Review Article

Page 1 of 11

Respiratory mechanics in patients with acute respiratory distress

syndrome
Vincenzo Russotto1, Giacomo Bellani1,2, Giuseppe Foti1,2
1
Department of Emergency and Intensive Care, University Hospital San Gerardo, Monza 20900, Italy; 2University of Milano Bicocca, Milano, Italy
Contributions: (I) Conception and design: All authors; (II) Administrative support: None; (III) Provision of study materials or patients: None; (IV)
Collection and assembly of data: None; (V) Data analysis and interpretation: None; (VI) Manuscript writing: All authors; (VII) Final approval of
manuscript: All authors.
Correspondence to: Vincenzo Russotto; Giacomo Bellani; Giuseppe Foti. Department of Emergency and Intensive Care, University Hospital San
Gerardo, ASST Monza, Via G. B. Pergolesi, 33, Monza 20900, Italy. Email: vinrussotto@gmail.com; giacomo.bellani1@unimib.it; g.foti@asst-monza.it.

Abstract: Despite the recognition of its iatrogenic potential, mechanical ventilation remains the mainstay
of respiratory support for patients with acute respiratory distress syndrome (ARDS). The low volume
ventilation has been recognized as the only method to reduce mortality of ARDS patients and plateau
pressure as the lighthouse for delivering safe ventilation. Recent investigations suggest that a ventilation
based on lung mechanics (tidal ventilation tailored to the available lung volume able to receive it, i.e., driving
pressure) is a successful approach to improve outcome. However, currently available bedside mechanical
variables do not consider regional mechanical properties of ARDS affected lungs, which include the role
of local stress risers at the boundaries of areas with different aeration. A unifying approach considers lung-
related causes and ventilation-related causes of lung injury. These last may be incorporated in the mechanical
power (i.e., amount of mechanical energy transferred per unit of time). Ventilation-induced lung injury (which
includes the self-inflicted lung injury of a spontaneously breathing patient) can therefore be prevented by the
adoption of measures promoting an increase of ventilable lung and its homogeneity and by delivering lower
levels of mechanical power. Prone position promotes lung homogeneity without increasing the delivered
mechanical power. This review describes the recent developments on respiratory mechanics in ARDS
patients, providing both bedside and research insights from the most updated evidence.

Keywords: Respiratory mechanics; acute respiratory distress syndrome (ARDS); ventilator-induced lung
injury (VILI)

Submitted Apr 15, 2018. Accepted for publication Aug 09, 2018.
doi: 10.21037/atm.2018.08.32
View this article at: http://dx.doi.org/10.21037/atm.2018.08.32

Introduction as a major contributor of lung stress during mechanical

ventilation (i.e., “volutrauma”) (3). Hyperinflation of lung
Despite 50 years of research, no specific lung-directed
regions coexists with other areas with loss in aerated lung
therapy for acute respiratory distress syndrome (ARDS) volume and repeated closing and opening of alveoli and
patients is available and mechanical ventilation remains the distal small airways (i.e., “atelectrauma”) (4). The local
mainstay of treatment for these patients (1). Since the first and systemic release of inflammatory mediators triggered
description of ARDS, stiff lungs and the need for elevated by both phenomena is responsible for the multiple organ
ventilation pressure to achieve normal gas exchange (i.e., dysfunction (i.e., biotrauma) which may occur in ARDS
increased elastance) has been reported as a hallmark patients (5). During the last decades, we assisted to a
of ARDS, which is invariably present in all affected paradigm shift on the role of mechanical ventilation: from
patients (2). Large tidal volumes have been recognized a life-saving intervention aiming to provide adequate

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Page 2 of 11 Russotto et al. Respiratory mechanics in ARDS

