95:2064-2071, 2003. First published Jul 18, 2003; doi:10.1152/japplphysiol.00385.

2003 J Appl Physiol

Gaillard, Franois Philit and Claude Gurin
Pommier, Jean-Pierre Perdrix, Jean-Christophe Richard, Michel Badet, Sandrine
Ccile Pereira, Julien Boh, Sylvaine Rosselli, Emmanuel Combourieu, Christian
You might find this additional information useful...
23 articles, 17 of which you can access free at: This article cites
http://jap.physiology.org/cgi/content/full/95/5/2064#BIBL
1 other HighWire hosted article: This article has been cited by

[PDF] [Full Text] [Abstract]
, February 1,2006; 96(2): 156-166. Br. J. Anaesth.
G. Mols, H.-J. Priebe and J. Guttmann
Alveolar recruitment in acute lung injury
including high-resolution figures, can be found at: Updated information and services
http://jap.physiology.org/cgi/content/full/95/5/2064
can be found at: Journal of Applied Physiology about Additional material and information
http://www.the-aps.org/publications/jappl
This information is current as of January 13, 2010 .

http://www.the-aps.org/. ISSN: 8750-7587, ESSN: 1522-1601. Visit our website at
Physiological Society, 9650 Rockville Pike, Bethesda MD 20814-3991. Copyright 2005 by the American Physiological Society.
those papers emphasizing adaptive and integrative mechanisms. It is published 12 times a year (monthly) by the American
publishes original papers that deal with diverse areas of research in applied physiology, especially Journal of Applied Physiology

o
n

J
a
n
u
a
r
y

1
3
,

2
0
1
0

j
a
p
.
p
h
y
s
i
o
l
o
g
y
.
o
r
g
D
o
w
n
l
o
a
d
e
d

f
r
o
m

Sigmoidal equation for lung and chest wall
volume-pressure curves in acute respiratory failure
Ce cile Pereira,
1
Julien Bohe ,
2
Sylvaine Rosselli,
3
Emmanuel Combourieu,
4
Christian Pommier,
3
Jean-Pierre Perdrix,
5
Jean-Christophe Richard,
1,6
Michel Badet,
1
Sandrine Gaillard,
1,6
Franc ois Philit,
1
and Claude Gue rin
1,6
1
Service de Reanimation Medicale et dAssistance Respiratoire, Hopital de la Croix-Rousse, 69004 Lyon;
2
Service
de Reanimation Medicale, Centre Hospitalier Lyon-Sud, 69310 Pierre Benite, France;
3
Service de Reanimation,
Centre Hospitalier Saint Luc-Saint Joseph, 69007 Lyon;
4
Service de Reanimation Polyvalente, Hopital dinstruction
Des Armees, 69003 Lyon;
5
Service de Reanimation Chirurgicale, Centre Hospitalier Lyon Sud, 69310 Pierre Benite;
and
6
Equipe daccueil 1896, Laboratoire de Physiologie, Claude Bernard University, 69008 Lyon, France
Submitted 17 April 2003; accepted in nal form 13 July 2003
Pereira, Ce cile, Julien Bohe , Sylvaine Rosselli, Em-
manuel Combourieu, Christian Pommier, Jean-Pierre
Perdrix, Jean-Christophe Richard, Michel Badet, San-
drine Gaillard, Franc ois Philit, and Claude Gue rin.
Sigmoidal equation for lung and chest wall volume-pressure
curves in acute respiratory failure. J Appl Physiol 95:
20642071, 2003. First published July 18, 2003; 10.1152/
japplphysiol.00385.2003.To assess incidence and magni-
tude of the lower inection point of the chest wall, the
sigmoidal equation was used in 36 consecutive patients in-
tubated and mechanically ventilated with acute lung injury
(ALI). They were 21 primary and 5 secondary ALI, 6 unilat-
eral pneumonia, and 4 cardiogenic pulmonary edema. The
lower inection point was estimated as the point of maximal
compliance increase. The low constant ow ination method
and esophageal pressure were used to partition the volume-
pressure curves into their chest wall and lung components on
zero end-expiratory pressure. The sigmoidal equation had an
excellent t with coefcients of determination 0.90 in all
instances. The point of maximal compliance increase of the
chest wall ranged from 0 to 8.3 cmH
2
O (median 1 cmH
2
O)
with no difference between ALI groups. The chest wall sig-
nicantly contributed to the lower inection point of the
respiratory system in eight patients only. The occurrence of a
signicant contribution of the chest wall to the lower inec-
tion point of the respiratory system is lower than anticipated.
The sigmoidal equation is able to determine precisely the
point of the maximal compliance increase of lung and chest
wall.
acute respiratory distress syndrome; mechanical ventilation;
volume-pressure curves; acute lung injury
THE CHOICE OF THE RIGHT LEVEL of positive end-expiratory
pressure (PEEP) and the way to select it in patients
with acute respiratory distress syndrome (ARDS) are
still a matter of debate (20). Although assessment of
the volume-pressure (V-P) curve of the respiratory sys-
tem is not one of the recommended criteria for man-
agement of ARDS, by setting PEEP above the lower
inection point of the respiratory system determined
from static ination V-P curve, two groups of investi-
gators observed an improvement of outcome in ARDS
patients. In a randomized controlled study, Amato et
al. (2) found a marked reduction of mortality in the
group in which PEEP was set above the lower inec-
tion point, the so-called lung-protective strategy, com-
pared with the control group in which PEEP was set
regardless of the V-P curve, so-called conventional ven-
tilation. Ranieri et al. (19) randomized ARDS patients
into a lung-protective ventilation group and a conven-
tional ventilation group. They observed a reduction of
both lung and systemic levels of proinammatory cy-
tokines together with less organ dysfunction in the
lung-protective ventilation group. For routine assess-
ment of V-P curves to determine the appropriate level
of PEEP, some methodological and semantic problems
should be resolved. First, the assessment of the ina-
tion limb of the V-P curve in ARDS patients is confus-
ing because various terms such as Pex, lower inec-
tion point, and knee are used to dene the sudden
increase in compliance that occurs at low lung volume
in most patients. Rightly speaking, the true inection
point in any curve is the point at which the curvature
changes direction or sign (8). The term lower inection
point is misused in the critical care literature and has
no scientic foundation. Second, an unbiased means to
detect lower inection point on the basis of an adequate
algorithm with physiological meaning is mandatory.
Indeed, the visual assessment of lower inection point
has been shown to have a large inter- and intraob-
server variability and, hence, is not reliable (9). Third,
one study has stressed that the chest wall may signif-
icantly contribute to lower inection point of the respi-
ratory system, indicating that determination of lower
inection point based on V-P curves of the respiratory
system may not be reliable to adequately set the level
of PEEP (14). It should be noted that in the latter
study, on the basis of the analysis proposed by Gatti-
noni et al. (7), the choice of volume steps may inuence
Address for reprint requests and other correspondence: C. Guerin,
Service de Reanimation Medicale et dAssistance Respiratoire, Ho-
pital de la Croix-Rousse, 103 Grande Rue de la Croix-Rousse, 69004
Lyon, France (E-mail: claude.guerin@chu-lyon.fr).
The costs of publication of this article were defrayed in part by the
payment of page charges. The article must therefore be hereby
marked advertisement in accordance with 18 U.S.C. Section 1734
solely to indicate this fact.
J Appl Physiol 95: 20642071, 2003.
First published July 18, 2003; 10.1152/japplphysiol.00385.2003.
8750-7587/03 $5.00 Copyright 2003 the American Physiological Society http://www.jap.org 2064

