Concern over the potential for lung injury due to mechanical ventilation has fueled investigations on lung protection in the operating room.1–3  Based on the intensive care literature,4  tidal volume (VT) and positive end-expiratory pressure (PEEP) settings have been the focus of intraoperative clinical trials.1–3  Recent results in acute respiratory distress syndrome (ARDS)5  and surgical patients6,7  have suggested that the benefits associated with VT and PEEP settings are mediated by driving pressures. As our understanding of the physical and biologic effects of mechanical ventilation evolves, the concepts of driving pressure and transpulmonary pressure have been increasingly used to quantify the mechanical forces acting over the lungs during mechanical ventilation and to guide clinical care. In this perspective, we discuss the definition of those concepts, their measurement in the clinical setting, their interpretation, and their use in typical scenarios.

To prevent lung injury during mechanical ventilation, the factors causing most injury to the lungs must be identified. In the centuries-old engineering field of materials science, limits of maximal stress and strain are listed as key possible causes for materials to fail and rupture under the action of external loads. Recently, these concepts of stress and strain have been applied to increase understanding of mechanisms of injury during mechanical ventilation8–10  and better explain the positive clinical outcomes associated with lung-protective ventilation.5–8,10–12 

Stress is defined as a force divided by the area over which it is applied. Intuitively, if a fixed force is distributed throughout a large cross-sectional area of lung tissue, the force per unit area (i.e., stress) will be smaller than if that same force were distributed over a smaller area of lung tissue. More stress is expected to increase the risk of injury.

Strain is a measure of a change in the dimension of a structure from its original dimension. For instance, linear strain is defined as change in length divided by the original length (fig. 1). The most pertinent strain in ventilation is the volumetric strain created by inspiration and expiration. Volumetric strain is defined as change in volume divided by initial volume. In elastic materials, strain is directly proportional to stress. Volumetric strain during ventilation has both static and dynamic components and is heterogeneous throughout the lungs.8 

Fig. 1.

Driving pressure (ΔP) is calculated as the difference between plateau pressure (Pplat) and positive end-expiratory pressure (PEEP). Driving pressure is composed of two pressures: that distributed to the lung itself, the transpulmonary pressure (ΔPL), and that applied to the chest wall (ΔPcw). Rearrangement of the standard respiratory system compliance (CRS) equation leads to driving pressure as equal to the tidal volume (VT) divided by CRS. Strain is a measure of material deformation relative to its original state. For example, the linear displacement of a spring (ΔL) relative to its rest length (Lo), or equivalently the ratio of VT to functional residual capacity (FRC). As CRS changes in proportion to FCR, i.e., FRC = k × CRS, VT/CRS is an approximation of tidal volume normalized to FRC, and ΔP is proportional to lung strain. TLC, total lung capacity; VL, lung volume.

Fig. 1.

Driving pressure (ΔP) is calculated as the difference between plateau pressure (Pplat) and positive end-expiratory pressure (PEEP). Driving pressure is composed of two pressures: that distributed to the lung itself, the transpulmonary pressure (ΔPL), and that applied to the chest wall (ΔPcw). Rearrangement of the standard respiratory system compliance (CRS) equation leads to driving pressure as equal to the tidal volume (VT) divided by CRS. Strain is a measure of material deformation relative to its original state. For example, the linear displacement of a spring (ΔL) relative to its rest length (Lo), or equivalently the ratio of VT to functional residual capacity (FRC). As CRS changes in proportion to FCR, i.e., FRC = k × CRS, VT/CRS is an approximation of tidal volume normalized to FRC, and ΔP is proportional to lung strain. TLC, total lung capacity; VL, lung volume.

Close modal

During tidal breathing, the change in lung volume is represented by VT, and the initial lung volume corresponds to the functional residual capacity (FRC). Global volumetric lung strain can, thus, be estimated as VT/FRC. This relationship shows that reduction of VT lowers lung strain, and also that FRC can have an effect on strain. The markedly low FRC of ARDS patients emphasizes the relevance of this concept. For instance, with a VT of 500 ml, a healthy lung during anesthesia (FRC, 2,000 ml) would have a strain of 25% (500/2,000). That same VT in an ARDS patient (FRC, 500 ml) would produce a strain of 100% (500/500), a fourfold increase in strain and augmented risk of injury.

These considerations also suggest that, while reducing VT is important in surgical and ARDS patients,4,12  VT is not the final determinant of lung injury. This is because it does not take the size of lung parenchyma to which that VT applies (FRC) into account. Consequently, simply controlling VT is not enough to minimize injurious lung strain. These arguments are consistent with recent clinical outcome results in ARDS and surgical patients showing that the effect of VT on clinical outcomes is mediated by a variable associated with lung strain.5–7 

The heterogeneity of lung expansion, e.g., as lung derecruitment develops, also increases the risk for lung injury. This is because this heterogeneity can produce regional strains larger than whole-lung strains in healthy and inflamed lungs of anesthetized ventilated large animals even if those whole-lung strains are acceptable.8,13  Theoretical computations indicated that in heterogeneously inflated lungs, regional pressures could be substantially larger than whole-lung pressures, by as much as three to four times when an atelectatic area is surrounded by expanded lung.14  Systemic inflammation, a common clinical finding, amplifies the injurious effect of strain.10,15 

Driving pressure is defined as plateau pressure minus PEEP (fig. 1).16  Plateau pressure is measured at the end of an inspiratory pause during volume-controlled constant flow ventilation and at the end of inspiration during pressure-controlled ventilation. Accordingly, in the absence of respiratory muscle effort by the patient, driving pressure is the pressure above PEEP applied to the entire respiratory system to achieve tidal ventilation. A caveat on the computation of plateau pressures is that they cannot be presumed to represent end-inspiratory alveolar pressures when end-inspiratory flows are not zero, indicating lack of equilibration between airway and alveolar pressures. During volume-controlled ventilation, an inspiratory pause greater than or equal to 3 s provides best accuracy for plateau pressure measurements in normal and diseased lungs.17,18  Short inspiratory pauses of 0.5 s overestimate plateau pressure by 11% in ARDS patients and 17% in chronic obstrictive pulmonary disease patients.17  Examination of the airway pressure tracing available in current anesthesia machines for the presence of a plateau at the end of the inspiratory pause allows for better decision on reliability of plateau pressure measurement. Auto-PEEP is another potential source of error by leading to driving pressure overestimation as the end-expiratory pressure in alveolar units would be higher than the PEEP set in the ventilator and used to compute the driving pressure.