oxygenation through large volumes, to a contributor and Notably, the product of Ers x ΔV, which describes the
amplifier of lung harm (4). In this scenario, respiratory pressure required to overcome the elastic recoil of the
mechanics gained a major role at the bedside. Firstly, respiratory system, corresponds to the driving pressure (10).
respiratory mechanics variables are used to titrate a less Differentiation of the mechanical properties of the lung
injurious (i.e., protective) ventilator support. Secondly, from those of the chest wall is necessary to estimate the
since some of mechanics variables are powerful predictors pressure applied to lungs (i.e., transpulmonary pressure, PL).
of ARDS mortality [e.g., driving pressure, respiratory
PL = Paw – Ppl
system compliance, stress index, pressure/volume (P/V)
curve etc.] (6), these may be considered a marker of disease This requires the measure of pleural pressure (Ppl), which
severity and be used to monitor its progression. Daily is obtained from an esophageal balloon catheter. Since
bedside assessment of respiratory mechanics is performed esophageal pressure (Pes) approximates pleural pressure (Ppl),
in less than half of patients with ARDS irrespective of their PL can be calculated from the difference between Paw and
severity (7). However, when systematically implemented, Pes (11). However, Ppl is not uniform, and a pressure gradient
respiratory mechanics measurements led to better tailoring exists between dependent and non-dependent lung regions:
of respiratory support with improved oxygenation and this gradient is increased in ARDS patients, so that P es is
reduced risk of overdistention (8). the expression of the pleural pressure at the esophageal
The aim of this review, rather than providing a ballon level only (11). Recently, esophageal elastance and
comprehensive description of lung mechanics in ARDS esophageal ballon filling volume have been also considered
patients, is to elucidate recent acquisitions in respiratory as a meaningful variables influencing Pes reliability and a
mechanics in ARDS, with insights for clinical and calibration procedure of esophageal balloon catheters been
experimental application of most updated evidence. proposed (12).
PL is proportional to Paw and to the ratio of lung elastance
(EL) to total respiratory system elastance (Ers):
Static measurements of the respiratory system
PL = Paw × EL/Ers
The mathematical ground of respiratory mechanics is
based on Newton’s third law (a body exerts a force equal in While in ARDS patients ECW accounts for an average of
magnitude and opposite in direction to the force applied 30% of the whole respiratory system elastance, Chiumello
to it), which, applied to the respiratory system, is known as et al. demonstrated a great variability exists in the ratio of
equation of motion (9): lung elastance to the total respiratory system elastance,
since this ranged from 0.33 to 0.92 in their cohort of ARDS
Paw + Pmus = Ers ΔV + Rrs V̇ + PEEPtot
patients (13). In this sense, the resulting PL may range from
Where P aw is the ventilator pressure, P mus is the approximately 10 to 28 cmH2O after applying 30 cmH2O to
pressure generated by the respiratory muscles, Ers is the the whole respiratory system. Noteworthy, in their series,
respiratory system elastance, ΔV is the volume difference EL/Ers ratio was lower (and the ECW significantly higher) in
from the resting volume, R rs is the respiratory system extrapulmonary than in pulmonary causes of ARDS (13).
resistance, V̇ is the rate of change in volume (i.e., flow)
and PEEPtot is the sum of applied and intrinsic PEEP. In
Respiratory system compliance (Crs) and the
a paralyzed patient, Pmus = 0. Paw under static (i.e., no flow)
baby lung concept
condition corresponds to the plateau pressure (Pplat), which
theoretically approximates alveolar pressure. Ers, which is Crs is commonly calculated at the bedside, due to its strong
the sum of chest wall elastance (Ecw) and lung elastance (EL) correlation with the underlying pathophysiology of ARDS,
can be calculated as follows: the possibility to use it for titration of ventilation and for
monitoring the progression of the disease. During ARDS,
Ers = (Pplat – PEEPtot)/VT
the decrease of lung compliance is attributable to the
Where V T is the tidal volume. Given the reciprocal reduction of airspace volume due to alveoli collapse by
relationship of compliance and elastance: inflammatory cells, fluid and superimposed pressure, along
with impairment of surfactant function.
Crs = VT /(Pplat – PEEPtot) The baby lung concept is approximately 30 years old

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Annals of Translational Medicine, 2018 Page 3 of 11