o
n

J
a
n
u
a
r
y

1
3
,

2
0
1
0

j
a
p
.
p
h
y
s
i
o
l
o
g
y
.
o
r
g
D
o
w
n
l
o
a
d
e
d

f
r
o
m

the results, in that the greater the magnitude of initial
volume steps, the greater the lower inection point.
Venegas et al. (22) introduced the sigmoidal equation
to t ination and deation V-P curves of the respira-
tory system. With this method, they objectively dened
the pressure at the point of maximal compliance in-
crease during ination or deation. They found that
the reproducibility of this method was excellent when
they retrospectively tested data pertaining to 1) the
lungs of 2 closed-chest dogs, 2) the lungs of 11 open-
chest dogs, and 3) the respiratory system of 10 ARDS
patients. To our knowledge, this method has not been
previously used to assess the V-P curve of the chest
wall and lungs in patients with acute respiratory fail-
ure (ARF).
Therefore, we undertook the present prospective
study to assess 1) the contribution of the chest wall to
the point of maximal compliance increase (Pmci) of the
respiratory system of patients with ARF and 2) the t
of the sigmoidal equation to both lung and chest wall
V-P curves in these patients.
MATERIALS AND METHODS
Patients. A prospective multicenter physiological investi-
gation was carried out in consecutive intubated and mechan-
ically ventilated patients with ARF in six intensive care units
(ICUs) of Lyon, France, between November 2001 and Sep-
tember 2002. Patients were included if they met all of the
following criteria: 1) age over 18 yr, 2) tracheal intubation
and mechanical ventilation, 3) unilateral or bilateral inl-
trates on frontal chest X-radiograph, 4) ratio of arterial PO
2
(Pa
O
2
) to inspired O
2
fraction (FI
O
2
) 300, 5) investigation
performed in the rst 5 days after ICU admission, 6) onset of
ARF within the last 3 days, 7) continuous intravenous seda-
tion and/or analgesia, and 8) written, informed consent pro-
vided from the next of kin. Patients were excluded if any of
the following criteria was present: 1) chronic interstitial lung
disease, 2) thoracic drainage, 3) hemodynamic instability, 4)
pregnancy, 5) impossibility to stop administration of inhaled
nitric oxide, and 6) informed consent denied.
Clinical data collection. At the time of investigation, the
following clinical variables were recorded: age, gender, ideal
body weight (23), simplied acute physiology score II (12),
and lung injury score (16). Acute lung injury (ALI) and ARDS
were dened according to the European-American consensus
conference criteria (3). Primary and secondary ALI/ARDS
were dened according to standard criteria (5). Unilateral
pneumonia (UP) was dened as unilateral radiographic in-
ltrates associated with Pa
O
2
/FI
O
2
300 and no echocardio-
graphic argument for an elevated left atrial pressure. Car-
diogenic pulmonary edema (CPE) was dened as bilateral
radiographic lung inltrates associated with Pa
O
2
/FI
O
2
300
and increased left atrial pressure assessed from echocardiog-
raphy. The ARF patients were therefore classied into four
groups, namely primary ALI/ARDS, secondary ALI/ARDS,
UP, and CPE.
Equipment. Airow (V

