Intensive Care Med (2014) 40:16701678

DOI 10.1007/s00134-014-3415-4

Davide Chiumello
Massimo Cressoni
Andrea Colombo
Giovanni Babini
Matteo Brioni
Francesco Crimella
Stefan Lundin
Ola Stenqvist
Luciano Gattinoni

ORIGINAL

The assessment of transpulmonary pressure

in mechanically ventilated ARDS patients

S. Lundin
O. Stenqvist
Department of Anesthesiology and
Intensive Care Medicine, Sahlgrenska
University Hospital, Gothenburg, Sweden

PEEP, respectively (P = 0.32,

P = 0.98, respectively), indicating
that these parameters were significantly related (r2 = 0.98, P \ 0.001
at 5 cmH2O of PEEP; r2 = 0.93, P \
0.001 at 15 cmH2O of PEEP). The
Take-home message: The end-inspiratory Abstract Purpose: The optimal
transpulmonary pressure can be accurately method for estimating transpulmopercentage error was 5.6 and 12.0 %,
computed by the elastance-derived method nary pressure (i.e. the fraction of the respectively. The mean directly meawhich, compared to the release method,
sured and release-derived
avoids the risk of ventilator disconnection, airway pressure transmitted to the
transpulmonary pressure were
while the directly measured end-expiratory lung) has not yet been established.
-8.0 3.8 and 3.9 0.9 cmH2O at
transpulmonary pressure is not related to the Methods: In this study on 44
release-derived transpulmonary pressure.
5 cmH2O of PEEP and -1.2 3.2
patients with acute respiratory disand 10.6 2.2 cmH2O at 15 cmH2O
tress syndrome (ARDS), we
Electronic supplementary material
computed the end-inspiratory trans- of PEEP, respectively, indicating that
The online version of this article
(doi:10.1007/s00134-014-3415-4) contains pulmonary pressure as the change in these parameters were not related
supplementary material, which is available airway and esophageal pressure from (r2 = 0.07, P = 0.08 at 5 cmH2O of
to authorized users.
2
end-inspiration to atmospheric pres- PEEP; r = 0.10, P = 0.53 at
sure (i.e. release derived) and as the 15 cmH2O of PEEP). Concluproduct of the end-inspiratory airway sions: Based on our observations,
elastance-derived transpulmonary
pressure and the ratio of lung to
D. Chiumello ())
L. Gattinoni
pressure can be considered to be an
respiratory system elastance (i.e.
Dipartimento di Anestesia, Rianimazione
adequate surrogate of the releaseelastance derived). The end-expira(Intensiva e Subintensiva) e Terapia del
derived transpulmonary pressure,
tory
transpulmonary
pressure
was
Dolore, Fondazione IRCCS Ca Granda
estimated as the product of positive while the release-derived and directly
Ospedale Maggiore Policlinico, Via F.
measured end-expiratory transpulmoend-expiratory pressure (PEEP)
Sforza 35, Milan, Italy
nary pressure are not related.
e-mail: chiumello@libero.it
minus the direct measurement of
Tel.: ?39-2-55033237
esophageal pressure and by the
release method. Results: The mean Keywords Acute respiratory
D. Chiumello
M. Cressoni

elastance- and release-derived trans- distress syndrome

A. Colombo
G. Babini

pulmonary pressure were 14.4 3.7 Computed tomography

M. Brioni
F. Crimella
L. Gattinoni
and
14.4 3.8 cmH2O at 5 cmH2O Transpulmonary pressure

Dipartimento di Fisiopatologia MedicoEsophageal pressure
PEEP
Chirurgica e dei Trapianti, Universita` degli of PEEP and 21.8 5.1 and
Studi di Milano, Milan, Italy
21.8 4.9 cmH2O at 15 cmH2O of
Received: 1 May 2014
Accepted: 19 July 2014
Published online: 12 August 2014
Springer-Verlag Berlin Heidelberg and
ESICM 2014

