Does high PEEP prevent alveolar cycling?

  • M. CressoniEmail author
  • C. Chiurazzi
  • D. Chiumello
  • L. Gattinoni
Review articles


Acute respiratory distress syndrome (ARDS) patients need mechanical ventilation to sustain gas exchange. Animal experiments showed that mechanical ventilation with high volume/plateau pressure and no positive end-expiratory pressure (PEEP) damages healthy lungs, while low tidal volumes and the application of higher PEEP levels are protective. PEEP makes the lung homogeneous, reducing the pressure multiplication at the interface between lung units with different inflation statuses and keeps the lung open through the whole respiratory cycle, avoiding intratidal opening and closing. Four randomized clinical trials tested a higher PEEP strategy compared to a lower PEEP strategy but failed to show any survival benefit. These results, which apparently contradict preclinical data, may be explained by CT scanning, which investigates the behaviour of ARDS lung upon inflation and deflation demonstrating that: (1) 15 cmH2O PEEP is insufficient to overcome the closing pressures of the lung and keep it open through the whole respiratory cycle; (2) lung recruitment is continuous along the volume-pressure curve. The application of a PEEP level around 15 cmH2O does not abolish opening and closing, but the lung region undergoing opening and closing is simply shifted downward, i. e. becomes more vertebral in the supine patient. (3) Recruited lung tissue becomes poorly inflated and not well inflated; poorly inflated tissue is inhomogeneous: while increasing PEEP the reduction in lung inhomogeneity is small or non-existent.


Acute respiratory distress syndrome Respiration, artificial Ventilator-induced lung injury Collapse and decollapse Opening and closing 

Verhindert ein hoher PEEP den zyklischen Kollaps der Alveolen?


Patienten mit akutem Lungenversagen („acute respiratory distress syndrome“ [ARDS]) müssen beatmet werden, um den Gasaustausch aufrechtzuerhalten. Tierversuche belegen, dass eine Beatmung mit hohen Atemzugvolumina bzw. hohem Plateaudruck und ohne positiven endexspiratorischen Druck (PEEP) die gesunde Lunge schädigt, während niedrige Atemzugvolumina und die Anwendung eines hohen PEEP protektiv wirken. Der PEEP sorgt für einen homogenen Zustand der Lunge, indem er die starke Druckerhöhung an Grenzflächen zwischen Lungenabschnitten mit unterschiedlich starker Belüftung verringert. Zudem hält er die Lunge über den gesamten Atemzyklus hinweg offen und vermeidet ein intratidales Öffnen und Schließen. In vier randomisierten klinischen Studien wurden Beatmungsstrategien mit hohem und niedrigem PEEP verglichen. Ein Überlebensvorteil konnte aber nicht belegt werden. Diese Ergebnisse widersprechen offensichtlich präklinischen Daten und könnten mithilfe computertomographischer Untersuchungen zum Verhalten der ARDS-Lunge bei Be- und Entlüftung erklärt werden. Hier zeigt sich: 1. Ein PEEP von 15 cmH2O reicht nicht aus, um die Verschlussdrücke der Lunge zu überwinden und die Lunge über den gesamten Atemzyklus offen zu halten; 2. Die Lungenrekrutierung nimmt entlang der Volumen-Druck-Kurve einen kontinuierlichen Verlauf. Mit einem PEEP von etwa 15 cmH2O lässt sich das Öffnen und Schließen nicht unterbinden. Der sich öffnende und schließende Lungenabschnitt wird schlicht nach unten verschoben, das heißt, er wird bei einem Patienten in Rückenlage vertebraler. 3. Rekrutiertes Lungengewebe wird nicht etwa gut, sondern schlecht belüftet. Schlecht belüftetes Gewebe ist inhomogen; bei Erhöhung des PEEP nimmt die Lungeninhomogenität nur geringfügig oder gar nicht ab.


Akutes Lungenversagen Beatmung Beatmungsinduzierter Lungenschaden Kollaps und Wiedereröffnung Öffnen und Schließen 