) was measured with a heated pneu-

motachograph (Fleisch no. 2, Fleisch, Lausanne, Switzer-
land) inserted between the endotracheal tube and the Y-piece
of the ventilator. The pressure drop across the two ports of
the pneumotachograph was measured with a differential
piezoresistive transducer (TSD160A 2 cmH
2
O; Biopac Sys-
tems, Santa Barbara, CA). Changes in lung volume were
obtained by numeric integration of the V

signal. Pressure at
the airway opening (Pao) was measured proximal to the
endotracheal tube with a piezoresistive pressure transducer
(Gabarith 682002, Becton Dickinson, Sandy, UT). Changes in
pleural pressure were estimated from changes in esophageal
pressure (Pes) using a thin-walled latex balloon (80-mm
length, 1.9-cm external diameter, 0.1-mm thickness), at-
tached to a 80-cm-long catheter of 1.9-mm external diameter
and 1.4-mminternal diameter (Marquat, Boissy-Saint-Leger,
France), positioned in the midesophagus and inated with 1
ml of air. The validity of the Pes measurement was assessed
in two ways. In patients with occasional spontaneous
breaths, the airways were occluded at the end of expiration
and patients were asked to make inspiratory efforts. The
correct position of the esophageal balloon was ascertained
from the correlation between Pao and Pes during this
maximal effort (15). In patients without spontaneous breath-
ing, the esophageal balloon was inserted into the stomach, as
reected by signicant positive change in pressure during a
gentle manual compression done on the abdominal left upper
quadrant. The esophageal balloon was then withdrawn up to
the point of no change in Pes tracing during the above
maneuver. The esophageal balloon was connected to a differ-
ential pressure transducer (Gabarith 682002; Becton Dickin-
son). Calibration was performed just before each experiment.
The same ventilator (Horus; Taema, Antony, France) was
provided by the Taema company to each participating ICU
for the purpose of this study. During the measurement, the
humidier was bypassed, and a single-use low-compliance
ventilator tubing of 60-cm length and 2-cm internal diameter
was used. The signals of V

, Pao, and Pes were recorded on a

portable personal computer with data-acquisition software
(MP 100; Biopac Systems). The records were stored and
subsequently analyzed by use of Acknowledge software (ver-
sion 3.7.1 for Microsoft Windows 98; Biopac Systems).
Protocol. The study was approved by the local ethics com-
mittee (Comite Consultatif pour la Protection des Personnes
se pretant a` la Recherche Biomedicale, CCPPRB Lyon-B).
Measurements were taken with the patients in the semire-
cumbent position. The patients were sedated with midazolam
(0.20.4 mg/kg) and fentanyl (13 g/kg) and paralyzed with
atracurium (0.30.5 mg/kg) for the purpose of the study.
The patient was connected to the study ventilator at the
ventilatory settings (volume-controlled mode under constant
V

ination) established by the physician-in-charge (see Table

2), which were kept constant in each patient throughout the
experiment, with the exception of PEEP and FI
O
2
. After a
stabilization period of 5 min, blood was drawn from the
arterial line to determine blood gases. Then FI
O
2
was in-
creased to 100% for 10 min.
Next, the V-P curve determination was made as follows
(Fig. 1). First, zero end-expiratory pressure was applied for
ve consecutive breaths. Second, the volume history was
standardized by using a respiratory frequency of 18 min
1
,
tidal volume of 10 ml/kg, and inspiratory time/total duration
of respiratory cycle of 0.33 for ve consecutive breaths (13).
Third, the low constant ow ination (LCFI) method, which
was automatically delivered by the ventilator, was achieved
by pressing the appropriate button. The LCFI software works
as follows (Fig. 1). The expiratory time is prolonged until the
rst zero V

was reached. Then a 3-s end-expiratory occlusion

is performed and followed by lung ination at a predeter-
mined constant ow of 8 l/min. Ination is interrupted either
when inspiratory pressure reached 50 cmH
2
O or volume
reached 2 liters, or on the clinicians decision. After this, the
baseline ventilation was resumed immediately. After stabi-
lization, usually obtained in 5 min, a second LCFI was
performed in the same way.
2065 LUNG AND CHEST WALL V-P CURVES IN ALI
J Appl Physiol VOL 95 NOVEMBER 2003 www.jap.org

o
n

J
a
n
u
a
r
y

1
3
,

2
0
1
0

j
a
p
.
p
h
y
s
i
o
l
o
g
y
.
o
r
g
D
o
w
n
l
o
a
d
e
d

f
r
o
m

Arterial blood pressure, heart rate, and pulse oximetry
were monitored continuously. During the study a physician
and a nurse not involved in the experiment were always
present to provide for patient care.
Data analysis. The transpulmonary pressure (PL) was ob-
tained by subtracting Pes from Pao. The change in end-
expiratory lung volume was assessed as difference in end-
expiratory lung volume between tidal deation and that
obtained after prolonging expiration just before starting the
LCFI.
Postsampling smoothing of the Pes signal was used to
allow for cardiac artifacts. The digital records of Pao, Pes, PL,
V