1671

Introduction
In clinical practice the monitoring of airway pressure is
used as a marker of lung stress, based on the assumption
that airway pressure adequately reflects transpulmonary
pressure (i.e. the difference between the airway and
pleural pressure) [1]. However, as the ratio between chest
wall and lung elastance is highly variable in patients with
acute respiratory distress syndrome (ARDS) [13], the
transpulmonary pressure may be variable at a constant
airway pressure in these patients [higher or lower lung
stress and ventilator-induced lung injury (VILI) for similar applied airway pressure] [4, 5].
Pleural pressure cannot be measured directly in the
clinical setting, which has led to esophageal pressure
being used as a reliable surrogate for more than 50 years
[68]. Two strategies have been developed to compute
transpulmonary pressure by the esophageal pressure
technique. The first one computes the changes in airway
and esophageal pressure during ventilation, estimating the
fraction of pressure which distends the lung and chest
wall, respectively [1, 4]. In this method, transpulmonary
pressure is measured as the change in airway and
esophageal pressure due to tidal inflation and positive
end-expiratory pressure (PEEP) from end-inspiration to
atmospheric pressure (i.e. release-derived transpulmonary
pressure). In the second strategy, which is a partially
modified method of the first, the transpulmonary pressure
is calculated as the product of the end-inspiratory airway
pressure and the ratio of lung to respiratory system elastance (i.e. elastance-derived transpulmonary pressure) [9,
10]. The ratio of lung and respiratory system elastance is
estimated as the change in airway and esophageal pressure during a tidal volume inflation (from PEEP to endinspiration). The elastance-derived method assumes that
in each patient the changes in esophageal and airway
pressure are linear during tidal volume inflation and by
PEEP. However, previous studies have shown that this
assumption is not always valid [3, 1113].
Although the reduction of tidal volume is commonly
indicated in ARDS, the optimal PEEP level in patients
with ARDS has not been defined [14, 15]. Among the
different criteria for bedside PEEP selection which have
been proposed [14, 15], Talmor et al. found a better
oxygenation and a trend in reduction in mortality by
selecting PEEP according to the end-expiratory transpulmonary pressure [16]. In Talmor et al.s study the
transpulmonary pressure was computed as the difference
in absolute airway and esophageal pressure (directly
derived transpulmonary pressure), assuming that esophageal pressure reflects the effective pleural pressure [7, 17].
However, the validity of using directly measured esophageal pressure is questionable in supine mechanically
ventilated patients because the value obtained can be
falsely high due to the mediastinum weight, abdominal

pressure and position of the catheter in the relevant part of

the thorax resulting in very low transpulmonary pressure
[1820]. For these reasons several correction factors for
directly measured esophageal pressure have been proposed [19, 21].
The aim of this study was to compare the different
methods described in literature for estimating end-inspiratory and end-expiratory transpulmonary pressure in a
population of patients with ARDS.

Materials and methods

Study population
Data on 44 patients affected by ARDS according to the
Berlin criteria [22], who had previously been enrolled
in a clinical trial, were analyzed [23]. Patients were
classified into mild, moderate and severe ARDS according to the PaO2/FiO2 (partial pressure arterial oxygen/
fraction of inspired oxygen) ratio obtained at a PEEP of
5 cmH2O [22].
Study design
Patients were sedated and paralyzed and maintained in
supine position. The clinical characteristics of the patients,
respiratory variables and ventilator settings were recorded
before the study. All patients were ventilated in volumecontrolled mode with a tidal volume of 68 mL/kg of
predicted body weight throughout the study protocol. The
oxygen fraction and respiratory rate were maintained
unchanged for the entire study. Immediately before each
step of the PEEP trial, a recruitment maneuver was performed to standardize the lung volume history [24]. The
recruitment maneuver was performed with pressure control ventilation at a PEEP of 5 cmH2O, with a plateau
pressure of 45 cmH2O, inspiration to expiration ratio of
1:1 and a respiratory rate of 10 bpm for 2 min [24]. After
the recruitment maneuver, 5 and 15 cmH2O of PEEP were
randomly applied. Respiratory mechanics and blood gas
analyses were measured after 20 min at each PEEP level.
At the end of the study, lungs were allowed to deflate from
end-inspiratory pressure down to atmospheric pressure
(i.e. at functional residual capacity). The patient was
subsequently transported to the radiological department
for a computed tomography (CT) scan.
Measurements
Respiratory mechanics
The respiratory flow rate was measured with a heated
Fleisch
pneumotachograph
(Fleish
2,
Fleisch,