It is important to recognize that driving pressure and total airway pressure measured during mechanical ventilation have two components: one related to the expansion of the lungs, the other to the expansion of the chest wall. Each of these two components can change substantially during disease and surgical conditions and affect the interpretation of the driving pressure measurements.

Transpulmonary pressure is defined as the pressure difference between the airway opening and the pleural surface (fig. 2).19,20  Accordingly, transpulmonary pressure comprises the pressure to move air through the airways (airway opening – alveolar pressure) and the pressure to overcome the lung tissue elastic recoil (alveolar – pleural pressure), the latter most frequently associated with lung injury.19  Although continuous estimation of transpulmonary pressure is feasible, it is usually assessed at two critical points during the breathing cycle: the end of inspiration, relevant to prevent hyperinflation, and the end of expiration, relevant to avoid lung derecruitment. If respiratory flows are zero at these points, the airway pressures (plateau pressure at end-inspiration and PEEP at end-expiration) are presumed to represent alveolar pressures, a reasonable assumption in the absence of gas trapping.21  This approach to measure transpulmonary pressure may have led to the misconception that it exclusively expresses pressures at the alveolar level.19,22,23  The essential concept is that in static, i.e., zero flow, conditions (end-inspiration and end-expiration), the transpulmonary pressure approximates the lung tissue elastic recoil component, which is the relevant pressure to quantify stress applied to lung tissue beyond airways,14  presumably responsible for injury during mechanical ventilation.19 

Fig. 2.

Airway opening, esophageal (Peso), and transpulmonary pressures (PL) measurements. PL is defined as the difference between airway opening pressure (blue lines) and pleural pressure. Pleural pressure is frequently estimated from esophageal balloon pressure measurements (Peso). Using a specific protocol, the esophageal balloon is placed in the lower third of the esophagus (A). Cardiac oscillations in Peso (B, green lines) indicate accurate placement of the balloon, which can be confirmed by observation of similar airway pressure and Peso measurements as gentle chest compressions are performed during expiratory pause or with occluded airway opening (A). PL can be estimated as the difference between airway and esophageal pressures (red and orange lines). Interventions such as pneumoperitoneum (B, mid panel) produce a marked change in driving pressures (ΔP = plateau pressure, PPlat, minus positive end-expiratory pressure, PEEP). In this example, ΔP increased by 7 cm H2O. Yet ΔPL (end-inspiratory PL, PL EI, minus end-expiratory PL, PL EE) does not increase to the same degree as ΔP and PPlat. The change in ΔPL in this example was 4 cm H2O. This demonstrates that part of the increases in ΔP and PPlat are due to the chest wall component and not to pressures applied to the lung parenchyma. This contribution of the chest wall is evidenced by the increased EI to EE oscillation in Peso after as compared to before pneumoperitoneum. In addition, the esophageal pressure at end-expiration (Peso EE, at ~4 s on time scale) is positive before pneumoperitoneum while it is negative after pneumoperitoneum. This implies mechanical conditions consistent with lung collapse after pneumoperitoneum. Indeed, while PL did not increase by the same magnitude as ΔP, it also increased, indicating loss of lung compliance. Such conditions could prompt use of higher PEEP to prevent lung derecruitment. EE, end-expiratory; EI, end-inspiratory.

Fig. 2.

Airway opening, esophageal (Peso), and transpulmonary pressures (PL) measurements. PL is defined as the difference between airway opening pressure (blue lines) and pleural pressure. Pleural pressure is frequently estimated from esophageal balloon pressure measurements (Peso). Using a specific protocol, the esophageal balloon is placed in the lower third of the esophagus (A). Cardiac oscillations in Peso (B, green lines) indicate accurate placement of the balloon, which can be confirmed by observation of similar airway pressure and Peso measurements as gentle chest compressions are performed during expiratory pause or with occluded airway opening (A). PL can be estimated as the difference between airway and esophageal pressures (red and orange lines). Interventions such as pneumoperitoneum (B, mid panel) produce a marked change in driving pressures (ΔP = plateau pressure, PPlat, minus positive end-expiratory pressure, PEEP). In this example, ΔP increased by 7 cm H2O. Yet ΔPL (end-inspiratory PL, PL EI, minus end-expiratory PL, PL EE) does not increase to the same degree as ΔP and PPlat. The change in ΔPL in this example was 4 cm H2O. This demonstrates that part of the increases in ΔP and PPlat are due to the chest wall component and not to pressures applied to the lung parenchyma. This contribution of the chest wall is evidenced by the increased EI to EE oscillation in Peso after as compared to before pneumoperitoneum. In addition, the esophageal pressure at end-expiration (Peso EE, at ~4 s on time scale) is positive before pneumoperitoneum while it is negative after pneumoperitoneum. This implies mechanical conditions consistent with lung collapse after pneumoperitoneum. Indeed, while PL did not increase by the same magnitude as ΔP, it also increased, indicating loss of lung compliance. Such conditions could prompt use of higher PEEP to prevent lung derecruitment. EE, end-expiratory; EI, end-inspiratory.