and changed the vision of ARDS pathophysiology. ARDS spontaneously breathing pattern preferentially distributes
was initially conceived as a homogeneous increase in lung volume to dependent regions (22) (due to more
lung elastance (and thus decrease in lung compliance). pronounced movement of the dorsal diaphragm portion),
Quantitative tomography studies demonstrated a with better ventilation-perfusion matching and oxygenation.
inhomogeneous picture with areas of lung consolidation The presence of some inspiratory efforts decreases mean
and atelectasis along with nearly normally aerated intrathoracic pressure favouring venous return and
lung portions with nearly normal intrinsic mechanical therefore promoting better hemodynamic in a vast majority
properties (14). From this perspective, diseased lung is of patients (23). Finally, a role may be played by reduced
stiffer simply because of reduced aeration of some of need for sedatives and their side effects (24,25). However,
its portion. The baby lung, originally described as an the potential for harm of vigorous inspiratory efforts during
anatomical feature located in the non-dependent portion of spontaneous breathing has been highlighted in a classical
the lung in a patient lying supine, it was soon reconsidered experiment performed by Mascheroni and colleagues
as a functional (dynamic) status since its size and location 30 years ago (26). They injected salicylate acid into the
may be modified by interventions such as recruitment cisterna magna of sheep to generate central metabolic
manoeuvres and prone positioning. Of note, it has been acidosis and increase their respiratory drive. Animal’s
reported a 1 to 1 ratio between the Crs to the fraction of oxygenation progressively worsened and at autopsy authors
expected normally aerated lung volume: a compliance observed injuries similar to those subsequently labelled
of 30 ml/cmH 2O approximately corresponds to 30% of as ventilator-induced lung injury (VILI), as opposed
open ventilable lung (15). Positron emission tomography to paralysed and mechanically ventilated animals (26).
(PET) showed an increased water permeability and Other investigators, more recently reappraised the role
metabolic rate in normally aerated areas of ARDS patients of spontaneous ventilation for generation of lung injury
(16,17). Moreover, lungs of patients with ARDS have been and these preclinical findings were also confirmed by
investigated with PET and CT scans at different lung clinical data. Papazian et al. demonstrated that blocking
volumes. To assess the inflammatory activity, investigators spontaneous ventilation with neuromuscular blockers for
used the analogue of glucose 18 fluorodeoxyglucose 48 hours reduced lung inflammation (27) and improved
(18 FDG), whose uptake by inflammatory cells (mainly survival (28). The detrimental effect of spontaneous
neutrophils) is proportional to their metabolic activity. breathing may be attributed to changes in PL, development
They observed a correlation between metabolic activity of patient-ventilator asynchronies (especially double
and Pplat in normally aerated lung portions, with a marked triggering and reverse triggering) and to the increase
increase observed with Pplat higher than 26–27 cmH2O (18). of transmural vascular pressure (29), which may led to
Beside estimate of baby lung size, Crs is affected also by distension of pulmonary vessels, augmentation of lung
chest wall elastance and possible phenomena of alveolar perfusion and edema (30). This last phenomenon has been
overdistension. In order to evaluate these mechanisms an frequently described also in normal lungs of patients with
esophageal catheter and an evaluation of the P/V curve, increased airway resistance (negative pressure pulmonary
respectively, is suggested. Assessment of stress index is a edema) (31), playing a major role in the context of increased
convenient surrogate of P/V curve analysis capable of vascular permeability as in ARDS.
detecting intratidal overdistension (19). For a given a tidal volume, transpulmonary pressure
swings are the same irrespective of their generation by
mechanical ventilator or spontaneous breathing (32).
The spontaneously breathing ARDS patient
However, in spontaneously breathing patients with already
Assisted spontaneous breathing may obviously be injured lungs, regional differences in P L , local stress
considered the most physiologic method of respiratory amplifiers and alveolar pressure drops in particular can
support. Indeed, it bears several advantages compared to all promote and amplify injurious patterns (two hit model).
controlled ventilation (possibly requiring muscle paralysis). The term patient self-inflicted injury (P-SILI) has been
Firstly, preserved diaphragmatic activity is associated proposed to identify these complex pathophysiologic
with a reduced risk of ventilation-induced diaphragm mechanisms (24,33).
dysfunction (20) along with maintenance of end-expiratory Moreover, forces acting at regional level, may result
lung volume with increased aeration (21). Secondly, the in a pendelluft phenomenon, i.e., the intrapulmonary gas