1672

Switzerland). Volume was measured as integration of the

flow. Airway pressure was measured proximally to the
endotracheal tube with a dedicated pressure transducer
(model MPX 2010 DP; Motorola, Schaumburg, IL).
Esophageal pressure was measured with a radio-opaque
balloon (SmartCath Bicore; GE Healthcare Life Sciences,
Little Chalfont, UK) inflated with 1.01.5 mL of air
connected to a pressure transducer. All traces were sampled at 100 Hz and processed on a dedicated data
acquisition system (Colligo and Computo, www.elekton.it).
The esophageal balloon was positioned in the lower third
of the esophagus between a depth of 3540 cm. A similar
catheter was positioned in the stomach to measure the
gastric pressure. The amount of gas in the balloon was
periodically checked throughout the experiment.
During an airway occlusion the concordant changes of
airway and esophageal pressure were verified to check the
correct position of the balloon [4]. The static airway
plateau pressure and esophageal pressure were measured
at end-inspiration, end-expiration at PEEP and end-expiration after a release maneuver disconnecting the patient

from the ventilator [4]. The occlusion was maintained

until both airway and esophageal pressure decreased from
a maximum to a plateau value [25]. The expired volume
from PEEP to atmospheric pressure was the gained lung
volume due to PEEP application. The gastric pressure was
measured during the release maneuver. An example
record of flow, airway and esophageal pressure is given in
Fig. 1.

Elastance
Elastance related to tidal volume Elastance of the
respiratory system (Ers), lung (El) and chest wall (Ecw)
during tidal inflation was calculated as the changes in
airway, transpulmonary and esophageal pressure
between end-inspiration and PEEP divided by the
inspired tidal volume (Fig. 1) [25].
Elastance related to PEEP The Ers, El and Ecw due to
PEEP were calculated as the changes in airway,
transpulmonary and esophageal pressure between PEEP

Fig. 1 Tracings of flow, airway pressure (Paw) and esophageal (Pes) pressure during an end-inspiratory occlusion and a release
maneuver in a representative patient. Pplat plateau pressure, Pmax maximum pressure

