechanical ventilation without intubation in
patients with ­CO2 retention was attempted during the
1960s [22], but without becoming widely accepted; intu-
bation with invasive mechanical ventilation remained the
rule for patients admitted for respiratory failure.
In the late 1980s, several groups treated patients
with chronic or acute-on-chronic hypercapnic respira-
tory failure with a face mask [23–26]. The success was
largely due to combining physiological assessment of
the mechanisms of respiratory failure (including respira-
tory muscle function [26]) with new technologies (pres-
sure support ventilation [27]). In the early 1990s several
studies demonstrated the efficacy of positive pressure
ventilation usually delivered with pressure support ven-
tilation and PEEP [28, 29]. It is remarkable that some of
the best results were obtained without any PEEP [26],
highlighting the importance of pressure delivered dur-
ing inspiration. Randomized clinical trials showed that
the intubation rate was dramatically reduced, resulting
in improved outcomes, with fewer complications related
to invasive mechanical ventilation and improved hospital
survival [30–32] (Fig. 3).
Implementing NIV into practice took more than a dec-
ade [33] but NIV became the benchmark for treating
acute respiratory failure due to severe COPD exacerba-
tion, bringing about a steady decrease in mortality over
time [33]. Concomitantly, the risk of mortality increased
in patients transitioned from NIV to invasive mechani-
cal ventilation. However, it is of note that COPD patients
who failed NIV and were subsequently intubated were
Fig. 1  Rates of acute chronic obstructive pulmonary disease (COPD) not at higher risk of mortality than those intubated as
exacerbation and severe asthma exacerbation among patients a first-line respiratory support [30, 33]. Technological
mechanically ventilated for acute respiratory failure (panel A) and improvements continued, stimulated by the need for
evolution of ICU mortality (panel B) and hospital mortality (panel C)
efficient techniques in the hospital and by the extensive
over time in these two populations. *p < 0.001 compared to period
1998 use of home NIV, which required more comfortable and
user-friendly equipment [34]. Automated management of
leaks progressively became the rule and ICU ventilators
eventually became as efficient as dedicated ventilators in
volume status, vasomotor tone, etc., making the individ- compensating for leaks and reducing patient-ventilator
ual patient’s response difficult to predict [17]. dyssynchronies [35, 36].
Finally, patients with COPD are at increased risk NIV is sometimes proposed as a ceiling of ventila-
of difficult weaning, and are susceptible to develop- tor assistance care [37–39]. A multicenter French study
ing weaning-induced pulmonary edema in particular showed that patients with “do-not-intubate” orders
[18]. Diuretics and nitroglycerin are efficient in treating who were managed with NIV had good quality of life
weaning-induced pulmonary edema in selected COPD 6  months after discharge; caregivers of patients treated
patients [19, 20]. with NIV had similar stress and anxiety levels to those
of caregivers of patients with no limitation on therapy
 2439

[39]. Because NIV relieves dyspnea [40], the technique NIV in severe asthma exacerbation, and the level of risk
has also been used to relieve dyspnea in dying patients may be very high in cases of respiratory failure. As a con-
receiving palliative care [41], although this approach has sequence, guidelines do not recommend NIV in severe
not gained widespread use. asthma exacerbation [43, 44].
In severe asthma exacerbation, retrospective studies
have suggested that cautious use of NIV was associated Management of invasive ventilation
with improved outcome [42]. However, no high-quality Invasive ventilation is indicated in patients suffering a
randomized controlled trial has highlighted benefits of respiratory arrest, for instance, or who have failed NIV