, and volume against time were exported into a spreadsheet

program (Matlab 6.1, The Mathworks, Natick, MA). An algo-
rithm was developed to t the experimental data points of
Pao, Pes, and PL to lung volume to the following sigmoidal
equation (22)
V a b/1 e
Pc/d
(1)
where V is the lung volume above functional residual capac-
ity (FRC) and P is the pressure of the respiratory system,
chest wall, or lung (Fig. 2). This equation has four parame-
ters with physiological signicance (22). Parameter a is ex-
pressed in units of volume and represents the lower asymp-
tote volume. Parameter b is also expressed in units of volume
and represents the total change in volume between lower and
upper asymptotes. Parameter c is the inection point of the
sigmoidal curve. Parameter d is proportional to the pressure
range within which most of the volume change takes place.
Initial guess coefcients were a 0 liters, b 2 liters, c 20
cmH
2
O, and d 10 cmH
2
O. According to Harris et al. (9), the
Pmci (where the rate of change of upward slope is maximal)
was dened as c 1.317d and was used as an estimator for
the lower inection point of the respiratory system (Pmci,rs),
chest wall (Pmci,w), and lung (Pmci,L). The point of maximal
compliance decrease (Pmcd) was dened as c 1.317 d and
was used as an estimate of the upper inection point (9).
To assess the contribution of the chest wall to Pmci,rs, we
reasoned that the chest wall contribution to Pmci,rs is as
great as the error in the determination of Pmci,L from Pm-
ci,rs is large. Therefore, we computed the quantity [(Pm-
ci,rs Pmci,L)/Pmci,L] 100 and decided that a value 50%
dened a signicant contribution of the chest wall to Pmci,rs.
Statistical analysis. Values were expressed as medians
(interquartile range). Nonparametric tests were used to com-
pare quantitative and qualitative values. Linear regression
was made by using least square method. For a given patient,
the V-P curve with the highest coefcient of determination
for Eq. 1 was retained for the analysis. Nonparametric cor-
relation of Spearmann was used. The level of statistical
signicance was set at a P value 0.05. SPSS for Windows
version 11.0.1 (SPSS, 2001) was used for the statistical anal-
ysis.
Fig. 1. Tracings of airway pressure (Pao; A), esophageal pressure
(Pes; B), and ow (C) over time during a whole experiment in a
representative patient. EEO, end-expiratory occlusion; LCFI, low
constant ow ination; PEEP, positive end-expiratory pressure;
ZEEP, zero end-expiratory pressure. Left vertical arrow indicates
the suppression of PEEP, middle vertical arrow the time at which
expiratory time is increased before starting LCFI, and right vertical
arrow the time at which the baseline ventilation is resumed. Hori-
zontal arrow indicates the period of LCFI.
Fig. 2. Schematic drawing of the sigmoidal equation used for curve-
tting volume-pressure (V-P) data. The 4 parameters of the model
and the way to compute the points of maximal compliance increase
(Pmci) and decrease (Pmcd) are indicated. For further explanations,
see text.
2066 LUNG AND CHEST WALL V-P CURVES IN ALI
J Appl Physiol VOL 95 NOVEMBER 2003 www.jap.org