1673

and atmospheric pressure divided by the expired volume 512 9 512. In each of the CT slices, lung profiles were
from PEEP to achieve atmospheric pressure (Fig. 1) manually delineated and analyzed with a dedicated soft[25].
ware package (Soft-E-Film; www.elekton.it).
We assumed that lung parenchyma is composed of two
compartments with very different density values: air
End-inspiratory transpulmonary pressure
[density -1,000 Hounsfield Units (HU)] and lung tissue
Elastance-derived end-inspiratory transpulmonary with a density close to that of water (0 HU). Based on
pressure Elastance-derived end-inspiratory transpulmo- these assumptions it is possible to compute the fractions
nary pressure was calculated as: Airway pressure at end- of gas and tissue in each voxel and, knowing the voxel
volume, it is also possible to measure lung weight and
inspiration 9 El/Ers.
Release-derived end-inspiratory transpulmonary pres- lung gas volume [26]. Lung recruitability was computed
sure Release-derived end-inspiratory transpulmonary as previously described [24].
pressure was calculated at: (Airway pressure at endinspiration-atmospheric pressure)-(esophageal pressure at end-inspiration-esophageal pressure at Statistical analysis
atmospheric pressure) [4].
Data are expressed as mean standard deviation (SD) or
as the median with interquartile range. Comparisons were
End-expiratory transpulmonary pressure
performed using Students t test when the variables were
Release-derived end-expiratory transpulmonary pres- normally distributed or with the MannWhitney rank sum
sure Release-derived end-expiratory transpulmonary test when variables did not appear to be normally dispressure was calculated as: PEEP-(esophageal pressure tributed on graphic inspection. The agreement between
at PEEP-esophageal pressure at atmospheric pressure) results was assessed using the BlandAltman analysis
[27] and linear regression. The bias was computed as the
[4].
Directly measured end-expiratory transpulmonary pres- mean difference between the two methods and the limits
sure Directly measured end-expiratory transpulmonary of agreement as 1.96 SD. The percentage error was calpressure was calculated as: Airway pressure at PEEP- culated as the SD of the bias divided by the mean [28].
Statistical significance was defined as P \ 0.05. Analysis
esophageal pressure at PEEP.
was performed with SAS 9.2 statistical software (SAS
An implicit assumption of all transpulmonary pressure Institute Inc, Cary, NC) and SigmaPlot 11.0 (Systat,
measurement methods is that pleural pressure at zero end- Chicago, IL).
expiratory pressure (ZEEP) is zero. In fact, we defined the
change in esophageal pressure between ZEEP and any
end-inspiratory pressure as being equal to the airway
pressure change multiplied by the ratio between chest Results
wall elastance and respiratory system elastance; it follows
that transpulmonary pressure at ZEEP results in zero as The main characteristics of the whole study population
there is no airway pressure change. In reality, the absolute and of patients categorized according to the severity of
value of transpulmonary pressure at ZEEP is slightly ARDS are summarized in Table 1. Among the 44 patients
negative. Consequently, both release-derived and elas- with ARDS enrolled in our study, ten (22 %), 26 (59 %)
tance-derived transpulmonary pressures must be regarded and eight (18 %) presented mild, moderate and severe
as delta-transpulmonary pressures starting from the ARDS, respectively. The overall mortality in the intensive
transpulmonary pressure at functional residual capacity care unit (ICU) was 41 %. The baseline ventilator settings
and that the transpulmonary pressure at functional resid- included a tidal volume of 6.6 1.5 mL of predicted
body weight and a respiratory rate of 16.7 4.9 bpm.
ual capacity can not be directly measured.
The directly measured esophageal pressure averaged
11.9 4.1 cmH2O at atmospheric pressure without any
difference according to the severity of ARDS.
Lung CT and quantitative analysis
Each patient received two lung CT scans in static condition at 5 cmH2O of PEEP and 45 cmH2O of airway End-inspiratory transpulmonary pressure
pressure, using the following parameters: 110 mAs, tube
voltage of 120 kV, rotation time of 0.5 s, collimation at The average elastance and release-derived transpulmo128 9 0.6 mm, pitch of 0.85 and reconstruction matrix of nary pressure were 14.4 3.7 and 14.4 3.8 cmH2O at

1674

Table 1 Baseline characteristics of the whole patient population

Characteristics

Overall
population
(N = 44)

Age (years)
Male sex, N (%)
Body mass index (kg/m2)
ICU mortality, N (%)
Cause of ARDS, N (%)
Pneumonia
Sepsis
Aspiration
Other
Study tidal volume/predicted body
weight (mL/kg)
Study respiratory rate (bpm)
Study minute ventilation (L/min)
PaO2/FiO2 ratio at PEEP 5 cmH2O
PaCO2 (mmHg) at PEEP 5 cmH2O
Respiratory system elastance at PEEP
5 cmH2O (L/cmH2O)
Chest wall elastance at PEEP 5 cmH2O
(L/cmH2O)
Lung elastance at PEEP 5 cmH2O (L/cmH2O)
Absolute esophageal pressure at ZEEP
(cmH2O)

60.3 16.4
30 (68 %)
26.8 5.2
18 (41 %)
25 (57 %)
7 (15 %)
2 (5 %)
10 (23 %)
8.6 1.5
16.0 3.6
9.1 2.1
156 61
44.8 7.5
26.6 7.8
6.5 3.8
20.1 6.9
11.9 4.1

Data are presented as the mean standard deviation (SD) unless

indicated otherwise
ICU Intensive care unit, ARDS acute respiratory distress syndrome,
PEEP positive end-expiratory pressure, ZEEP zero end-expiratory
pressure (=atmospheric pressure), PaO2/FiO2 ratio between arterial
partial pressure of oxygen and inspired oxygen fraction, PaCO2
partial pressure of carbon dioxide, ICU mortality, mortality recorded in the ICU