Fig. 2  Pressure–volume (P–V) relationship of the respiratory system when pressure is measured at the airway opening. In normal subjects, the
end-expiratory lung volume ­(EELVNormal) is the relaxation volume of the respiratory system or functional residual capacity (FRC), where no inward or
outward recoil pressure exists (the pressure of the respiratory system is 0 cmH2O relative to the atmosphere). To trigger the ventilator, the patient’s
inspiratory muscles have to develop an inspiratory effort ≥ the trigger threshold set on the ventilator (2 cmH2O in the example). A tidal breath of
500 ml delivered by the ventilator will increase the volume of the respiratory system to its end-inspiratory lung volume (­ EILVNormal). The normal elas‑
tic work of breathing ­( Wel,n) represented by the triangular area is not excessive. In hyperinflated COPD or asthma patients, the end-expiratory lung
volume ­(EELVHyperinfl) is greater than the respiratory system relaxation volume, increasing ΔFRC (Δ denoting the increase in volume from the normal
FRC); at this increased volume, an inward recoil pressure exists (the pressure of the respiratory system is 7 cmH2O relative to the atmosphere). This
pressure is called the intrinsic positive end-expiratory pressure (PEEPi). (This pressure is usually measured by the end-expiratory occlusion method
with the patient relaxed). To trigger the ventilator, the patient’s inspiratory muscles first have to develop an inspiratory effort to overcome the
positive inward recoil of the respiratory system present at the end of expiration (7 cmH2O, PEEPi) and then the trigger threshold set on the ventila‑
tor (2 cmH2O in the example). The pressure required to effectively trigger the ventilator (Peffect,trigger = 7 + 2 = 9 cmH2O in the example). If they fail
to generate this amount (9 cmH2O), an ineffective triggering effort ensues, which does not trigger the ventilator. A similar tidal breath of 500 ml
delivered by the ventilator will increase the volume of the respiratory system to its new end-inspiratory lung volume (­ EILVhyperinfl), where there is risk
of overdistension (stress and strain of the lung) with its potentially injurious sequalae (this is the plateau pressure if measured by the end-inspiratory
occlusion method with the patient relaxed). The elastic work of breathing is mainly attributed to PEEPi (square shaded area, ­WPEEPi) and is greatly
increased leading to increased delivered mechanical power
2440

for any reason, including persistent clinical signs of expected to increase hyperinflation. However, the physi-
increased work of breathing. As previously explained (see ology appears more complex, with three possible effects
above section “Respiratory system mechanics and gas of PEEP on hyperinflation [48]: (1) in patients with pure
exchange”), acute exacerbations of COPD are character- expiratory flow limitation, there is no change in hyperin-
ized by dynamic hyperinflation leading to development flation (assessed by Pplat and by changes in end-expira-
of PEEPi. The presence of dynamic hyperinflation and tory lung volume) during progressive increase in PEEP
PEEPi should be considered if expiratory flow does not until a threshold is reached; (2) any increase in PEEP
cease at end-expiration (Fig. 4). With controlled mechan- increases Pplat and end-expiratory lung volume, and (3)
ical ventilation, total PEEP is measured during end- a “paradoxical response” occurs, whereby increases in
expiratory occlusion. The reference standard technique PEEP decrease Pplat and end-expiratory lung volume. A
for quantifying dynamic hyperinflation is measurement paradoxical response may be expected in patients with
of end-inspiratory lung volume [45]. As this is cumber- expiratory flow limitation and highly heterogeneous
some in clinical practice, end-inspiratory plateau pres- lungs [7, 49]. At the bedside, the effect of PEEP on hyper-
sure (Pplat) during controlled mechanical ventilation is a inflation is unpredictable [48], and it is therefore advised
reasonable, albeit less sensitive, surrogate for monitoring to measure Pplat while cautiously titrating PEEP. PEEP
hyperinflation [45]. Pplat is measured with end-inspir- titration should be immediately stopped if Pplat increases
atory occlusion for ± 3  s. Peak pressure is not a reliable [12].
measure for hyperinflation. In passively ventilated patients with expiratory flow
It is important to stress that in the early phase of limitation, the addition of external PEEP does not change
mechanical ventilation, the primary goal in these patients either the degree of hyperinflation or the total PEEP until
is not to normalize blood gases, but to prevent compli- it approximates 80% of the original PEEPi. As soon as the
cations due to hyperinflation while maintaining a pH of patient is able to trigger the ventilator, moderate exter-
around 7.25–7.30 [46]. nal PEEP is added to counterbalance PEEPi and hence
Many ventilator modes are used in intubated patients to reduce the effort needed to trigger the ventilator and
with COPD; however, it is not known whether one is improve patient-ventilator interaction [50]. It is of note
superior to another. A common ventilator mode is vol- that patients with COPD are susceptible to ventilator-
ume assist-control ventilation. With volume assist- induced hyperinflation and dyssynchronies such as inef-
control ventilation, the inspiratory flow waveform can fective triggering (also called ineffective efforts or wasted
be set in the square pattern to facilitate monitoring of efforts, Fig.  5) [50]. Because PEEPi increases the effort
mechanics. To limit hyperinflation, minute ventilation required to trigger the ventilator, a weak respiratory effort
is minimized, and sufficient time is allowed for expira- may fail to trigger it [51]. Ineffective triggering is associ-
tion [45]. As a reasonable starting point, use of a moder- ated with a less sensitive inspiratory trigger, a higher level
ate tidal volume, of around 6–8 ml/Kg, and a respiratory of pressure support, a higher tidal volume, and a higher
rate of 12/min, with constant inspiratory flow delivered pH [50]. In patients with a high prevalence of ineffective
at 60–90 l/min, has been proposed [47]. It has been pro- triggering, markedly reducing pressure support or inspir-
posed to keep the inspiration-to-expiration ratio low, atory duration to reach a tidal volume of about 6 ml/Kg
e.g., 1:4. If, with these ventilator settings, Pplat is not predicted body weight was found to eliminate ineffective
too high (e.g., < 28  cmH2O), the respiratory rate can triggering in two-thirds of patients [52]. When pressure
be increased to improve gas exchange. If Pplat is high support is used, the pressure support level should not be
(e.g. > 28  cmH2O), minute ventilation could be reduced set too high, to limit tidal volume (to around 6–8 ml/Kg)
by limiting tidal volume and/or respiratory rate in and subsequent dynamic hyperinflation [52]. Shortening
patients with PEEPi. Increasing expiration time at similar insufflation time by decreasing the level of the expiratory
minute ventilation (e.g. by increasing inspiratory airflow trigger (also called cycling-off ) may also help to reduce
thus decreasing inspiratory time with constant respira- dynamic hyperinflation [52].
tory rate and tidal volume) has a much smaller effect on In severe asthma exacerbation, invasive mechani-
hyperinflation [45]. cal ventilation is associated with an increased risk of
Selecting appropriate PEEP in acute COPD exacerba- complications and significant mortality [53]. Post-
tion may be complex and depends on whether or not the intubation hypotension is common, due to major
patient triggers her/his ventilator. In general, at the early lung hyperinflation, hypovolemia and sedation.
phase of intubation, patients do not trigger their ven- Therefore, the indication for intubation should be
tilator. In theory, zero PEEP would be optimal in these limited to patients in life-threatening conditions (res-
COPD patients with “pure” high airway resistance, as piratory arrest, bradypnea, altered consciousness,
PEEP reduces expiratory driving pressure and is therefore patients totally exhausted and/or with severe and
 2441