Close modal

While assessment of airway pressures to calculate transpulmonary pressure is simple, estimates of pleural pressure are difficult to obtain. Esophageal manometry is currently the most widely accepted method to estimate pleural pressures in the clinical setting.24–26  For this, a special balloon, either incorporated in a stand-alone catheter or as part of a naso- or orogastric tube, is positioned with a specific protocol24,27  in the lower third of the esophagus and connected to a pressure transducer (fig. 2A). Correct balloon position is confirmed by the presence of cardiac oscillation in the esophageal pressure trace (fig. 2B) and measurement of airway opening and esophageal pressure swings with occluded airway opening (fig. 2A).28  Esophageal pressure measurements obtained in this manner more specifically assess periesophageal values, approximately at a third to half of the dorsal-to-ventral chest length.26,29  In supine patients, they overestimate ventral pleural pressures and underestimate dorsal values given the ventral–dorsal increase of pleural pressure.30 

Two approaches are used to apply esophageal pressure as a surrogate for pleural pressure and computation of transpulmonary pressure. One assumes pleural pressure as equal to the absolute esophageal pressure directly read from the transducer measurements along the breathing cycle.24  These measurements can be made at end-inspiration (transpulmonary pressure is equal to plateau pressure minus esophageal pressure at end-inspiration) and end-expiration (transpulmonary pressure is equal to PEEP minus esophageal pressure at end-expiration). Such esophageal pressure measurements can be affected by the weight of the mediastinum, abdominal pressure, and esophageal balloon positioning, and correction factors have been proposed to account for those.31,32 

The second approach assumes that, while absolute esophageal and pleural pressures can differ, their changes are equivalent.24,33  Using this approach, pleural pressures and transpulmonary pressure can be measured in two ways, which present close agreement33 : compliance-derived and release-derived. In the compliance-derived strategy, transpulmonary pressure is calculated as the product of the plateau pressure and the ratio of compliances of the respiratory system and lung.34,35  The compliance ratio is estimated during a tidal volume inflation (from PEEP to end-inspiratory pressures) from VT and changes in airway and esophageal pressures. This compliance-derived method assumes that in each patient, the changes in esophageal and airway pressures are linear during tidal volume inflation and PEEP changes. In the release-derived strategy, transpulmonary pressure is measured as the change in airway and esophageal pressure from atmospheric pressure due to tidal inflation and PEEP.33  The release-derived strategy involves opening of the ventilatory circuit to atmosphere, with risk of lung derecruitment and hypoxemia, while the compliance-based strategy does not. A key assumption of the second approach is that pleural pressures are zero at zero airway pressure. This would be questionable in resting conditions, and, more markedly, in conditions consistent with increased pleural pressures such as in obese and ARDS patients,19  and presumably during laparoscopic and abdominal procedures. In such cases, that assumption could lead to inadequate use of PEEP. The approaches based on absolute or differential esophageal pressure to estimate pleural pressure do not provide equivalent measurements,33,36  and direct comparison to an accepted standard are needed.

Recently, an alternative method to assess transpulmonary pressure without an esophageal balloon has been proposed and validated.37  It is based on a PEEP-step maneuver and measurement of changes in end-expiratory lung volumes using the spirometer available in some ventilators.37 

Driving pressures provide an easily measured correlate of global lung strain.5,7  Driving pressure can be expressed as the ratio between VT and respiratory system compliance (fig. 1). Respiratory system compliance correlates with the aerated lung volume.38  Accordingly, driving pressure can be interpreted as a measurement proportional to the VT normalized to aerated lung volume and, thus, to be related to global lung strain.5  This concept also clarifies the contrast between the strictly volumetric information provided by VT and the additional information on lung strain (VT/initial lung volume) contained in the driving pressure (fig. 1).

In agreement with these physiologic principles, recent studies confirmed that driving pressure explains clinical outcomes related to lung-protective mechanical ventilation better than tidal volumes both in the intraoperative6,7  and the intensive care5  settings. Intraoperatively, a large registry study on patients undergoing noncardiothoracic surgery with general anesthesia and mechanical ventilation indicated that the driving pressure presented a continuous and dose-dependent relationship to the odds ratio of major postoperative pulmonary complications (pneumonia, pulmonary edema, need for reintubation, and ARDS).7  A meta-analysis of randomized controlled trials of protective ventilation during general anesthesia indicated that the only ventilatory parameter associated with an increase in postoperative pulmonary complications was driving pressure with an odds ratio of 1.16.6 

In intensive care, an analysis of randomized trials of ventilation in ARDS patients found that an increase in driving pressure of 7 cm H2O was associated with increased mortality (relative risk, 1.41), even if plateau pressures and VT were in ranges accepted as protective (plateau pressures less than or equal to 30 cm H2O and VT less than or equal to 7 ml/kg; relative risk, 1.36).5  In that study, a driving pressure greater than 15 cm H2O was associated with increased mortality.5  A subsequent investigation of ARDS patients with driving pressures above and less than that threshold found that the higher driving pressure was associated with higher lung stress.39 

While these are not prospective studies, the broad range of cases and patients included support the use of driving pressure as a marker of outcomes in mechanically ventilated patients. These studies also suggest that the traditional limits of airway pressure (e.g., less than or equal to 30 cm H2O2,4 ) may not be enough to prevent lung injury. Instead, limiting or minimizing driving pressures could be a more relevant target. Current estimates for safe driving pressures range from 14 to 18 cm H2O.5–7   Yet there are caveats to such a concept to be discussed below.

Of note, spontaneously breathing patients during pressure-support ventilation can generate negative pleural pressures large enough to result in large VT and resulting end-inspiratory plateau pressures above set peak pressures. Such plateau pressures can be measured with an inspiratory hold and allow for assessment of driving pressures.40  Importantly, such observation is indicative of large and potentially injurious transpulmonary pressures.