Acute respiratory distress syndrome (ARDS) is characterized by widespread lung inflammation with permeability alteration of the lung microvasculature and edema involving the whole lung parenchyma [2, 31, 38]. No etiologic treatment is available and supportive treatment with mechanical ventilation is associated with a mortality rate of up to 43% in severe ARDS [3]. The causes of mortality in ARDS patients are still debated, but hypoxemia is the leading cause of death in a minority of cases [37]. In most patients with unfavorable outcome the lung does not heal, but the persistence of the inflammatory process leads to widespread lung fibrosis [29] and the patient cannot be weaned from the ventilator. Some authors have shown that the inflamed lung releases cytokines into the blood stream, possibly leading to multi-organ failure [7, 34]. There is extensive experimental evidence that mechanical ventilation itself can damage healthy lungs [15, 19, 26]. Several theories to explain the possible mechanisms of lung damage in healthy and diseased lungs have been proposed over the years [17, 19]. Most of the literature accepts that excessive stress and strain (barotrauma and volutrauma) in healthy lungs [8] lead to mechanical rupture of lung parenchyma and activation of inflammatory cascade [7]. In contrast, a diseased lung is non-homogeneous on the small scale, presenting lung regions with different inflation statuses. Consequently, in the ARDS lung, two additional disease mechanisms apply: pressure multiplication at the interface between lung regions with different inflation statuses [13, 15, 27] and intratidal collapse/decollapse [32]. Mead showed that the applied pressure is regionally multiplied at the interface between lung regions with different inflation statuses [7, 13]. A second possible mechanism of ventilator-induced lung injury (VILI) in a diseased lung is intratidal collapse and decollapse of lung units (atelecrauma) [32, 38], which may be seen both as an extension of the Mead model or a different disease mechanism. Lung damage may occur at the small airway level where the applied pressure acts on the fluid meniscus, accelerating it towards the alveoli and damaging the epithelium [23]. A series of rat experiments showed that when the lungs were allowed to cyclically collapse and re-inflate, serious histological lung damage occurred [32], associated with cytokine release [7].

High PEEP mechanisms

Intratidal collapse and decollapse is almost unavoidable in ARDS, as it is related to the pathophysiology of the disease and, in particular, to the mechanism of lung collapse. The edematous lung becomes heavy and collapses under its own weight [14, 33]. The dependent (vertebral) lung regions become gasless, while the non-dependent ones (sternal), even if they are edematous, remain inflated [33]. If the patient is positioned prone, the verterbral lung regions become non-dependent and re-inflate, while the sternal ones become dependent and collapse [20]. PEEP (positive end-expiratory pressure) works by overcoming the superimposed pressure and keeping open whatever lung region had been opened during the previous inspiration [21].

When a tidal volume/plateau pressure are applied, they overcome the surface forces at the level of the small airways and open up the previously collapsed lung units [18]. Fig. 1 shows the effect of different tidal volumes, and consequently opening pressures on a collapsed ARDS lung ventilated at zero end-expiratory pressure (ZEEP). The amount of collapsed lung tissue that regains inflation depends on the plateau pressure/tidal volume applied, and the greater the applied plateau pressure, the greater the amount of lung tissue undergoing intratidal collapse and decollapse [18].
Fig. 1

Effects of plateau pressure—no PEEP (positive end-expiratory pressure). The effects of different plateau pressures/tidal volumes on intratidal collapse and decollapse on a near completely collapsed ARDS lung. As shown, while increasing the plateau pressure/tidal volume the amount of tissue undergoing collapse/decollapse (light blue) increases

PEEP mechanism

PEEP acts on the closing pressures of the lung: at the end of inspiration the lung tissue collapses under its own weight. If an external counter-pressure is applied from the airways, the lung and this pressure is greater than the superimposed pressure and at least part of the lung parenchyma will be kept open through the respiratory cycle [21]. If we apply a PEEP to the model lung described above, part of the lung will be kept open and the fraction of the lung undergoing intratidal collapse and decollapse will be reduced (Fig. 2a). If the applied PEEP is increased in a model of “higher PEEP,” a further reduction in intratidal collapse and decollapse is expected (Fig. 2b). To summarize, higher PEEP keeps the lung open through the whole respiratory cycle, reducing opening and closing; in turn, the reduction in opening and closing would reduce VILI and improve patient survival.
Fig. 2

Effect of PEEP. a The effect of adding a low PEEP level to the lung model shown in Fig. 1. As shown, part of the lung parenchyma would always be kept open through the respiratory cycle (gray), while the lung region undergoing intratidal opening and closing (light blue) should be reduced. b The putative effect of adding a higher PEEP level to the lung model shown in Fig. 1. As shown, a greater part of the lung parenchyma would be always kept open through the respiratory cycle compared to a lower PEEP model (gray), while the lung region undergoing intra-tidal opening and closing (light blue) should be reduced