5 cmH2O of PEEP (P = 0.32) and 21.8 5.1 and

21.8 4.9 cmH2O at 15 cmH2O of PEEP, respectively
(P = 0.98). These two parameters were significantly
related (r2 = 0.98, P \ 0.001 at 5 cmH2O of PEEP;
r2 = 0.93, P \ 0.001 at 15 cmH2O of PEEP) [Electronic
Supplementary Material (ESM) Fig. E1]. In the Bland
Altman analysis the bias and agreement bands for the
elastance and release-derived transpulmonary pressure
were 0.06 (agreement bands -0.74 to 0.87) at 5 cmH2O
and 0.02 at 15 cmH2O of PEEP (agreement bands -2.65
to 2.60) (Fig. 2). The percentage error was 5.6 and
12.0 %, respectively.
The mean ratio between lung elastance and respiratory
system elastance due to tidal inflation and PEEP were
0.75 0.11 and 0.75 0.12 cmH2O at 5 cmH2O
(P = 0.86) and 0.75 0.15 and 0.75 0.12 cmH2O at
15 cmH2O of PEEP, respectively (P = 0.87) (ESM Fig.
E2). The ratio between lung elastance and respiratory
system elastance due to tidal inflation and PEEP were
related both at 5 and 15 cmH2O of PEEP (r2 = 0.62, P \
0.00 at 5 cmH2O of PEEP; r2 = 0.42, P \ 0.001, at
15 cmH2O of PEEP) (Fig. 3 upper and lower panel).

Fig. 2 BlandAltman analysis of end-inspiratory transpulmonary

pressure computed by the elastance- and release-derived method at
5 cmH2O of positive end-expiratory pressure (PEEP) (upper panel)
and 15 cmH2O of PEEP (lower panel). x-axis Mean of the two
measurements, y-axis difference between the elastance and release
method. Bias (limits of agreement): 0.06 (agreement bands -0.74
to 0.87) at PEEP 5 cmH2O and -0.02 (agreement bands -2.65 to
2.60) at PEEP 15 cmH2O. Percentage error: 5.6 % at PEEP
5 cmH2O and 12.0 % at PEEP 15 cmH2O. Green solid horizontal
line Mean Bias, red broken horizontal line limits of agreement

End-expiratory transpulmonary pressure

The mean directly measured and release-derived transpulmonary
pressure
were
-8.0 3.8
and
3.9 0.9 cmH2O at 5 cmH2O of PEEP and -1.2 3.2
and 10.6 2.2 cmH2O at 15 cmH2O of PEEP. These
parameters were not related (r2 = 0.070, P = 0.082 at
5 cmH2O of PEEP; r2 = 0.10, P = 0.528 at 15 cmH2O

1675

Fig. 3 Linear regression between the ratio of lung elastance and

respiratory system elastance due to PEEP and tidal volume at 5
cmH2O (upper panel) and 15 cmH2O of PEEP (lower panel).
Upper panel y = -0.212 ? 1.025x, r2 = 0.62 P \ 0.001, lower
panel y = 0.186 ? 0.755x, r2 = 0.42, P \ 0.001

Fig. 4 Linear regression between the end-expiratory transpulmonary pressure computed by the directly measured and releasederived method at 5 cmH2O of PEEP (upper panel) and 15 cmH2O
of PEEP (lower panel). Upper panel y = -3.498 -1.173x,
r2 = 0.07 P = 0.082; lower panel y = 0.2660.138x, r2 = 0.01,
P = 0.528. Open circles Patients with primary ARDS, filled circles
patients with secondary ARDS

of PEEP) (Fig. 4). The release-derived end expiratory

transpulmonary pressure in the individual patients at 5
and 15 cmH2O of PEEP is shown in ESM Fig. E3.
Discussion
Directly measured esophageal pressure and lung
function
The distribution of directly measured esophageal pressure
at 5 cmH2O of PEEP in the whole population is shown in
Fig. 5, which shows that this parameter was not significantly correlated with lung weight, lung recruitability,
amount of not aerated lung tissue, hypoxemia, chest wall
elastance and gastric pressure (ESM Figs. E4E9).