o
n

J
a
n
u
a
r
y

1
3
,

2
0
1
0

j
a
p
.
p
h
y
s
i
o
l
o
g
y
.
o
r
g
D
o
w
n
l
o
a
d
e
d

f
r
o
m

RESULTS
Among the 42 patients enrolled during the study
period, six with negative values of point of maximal
compliance increase were excluded from the present
analysis. These were ve men and one woman whose
baseline characteristics, ventilatory settings, and arte-
rial blood gases were not signicantly different from
the 36 other patients. Two had indirect and one direct
ALI/ARDS, two had UP, and one had CPE. One had
negative Pmci,L only, one had both negative Pmci,rs
and Pmci,L, and the remaining four had negative Pm-
ci,w only. The present report is therefore based on 36
patients (25 men): 21 primary ALI/ARDS, 5 secondary
ALI/ARDS, 6 UP, and 4 CPE. The characteristics of the
36 patients are given in Table 1. As shown in Table 2
and Fig. 3 in a representative patient, Eq. 1 provided
an excellent t, with coefcients of determination rang-
ing from 0.991 to 0.999 for the respiratory system,
0.975 to 0.999 for the lung, and 0.931 to 0.999 for the
chest wall. In the six patients excluded from the nal
Table 1. Data of the 36 patients at time
of measurements
Median IQR
Age, yr 68 5975
Ideal body weight, kg 66 5975
BMI, kg/m
2
26 2227
SAPS II (range 0194) 60 4775
Lung injury score (range 04) 1.8 1.42.5
Days to investigation 2 13
Tidal volume, ml/kg ideal body wt 6.8 6.18.0
PEEP, cmH2O 8 610
Respiratory frequency, min
1
16 1420
Inspiratory time, s 1.2 1.01.4
Expiratory time, s 2.2 1.92.8
FIO
2
52 4070
PaO
2
, Torr 90 77105
PaO
2
/FIO
2
174 138200
PaCO
2
, Torr 42 3649
pH 7.37 7.337.43
IQR, interquartile range; BMI, body mass index, SAPS II, Simpli-
ed Acute Physiology Score; PEEP, positive end-expiratory pressure;
FIO
2
, inspired O2 fraction; PaO
2
, arterial PO2; PaCO
2
, arterial PCO2.
Table 2. Individual values of Pmci and Pmcd for respiratory system, lung, and chest wall obtained from Eq. 1
on zero end-expiratory pressure classied according to the group of acute respiratory failure
Patient Group
Respiratory System Lung Chest Wall
Pmci,
cmH2O
Pmcd,
cmH2O R
2
Pmci,
cmH2O
Pmcd,
cmH2O R
2
Pmci,
cmH2O
Pmcd,
cmH2O R
2
1 P 11.6 31.0 0.998 9.2 25.0 0.997 2.3 6.4 0.997
2 P 6.4 20.0 0.992 5.5 16.5 0.990 0.4 4.0 0.992
3 P 9.4 32.5 0.997 6.2 24.6 0.996 3.2 8.2 0.989
4 P 2.8 14.1 0.999 2.4 13.2 0.997 0.9 2.6 0.991
7 P 5.7 15.0 0.995 4.3 7.3 0.975 1.1 8.2 0.999
8 P 14.2 31.0 0.997 12.0 23.7 0.995 2.0 7.3 0.996
9 P 7.1 37.4 0.998 5.8 29.7 0.995 2.5 6.2 0.983
10 P 4.3 28.5 0.997 2.9 21.2 0.995 2.0 7.5 0.998
11 P 1.3 27.9 0.999 0.5 7.1 0.989 1.7 25.1 0.999
12 P 13.3 37.9 0.999 12.8 34.6 0.999 1.1 2.6 0.983
13 P 6.8 36.1 0.995 1.9 29.6 0.993 3.8 5.1 0.952
16 P 14.2 28.4 0.997 14.3 25.2 0.997 0.6 3.6 0.981
17 P 13.5 33.9 0.991 11.5 26.8 0.992 2.1 7.6 0.980
18 P 5.2 26.1 0.998 3.6 18.1 0.997 0.4 9.3 0.999
19 P 6.3 31.0 0.999 5.6 28.0 0.998 1.4 4.0 0.931
25 P 12.6 24.4 0.991 12.4 22.7 0.989 0.5 1.4 0.991
26 P 11.4 29.3 0.999 6.5 15.8 0.998 5.7 13.0 0.999
27 P 6.7 28.4 0.999 3.6 21.9 0.998 3.7 5.9 0.975
29 P 8.7 31.0 0.999 7.5 26.0 0.998 1.4 5.6 0.995
30 P 3.6 18.0 0.999 2.8 12.5 0.994 2.4 5.5 0.985
34 P 16.0 42.0 0.997 16.0 39.0 0.997 0.6 3.0 0.997
21 S 6.0 22.0 0.996 5.6 21.0 0.996 0.8 2.7 0.932
23 S 10.0 34.6 0.999 10.4 32.5 0.998 0.5 1.5 0.983
32 S 17.9 45.0 0.998 16.2 36.0 0.995 2.0 6.1 0.973
33 S 7.5 33.0 0.999 7.4 32.4 0.999 0.3 1.3 0.993
36 S 16.4 40.6 0.994 15.6 35.5 0.994 0.9 1.8 0.989
20 UP 20.4 43.2 0.992 20.8 39.0 0.986 0.0 3.2 0.986
22 UP 7.7 35.7 0.999 3.3 28.0 0.999 2.7 8.6 0.984
24 UP 18.0 34.8 0.994 16.3 29.9 0.991 1.6 5.1 0.999
28 UP 12.0 36.6 0.998 11.2 36.0 0.997 0.5 1.1 0.967
31 UP 10.3 34.0 0.996 10.8 33.0 0.998 0.0 1.1 0.969
35 UP 4.7 20.2 0.996 0.9 12.0 0.989 3.7 9.9 0.999
5 CPE 6.0 26.0 0.994 5.2 16.0 0.992 0.7 6.0 0.994
6 CPE 8.7 43.6 0.998 3.5 24.3 0.993 8.3 16.4 0.992
14 CPE 13.1 30.1 0.994 12.9 28.4 0.991 1.1 2.3 0.995
15 CPE 5.5 29.3 0.996 5.2 25.6 0.994 0.2 4.9 0.995
Pmci, point of maximal compliance increase; Pmcd, point of maximal compliance decrease; R
2
, coefcient of determination; P, primary
acute lung injury; S, secondary acute lung injury; UP, unilateral pneumonia; CPE, cardiogenic pulmonary edema. The numbers of patients
in the left rst column refer to the order in which the investigation has been done.
2067 LUNG AND CHEST WALL V-P CURVES IN ALI
J Appl Physiol VOL 95 NOVEMBER 2003 www.jap.org

o
n

J
a
n
u
a
r
y

1
3
,

2
0
1
0

j
a
p
.
p
h
y
s
i
o
l
o
g
y
.
o
r
g
D
o
w
n
l
o
a
d
e
d

f
r
o
m

analysis because negative value of Pmci was found, the
tting was nevertheless excellent, with coefcients of
determination 0.990. In the 36 patients, for the
respiratory system, lung, and chest wall, the median
(interquartile range) values of Pmci were 9 (613), 6
(412), and 1 (12) cmH
2
O, respectively; those of Pmcd
were 31 (2636), 25 (1932), and 5 (38) cmH
2
O,
respectively; those of c were 21 (1623), 17 (1121),
and 3 (25) cmH
2
O, respectively. Between the respira-
tory system and the lung, the values of Pmci, Pmcd,
and c were statistically signicantly different (P
0.001). Between the four groups of patients, the values
of Pmci, Pmcd, and c did not signicantly differ.
There was a signicant contribution of the chest wall
to Pmci,rs in eight patients (22% of the whole sample)
(Table 2): 5 out of 21 (23.8%) with primary ALI/ARDS
(patients 3, 11, 13, 26, 27), 2 out of 6 (33%) with UP
(patients 22, 35), and 1 out of 4 (25%) with CPE (patient
6). As shown on Fig. 4, there was a close correlation
between Pmci,rs and Pmci,L. The increase in slope was
10%, indicating that Pmci,rs reects Pmci,L, on aver-
age, in this sample. The difference (Pmci,rs Pmci,L)
and Pmci,w (Fig. 5) correlate up to Pmci,w of 3 cmH
2
O.
Above this value, the relationship is much more scat-
tered, indicating that the curvature of the V-P curve of
the chest wall plays a role in these patients and there-
fore the chest wall mechanics must be taken into ac-
count.
DISCUSSION
In this study, the sigmoidal equation was used to
assess the presence and the magnitude of the lower
Fig. 3. V-P curves of respiratory system (A), lung (B), and chest wall
(C) in patient 26. Continuous black lines are the experimental raw
data obtained from the LCFI method. Continuous green lines are the
sigmoidal equation curve-tted data. Vertical bars are the Pmci and
Pmcd whose values can be found in Table 2.
Fig. 4. Relationship of Pmci of the respiratory system (Pmci,rs) to
that of the lung (Pmci,L). Dotted line is the identity line, and
continuous line is the regression line.
Fig. 5. Relationship of the difference between Pmci,rs and Pmci,L to
Pmci of the chest wall (Pmci,w). Continuous middle line is the
regression line, and 2 outer continuous lines are the 95% condence
interval limits over all the experimental points.
2068 LUNG AND CHEST WALL V-P CURVES IN ALI
J Appl Physiol VOL 95 NOVEMBER 2003 www.jap.org