The open lung theory and the lung protective strategy

The possible clinical translation of the experimental results, considering both the effects of high pressures/tidal volumes and intratidal collapse and decollapse can be summarized in the “lung protective strategy.” The lung protective strategy prescribes low tidal volumes to reduce lung stress and strain and high PEEP to make the lung homogeneous and abolish intra-tidal opening and closing. This strategy, as a whole, was tested in two randomized clinical trials, a small one by Amato [1] and a larger one by Villar et al. [40], both showing improved survival in the treatment arm. When the effects of tidal volume and PEEP were separated, tidal volume reduction was associated with improved survival [36], while higher PEEP was not [6, 28, 30, 41]. The ARDS network trial showed that 6 ml/Kg ideal body weight compared with 12 ml/Kg ideal body weight led a 10% reduction of mortality [36] and 6 ml/Kg is now recommended for the mechanical ventilation setting. Higher PEEP (approximately 15 cmH2O) was compared with lower PEEP (approximately 8 cmH2O or 13 cmH2O in the ART trial) in four randomized clinical trials enrolling 3264 patients (1010 in the ART trial [27] and 2264 in the ALVEOLI [6], ExPress [30], and LOV [28] trials). Average PEEP levels applied in randomized clinical trials are summarized in Table 1. None of the trials showed improved survival in the higher PEEP group even if meta-analyses of the first three trials (ALVEOLI, LOV, ExPress) suggested a survival benefit in the more sick patients [5]. The ART trial [41], surprisingly, gave the paradoxical result of increased mortality in the higher PEEP group.
Table 1

PEEP levels used in randomized clinical trials at day 1. Table 1 summarizes the PEEP levels (cmH2O) applied in randomized clinical trials at day 1. Data represent mean and standard deviation except for the ART trial, where they are reported as mean and 95% confidence interval


Lower PEEP group

Higher PEEP group


N Engl J Med 2004;351:327–36 [6]

8.9 ± 3.5

14.7 ± 3.5


JAMA.2008;299(6):637–645 [28]

10.1 ± 3

15.6 ± 3.9


JAMA.2008;299(6):646–655 [30]

7.1 ± 1.8

14.6 ± 3.2

ART trial

JAMA.2017, Sept 27 [41]





Bedside implementation of PEEP setting strategy

Several possible explanations for the failure of higher PEEP to provide increased survival have been proposed. A first possibility is that the random application of higher PEEP levels in an unselected patient population led to a reduction in intra-tidal collapse and decollapse in patients with higher recruitability and overdistension and damage in lower recruiters [22]. This hypothesis is supported by the results of meta-analyses that showed a possible benefit for higher PEEP in more severe and hypoxemic patients, who, putatively, have the greatest recruitability [5, 24]. The PEEP mechanism in protecting patients from VILI consists inabolishing lung inhomogeneity [15, 27] and opening and closing [32], which both target the anatomical lung status. These phenomena are not visible at the bedside and the better ventilatory treatment to heal the lung is not necessarily mirrored by an improvement in the parameters directly observable by the physician. Patients in the treatment group of the ARDS Network [36] that had lower mortality presented with worse oxygenation, higher carbon dioxide tension, and lower compliance (see Table 2). An extreme example of what could have happened in the control group of the ARDS network is shown in Fig. 3, where end-expiratory and end-inspiratory CT scans of an experimental ARDS model are shown [15]. The lung is completely collapsed at end-expiration, but re-inflates completely at end-inspiration. PaO2/FiO2 was 365 ± 160, PaCO2 17 ± 7 mm Hg, and pH 7.53 ± 0.17 as gas exchange occurred during tidal ventilation but the ventilatory setting was lethal and the lung became unventilable within a few hours [15]. All these data taken together suggest that inflation-based methods like lung mechanics (applied in the Express trial, [30], stress-index [25], lung ultrasound [4], electrical impedance tomography [EIT], [12], or the absolute esophageal pressure values [9, 35]) do not target the underlying pathophysiology and, in randomized clinical trials, did not select the patients who needed higher PEEP. The lung mechanics-based methods tend to select higher PEEP in less severe patients [9]. This may be relevant in explaining the results of the ART trial where PEEP was selected according to lung compliance, even if the PEEP difference in the two groups was limited to few cmH2O. Oxygenation-based methods (applied in the LOV [28] and ALVEOLI [6] trials) are roughly related to recruitability [9], but the sensibility and specificity in predicting recruitability is poor [22]. A second possible explanation for the failure of higher PEEP in improving survival is the possible detrimental effects of high PEEP on the right heart. High pressure levels during ventilation lead to the development of West zone 2 with increased shunt, dead space, and right ventricle afterload [39], leading to both the need to increase mechanical ventilation/power on the lung to maintain gas exchange and hemodynamic failure.
Table 2