worsening hypercapnia or major respiratory distress Weaning from mechanical ventilation

despite adequate medical treatment). Because of the Readiness to wean needs to be screened on a daily basis
major increase in expiratory resistance due to airway according to guidelines (Fig.  3) [55]. In ready-to-wean
obstruction related to edema and bronchospasm, pul- patients, a spontaneous breathing trial is performed,
monary hyperinflation might be extremely high in with either T-tube or pressure support ventilation [56].
asthmatics. The key ventilatory strategy is to mini- In patients who tolerate the spontaneous breathing
mize hyperinflation, which is best achieved by reduc- trial, it is possible to proceed with extubation.
ing minute ventilation and lengthening expiratory time In COPD patients, prophylactic post-extubation NIV
(low tidal volume, low respiratory rate [45] and high and use of high-flow nasal cannula both decrease the
inspiratory airflow rate with the objective of targeting occurrence of acute respiratory failure and subsequent
an inspiratory-to-expiratory time of 1:4 to 1:6). A low reintubation (Fig. 3) [57, 58]. The addition of NIV ses-
level of external PEEP (≤ 5  cmH2O) is recommended sions to high-flow nasal cannula use seems to be more
by some authors, although this strategy is disputed efficient for preventing reintubation than use of high-
[54]. The degree of hyperinflation must be closely flow nasal cannula alone [59]. Finally, NIV can also
monitored (using end-inspiratory and end-expiratory hasten weaning in COPD patients who repeatedly fail
holds) with the aim of limiting Pplat and obtaining the spontaneous breathing trials [60].
lowest possible total PEEP [53]. As in COPD, using a In a series of 208 patients intubated for hypercapnic
volumetric mode with square wave airflow delivery respiratory failure, 4.4% required ventilation via tra-
allows easier monitoring. As an effect of major reduc- cheostomy at discharge [61]. The decision to opt for
tion of minute ventilation, P ­aCO2 might increase tracheostomy is made on the basis of considerations
dramatically [46]; reduction of P­ aCO2 is very much a about, for example, the risks of the procedure versus
secondary goal. its anticipated but unproven benefits [62]. In the diffi-
cult-to-wean patient, possible tracheostomy should be

Fig. 3  Therapeutic options at the different stages of patient management. NIV non-invasive ventilation, PEEP positive end-expiratory pressure, NAVA
neurally adjusted ventilator assist; PAV proportional assist ventilation
2442