The major findings of this study are that (1) the elastanceand release-derived end-inspiratory transpulmonary
pressure were quite similar; (2) the release-derived and
directly measured end-expiratory transpulmonary pressure were not related; (3) the directly measured
esophageal pressure was not related to lung weight,
amount of non-aerated tissue, chest wall elastance and
gastric pressure.
In ARDS patients the mechanical ventilation should
provide adequate gas exchange and minimize the VILI,

1676

Elastance versus release-derived end-inspiratory

transpulmonary pressure

Fig. 5 Distribution (histogram) of directly measured esophageal

pressure at 5 cmH2O of PEEP

reducing both lung stress at end-inspiration and alveolar

collapse at end-expiration. In clinical practice, airway
pressure is commonly used as a reliable marker of lung
stress [1]. However, in their study of 50 patients with
ARDS and 30 controls, Chiumello et al. [4] found that
plateau pressure and tidal volume were inadequate surrogates for lung stress and strain as the ratio between lung
elastance and respiratory system elastance was highly
variable (range 0.330.95). As the baby lung size (i.e.
the functional residual capacity) in patients with ARDS is
also highly variable, it follows that for the same applied
tidal volume the strain variability is large. Therefore, low
or high tidal volume, such as 6 and 12 mL/kg, respectively, could produce similar stress and strain in a notable
fraction of patients in each subgroup.
The impossibility to directly measure pleural pressure
in clinical practice has led to the proposal that esophageal
pressure be used as an adequate surrogate due the passive
behavior of the esophagus [7, 18, 30, 31]. The esophageal
lumen is separated from the pleural space by the muscular
wall of the esophagus and mediastinal soft tissue. If all
these tissues were flaccid, pressure changes in the pleural
space would be transmitted unattenuated to the esophageal lumen. It follows that the changes in esophageal
pressure should reflect the changes in pleural pressure. A
study in dogs has shown that esophageal pressure reflects
pleural pressure only at the level of the mid-lung [37]. It
is also known that esophageal pressure can be influenced
by the shape of the pressurevolume curve, lung volume,
weight of the heart, reactivity of the esophageal smooth
muscle wall and mechanical properties of the balloon
[18]. However due to the possible difficulties in esophageal catheter positioning, interpretation of the data and the
relatively paucity of available catheters, the measurements of esophageal pressure at bedside is seldom
performed [32].

The airway pressure applied to the respiratory system is

used to inflate the lung and chest wall; thus, the elastance
of the lung and chest wall determines how much of this
pressure is used in each compartment [1]. Accordingly,
the transpulmonary pressure is computed as the total
difference in airway and esophageal pressure between
end-inspiration and atmospheric pressure, thus taking into
account the effect of PEEP and tidal volume. This method
cannot measure the transpulmonary pressure at functional
residual capacity since only delta-transpulmonary pressure can be computed. The pleural pressure at functional
residual capacity is slightly negative (directed outwards)
to counterbalance the retracting force of the lung and keep
it expanded [1, 4].
A simplified method which computes transpulmonary
pressure as the product of the changes in airway pressure
during tidal inflation and the ratio between lung and
respiratory system elastance has been introduced [9, 10].
This method assumes that the lung and respiratory system
pressurevolume curves are linear in the range of PEEP
and the tidal volume used in the clinical setting.
The computed values of transpulmonary pressure by
the elastance and release methods were quite similar in
our study, with a mean percentage of error of 5 and 12 %,
respectively, which is clinically acceptable. This similarity can be due to a good relationship between the ratio
of lung and respiratory system elastance as a result of a
change in tidal volume and to PEEP, suggesting that in
the range of PEEP and tidal volume used, the respiratory
mechanics of the lung and chest wall are similar. In their
published study, Chiumello et al. reported that a linear
fitting was adequate to describe the pressurevolume
curve in 75 % of patients with ALI/ARDS and in 78 % of
control subjects (r2 [ 0.95), suggesting that the assumption of linearity of the pressurevolume curve is adequate
in most patients [4]. We can conclude that transpulmonary pressure, which is used as a marker of endinspiratory stress, can be satisfactorily estimated by the
elastance method, which does not require any disconnection from the ventilator, thereby avoiding possible
risks of lung derecruitment and hypoxemia due to the loss
of PEEP.
Directly measured and release-derived end-expiratory
transpulmonary pressure
In contrast to the reduction in tidal volume which has
been extensively shown to reduce the mortality in patients
with ARDS, several trials comparing high and low levels
of PEEP have failed to find significant benefits of higher
PEEP. Consequently, the optimum level of PEEP is still
being debated [14, 33]. If the main beneficial effect of