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Page 4 of 11 Russotto et al. Respiratory mechanics in ARDS

redistribution occurring in the absence of tidal volume measure Pplat to estimate driving pressure in spontaneously
generation. breathing patients since we consider it a sufficiently reliable
Yoshida et al. described the occurrence of the occult mechanical variable (32).
pendelluft phenomenon in a patient with lung injury and Whitelaw at al. found that a decrease in airway pressure
in an animal model (34). In the presence of spontaneous during the first 100 msec (i.e., 0.1 sec) of an occluded breath
efforts, authors observed a shift of alveolar air from non- was constant in each patient during a given condition and
dependent to dependent lung regions. In the animal model, it reflected respiratory center output better than minute
this was associated with overstretch of the dependent ventilation (37). Besides, this is also a good indicator of the
lung, corresponding to what would be observed with patient’s work of breathing (38,39). P0.1 is regarded as a
driving pressure three-fold higher than that measured reliable index of respiratory drive for titration of respiratory
in the airways. Notably, this occurred in the absence of support level and as a weaning outcome predictor. Finally,
tidal volume variations and despite the adoption of a it is a sensitive indicator of respiratory drive in severe
tidal volume of 6 mL/kg. Pendelluft was detected using ARDS patients under venous-venous extracorporeal
the electrical impedance tomography as opposed to oxygenation (40).
standard ventilation monitoring traces (34). Noteworthy, The electrical activity of the diaphragm (Eadi) tightly
all the previously described phenomena are in play also correlates with pressure generated by respiratory muscles
in non-intubated patients during noninvasive ventilation (P mus). The ratio of P mus to Eadi (cmH 2O/µV) has been
(NIV) (24). In patients with high respiratory drive, NIV termed PEI [or neuromuscular efficiency (NME)] and
may simply promote the development of high tidal volume, it indicates the amount of pressure generated for each
with the additional challenge posed by the lack of control microvolt of electrical activity (41). PEI is a useful index
over respiratory drive both by pharmacologic and non which remains constant in each patient irrespective of the
pharmacologic means (35). Moreover intra-tidal pendelluft level of ventilator assistance. Moreover, since its estimation
decrease alveolar ventilation efficiency, promoting after an occlusion manoeuvre is tightly correlated to its
hyperventilation and further lung damage. value registered during tidal ventilation, it can be used as a
The risks of P-SILI should be weighted against the short multiplication factor for Eadi to estimate pressure generated
and long term consequences of heavy sedation and paralysis, by the respiratory muscles (Pmusc), work of breathing and
in regard to neurocognitive and neuromuscular function. PEEPi (42).
In light of this growing amount of data, clinicians should It should be highlighted that an inadequate selection
systematically monitor spontaneous breathing at the bedside of respiratory support in partially assisted modes may lead
in both intubated and non-intubated patients in the attempt to overassistance and complete diaphragm unloading,
to monitor the development of injurious ventilation patterns eliminating the advantages of respiratory muscle training
but also tailor the level of respiratory support avoiding both typical of assisted ventilation (25). Typical indicator of such
underassistance and overassistance. This may be addressed occurrence is: PMI ≤0, P0.1 <1 cmH2O, Pmusc <2 cmH2O.
through the adoption of widespread available tools such
as Pmusc index (PMI), P0.1 (airway pressure drop during
Ventilation tailored on respiratory mechanics:
the first 100 msec due to the inspiratory effort against
driving pressure
an occluded airway) (36) or more advanced respiratory
muscle activity monitors (esophageal pressure or electrical Amato and colleagues recently revamped the concept of
diaphragmatic activity) (24). PMI is based on the concept driving pressure (ΔP), which equals VT/Crs and it describes
that the difference between plateau pressure registered with the relationship between VT and the lung volume available
an end-inspiratory occlusion (Pplat) and pressure applied to receive it. Authors compared the predictive role of tidal
by the ventilator (PEEP + PSV), represent an index of volume normalized to ideal body weight, which up to
patient elastic workload (Figure 1). The advantage of PMI that moment represented the standard for tailoring tidal
is bedside calculation with standard ventilators, without ventilation, to tidal volume normalized to estimated lung
additional equipment. Respiratory muscles relaxation compliance (driving pressure) (10) and identified ΔP as the
during end inspiratory occlusion is necessary to evaluate variable with the best ability to predict 60-day survival in
Pplat and in clinical practice this happens in the majority of ARDS (6).
cases. Noteworthy, in our clinical practice, we normally A cut-off of 15 cmH 2 O was thus considered as a

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Annals of Translational Medicine, 2018 Page 5 of 11