A B

Pressure

Flow

Fig. 4  Schematic representation of pressure and flow recordings in two mechanically ventilated patients. In a healthy subject (panel A) expiratory
flow ceases at end-expiration, ruling out dynamic hyperinflation. In a COPD patient (panel B), expiratory flow does not cease at end-expiration,
which suggests dynamic hyperinflation and intrinsic positive end-expiratory pressure (PEEPi)

the subject of a multidisciplinary discussion [63]. The Do particular features emerge in middle‑income
patient and his or her family must be informed that tra- countries?
cheostomy does not alter the prognosis of the causal The burden of COPD and asthma is disproportionally
disease. Although tracheostomy can improve comfort high in low-resource countries due to high indoor/out-
[64], it may unduly prolong suffering associated with door air pollution (smoking, exposure to coal indoors
the underlying illness. In a context of chronic respira- and to dust in the workplace) [70, 71]. The death toll from
tory failure, these ethical considerations must be care- chronic respiratory diseases is a real challenge to the
fully thought through and discussed with the patient public health systems in developing countries, since the
and his or her family before performing a tracheostomy. highest risk of dying from non-communicable disease is
observed in low- and middle-income countries [72].
Long‑term outcome In addition, in most low- and middle-income countries,
In a small series of patients with COPD requiring pro- ICUs are scarce, and resources are limited. The avail-
longed mechanical ventilation (> 21 days), 2-year survival ability of invasive mechanical ventilation, in particular, is
was 40% (68% in patients weaned from the ventilator limited, and its use is associated with a high risk of mor-
and 22% in those not weaned) [65]. In another cohort of tality, especially from ventilator-associated pneumonia
patients (59% with COPD) requiring prolonged ventila- [73–75]. As in high-income countries, NIV should be
tion at a weaning center, 1-year survival was 49% [66]. preferred to invasive ventilation, particularly in cases of
A prospective longitudinal study investigated the effect COPD exacerbation. A recent meta-analysis summariz-
of prolonged mechanical ventilation on survival and qual- ing experience of NIV in these countries reported a mod-
ity of life in 315 patients with various causes of respira- erate risk of mortality in adults (16%), and a mean NIV
tory failure (95 had COPD as primary or secondary cause failure rate of 28.5% in adults in this population [73]. For
of respiratory failure) [67, 68]. Among the patients who COPD exacerbation, the use of NIV as the primary venti-
survived to discharge from the weaning facility, 54% were latory mode increased from a rate of 29% in 2000 to 97%
detached from the ventilator and 30% were still attached in 2012 [76]. This change was associated with gradual
to the ventilator at the time of discharge from the facil- falls in the rates of NIV failure (learning curve), ventila-
ity. The 1-year survival was 63% for ventilator-detached tor-associated pneumonia, and concurrent use of antibi-
patients and 22% for the ventilator-attached patients. otics [76]. These data suggest that guidelines regarding
Survival was not influenced by the underlying cause of the preferential use of NIV therapy are not specific to
respiratory failure, including COPD [68]. By 12 months, high-income countries and should also be applied to low-
the SF36 physical-summary score and mental-summary and middle-income countries.
score returned to pre-illness values, and 85% of patients
indicated their willingness to undergo ventilation again New avenues of research
[68, 69]. NIV has well-known drawbacks. Patient tolerance may
be poor due to patient discomfort, dyspnea, skin dam-
age, and claustrophobia [40]. Furthermore, caregiver skill
 2443

is important to the success of this technique. High-flow complex setting and a specific ventilator. Because of its
nasal cannula may be an alternative method [77, 78]. low density compared with air, helium/oxygen markedly
In a recent study conducted in 12 hypercapnic COPD enhanced the ability of NIV to reduce patients’ effort and
patients with mild to moderate exacerbation who had ini- to improve gas exchange [81]. However, despite some
tially required NIV, applying high-flow nasal cannula at improvement of several physiological variables, rand-
30 l/min for a short duration reduced inspiratory effort, omized controlled trials did not show a clinical benefit
and resulted in an effect similar to that of NIV delivered (i.e., reduction in intubation rate or mortality) [82, 83]
at moderate levels of pressure support [78]. In addition, with the use of helium/oxygen mixture. The relatively low
high-flow nasal cannula is a more comfortable technique rate of intubation already achieved with NIV alone may
than NIV [79, 80]. explain the lack of benefit with helium/oxygen mixture.
Given the fact that approximately 15% of COPD More recently, extracorporeal C ­ O2 removal has been
patients fail NIV, attempts have been made to improve considered as a possible adjunct to NIV to avoid intuba-
the efficacy of NIV. These attempts include inhalation tion in patients not responding to NIV [84]. Combining
of helium and oxygen gas mixtures, which requires a NIV with direct removal of ­CO2 is postulated to improve