Transpulmonary pressure is the physical quantity measuring the mechanical load applied to the lung during ventilation. Accordingly, transpulmonary pressure represents the stress applied to the lung parenchyma11,19  potentially conducive to ventilator-induced lung injury14,19,27  (note that pressure has units of force/area). Traditional teaching has focused on airway pressures as measures of risk for barotrauma and lung injury. Values such as 30 to 32 cm H2O have been cited as maximum safe limits during mechanical ventilation.2,4  The concept of transpulmonary pressure, and the clinical and experimental evidence that followed,24,41  emphasize that absolute airway pressures available in the anesthesia machine or mechanical ventilator are not the ultimate measure of lung stress. Instead, the transpulmonary pressure provides a more accurate measurement of lung stress and risk of injury.42 

In healthy lungs, ventilator-induced lung injury occurs when stresses result in lung volumes nearing total lung capacity, corresponding to a transpulmonary pressure approximately 26 cm H2O.20  In the clinical setting, upper limits for tidal changes in transpulmonary pressure of 15 to 20 cm H2O in healthy patients and 10 to 12 cm H2O for ARDS patients have been recommended.24 

Transpulmonary pressure has been used most frequently in the intensive care unit to guide PEEP setting in the most difficult patients, including patients with ARDS and obese patients.25,43–45  The essential rationale is to adjust PEEP to values assuring a positive end-expiratory transpulmonary pressure (e.g., end-expiratory transpulmonary pressure, 0 to 10 cm H2O). Based on the definition of transpulmonary pressure, titration of mechanical ventilation to these values would avoid end-expiratory alveolar collapse.

Application of such transpulmonary pressure based approaches lead to improved oxygenation, respiratory system compliance, and a trend to reduction in mortality in patients with ARDS.25,43  Given the significant number of hypoxemic patients with unrecognized ARDS,46  use of esophageal pressure monitoring might be considered in any patient with worsening hypoxemia. In obese patients with respiratory failure, low to negative transpulmonary pressure predicted lung collapse and intratidal recruitment/derecruitment, providing guidance for PEEP selection and recruitment maneuvers.45  In the intraoperative setting, transpulmonary pressure has been used to determine optimal PEEP in patients undergoing laparoscopic bariatric surgery.44 

The use of transpulmonary pressure as a correlate of lung stress has limitations.27  Compared to the simple measurement of driving pressure, esophageal manometry requires additional equipment and training in placement and interpretation, hindering its clinical use.27  The esophageal pressure is affected by several factors such as posture, weight of the mediastinum, esophageal smooth muscle compliance and reactivity, and patient effort.27  The esophageal balloon pressures reflect measurements at the location where the balloon is actually placed, i.e., at the height of the esophagus.26  Regional variations in lung expansion are not necessarily accurately captured by esophageal manometry. Despite such limitations, recent data in supine large animals and cadavers support that end-expiratory esophageal balloon pressures are reliable estimates of end-expiratory pleural pressures at the level of the esophagus, and that end-inspiratory transpulmonary pressure estimates end-inspiratory pressures in the nondependent lung,26  providing a bedside measurement with value superior to other current clinical measurements to guide safe mechanical ventilation.

While driving pressures are easier to assess for guidance to avoid ventilator-induced lung injury, there are limitations. A major limitation of driving pressure is its dependence on the properties of the whole respiratory system and not exclusively the lungs. External to the lungs, the properties of the chest wall including the abdomen influence driving pressure measurements. This influence could be misleading as chest wall properties do not reflect increased risk of injury.16  Thus, in conditions where the chest wall compliance is normal and constant, changes in driving pressure will provide an appropriate surrogate for changes in transpulmonary pressures and lung strain. However, when chest wall compliance is abnormal or variable, direct assessment of transpulmonary pressure could be required to appropriately quantify potentially damaging stress applied to the lungs. Common clinical situations in which chest wall compliance leads to a divergence between driving pressures and transpulmonary pressures are related to increased intraabdominal pressure due to abdominal insufflation, intraabdominal hypertension, obesity, ascites, and body position47–50  and also to thoracic trauma, edema of intrathoracic and abdominal tissues, and pleural effusion.27  In such cases, airway pressures by themselves may be misleading to set mechanical ventilation.

Laparoscopic surgery reduces the compliance of the chest wall, increasing airway pressures.51,52  Yet, because airway pressures are distributed to the lung and chest wall according to their corresponding compliances, airway pressures are not fully transmitted to the lungs in terms of equivalent increases in transpulmonary pressures (fig. 2B). Robotic surgery, a specific type of laparoscopic surgery, presents analogous situations frequently exacerbated by the Trendelenburg position and use of special framework (fig. 2B).53  Direct human data in these conditions to provide quantification of the distribution of airway pressures to the lungs and chest wall have only recently been presented.53 

Measurements of transpulmonary pressure have highlighted the possibility of distinct lung stresses during experimental intraabdominal hypertension.48,54  Increasing intraabdominal pressure increased plateau pressure by about half of the applied intraabdominal pressure, but produced minimal change in transpulmonary pressure in healthy lungs, emphasizing that airway pressures do not reflect transpulmonary pressures.54  Increased driving pressures with high intraabdominal pressures without a corresponding transpulmonary pressure increase have been also observed for unilateral atelectasis.48  In contrast, both driving and transpulmonary pressures increased with high intraabdominal pressures in the presence of lung injury,48  indicating that lung mechanical properties and chest wall compliance affect changes in driving and transpulmonary pressures.

Obese patients frequently pose challenges for effective mechanical ventilation.55  Increased abdominal weight exerts pressure on the diaphragm, increasing pleural pressure.45  Measuring esophageal pressure in obese patients can help to determine optimal levels of PEEP and guide lung recruitment.45  When directly guided by esophageal manometry44  or indirectly through electrical impedance tomography,56  PEEP levels to achieve an end-expiratory transpulmonary pressure greater than or equal to 0 cm H2O during laparoscopic bariatric surgeries were higher than routinely used PEEP values: 15 to 18 cm H2O before abdominal insufflation and 19 to 40 cm H2O after insufflation. These numbers are consistent with average supine esophageal pressures of 12.5 ± 3.9 in the obese versus 6.9 ± 3.1 cm H2O in controls.57 

In summary, driving pressures are easily measured during routine clinical mechanical ventilation and should be monitored. Increases in driving pressures should prompt identification of potential causes and, if required, interventions to reduce them. In the several discussed clinical conditions in which driving and transpulmonary pressures diverge, if there is substantial risk for ventilator-induced lung injury, the use of methods to estimate transpulmonary pressure such as esophageal manometry is advisable to guide ventilatory management (fig. 3).