A Flow
1.0
0.8
0.6
0.4
0.2
L/min

0.0
–0.2
–0.4
–0.6
–0.8

B 30
Paw
25
20 PMI
cmH2O

15 PS Pplat
10
5 PEEP

C 30
Pes
25
cmH2O

20
15
10
5

2 sec 4 sec 6 sec 8 sec

Figure 1 Ventilatory waveform of a patient under assisted ventilation. (A) Flow; (B) airway pressure (Paw); Pmusc index (PMI) is the difference
between the plateau pressure (Pplat) and the sum of positive end-expiratory pressure (PEEP) and pressure support (PS) and it represents an
index of patient’s elastic workload; (C) esophageal pressure waveform.

clinically relevant potential novel target to achieve a lung the EPvent study (49) in which they compared ΔP and ΔPL
protective ventilation (6,43). The increased survival of a in 28-day survivors and non-survivors. They highlighted
low VT as observed in the landmark ARMA trial (44), is that, although the majority of respiratory system ΔP was
critically dependent on the reduction in ΔP which results determined by the lung mechanical properties, an amount
from this intervention. The same holds true also for PEEP corresponding approximately to 33% was accounted by the
selection: the benefit of higher PEEP levels in terms of lung chest wall (48). This proportion may be more relevant in
protection are seen only when coupled with a reduction those patient categories with recognized increased Ecw (e.g.,
of ΔP at a given V T. This observation may explain the abdominal distension, chest wall edema, pleural effusion).
reported inconsistent survival benefit of high PEEP in A prospective, more powered study is needed to evaluate
previously published studies (45-47). In other words, whether ΔPL has a better performance than ΔP for tailoring
PEEP is beneficial only when associated with an increase ventilation of ARDS patients.
of functional lung volume (in a patient with high lung
recruitability), with potential deleterious effects in case of
Lung mechanics in prone position
lung overdistention. On the opposite, an inappropriately
low PEEP level may be associated with atelectasis, leading Prone position was proposed approximately forty years
to a reduced lung compliance (and, again, in functional lung ago as an intervention to improve oxygenation in patients
volume) and higher ΔP. VT and PEEP should therefore be with acute respiratory failure (50). The benefits of prone
reconsidered within a bundle of interventions which, to be positioning ARDS patients are beyond those of improved
beneficial, should ultimately lead to a ΔP reduction. Amato gas exchange and may be also attributed to more favourable
and colleagues’ study did not account for E cw since they respiratory system mechanics and VILI reduction.
considered ΔP of the whole respiratory system an adequate Lung mechanics in prone position is the result of the
surrogate of transpulmonary driving pressure (ΔPL) (6). interaction of the lungs with the surrounding structures,
Baedorf Kassis et al. (48) performed a secondary analysis of playing a role as Ecw, abdominal wall elastance, diaphragm

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Page 6 of 11 Russotto et al. Respiratory mechanics in ARDS