Fig. 5  Tracings (from top to bottom) of airway pressure (Paw), airflow (Flow), esophageal pressure (Pes), gastric pressure (Pga), transdiaphragmatic
pressure (Pdi) and tidal volume (VOLUME) in a chronic obstructive pulmonary disease (COPD) patient exhibiting significant respiratory muscle effort
during an episode of acute respiratory failure—due to a congestive heart failure during weaning—while mechanically ventilated with positive
end-expiratory pressure (PEEP) of 6 cmH2O and a pressure support level of 8 cmH2O. This patient shows dynamic hyperinflation (average corrected
intrinsic PEEPi 8 cmH2O), and major recruitment of expiratory muscles (as reflected by the raising Pga during expiration). Of note, the presence of
numerous ineffective triggering efforts indicated by the arrows (ventilator respiratory rate is about 18 breaths/min and the patient’s respiratory rate
is about 28 breaths/min). From Cabello B, Mancebo J (2003) Withdrawal from mechanical ventilation in patients with COPD: the issue of congestive
heart failure. In: Vincent J-L (ed) Yearbook of intensive care and emergency medicine. Springer-Verlag, Berlin, Heidelberg, pp 295–301
2444

alveolar ventilation and reduce the respiratory muscle Ultrasound can be used to evaluate respiratory mus-
workload. Extracorporeal C ­ O2 removal can also be used cle function and help manage mechanically ventilated
to accelerate weaning from endotracheal intubation as it patients [99], as it can give a gross estimation of dia-
may prevent ineffective shallow-breathing patterns and phragm function [100]. In patients presenting with
reduce inspiratory work by maintaining stable ­ PaCO2 acute exacerbations of COPD in the emergency room,
levels during unsupported breathing [85]. Although these diaphragm dysfunction was associated with NIV failure
devices eliminate carbon dioxide efficiently, experimental [101], but these results have not been prospectively vali-
evidence of their effectiveness in patients with COPD is dated. Diaphragm dysfunction is also associated with a
limited. Demonstrating benefits in COPD will be chal- higher risk of weaning failure [102, 103]. Ultrasound can
lenging because of complications associated with extra- also be used to examine extra-diaphragmatic inspiratory
corporeal ­CO2 removal [86]. muscle function, focusing on the intercostal parasternal
Another strategy to improve the prognosis of COPD muscle for example [104] (Fig.  6). Increased parasternal
patients is to optimize patient-ventilator interaction. intercostal activity is associated with diaphragm dys-
Contrary to what occurs with pressure support ventila- function and weaning failure [104]. Ultrasound can also
tion, proportional modes of ventilation assist the patient be applied to image the lungs in COPD, and may be use-
by delivering a level of assistance that is proportional ful in differentiating causes of acute dyspnea in these
to his/her inspiratory effort [87]. There are two propor- patients [105]. It can also help in identifying pneumo-
tional modes: neurally adjusted ventilatory assist (NAVA) thorax, pleural effusion, consolidation or cardiogenic
and proportional assist ventilation (PAV). NAVA is a edema. Whether such ultrasound imaging of the respira-
mode that triggers, cycles and regulates inspiratory air- tory muscles improves patient outcomes remains to be
flow based on the diaphragmatic electromyography sig- determined. In addition, training and skills are required
nal. There is no influence of PEEPi during the ventilator to ensure safe and worthwhile implementation.
assistance, since it starts with the patient’s own breathing
effort; furthermore, thanks to better patient-ventilator Summary
interaction, there should be no effect of leaks during NIV Mechanical ventilation is the cornerstone of the man-
[88–90]. Several studies have shown that NAVA improves agement of COPD and asthma patients presenting with
patient-ventilator interaction, diaphragm efficiency and life-threatening respiratory failure. Although NIV pre-
patient comfort, as compared with pressure support vents the majority of patients with COPD exacerbation
ventilation [91]. However, no clear clinical advantage of from subsequently needing invasive ventilation, future
NAVA over PAV has been demonstrated, although NAVA efforts should focus on improving the efficacy of NIV and
might be beneficial in difficult weaning [91, 92]. With on evaluation of the high-flow nasal cannula technique.
PAV, the inspiratory assist is proportional to the activity Invasive mechanical ventilation is reserved for patients
of the inspiratory muscles, which is calculated from the who fail NIV and are subsequently intubated. The major
measured flow and volumes using the equation of motion goal during invasive mechanical ventilation is to limit
of the respiratory system [87]. PAV protects against high hyperinflation; this is achieved through reduced minute
tidal volume and subsequent dynamic hyperinflation ventilation, low tidal volumes and prolonged expiratory
[93]. The use of PAV is associated with a shorter weaning time. Normalization of blood gas is a secondary thera-
time compared with pressure support ventilation [94]. peutic goal. A low level of external PEEP may be applied
A striking feature of patients treated with NIV or to patients triggering their ventilator. Mechanical ventila-
invasive ventilation is the high rate of ICU or hospital tion of asthma patients follows the same rules except that
readmissions [95]. At least 50% of patients surviving an the use of NIV is not presently recommended despite
ICU stay will be readmitted within a year, and this per- promising recent data. Weaning should be performed as
centage can reach 80% in some studies. Two factors may expeditiously as possible with a daily screening test fol-
explain this high rate. First, patients may continue to lowed by a trial of spontaneous breathing. In selected
need ventilation at home [96], but this practice has not patients, prophylactic post-extubation NIV prevents
been developed widely. Recent trials of home NIV for post-extubation acute respiratory failure and subsequent
patients surviving an ICU admission suggest important reintubation. High-flow nasal cannula seems as efficient
potential benefits [34]. Second, many of these patients as NIV to prevent reintubation and the combination of
have untreated or undiagnosed comorbidities, especially NIV and high-flow nasal cannula may be even more effi-
sleep-related breathing disorders and cardiac dysfunction cient. Finally, tracheostomy should be the subject of a
[97, 98]. New approaches are needed to reduce this high multidisciplinary discussion.
readmission rate.
 2445