Bedside variables in lower and higher tidal volume groups of the ARDS Network study. Table 2 summarizes data of PaO2/FiO2, PaCO2, and compliance of the respiratory system in the ARDS network trial (New England Journal of Medicine, 2000 [36]). Compliance of the respiratory system is computed from the averages presented in Table 3 of the original manuscript as: (minute ventilation/respiratory rate)/(plateau pressure—PEEP)


Low tidal volume group

High tidal volume group


158 ± 73

176 ± 76

PaCO2 (mm Hg)

40 ± 10

35 ± 8

Respiratory system compliance (ml/cmH2O)



Fig. 3

Dissociation between bedside data and ventilator-induced lung injury. Fig. 3 presents the end-expiratory and end-inspiratory CT scans of an experimental model of ARDS ventilated with a tidal volume close to the total lung capacity, which is always lethal within 54 h (Cressoni, Anesthesiology, [15]). PaO2/FiO2 was 365 ± 160, PaCO2 17 ± 7 (cmH2O), and pH 7.53 ± 0.17

Is opening and closing real and what is the “real” effect of PEEP?

As clinical trials failed to show any clear survival benefit, one may wonder whether the “opening and closing” theory is real or if it is a mechanism occurring only in some experimental models, mainly rats [32]. Direct proof of VILI is nearly impossible to obtain in “real” ARDS patients, but a recent PET study [16] showed that the non-homogeneous lung regions at the interface between collapsed and inflated lung tissue, where putatively intra-tidal collapse and decollapse occur, are always inflamed.

Despite the relevance of the issue of opening and closing, just two studies measured intra-tidal collapse and decollapse at two different PEEP levels keeping the tidal volume constant and both were unable to demonstrate a significant intra-tidal collapse and decollapse reduction [11, 18]. We measured intra-tidal collapse and decollapse in 34 ARDS patients (18 severe ARDS) keeping the tidal volume constant at two PEEP levels, 5 and 15, which are close to the PEEP levels applied in all clinical trials. Intra-tidal collapse and decollapse was similar at the two PEEP levels (see Fig. 4) and this pattern was similar independently of ARDS severity [18]. The absolute and percentage amount of collapse and decollapse increased with ARDS severity, but the effect of PEEP was similar in the three groups [18].
Fig. 4

Effect of higher and lower PEEP on intra-tidal collapse and decollapse at constant tidal volume in 34 ARDS patients. The amount of intra-tidal collapse and decollapse (gram of lung tissue) at PEEP 5 and 15 cmH2O as mean and standard deviation, keeping the tidal volume constant. Data are taken from 34 ARDS patients published in Cressoni, Intensive Care Medicine [18]

In fact, when a high PEEP is applied keeping the tidal volume unchanged, two different phenomena occur simultaneously: first, the increased PEEP level keeps open a greater fraction of lung parenchyma located in the more dependent lung regions; second, at the same time, the tidal volume opens up some lung regions in the more dependent lung, shifting downwards the area of intra-tidal collapse and decollapse (Fig. 5). This explains why higher PEEP do not abolish intra-tidal collapse and decollapse.
Fig. 5

The “real” effect of higher PEEP. A lung model of lower and higher PEEP: as shown with higher PEEP, the region of intra-tidal collapse and decollapse is shifted downwards in the more dependent lung region

The second assumption beyond the use of higher PEEP is that the lung would become more homogeneous upon recruitment. This would happen in a pure atelectasis model where all recruited lung units would re-gain normal gas/tissue status and normal mechanical properties; in ARDS, this does not happen, as the recruited lung units mainly become poorly inflated [10]. Upon recruitment, especially in the more severe patients, one may see an increase in poorly inflated tissue, [10], which is strongly related to the lung inhomogeneity [15]. The lung inhomogeneity itself is not completely abolished, but is slightly reduced or may paradoxically increase [18].