curvature, heart and mediastinal mass. E rs results from patients (55). Prone position increased lung recruitment
the effects of two serial elastic bodies and their elastance and this occurred without an increase in hyperinflation and
(lung elastance, E L and E cw). The elastic behaviour of PL. This was also observed in patients without evidence of
the abdominal wall, which is commonly included as lung recruitability tested by high PEEP levels applied in
a component of the E cw, has been questioned and the supine position. Prone position and PEEP had a synergistic
variation of its contribution to the Ers has been attributed effect in enhancing lung recruitment and reducing the
to displacement of its mass (coupled with diaphragm cyclic recruitment/derecruitment. Notably, prone position
displacement). Prone position often increases Ecw of patients reduced the degree of hyperinflation (and Pplat) at higher
with ARDS (51) by means of increased abdominal pressure, PEEP levels in comparison with the same levels applied in
cranial diaphragm displacement, greater rib cage rigidity. supine position (55). This effect may be, again, attributed
Indeed, the anterior (sternal) portion of the rib cage has a to a greater homogeneity of P L which translates in an
higher compliance than its posterior (vertebral) portion. increased therapeutic index (a better benefit to harm ratio)
Lung inflation occurs between two rigid walls, the sternum of PEEP in prone position (56). In summary, the benefit in
and the vertebral column, making tidal ventilation more terms of reduced VILI may be attributed to the increase in
homogeneous and gas exchange improved. Pelosi et al. the baby lung volume along with a reduction of the number
observed a decrease in Ccw (increase in Ecw) while prone of interfaces between differently aerated lung units which
which correlated with the oxygenation improvement. promote a local amplification of applied stress (i.e., stress
Moreover, authors found that oxygenation improvement was risers, see below) (57). Noteworthy, prone position is the only
predictable from baseline, supine Ccw: the higher its value available intervention which promotes lung homogeneity
the greater its decrease in prone position and improved without increasing the delivered mechanical power (58).
oxygenation (51). Notably, when turned back supine, Recently, the results of a large observational study on the
patients had an increased Crs which was mainly attributable prevalence of use of prone position in ARDS patients
to improved lung compliance (51). Another effect of prone highlighted how this manoeuvre is still underused despite
position is the reduction of compressive force of the heart the strong evidence supporting its adoption in moderate/
on the underlying lung. A CT scan study showed how its severe ARDS patients (59,60).
weight is directed towards the sternum unloading the lung,
and the benefit of this effect may be more pronounced in
Lung inhomogeneity and stress risers
patients with cardiac enlargement and associated cardiogenic
pulmonary edema (52,53). This may help reduce the Global measurement of respiratory mechanics may
fraction of shunt through a reduction of hydrostatic edema not reflect regional increases of stress, which are the
and lymphatic drainage improvement. Distribution of air consequence of local inhomogeneity of affected lungs.
within the lungs has been investigated by CT scan. In a Indeed, injury may exert its effect in specific portions of
normal subject in supine position, the gas to tissue ratio lung parenchyma. Lung inhomogeneity has been claimed
decreases from ventral to dorsal regions according to an to be responsible for generation of local stress amplifiers.
exponential behaviour expressed by a decay constant (Kd). Cressoni and co-workers (57) identified and quantified lung
This normally corresponds to 13.6±2.5 cm, which means inhomogeneity through CT scans. They measured the gas
that at this distance from the ventral surface, the gas to tissue to tissue ratio of lung parenchima, identifying not-inflated,
ratio is 37% of that measured at the ventral surface. In other poorly inflated, well-inflated and overinflated areas. When
words, dimensions of dorsal regions alveoli are approximately a lung region expands less than the surrounding regions,
one-third of those at the ventral surface. When a healthy these latter are exposed to increased strain, to compensate
subject is shifted to the prone position, inflation distribution for the non-expanded or less-expanded regions. Less aerated
changes, with a Kd of 26.2±2.2 cm (54). This indicates a more regions become, hence, stress risers in which an increased
homogeneous distribution of regional inflation while prone local stress insists. The extracellular matrix is involved in the
compared to supine. The mechanism behind the variation applied load distribution so that fibers of expanded regions
of regional inflation is a more homogeneous distribution carry the additional force of non-expanding fibers, locally
of PL. Cornejo and co-workers investigated the effect of multiplying stress and strain (Figure 2). These concepts
prone position and PEEP on lung recruitment, cyclic were originally theoretically described by Mead and co-
recruitment/derecruitment and hyperinflation in ARDS workers (61). The transpulmonary pressure is the total

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Annals of Translational Medicine, 2018 Page 7 of 11