o
n

J
a
n
u
a
r
y

1
3
,

2
0
1
0

j
a
p
.
p
h
y
s
i
o
l
o
g
y
.
o
r
g
D
o
w
n
l
o
a
d
e
d

f
r
o
m

inection point of the chest wall in intubated, sedated,
and mechanically ventilated patients with various
ARF conditions. We have found that 1) a signicant
lower inection point of the chest wall was present in
22% of the patients (8/36) and 2) the sigmoidal equa-
tion was of value to assess the lower inection point of
the chest wall.
Our study suffered from several limitations. First,
the investigation was done only at zero end-expiratory
pressure and, therefore, the effects of PEEP on the
parameters of the sigmoidal model were not investi-
gated. Second, the use of the esophageal balloon to
estimate pleural pressure in the supine position has
been questioned. We have tried to minimize the cardiac
artifacts as much as possible. Moreover, the absolute
value of esophageal pressure is highly dependent on
the initial pressure and volume of the esophageal bal-
loon and the volume injected to it. On the other hand,
relative changes in these pressures during ination
tend to be more reliable. In this connection, it should be
noted that the esophageal balloon method is currently
the only way to estimate pleural pressure in humans.
Whether the chest wall should be taken into account
as part of management of patients with ARF is a
question of clinical relevance. The determination of
chest wall mechanics indeed gives access to lung me-
chanics and therefore allows setting the ventilator
from targets pertaining to the lungs directly.
Pelosi et al. (17) have found chest wall mechanics
abnormalities in patients with ALI. The same group
also reported that chest wall elastance was normal in
patients with primary ALI but markedly increased in
patients with secondary ALI (5). The chest wall elas-
tance correlated with intra-abdominal pressure in this
study (5), a result in line with the ndings of Ranieri et
al. (18), who emphasized on the role of abdominal
distension as observed in the postoperative setting.
Mergoni et al. (14) rst suggested that the chest wall
mechanics could contribute to the lower inection point
of the respiratory system by studying 13 patients with
ALI/ARDS (four with primary lung injury). Eleven of
them exhibited a lower inection point of the chest
wall, which was in seven of them (53% of the whole
sample) the major or the unique contributor to the
lower inection point of the respiratory system. In our
study, a signicant contribution of the chest wall to the
Pmci,rs was less prevalent than in the study of Mer-
goni et al., regardless the ARF group studied. Some
differences between the two studies should, however,
be pointed out. First, we investigated more patients,
earlier after onset of mechanical ventilation. Second,
the method to construct the V-P curve was different in
that we used LCFI at 8 l/min whereas Mergoni et al.
inated the respiratory system with an automated
supersyringe that delivered a constant ow rate of 3
l/min. It is unlikely that this discrepancy inuenced
the results. In a previous study, our laboratory found
that the rate of ination below 15 l/min during LCFI
did not change the value of the lower inection point of
the respiratory system (4). Third, the analysis of the
chest wall V-P curve was performed in our study for
two reasons. Contrary to Mergoni et al., we did not just
use the raw data of the Pes signal but smoothed it to
avoid cardiac artifacts. Moreover, we used a mathe-
matical model to perform an unbiased determination of
the lower inection point of the chest wall (see below).
Finally, assessment of the contribution of chest wall to
Pmci,rs is a difcult task actually. In their study,
Mergoni et al. (14) did not quantitatively determine the
contribution of chest wall to lower inection point of
the respiratory system. By using a quantitative at-
tempt, we have found a lower prevalence of a signi-
cant contribution of the chest wall to Pmci,rs. The
correlation between Pmci,rs Pmci,L and Pmci,w is
signicant (Fig. 5) as evidenced by a coefcient of
determination of 0.77, i.e., 77% of the variance of the
relationship are explained by the linear model. How-
ever, there are too few points above 3 cmH
2
O to make
any meaningful statements about scatter above and
below this level. Moreover, there is quite a low number
of data within the 95% condence interval limits.
In our study, the sigmoidal equation was able to
precisely t the chest wall and lung V-P curve of 36
patients with ARF of various etiology. To our knowl-
edge, this is the rst study that provides such results
in human lung and chest wall. As already pointed out
(9), Eq. 1 is symmetric around the true inection point
and there is no physiological reason of the V-P curve to
have symmetric upward concavity and downward con-
cavity. Harris et al. (9) explained the excellent t of
their data by the fact that ination pressures were 40
cmH
2
O, and therefore most of the data were included
to the left of Pmci,rs. In the present study, we have
observed that the sigmoidal model tted the experi-
mental data very well with ination pressure of the
respiratory system 40 cmH
2
O. By using the sigmoi-
dal equation, Harris et al. compared Pmci,rs and lower
inection point as identied by eye by seven clinicians.
They found a large variability among and within ob-
servers and that the lower inection point rarely coin-
cided with Pmci,rs (9). The procedure introduced by
Gattinoni et al. (7) and used by Mergoni et al. (14) is
close to the graphical determination of the lower inec-
tion point performed by the clinicians in the study of
Harris et al (9). The interpretation of the nature of
lower inection point is not entirely clear. It has long
been recognized that the lower inection point reects
reopening of previously closed small airways (8). The
presence of airway closure has also been evidenced
from the V-P curve in the experimental model of acute
lung injury (21). There is no single reopening pressure,
however, and hence the lower inection point may
reect where the majority of the airways open. Recent
investigations pointed out that alveolar recruitment
during ARDS continues to occur well above the lower
inection point (10, 11). In short, this is not the closing
pressure that determines the location of lower inec-
tion point. The distribution of the alveolar damage can
also contribute to the nonlinearity of the V-P curve of
the respiratory system, as evidenced from lung com-
puted tomographic scan studies (24). In case of diffuse
involvement, i.e., homogenous distribution of air and
2069 LUNG AND CHEST WALL V-P CURVES IN ALI
J Appl Physiol VOL 95 NOVEMBER 2003 www.jap.org

