Lung stress and strain during mechanical ventilation for acute respiratory distress syndrome.

Abstract

Lung injury caused by a ventilator results from nonphysiologic lung stress (transpulmonary pressure) and strain (inflated volume to functional residual capacity ratio).
To determine whether plateau pressure and tidal volume are adequate surrogates for stress and strain, and to quantify the stress to strain relationship in patients and control subjects.
Nineteen postsurgical healthy patients (group 1), 11 patients with medical diseases (group 2), 26 patients with acute lung injury (group 3), and 24 patients with acute respiratory distress syndrome (group 4) underwent a positive end-expiratory pressure (PEEP) trial (5 and 15 cm H2O) with 6, 8, 10, and 12 ml/kg tidal volume.
Plateau airway pressure, lung and chest wall elastances, and lung stress and strain significantly increased from groups 1 to 4 and with increasing PEEP and tidal volume. Within each group, a given applied airway pressure produced largely variable stress due to the variability of the lung elastance to respiratory system elastance ratio (range, 0.33-0.95). Analogously, for the same applied tidal volume, the strain variability within subgroups was remarkable, due to the functional residual capacity variability. Therefore, low or high tidal volume, such as 6 and 12 ml/kg, respectively, could produce similar stress and strain in a remarkable fraction of patients in each subgroup. In contrast, the stress to strain ratio-that is, specific lung elastance-was similar throughout the subgroups (13.4 +/- 3.4, 12.6 +/- 3.0, 14.4 +/- 3.6, and 13.5 +/- 4.1 cm H2O for groups 1 through 4, respectively; P = 0.58) and did not change with PEEP and tidal volume.
Plateau pressure and tidal volume are inadequate surrogates for lung stress and strain. Clinical trial registered with www.clinicaltrials.gov (NCT 00143468).

Full text

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Lung stress and strain during mechanical ventilation of
the Acute Respiratory Distress Syndrome
1Davide Chiumello MD, 2Eleonora Carlesso MSc, 2Paolo Cadringher MSc, 1,2Pietro Caironi
MD, 1,2Franco Valenza MD, 2Federico Polli MD, 2Federica Tallarini MD, 2Paola Cozzi MD,
2Massimo Cressoni MD, 1Angelo Colombo MD, 3John J. Marini MD, 1,2Luciano Gattinoni
MD FRCP

1 Dipartimento di Anestesia, Rianimazione (Intensiva e Subintensiva) e Terapia del Dolore,
Fondazione IRCCS – “Ospedale Maggiore Policlinico Mangiagalli Regina Elena” di Milano,
Italy
2 Istituto di Anestesiologia e Rianimazione, Fondazione IRCCS – “Ospedale Maggiore
Policlinico Mangiagalli Regina Elena” di Milano, Italy; Università degli Studi, Milano, Italy
3 Pulmonary and Critical Care, University of Minnesota (Regions Hospital), St Paul,
Minnesota, USA.

Address correspondence to:
Prof. Luciano Gattinoni
Istituto di Anestesiologia e Rianimazione,
Fondazione IRCCS - “Ospedale Maggiore Policlinico, Mangiagalli, Regina Elena" di Milano
Via Francesco Sforza, 35
20122 Milano, ITALY
Phone: +39-02-55033232
Fax: +39-02-50320465
E-mail: gattinon@policlinico.mi.it

Running head: Lung stress and strain in ALI/ARDS
Descriptor number: 2 ARDS and ALI: patient studies; 10 Ventilator-induced lung injury
Word count: 3779
AT A GLANCE COMMENTARY
Scientific Knowledge on the Subject;
Lung stress and strain are the primary determinants of VILI. Their surrogates are airway
pressure and VT IBW. VILI prevention is primarily based on recognizing “harmful” threshold
for these surrogates (30 cmH2O airway plateau pressure and 6 mL/kg VT IBW).

AJRCCM Articles in Press. Published on May 1, 2008 as doi:10.1164/rccm.200710-1589OC
Copyright (C) 2008 by the American Thoracic Society.

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What This Study Adds to the Field
In this study we showed that VT IBW and airway plateau pressure are inadequate surrogates
for lung stress and strain.