To date, the only available intervention to reduce the

number of these hot spot of stress amplifiers is to increase
the homogeneity of lung aeration. Their recognition
invites clinicians to have a regional (or even microscopic)
perspective of mechanical properties at the bedside. Finally,
in the absence of a bedside tool to estimate the proportion
1 kg 1 kg 1 kg of local stress amplifiers, the threshold of the delivered
A B C (global) mechanical power may be lowered in a given
patient.
Figure 2 Graphical representation of Mead’s model (61). When a
load (1 kg in this example) is imposed to elastic fibers, the load is
equally distributed among them (A), When a fiber does not provide The unifying vision on lung-injury: the
its contribution, a higher load is imposed to the remaining fibers mechanical power
(1.11 for each of the 9 fibers) (B). For the 8 remaining fibers, the Gattinoni and colleagues considered the determinants of
load is 1.25 and so on (C). VILI identifying lung-related causes and ventilation-related
causes of lung injury (63). Lung-related causes depend on the
well-known pathophysiologic changes of lung parenchima
load imposed to the elastic fibers. The multiplication factor
(i.e., lung inhomogeneity, reduced lung volume), leading
of the additional load imposed at the interface between
to the uneven distribution of the applied energy, which is
completely distended pulmonary units (volume =10) and
the second determinant of VILI (ventilation-related cause)
collapsed ones (volume =1) was calculated by Mead and
(Figure 3). The novelty of this approach is its unifying
co-workers according to the following formula (61): perspective: VILI results from the interaction between
(10/1)2/3 the administered ventilation power and lung-related
predisposing factors (i.e., how baby and inhomogeneous the
This means that, according to the model, a P L of lung is). Starting from the previously described equation of
30 cmH 2O may locally reach a value of approximately motion, they calculated the power equation by multiplying
120 cmH 2O. However, their calculated multiplication each component of this equation by the variation of volume
factor (local stress amplifier) was higher than the one and respiratory rate:
calculated by Cressoni and co-workers, which averaged 1.9.
According to this estimation, PL applied at the interfaces Energybreath = {ΔV2 ⋅ [½⋅ ELrs + RR ⋅
between open and closed regions doubles the global PL that (1 + I:E)/(60 ⋅ I:E) ⋅Raw] + ΔV ⋅ PEEP}
would be registered in the absence of lung inhomogeneity.
Notably, the extent of lung inhomogeneities correlated Powerrs = RR ⋅ {ΔV2 ⋅ [½⋅ ELrs + RR ⋅
with ARDS severity and physiologic dead space and these (1 + I:E)/(60 ⋅ I:E) ⋅Raw] + ΔV ⋅ PEEP}
were reduced by the application of PEEP. Finally, survivors
had a lesser extent of inhomogeneities than non survivors. Authors then compared the calculated energy to the
These findings may explain the lower threshold for lung measured energy as obtained from the dynamic P/V curves
damage observed in experimental models of VILI when recorded during tidal ventilation of a sample of healthy
compared to healthy lungs. In other words, what may be and ARDS patients at different PEEP levels. Finally they
considered a safe PL limit for the globally considered lung verified which ventilation variable included in the equation
parenchima, may locally exert a damaging effect of stress mostly influenced the final ventilation power.
at the boundaries of regions with a different degree of Authors calculated the changes of mechanical power
aeration (57). As a proof of concept of the presence of as a function of the increase (in 10% steps) of one of its
generation of stress risers, Cressoni and co-workers determinants while keeping other components constant.
observed the initial development of lesions between visceral Tidal volume, driving pressure and inspiratory flow
pleura and sub-pleural alveoli after 8 hours of ventilation. exponentially increased mechanical power by a factor of 2. A
From these areas, lesions subsequently involve the whole 1.4 exponential increase in mechanical power was registered
parenchima (62). with frequency, while a linear increase was observed with

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Page 8 of 11 Russotto et al. Respiratory mechanics in ARDS

Ventilation-associated lung injury

Lung-related causes of VILI

Ventilation-related causes of VILI
• Lung size (how baby the baby
lung is) Mechanical power
• Degree of inhomogeneity
(stress risers) • Driving pressure
• Recruitability • Tidal volume
• Respiratory rate
• PEEP
• Flow

Figure 3 VILI results from the interaction of lung-related causes of VILI (baby lung size and stress risers) and ventilation-related causes of
VILI (conceptually and mathematically unified in the concept of mechanical power) (63). VILI, ventilator-induced lung injury.