o
n

J
a
n
u
a
r
y

1
3
,

2
0
1
0

j
a
p
.
p
h
y
s
i
o
l
o
g
y
.
o
r
g
D
o
w
n
l
o
a
d
e
d

f
r
o
m

tissue throughout the lung, the V-P curve exhibited a
nonlinear pattern with a visible lower inection point
(24). By contrast, in case of lobar involvement, i.e.,
nonaerated lung areas coexisting with aerated lung
areas, a linear pattern of the V-P curve was observed
with no detectable lower inection point (24). In the
present study, we addressed the issue of the nonlinear-
ity of the chest wall V-P curve as a participating factor
of nonnegative Pmci,rs. The contributing factors of
Pmci,w in patients with ARF are not entirely under-
stood. In normal humans, the shape of the V-P curve of
the chest wall is determined by factors such as age,
body size, volume and time history (1). The V-P curve
of chest wall is essentially linear over a small volume
range above FRC. Over a larger range of volume dis-
placement, i.e., by studying the lung from below FRC
near residual volume, the V-P curve becomes nonlinear
and exhibits a concavity toward the volume axis. In
this condition, the V-P curve of the chest wall has a
typical knee at lung volumes below 30% of the vital
capacity (1). Therefore, the reduction of FRC, which is
a hallmark of ALI/ARDS, is probably a major factor
explaining the occurrence of Pmci,w in ARF patients.
Because we did not measure FRC, this hypothesis
cannot be supported from our results.
In the present investigation, six patients exhibited
negative values of Pmci and were excluded from the
present analysis. All the V-P curves in the present
study that were excluded for negative Pmci were linear
up to the upper inection point. Therefore, the hypoth-
esis subtending the use of the sigmoidal equation was
not veried. Moreover, because we did not perform a
negative pressure ventilation, the negative values of
Pmci did not pertain to any actual experimental data.
In the study of Harris et al. (9), three patients had also
negative values of Pmci,rs. The interpretation of a
negative value of Pmci with the sigmoidal model is that
the maximal rate of compliance increase had occurred
below the volume range investigated (9).
Our study is clinically useful in that it proposes a
diagnostic procedure that combines different advan-
tages. Now, by the means of 1) esophageal balloon, 2)
LCFI directly delivered from the ventilator without
patient disconnection, and 3) sigmoidal equation, clini-
cians can have a safe, quick, reliable, and accurate
method to set the ventilator from a comprehensive
physiological background. Whether this approach may
change the outcome of ARF patients has as yet to be
determined.
In conclusion, this is the rst study applying the
sigmoidal model to the analysis of chest wall and lung
V-P curves in human ARF. The occurrence of a signif-
icant contribution of the chest wall to the lower inec-
tion point of the respiratory system is lower than
anticipated. The sigmoidal equation is able to deter-
mine precisely the point of the maximal compliance
increase of chest wall and lung.
We thank Olivier Tessier of Taema, Antony, France, for providing
us with the ventilators dedicated to the study; Guy Annat and
Jean-Paul Viale, EA 1896 Claude Bernard University Lyon, France;
and all nurses and physicians of the participating ICUs for invalu-
able help.
DISCLOSURES
This study was sponsored by the Hospices Civils de Lyon and
partly supported by a grant from Taema, Antony, France.
Cecile Pereira was a research fellow and was supported by a grant
fromTaema, Antony, France and by a Grant fromthe Hospices Civils
de Lyon.
REFERENCES
1. Agostoni E and Hyatt R. Static behavior of the respiratory
system. In: Handbook of Physiology. The Respiratory System.
Mechanics of Breathing. Bethesda, MD: Am. Physiol. Soc., 1986,
sect. 3, vol. III, pt. 1, chapt. 9, p. 113130.
2. Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schet-
tino GP, Lorenzi-Filho G, Kairalla RA, Deheinzelin D,
Munoz C, Oliveira R, Takagaki TY, and Carvalho CR.
Effect of a protective-ventilation strategy on mortality in the
acute respiratory distress syndrome. N Engl J Med 338: 347
354, 1998.
3. Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K,
Hudson L, Lamy M, Legall JR, Morris A, and Spragg R. The
American-European Consensus Conference on ARDS. Deni-
tions, mechanisms, relevant outcomes, and clinical trial coordi-
nation. Am J Respir Crit Care Med 149: 818824, 1994.
4. Blanc Q, Sab JM, Philit F, Langevin B, Thouret JM, Noel
P, Robert D, and Guerin C. Inspiratory pressure-volume
curves obtained using automated low constant ow ination and
automated occlusion methods in ARDS patients with a new
device. Intensive Care Med 28: 990994, 2002.
5. Gattinoni L, Pelosi P, Suter PM, Pedoto A, Vercesi P, and
Lissoni A. Acute respiratory distress syndrome caused by pul-
monary and extrapulmonary disease. Different syndromes?
Am J Respir Crit Care Med 158: 311, 1998.
7. Gattinoni L, Pesenti A, Avalli L, Rossi F, and Bombino M.
Pressure-volume curve of total respiratory system in acute re-
spiratory failure. Computed tomographic scan study. Am Rev
Respir Dis 136: 730736, 1987.
8. Glaister DH, Schroter RC, Sudlow MF, and Milic-Emili J.
Bulk elastic properties of excised lungs and the effect of a
transpulmonary pressure gradient. Respir Physiol 17: 347364,
1973.
9. Harris RS, Hess DR, and Venegas JG. An objective analysis
of the pressure-volume curve in the acute respiratory distress
syndrome. Am J Respir Crit Care Med 161: 432439, 2000.
10. Hickling KG. Best compliance during a decremental, but not
incremental, positive end-expiratory pressure trial is related to
open-lung positive end-expiratory pressure: a mathematical
model of acute respiratory distress syndrome lungs. Am J Respir
Crit Care Med 163: 6978, 2001.
11. Jonson B, Richard JC, Straus C, Mancebo J, Lemaire F,
and Brochard L. Pressure-volume curves and compliance in
acute lung injury: evidence of recruitment above the lower in-
ection point. Am J Respir Crit Care Med 159: 11721178, 1999.
12. Le Gall JR, Lemeshow S, and Saulnier F. A new Simplied
Acute Physiology Score (SAPS II) based on a European/North
American multicenter study. JAMA 270: 29572963, 1993.
13. Lu Q, Vieira SR, Richecoeur J, Puybasset L, Kalfon P,
Coriat P, and Rouby JJ. A simple automated method for
measuring pressure-volume curves during mechanical ventila-
tion. Am J Respir Crit Care Med 159: 275282, 1999.
14. Mergoni M, Martelli A, Volpi A, Primavera S, Zuccoli P,
and Rossi A. Impact of positive end-expiratory pressure on
chest wall and lung pressure-volume curve in acute respiratory
failure. Am J Respir Crit Care Med 156: 846854, 1997.
15. Milic-Emili J, Mead J, Turner JM, and Glaiser EM. Im-
proved technique for estimating pleural pressure from esopha-
geal balloons. J Appl Physiol 19: 207211, 1964.
16. Murray JF, Matthay MA, Luce JM, and Flick MR. An
expanded denition of the adult respiratory distress syndrome.
Am Rev Respir Dis 138: 720723, 1988.
2070 LUNG AND CHEST WALL V-P CURVES IN ALI
J Appl Physiol VOL 95 NOVEMBER 2003 www.jap.org