Fig. 3.

Approach for use of driving and transpulmonary pressures to guide mechanical ventilation during anesthesia. Limits presented are based on current experimental and clinical literature. Safety limits have not yet been defined in clinical trials. PBW, predicted body weight; PEEP, positive end-expiratory pressure; VT, tidal volume.

Fig. 3.

Approach for use of driving and transpulmonary pressures to guide mechanical ventilation during anesthesia. Limits presented are based on current experimental and clinical literature. Safety limits have not yet been defined in clinical trials. PBW, predicted body weight; PEEP, positive end-expiratory pressure; VT, tidal volume.

Close modal

Supported by National Institutes of Health grant Nos. R01 HL121228 and UG3HL140177 (Bethesda, Maryland; to Dr. Vidal Melo) and Harvard Anesthesia T32 grant No. 4T32GM007592-39 (to Dr. Williams).

The authors declare no competing interests.

1.
Ferrando
C
,
Soro
M
,
Unzueta
C
,
Suarez-Sipmann
F
,
Canet
J
,
Librero
J
,
Pozo
N
,
Peiro
S
,
Llombart
A
,
Leon
I
,
India
I
,
Aldecoa
C
:
Individualised perioperative open-lung approach versus standard protective ventilation in abdominal surgery (iPROVE): A randomised controlled trial.
Lancet Respir Med
2018
;
6
:
193
203
.
2.
Futier
E
,
Constantin
JM
,
Paugam-Burtz
C
,
Pascal
J
,
Eurin
M
,
Neuschwander
A
,
Marret
E
,
Beaussier
M
,
Gutton
C
,
Lefrant
JY
,
Allaouchiche
B
,
Verzilli
D
,
Leone
M
,
De Jong
A
,
Bazin
JE
,
Pereira
B
,
Jaber
S
;
IMPROVE Study Group
:
A trial of intraoperative low-tidal-volume ventilation in abdominal surgery.
N Engl J Med
2013
;
369
:
428
37
.
3.
PROVE Network Investigators for the Clinical Trial Network of the European Society of Anaesthesiology
.
Hemmes
SN
,
Gama de Abreu
M
,
Pelosi
P
,
Schultz
MJ
;
PROVE Network Investigators for the Clinical Trial Network of the European Society of Anaesthesiology
:
High versus low positive end-expiratory pressure during general anaesthesia for open abdominal surgery (PROVHILO trial): A multicentre randomised controlled trial.
Lancet
2014
;
384
:
495
503
.
4.
Acute Respiratory Distress Syndrome Network
.
Brower
RG
,
Matthay
MA
,
Morris
A
,
Schoenfeld
D
,
Thompson
BT
,
Wheeler
A
;
Acute Respiratory Distress Syndrome Network
:
Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.
N Engl J Med
2000
;
342
:
1301
8
.
5.
Amato
MB
,
Meade
MO
,
Slutsky
AS
,
Brochard
L
,
Costa
EL
,
Schoenfeld
DA
,
Stewart
TE
,
Briel
M
,
Talmor
D
,
Mercat
A
,
Richard
JC
,
Carvalho
CR
,
Brower
RG
:
Driving pressure and survival in the acute respiratory distress syndrome.
N Engl J Med
2015
;
372
:
747
55
.
6.
Neto
AS
,
Hemmes
SN
,
Barbas
CS
,
Beiderlinden
M
,
Fernandez-Bustamante
A
,
Futier
E
,
Gajic
O
,
El-Tahan
MR
,
Ghamdi
AA
,
Günay
E
,
Jaber
S
,
Kokulu
S
,
Kozian
A
,
Licker
M
,
Lin
WQ
,
Maslow
AD
,
Memtsoudis
SG
,
Reis Miranda
D
,
Moine
P
,
Ng
T
,
Paparella
D
,
Ranieri
VM
,
Scavonetto
F
,
Schilling
T
,
Selmo
G
,
Severgnini
P
,
Sprung
J
,
Sundar
S
,
Talmor
D
,
Treschan
T
,
Unzueta
C
,
Weingarten
TN
,
Wolthuis
EK
,
Wrigge
H
,
Amato
MB
,
Costa
EL
,
de Abreu
MG
,
Pelosi
P
,
Schultz
MJ
;
PROVE Network Investigators
:
Association between driving pressure and development of postoperative pulmonary complications in patients undergoing mechanical ventilation for general anaesthesia: A meta-analysis of individual patient data.
Lancet Respir Med
2016
;
4
:
272
80
.
7.
Ladha
K
,
Vidal Melo
MF
,
McLean
DJ
,
Wanderer
JP
,
Grabitz
SD
,
Kurth
T
,
Eikermann
M
:
Intraoperative protective mechanical ventilation and risk of postoperative respiratory complications: Hospital based registry study.
BMJ
2015
;
351
:
h3646
.
8.
Motta-Ribeiro
GC
,
Hashimoto
S
,
Winkler
T
,
Baron
RM
,
Grogg
K
,
Paula
LFSC
,
Santos
A
,
Zeng
C
,
Hibbert
K
,
Harris
RS
,
Bajwa
E
,
Vidal Melo
MF
:
Deterioration of regional lung strain and inflammation during early lung injury.
Am J Respir Crit Care Med
2018
;
198
:
891
902
.
9.
Protti
A
,
Cressoni
M
,
Santini
A
,
Langer
T
,
Mietto
C
,
Febres
D
,
Chierichetti
M
,
Coppola
S
,
Conte
G
,
Gatti
S
,
Leopardi
O
,
Masson