PEEP. As an example, a tidal volume increase from 4 to the value of 58 mJ/min/mL (approximately 20-times the
8 ml/Kg produces a fourfold increase of the delivered mechanical power applied to a healthy lung with the same
mechanical power. Although PEEP may be considered a ventilator setting) (64). This approach provides a simple
static variable not contributing to the cyclic energy load mathematical description of forces involved in the energy
delivered to lungs with each breath, its linear relationship transfer from ventilator to lungs, their relative contribution
with mechanical power has been elucidated. Indeed, the and the possibility to anticipate the effect of their changes
applied PEEP multiplied by the tidal volume corresponds on the final energy and power delivered to patients. Further
to the energy level to be overcome for generation of each studies should verify the association of the mechanical
tidal breath (10). From the recent findings, the behaviour power with injury. Cressoni and co-workers performed a
of PEEP in relation to VILI may be considered ambiguous. study aiming at identifying a mechanical power threshold
Indeed, as mechanical variable contributes to the amount of associated with documented VILI in piglets (65). All
energy (and eventually injury) applied. On the other hand, piglets ventilated with a power above 12 J/min developed
its application may reduce the contribution of lung-related whole-lung edema whereas in those ventilated with a
causes of VILI (e.g., lung inhomogeneities, atelectrauma). lower mechanical power, CT scans showed mostly isolated
A given PEEP level may linearly increase the applied densities. Authors found a significant relationship between
power to lung (i.e., negative effect on ventilation-related power, increased lung weight and lung elastance, along with
determinants of VILI) without any positive effect on lung- worsened oxygenation. Recently, a secondary analysis of
related determinants of VILI. A different behaviour may be data from 787 ARDS patients included in the Acurasys (28)
observed in another patient or even in a different lung area and Proseva (66) randomized trials investigated the role
of the same patient. of mechanical power as predictor of 90-day survival (67).
As the same mechanical power may be safely applied Authors confirmed a role of mechanical power and similarly
to a normal lung while be injurious to a diseased lung, to Cressoni ad co-workers’ study, they identified the
consider the mechanical power applied during general meaningful threshold of 12 J/min as associated with a low
anesthesia of a healthy patient, which correspond to probability of survival (67). Prospective studies should verify
4 J/min and to 2.7 mJ/min/mL when normalized to a the association of mechanical power with patient-relevant
normal FRC of 1,500 mL. One may argue that the smaller outcomes and their improvement with the reduction (or
the lung available for ventilation, the higher the potential tailoring) of delivered power. The inclusion of the power
harm delivered with the same power amount. In this sense, equation in ventilator software may improve its precision,
the mechanical power normalized for the lung volume overcoming the limitations of its assumptions needed for
would provide a more accurate picture of injury potential. easier calculation (e.g., linear pressure-volume relationship).
The reduction of FRC which accompanies ARDS is Moreover, this may allow clinicians to evaluate or even
associated with a higher normalized power which, in case anticipate their choices in terms of mechanical power at the
of severe ARDS (with FRC as low as 500 mL) may reach bedside (and with their hands at the control knobs).

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Annals of Translational Medicine, 2018 Page 9 of 11

Conclusions 50 Countries. JAMA 2016;315:788-800.

8. Chen L, Chen GQ, Shore K, et al. Implementing a bedside
In patients with ARDS, recent evidence supports the
assessment of respiratory mechanics in patients with acute
titration of ventilation according to lung mechanics (i.e.,
respiratory distress syndrome. Crit Care 2017;21:84.
driving pressure) rather than patient-based prescriptions
9. Rohrer F. Der Zusammenhang der Atemkräfte und ihre
(i.e., tidal volume based on ideal body weight). However,
Abhängigkeit vom Dehnungszustand der Atmungsorgane.
regional characteristics of lung parenchyma may locally
Pflüger's Archiv für die Gesamte Physiologie des
amplify (i.e., stress risers) the applied ventilation power and
Menschen und der Tiere 1916;165:419-44.
contribute to VILI. Prone position should be applied not
10. Tonetti T, Vasques F, Rapetti F, et al. Driving pressure and
only to improve oxygenation but also as an intervention to
mechanical power: new targets for VILI prevention. Ann
reduce stress risers and increase functional lung volume. Transl Med 2017;5:286.
Finally, in the single patient, advantages of spontaneous 11. Mauri T, Yoshida T, Bellani G, et al. Esophageal and
ventilation (e.g., improved oxygenation, preserved transpulmonary pressure in the clinical setting: meaning,
diaphragmatic activity) should be weighted against the risk usefulness and perspectives. Intensive Care Med
of increased (and uncontrolled) transpulmonary pressure 2016;42:1360-73.
and the potentially injurious pendelluft phenomenon. 12. Mojoli F, Iotti GA, Torriglia F, et al. In vivo calibration of
esophageal pressure in the mechanically ventilated patient
Acknowledgements makes measurements reliable. Crit Care 2016;20:98.
13. Chiumello D, Carlesso E, Cadringher P, et al. Lung
None. stress and strain during mechanical ventilation for acute
respiratory distress syndrome. Am J Respir Crit Care Med
Footnote 2008;178:346-55.
14. Gattinoni L, Mascheroni D, Torresin A, et al.
Conflicts of Interest: The authors have no conflicts of interest Morphological response to positive end expiratory pressure
to declare. in acute respiratory failure. Computerized tomography
study. Intensive Care Med 1986;12:137-42.
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effects of prone positioning in acute respiratory distress

Cite this article as: Russotto V, Bellani G, Foti G. Respiratory

mechanics in patients with acute respiratory distress syndrome.
Ann Transl Med 2018. doi: 10.21037/atm.2018.08.32

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