o
n

J
a
n
u
a
r
y

1
3
,

2
0
1
0

j
a
p
.
p
h
y
s
i
o
l
o
g
y
.
o
r
g
D
o
w
n
l
o
a
d
e
d

f
r
o
m

17. Pelosi P, Cereda M, Foti G, Giacomini M, and Pesenti A.
Alterations of lung and chest wall mechanics in patients with
acute lung injury: effects of positive end-expiratory pressure.
Am J Respir Crit Care Med 152: 531537, 1995.
18. Ranieri VM, Brienza N, Santostasi S, Puntillo F, Mascia L,
Vitale N, Giuliani R, Memeo V, Bruno F, Fiore T, Brienza A,
and Slutsky AS. Impairment of lung and chest wall mechanics in
patients with acute respiratory distress syndrome: role of abdomi-
nal distension. Am J Respir Crit Care Med 156: 10821091, 1997.
19. Ranieri VM, Suter PM, Tortorella C, De Tullio R, Dayer
JM, Brienza A, Bruno F, and Slutsky AS. Effect of mechan-
ical ventilation on inammatory mediators in patients with
acute respiratory distress syndrome: a randomized controlled
trial. JAMA 282: 5461, 1999.
20. Rouby JJ, Lu Q, and Goldstein I. Selecting the right level of
positive end-expiratory pressure in patients with acute respira-
tory distress syndrome. Am J Respir Crit Care Med 165: 1182
1186, 2002.
21. Slutsky AS, Scharf SM, Brown R, and Ingram RH. The effect
of oleic acid-induced pulmonary edema on pulmonary and chest
wall mechanics in dogs. Am Rev Respir Dis 121: 9196, 1980.
22. Venegas JG, Harris RS, and Simon BA. A comprehensive
equation for the pulmonary pressure-volume curve. J Appl
Physiol 84: 389395, 1998.
23. Ventilation with lower tidal volumes as compared with tradi-
tional tidal volumes for acute lung injury and the acute respira-
tory distress syndrome. The Acute Respiratory Distress Syn-
drome Network. N Engl J Med 342: 13011308, 2000.
24. Vieira SRR, Puybasset L, Lu Q, Richecoeur J, Cluzel P,
Coriat P, and Rouby JJ. A scanographic assessment of pul-
monary morphology in acute lung injury. Am J Respir Crit Care
Med 159: 16121623, 1999.
2071 LUNG AND CHEST WALL V-P CURVES IN ALI
J Appl Physiol VOL 95 NOVEMBER 2003 www.jap.org

o
n

J
a
n
u
a
r
y

1
3
,

2
0
1
0

j
a
p
.
p
h
y
s
i
o
l
o
g
y
.
o
r
g
D
o
w
n
l
o
a
d
e
d

f
r
o
m