S
,
Lombardi
L
,
Lazzerini
M
,
Rampoldi
E
,
Cadringher
P
,
Gattinoni
L
:
Lung stress and strain during mechanical ventilation: Any safe threshold?
Am J Respir Crit Care Med
2011
;
183
:
1354
62
.
10.
Wellman
TJ
,
Winkler
T
,
Costa
EL
,
Musch
G
,
Harris
RS
,
Zheng
H
,
Venegas
JG
,
Vidal Melo
MF
:
Effect of local tidal lung strain on inflammation in normal and lipopolysaccharide-exposed sheep*.
Crit Care Med
2014
;
42
:
e491
500
.
11.
Gattinoni
L
,
Carlesso
E
,
Caironi
P
:
Stress and strain within the lung.
Curr Opin Crit Care
2012
;
18
:
42
7
.
12.
Serpa Neto
A
,
Hemmes
SN
,
Barbas
CS
,
Beiderlinden
M
,
Biehl
M
,
Binnekade
JM
,
Canet
J
,
Fernandez-Bustamante
A
,
Futier
E
,
Gajic
O
,
Hedenstierna
G
,
Hollmann
MW
,
Jaber
S
,
Kozian
A
,
Licker
M
,
Lin
WQ
,
Maslow
AD
,
Memtsoudis
SG
,
Reis Miranda
D
,
Moine
P
,
Ng
T
,
Paparella
D
,
Putensen
C
,
Ranieri
M
,
Scavonetto
F
,
Schilling
T
,
Schmid
W
,
Selmo
G
,
Severgnini
P
,
Sprung
J
,
Sundar
S
,
Talmor
D
,
Treschan
T
,
Unzueta
C
,
Weingarten
TN
,
Wolthuis
EK
,
Wrigge
H
,
Gama de Abreu
M
,
Pelosi
P
,
Schultz
MJ
;
PROVE Network Investigators
:
Protective versus conventional ventilation for surgery: A systematic review and individual patient data meta-analysis.
Anesthesiology
2015
;
123
:
66
78
.
13.
Paula
LF
,
Wellman
TJ
,
Winkler
T
,
Spieth
PM
,
Guldner
A
,
Venegas
JG
,
Gama de Abreu
M
,
Carvalho
AR
,
Vidal Melo
MF
:
Regional tidal lung strain in mechanically ventilated normal lungs.
J Appl Physiol (1985)
2016
;
121
:
1335
47
.
14.
Mead
J
,
Takishima
T
,
Leith
D
:
Stress distribution in lungs: A model of pulmonary elasticity.
J Appl Physiol
1970
;
28
:
596
608
.
15.
Costa
EL
,
Musch
G
,
Winkler
T
,
Schroeder
T
,
Harris
RS
,
Jones
HA
,
Venegas
JG
,
Vidal Melo
MF
:
Mild endotoxemia during mechanical ventilation produces spatially heterogeneous pulmonary neutrophilic inflammation in sheep.
Anesthesiology
2010
;
112
:
658
69
.
16.
Tonetti
T
,
Vasques
F
,
Rapetti
F
,
Maiolo
G
,
Collino
F
,
Romitti
F
,
Camporota
L
,
Cressoni
M
,
Cadringher
P
,
Quintel
M
,
Gattinoni
L
:
Driving pressure and mechanical power: New targets for VILI prevention.
Ann Transl Med
2017
;
5
:
286
.
17.
Barberis
L
,
Manno
E
,
Guérin
C
:
Effect of end-inspiratory pause duration on plateau pressure in mechanically ventilated patients.
Intensive Care Med
2003
;
29
:
130
4
.
18.
D’Angelo
E
,
Calderini
E
,
Torri
G
,
Robatto
FM
,
Bono
D
,
Milic-Emili
J
:
Respiratory mechanics in anesthetized paralyzed humans: Effects of flow, volume, and time.
J Appl Physiol (1985)
1989
;
67
:
2556
64
.
19.
Loring
SH
,
Topulos
GP
,
Hubmayr
RD
:
Transpulmonary pressure: The importance of precise definitions and limiting assumptions.
Am J Respir Crit Care Med
2016
;
194
:
1452
7
.
20.
Protti
A
,
Andreis
DT
,
Monti
M
,
Santini
A
,
Sparacino
CC
,
Langer
T
,
Votta
E
,
Gatti
S
,
Lombardi
L
,
Leopardi
O
,
Masson
S
,
Cressoni
M
,
Gattinoni
L
:
Lung stress and strain during mechanical ventilation: Any difference between statics and dynamics?
Crit Care Med
2013
;
41
:
1046
55
.
21.
Loring
SH
,
O’Donnell
CR
,
Behazin
N
,
Malhotra
A
,
Sarge
T
,
Ritz
R
,
Novack
V
,
Talmor
D
:
Esophageal pressures in acute lung injury: Do they represent artifact or useful information about transpulmonary pressure, chest wall mechanics, and lung stress?
J Appl Physiol (1985)
2010
;
108
:
515
22
.
22.
Gattinoni
L
,
Carlesso
E
,
Cadringher
P
,
Valenza
F
,
Vagginelli
F
,
Chiumello
D
:
Physical and biological triggers of ventilator-induced lung injury and its prevention.
Eur Respir J Suppl
2003
;
47
:
15s
25s
.
23.
Slutsky
AS
,
Ranieri
VM
:
Ventilator-induced lung injury.
N Engl J Med
2013
;
369
:
2126
36
.
24.
Mauri
T
,
Yoshida
T
,
Bellani
G
,
Goligher
EC
,
Carteaux
G
,
Rittayamai
N
,
Mojoli
F
,
Chiumello
D
,
Piquilloud
L
,
Grasso
S
,
Jubran
A
,
Laghi
F
,
Magder
S
,
Pesenti
A
,
Loring
S
,
Gattinoni
L
,
Talmor
D
,
Blanch
L
,
Amato
M
,
Chen
L
,
Brochard
L
,
Mancebo
J
;
PLeUral pressure working Group (PLUG—Acute Respiratory Failure section of the European Society of Intensive Care Medicine)
:
Esophageal and transpulmonary pressure in the clinical setting: meaning, usefulness and perspectives.
Intensive Care Med
2016
;
42
:
1360
73
.
25.
Talmor
D
,
Sarge
T
,
Malhotra
A
,
O’Donnell
CR
,
Ritz
R
,
Lisbon
A
,
Novack
V
,
Loring
SH
:
Mechanical ventilation guided by esophageal pressure in acute lung injury.
N Engl J Med
2008
;
359
:
2095
104
.
26.
Yoshida
T
,
Amato
MBP
,
Grieco
DL
,
Chen
L
,
Lima
CAS
,
Roldan
R
,
Morais
CCA
,
Gomes
S
,
Costa
ELV
,
Cardoso
PFG
,
Charbonney
E
,
Richard
JM
,
Brochard
L
,
Kavanagh
BP
:
Esophageal manometry and regional transpulmonary pressure in lung injury.
Am J Respir Crit Care Med
2018
;
197
:
1018
26
.
27.
Akoumianaki
E
,
Maggiore
SM
,
Valenza
F
,
Bellani
G
,
Jubran
A
,
Loring
SH
,
Pelosi
P
,
Talmor
D
,
Grasso
S
,
Chiumello
D
,
Guérin
C
,
Patroniti
N
,
Ranieri
VM
,
Gattinoni
L
,
Nava
S
,
Terragni
PP
,
Pesenti
A
,
Tobin
M
,
Mancebo
J
,
Brochard
L
;
PLUG Working Group (Acute Respiratory Failure Section of the European Society of Intensive Care Medicine)
:
The application of esophageal pressure measurement in patients with respiratory failure.
Am J Respir Crit Care Med
2014
;
189
:
520
31
.
28.
Baydur
A
,
Behrakis
PK
,
Zin
WA
,
Jaeger
M
,
Milic-Emili
J
:
A simple method for assessing the validity of the esophageal balloon technique.
Am Rev Respir Dis
1982
;
126
:
788
91
.
29.
Pelosi
P
,
Goldner
M
,
McKibben
A
,
Adams
A
,
Eccher
G
,
Caironi
P
,
Losappio
S
,
Gattinoni
L
,
Marini
JJ
:
Recruitment and derecruitment during acute respiratory failure: an experimental study.
Am J Respir Crit Care Med
2001
;
164
:
122
30
.
30.
Agostoni
E
:
Mechanics of the pleural space.
Physiol Rev
1972
;
52
:
57
128
.
31.
Talmor
D
,
Sarge
T
,
O’Donnell
CR
,
Ritz
R
,
Malhotra
A
,
Lisbon
A
,
Loring
SH
:
Esophageal and transpulmonary pressures in acute respiratory failure.
Crit Care Med
2006
;
34
:
1389
94
.
32.
Guérin
C
,
Richard
JC
:
Comparison of 2 correction methods for absolute values of esophageal pressure in subjects with acute hypoxemic respiratory failure, mechanically ventilated in the ICU.
Respir Care
2012
;
57
:
2045
51
.
33.
Chiumello
D
,
Cressoni
M
,
Colombo
A
,
Babini
G
,
Brioni
M
,
Crimella
F
,
Lundin
S
,
Stenqvist
O
,
Gattinoni
L
:
The assessment of transpulmonary pressure in mechanically ventilated ARDS patients.
Intensive Care Med
2014
;
40
:
1670
8
.
34.
Grasso
S
,
Terragni
P
,
Birocco
A
,
Urbino
R
,
Del Sorbo
L
,
Filippini
C
,
Mascia
L
,
Pesenti
A
,
Zangrillo
A
,
Gattinoni
L
,
Ranieri
VM
:
ECMO criteria for influenza A (H1N1)-associated ARDS: Role of transpulmonary pressure.
Intensive Care Med
2012
;
38
:
395
403
.
35.
Staffieri
F
,
Stripoli
T
,
De Monte
V
,
Crovace
A
,
Sacchi
M
,
De Michele
M
,
Trerotoli
P
,
Terragni
P
,
Ranieri
VM
,
Grasso
S
:
Physiological effects of an open lung ventilatory strategy titrated on elastance-derived end-inspiratory transpulmonary pressure: study in a pig model*.
Crit Care Med
2012
;
40
:
2124
31
.
36.
Gulati
G
,
Novero
A
,
Loring
SH
,
Talmor
D
:
Pleural pressure and optimal positive end-expiratory pressure based on esophageal pressure versus chest wall elastance: Incompatible results*.
Crit Care Med
2013
;
41
:
1951
7
.
37.
Persson
P
,
Stenqvist
O
,
Lundin
S
:
Evaluation of lung and chest wall mechanics during anaesthesia using the PEEP-step method.
Br J Anaesth
2018
;
120
:
860
7
.
38.
Gattinoni
L
,
Pesenti
A
,
Avalli
L
,
Rossi
F
,
Bombino
M
:
Pressure-volume curve of total respiratory system in acute respiratory failure. Computed tomographic scan study.
Am Rev Respir Dis
1987
;
136
:
730
6
.
39.
Chiumello
D
,
Carlesso
E
,
Brioni
M
,
Cressoni
M
:
Airway driving pressure and lung stress in ARDS patients.
Crit Care
2016
;
20
:
276
.
40.
Bellani
G
,
Grassi
A
,
Sosio
S
,
Foti
G
:
Plateau and driving pressure in the presence of spontaneous breathing.
Intensive Care Med
2019
;
45
:
97
8
.
41.
Morais
CCA
,
Koyama
Y
,
Yoshida
T
,
Plens
GM
,
Gomes
S
,
Lima
CAS
,
Ramos
OPS
,
Pereira
SM
,
Kawaguchi
N
,
Yamamoto
H
,
Uchiyama
A
,
Borges
JB
,
Vidal Melo
MF
,
Tucci
MR
,
Amato
MBP
,
Kavanagh
BP
,
Costa
ELV
,
Fujino
Y
:
High positive end-expiratory pressure renders spontaneous effort noninjurious.