This article has an online data supplement, which is accessible from this issue’s table of
content online at www.atsjournals.org

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Abstract
RATIONALE: Lung injury due to ventilator results from un-physiological lung stress
(transpulmonary pressure) and strain (inflated volume to functional residual capacity ratio).
OBJECTIVE: to determine whether the plateau pressure and the tidal volume are adequate
surrogates for stress and strain. To quantify the stress to strain relationship in patients and
control subjects.
METHODS: Nineteen post-surgical healthy patients (group 1), 11 patients with medical
diseases (group 2), 26 patients with acute lung injury (group 3) and 24 patients with ARDS
(group 4) underwent a PEEP trial (5 and 15 cmH2O) with 6, 8, 10 and 12 mL/kg tidal volume.
MEASUREMENTS AND MAIN RESULTS: plateau airway pressure, lung and chest wall
elastances, lung stress and strain significantly increased from group 1 to 4 and increasing
PEEP and tidal volume. Within each group a given applied airway pressure produced largely
variable stress due to the variability of the lung elastance to respiratory system elastance ratio
(range 0.33-0.95). Analogously for the same applied tidal volume the strain variability within
subgroups was remarkable, due to the functional residual capacity variability. Therefore low
or high tidal volume as 6 and 12 mL/kg could produce similar stress and strain in a
remarkable fraction of patients in each subgroup. In contrast, the stress to strain ratio, i.e.
specific lung elastance, was similar throughout the subgroups (13.4±3.4, 12.6±3.0, 14.4±3.6
and 13.5±4.1 cmH2O, P=0.58) and did not change with PEEP and tidal volume.
CONCLUSIONS: Plateau pressure and tidal volume are inadequate surrogates for lung stress
and strain.
Abstract word count: 250
Keywords: Acute Respiratory Distress Syndrome; Acute Lung Injury; Stress, Mechanical;
Strain; Ventilator Induced Lung Injury
Clinical Trial Registry Information: ID# NCT00143468 at www.clinicaltrials.gov.

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Introduction
Damages from mechanical ventilation have been attributed to excessive pressure
(barotrauma1;2) or volume (volutrauma3) applied to the lung parenchyma, to shear stresses
occurring at the interface of open and close lung regions (atelectrauma4;5) and to cellular
inflammatory response (biotrauma6). The force-bearing structure is the lung skeleton which is
composed of a fibrous network (elastin and collagen), embedded in the extracellular matrix.
One fibre system originates from the hilum, the other one from the lung periphery (visceral
pleura) and the two systems are connected at the alveolar level.7 The elastin fibres are the
determinant of the elastic recoil, while the inextensible collagen fibres, folded when the lung
is in its resting position, act as a stop-length when completely unfolded at total lung
capacity.8;9 Lung cells, anchored to the extracellular matrix, do not bear directly the force, but
may activate the inflammatory cascade if subjected to excessive shape changes. When a force
is applied to the fibre system the upper limit of expansion is total lung capacity (fully
unfolded collagen), after which stress may induce rupture. Before this limit, however, the un-
physiological distension of the lung cells may result in generalized lung inflammation.10-12

In bioengineering parlance, stress and strain are mechanical phenomena properly referred to
microstructures or to small areas of a body. “Stress” is defined as the internal distribution of
the counterforce per unit of area that balances and reacts to an external load. The associated
deformation of the structure is called “strain”, which is defined as the change in size or shape
referred to the initial status. Stress and strain are linked by the following formula:13
strainkstress
*
=
(Equation 1)
We reasoned that the clinical equivalent of stress is transpulmonary pressure (airway pressure
minus pleural pressure) and the clinical equivalent of strain is the ratio of volume change
(∆V) to the functional residual capacity (FRC), which is the resting lung volume.14 We used

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FRC as a reference point, as at this volume the fibres of the lung skeleton are in their natural
resting position, at atmospheric airway pressure, and the respiratory muscles, which are the
“engine” of the strain, are inactive and relaxed. Accordingly, within the range of pressures
and volumes for which the stress and strain relationship is linear we get:
∆
)(*)()(
strain
FRC
V
anceelastlungspecificE stressP
specLL
∆
=
(Equation 2)
FRC must not be confused with end expiratory lung volume (EELV) measured with positive
end expiratory pressure (PEEP), in this case the volume due to PEEP is part of ∆V and must
be added to numerator and not to denominator. This equation shows that the proportionality
constant between stress and strain, called specific lung elastance, is the transpulmonary
pressure at which FRC doubles. This parameter reflects the intrinsic elasticity of the lung
parenchyma open to gases.

As the determinants of ventilator-induced lung injury (VILI), stress and strain, are not
measured in clinical practice, we sought to determine the extent to which they can be
described by their clinical surrogates, the plateau airway pressure and the tidal volume (VT)
referenced to ideal body weight (IBW). Therefore in this paper we measured the global
average end-tidal stress and defined the stress to strain relationship (specific lung elastance)
both in ALI/ARDS and control subjects. If lung stress and strain were not predictable from
plateau airway pressure and VT per IBW their measurement would ideally allow to tailor a
safer mechanical ventilation in the individual patient in question.