Fig. 6  Schematic representation (A) and ultrasound images of the parasternal intercostal muscle with B mode (B) and time motion mode allowing
measurement of inspiratory and expiratory thickness (C)

Author details Care Medicine, Hines Veterans Affairs Hospital, Loyola University of Chicago
1
 Service de Pneumologie, Médecine Intensive—Réanimation (Département Stritch School of Medicine, Hines, IL 60141, USA. 7 Service de Médecine
“R3S”), Hôpital Pitié‑Salpêtrière, AP-HP, Sorbonne Université, 75013 Paris, Intensive Réanimation, AP-HP, Hôpitaux Universitaires Henri Mondor, DHU
France. 2 INSERM, UMRS1158 Neurophysiologie Respiratoire Expérimentale A-TVB, 94010 Créteil, France. 8 Faculté de Médecine de Créteil, Université Paris
et Clinique, Sorbonne Université, Paris, France. 3 Interdepartmental Division Est Créteil, IMRB GRC CARMAS, 94010 Créteil, France. 9 Department of Clinical,
of Critical Care Medicine, University of Toronto, Toronto, Canada. 4 Keenan Cen‑ Integrated, and Experimental Medicine (DIMES), Respiratory and Critical Care,
tre for Biomedical Research, Li Ka Shing Knowledge Institute, St. Michael’s Hos‑ Sant’Orsola Malpighi Hospital, Bologna, Italy. 10 Intensive Care Unit, Fattouma
pital, Toronto, Canada. 5 Department of Intensive Care, Amsterdam UMC, Loca‑ Bourguiba University Hospital, Rue 1er Juin, 5000 Monastir, Tunisia. 11 Labo‑
tion VUmc, Amsterdam, The Netherlands. 6 Division of Pulmonary and Critical ratoire de Recherche (LR12SP15), University of Monastir, Monastir, Tunisia.
2446

12
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de Enfermedades Respiratorias, CIBERES, Madrid, Spain. 14 Adult Intensive Care driving pressure. Intensive Care Med 42:1597–1600. https​://doi.
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Research and Training Center, Medical School, Evangelismos Hospital, Univer‑ tory pressure: lessons learned over 30 years. Am J Respir Crit Care Med
sity of Athens, Athens, Greece. 16 3rd Department of Critical Care Medicine, 184:756–762. https​://doi.org/10.1164/rccm.20110​2-0226P​P
Evgenideio Hospital, Medical School, University of Athens, Athens, Greece. 8. Smith TC, Marini JJ (1988) Impact of PEEP on lung mechanics and work
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lished maps and institutional affiliations. 4-016-1533-9
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