Am J Respir Crit Care Med
2018
;
197
:
1285
96
.
42.
Chiumello
D
,
Carlesso
E
,
Cadringher
P
,
Caironi
P
,
Valenza
F
,
Polli
F
,
Tallarini
F
,
Cozzi
P
,
Cressoni
M
,
Colombo
A
,
Marini
JJ
,
Gattinoni
L
:
Lung stress and strain during mechanical ventilation for acute respiratory distress syndrome.
Am J Respir Crit Care Med
2008
;
178
:
346
55
.
43.
Baedorf Kassis
E
,
Loring
SH
,
Talmor
D
:
Mortality and pulmonary mechanics in relation to respiratory system and transpulmonary driving pressures in ARDS.
Intensive Care Med
2016
;
42
:
1206
13
.
44.
Eichler
L
,
Truskowska
K
,
Dupree
A
,
Busch
P
,
Goetz
AE
,
Zöllner
C
:
Intraoperative ventilation of morbidly obese patients guided by transpulmonary pressure.
Obes Surg
2018
;
28
:
122
9
.
45.
Fumagalli
J
,
Berra
L
,
Zhang
C
,
Pirrone
M
,
Santiago
RRS
,
Gomes
S
,
Magni
F
,
Dos Santos
GAB
,
Bennett
D
,
Torsani
V
,
Fisher
D
,
Morais
C
,
Amato
MBP
,
Kacmarek
RM
:
Transpulmonary pressure describes lung morphology during decremental positive end-expiratory pressure trials in obesity.
Crit Care Med
2017
;
45
:
1374
81
.
46.
Bellani
G
,
Laffey
JG
,
Pham
T
,
Fan
E
,
Brochard
L
,
Esteban
A
,
Gattinoni
L
,
van Haren
F
,
Larsson
A
,
McAuley
DF
,
Ranieri
M
,
Rubenfeld
G
,
Thompson
BT
,
Wrigge
H
,
Slutsky
AS
,
Pesenti
A
;
LUNG SAFE Investigators; ESICM Trials Group
:
Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries.
JAMA
2016
;
315
:
788
800
.
47.
Aldenkortt
M
,
Lysakowski
C
,
Elia
N
,
Brochard
L
,
Tramèr
MR
:
Ventilation strategies in obese patients undergoing surgery: A quantitative systematic review and meta-analysis.
Br J Anaesth
2012
;
109
:
493
502
.
48.
Cortes-Puentes
GA
,
Keenan
JC
,
Adams
AB
,
Parker
ED
,
Dries
DJ
,
Marini
JJ
:
Impact of chest wall modifications and lung injury on the correspondence between airway and transpulmonary driving pressures.
Crit Care Med
2015
;
43
:
e287
95
.
49.
Keenan
JC
,
Cortes-Puentes
GA
,
Zhang
L
,
Adams
AB
,
Dries
DJ
,
Marini
JJ
:
PEEP titration: The effect of prone position and abdominal pressure in an ARDS model.
Intensive Care Med Exp
2018
;
6
:
3
.
50.
Pelosi
P
,
Vargas
M
:
Mechanical ventilation and intra-abdominal hypertension: “Beyond Good and Evil.”
Crit Care
2012
;
16
:
187
.
51.
Cinnella
G
,
Grasso
S
,
Spadaro
S
,
Rauseo
M
,
Mirabella
L
,
Salatto
P
,
De Capraris
A
,
Nappi
L
,
Greco
P
,
Dambrosio
M
:
Effects of recruitment maneuver and positive end-expiratory pressure on respiratory mechanics and transpulmonary pressure during laparoscopic surgery.
Anesthesiology
2013
;
118
:
114
22
.
52.
Loring
SH
,
Behazin
N
,
Novero
A
,
Novack
V
,
Jones
SB
,
O’Donnell
CR
,
Talmor
DS
:
Respiratory mechanical effects of surgical pneumoperitoneum in humans.
J Appl Physiol (1985)
2014
;
117
:
1074
9
.
53.
Brandao
JC
,
Lessa
MA
,
Motta-Ribeiro
G
,
Hashimoto
S
,
Paula
LF
,
Torsani
V
,
Le
L
,
Deng
H
,
Bao
X
,
Eikermann
M
,
Dahl
DM
,
Tabatabaei
S
,
Amato
MBP
,
Vidal Melo
MF
:
Global and regional respiratory mechanics during robotic-assisted laparoscopic surgery: A randomized study.
Anesth Analg
2019
.
(in press)
.
54.
Cortes-Puentes
GA
,
Gard
KE
,
Adams
AB
,
Faltesek
KA
,
Anderson
CP
,
Dries
DJ
,
Marini
JJ
:
Value and limitations of transpulmonary pressure calculations during intra-abdominal hypertension.
Crit Care Med
2013
;
41
:
1870
7
.
55.
Fernandez-Bustamante
A
,
Hashimoto
S
,
Serpa Neto
A
,
Moine
P
,
Vidal Melo
MF
,
Repine
JE
:
Perioperative lung protective ventilation in obese patients.
BMC Anesthesiol
2015
;
15
:
56
.
56.
Nestler
C
,
Simon
P
,
Petroff
D
,
Hammermüller
S
,
Kamrath
D
,
Wolf
S
,
Dietrich
A
,
Camilo
LM
,
Beda
A
,
Carvalho
AR
,
Giannella-Neto
A
,
Reske
AW
,
Wrigge
H
:
Individualized positive end-expiratory pressure in obese patients during general anaesthesia: A randomized controlled clinical trial using electrical impedance tomography.
Br J Anaesth
2017
;
119
:
1194
205
.
57.
Behazin
N
,
Jones
SB
,
Cohen
RI
,
Loring
SH
:
Respiratory restriction and elevated pleural and esophageal pressures in morbid obesity.
J Appl Physiol (1985)
2010
;
108
:
212
8
.