1677

PEEP should be to keep the recruited lung open, an

identical level of PEEP could be adequate in a given
patient, whereas in a different patient it might not be
sufficient to prevent alveolar collapse due to extremely
variability in chest wall elastance among the subjects.
Working under the assumption that directly measured
esophageal pressure is similar to pleural pressure and
reflects collapse of the lung, Talmor et al. showed better
oxygenation and respiratory mechanics using a PEEP
selected to minimize alveolar collapse at end-expiration
by maintaining a directly measured transpulmonary
pressure ranging between 0 and 10 cmH2O compared to
PEEP selected according to gas exchange [16]. Unfortunately, Talmor et al.s study did not use CT to
demonstrate a reduction of lung collapse; rather they used
the increase in oxygenation as the primary endpoint,
which can be related to factors independent of lung
recruitment (i.e. perfusion redistribution) [34].
In our study, directly measured and release-derived
transpulmonary pressure were not related, and at both
levels of PEEP tested the directly measured transpulmonary pressure were significantly lower than the releasederived transpulmonary pressure. The former was calculated as simply the difference between PEEP and
esophageal pressure, with the assumption that the pleural
pressure is equal to the esophageal pressure. However,
this assumption is highly controversial due to the elastance of the esophageal catheter, tone of the esophageal
wall, weight of the mediastinum organ and patient position, all of which could alter the measured value so that
absolute esophageal pressure would not reflect pleural
pressure [18, 35, 36]. Furthermore, in an experimental
model the esophageal pressure was found to be nearly
similar to that of the pleural space measured in the middle
part of the lung, while it overestimated and underestimated the pleural pressure in the nondependent and
dependent lung regions, respectively [37]. In contrast, the
variations in pleural pressure were similar to those in
esophageal pressure at each lung level, as previously
observed by other investigators [7, 38].

When the PEEP selected accordingly to the directly

measured and elastance-derived transpulmonary pressure
was compared, the values differed by as much as
10 cmH2O in a given patient [39]. Several factors for
correcting the directly measured esophageal pressure have
been proposed with the aim of reducing such bias [19,
21]. However, Guerin et al., comparing the directly
measured transpulmonary pressure corrected for a fixed
value of 5 cmH2O to the release transpulmonary pressure,
still found that the directly measured transpulmonary
pressure was significantly lower and that the two parameters were not related [40]. Similarly, in a previous study
we showed that setting PEEP equal to the directly measured esophageal pressure (i.e. to obtain a end-expiratory
transpulmonary pressure equal to zero) was not related to
lung recruitment [23].
In our study the directly measured esophageal pressure
was highly variable between the subjects and was not
related to lung weight, chest wall elastance and amount of
lung collapse, suggesting that the use of directly measured
transpulmonary pressure to set PEEP for avoiding alveolar collapse is highly questionable.

Conclusions
The elastance-derived method may be used instead of the
release-derived method to estimate the end-inspiratory
transpulmonary pressure, thereby avoiding ventilator
disconnection, PEEP loss and derecruitment. The directly
measured end-expiratory transpulmonary pressure is not
related to the release-derived transpulmonary pressure.
All methods of estimating transpulmonary pressures are
based on assumptions; thus, the decision on which method
to use should be guided by further clinical trials.
Conflicts of interest On behalf of all authors, the corresponding
author states that there is no conflict of interest.

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