In conclusion, the application of 15 cmH2O PEEP does not reduce intra-tidal collapse and decollapse and lung inhomogeneity [18]. In consequence, the “open lung strategy” has never been tested as a whole in the published randomized clinical trials. One may wonder how a mechanical ventilation protocol aimed at the “open lung strategy” should be designed and if it would reduce mortality, as the effect on lung inhomogeneity is limited/non-existent [10, 13, 18]. To really apply the “open lung” strategy, a PEEP level sufficient to overcome the lung superimposed pressure [14, 21, 33], to keep the lung parenchyma open thorough the whole respiratory cycle, and to lift the chest wall is needed [9, 14]. This PEEP level would be around 20 cmH2O, [14] greater than the one applied in clinical trials and higher than the one selected by the absolute esophageal pressure [9]. A recruitment maneuver performed at 45 cmH2O should completely open up the lung and a PEEP around 20 cmH2O should keep it open. Afterwards, one should set a tidal volume, perhaps keeping a plateau pressure limit of 30 cmH2O (i. e., allowing for a driving pressure up to 10 cmH2O). Two questions remain unsolved: first, what would happen to the lung units with opening pressure between 30 and 45 cmH2O: would they stay open as PEEP overcomes their closing pressure or collapse again in the next few breaths? Second, would the tidal volume be sufficient to allow carbon dioxide removal?


Compliance with Ethical Guidelines

Conflict of interest

M. Cressoni and L. Gattinoni hold an Italian patent (0001409041) and US patent (14/364,551) for the determination of lung inhomogeneities. C. Chiurazzi and D. Chiumello declare that they have no competing interests.

This article does not contain any studies with human participants or animals performed by any of the authors.

The supplement containing this article is not sponsored by industry.


  1. 1.
    Amato MB, Barbas CS, Medeiros DM et al (1998) Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 338(6):347–354CrossRefPubMedGoogle Scholar
  2. 2.
    ARDS Definition Task Force, Ranieri VM, Rubenfeld GD et al (2012) Acute respiratory distress syndrome: the Berlin Definition. JAMA 307(23):2526–2533Google Scholar
  3. 3.
    Bellani G, Laffey JG, Pham T et al (2016) Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA 315(8):788–800CrossRefPubMedGoogle Scholar
  4. 4.
    Bouhemad B, Brisson H, Le-Guen M et al (2011) Bedside ultrasound assessment of positive end-expiratory pressure-induced lung recruitment. Am J Respir Crit Care Med 183(3):341–347CrossRefPubMedGoogle Scholar
  5. 5.
    Briel M, Meade M, Mercat A et al (2010) Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA 303(9):865–873CrossRefPubMedGoogle Scholar
  6. 6.
    Brower RG, Lanken PN, MacIntyre N et al (2004) Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med 351(4):327–336CrossRefPubMedGoogle Scholar
  7. 7.
    Chiumello D, Pristine G, Slutsky AS (1999) Mechanical ventilation affects local and systemic cytokines in an animal model of acute respiratory distress syndrome. Am J Respir Crit Care Med 160(1):109–116CrossRefPubMedGoogle Scholar
  8. 8.
    Chiumello D, Carlesso E, Cadringher P et al (2008) Lung stress and strain during mechanical ventilation for acute respiratory distress syndrome. Am J Respir Crit Care Med 178(4):346–355CrossRefPubMedGoogle Scholar
  9. 9.
    Chiumello D, Cressoni M, Carlesso E et al (2014) Bedside selection of positive end-expiratory pressure in mild, moderate, and severe acute respiratory distress syndrome. Crit Care Med 42(2):252–264. CrossRefPubMedGoogle Scholar
  10. 10.
    Chiumello D, Marino A, Brioni M et al (2016) Lung recruitment assessed by respiratory mechanics and computed tomography in patients with acute respiratory distress syndrome. What is the relationship? Am J Respir Crit Care Med 193(11):1254–1263CrossRefPubMedGoogle Scholar
  11. 11.
    Cornejo RA, Díaz JC, Tobar EA et al (2013) Effects of prone positioning on lung protection in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 188(4):440–448CrossRefPubMedGoogle Scholar
  12. 12.
    Costa ELV, Borges JB, Melo A et al (2009) Bedside estimation of recruitable alveolar collapse and hyperdistension by electrical impedance tomography. Intensive Care Med 35(6):1132–1137CrossRefPubMedGoogle Scholar
  13. 13.
    Cressoni M, Cadringher P, Chiurazzi C et al (2014) Lung inhomogeneity in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 189(2):149–158PubMedGoogle Scholar
  14. 14.
    Cressoni M, Chiumello D, Carlesso E et al (2014) Compressive forces and computed tomography-derived positive end-expiratory pressure in acute respiratory distress syndrome. Anesthesiology 121(3):572–581CrossRefPubMedGoogle Scholar
  15. 15.
    Cressoni M, Chiurazzi C, Gotti M et al (2015) Lung inhomogeneities and time course of ventilator-induced mechanical injuries. Anesthesiology 123(3):618–627. CrossRefPubMedGoogle Scholar
  16. 16.
    Cressoni M, Chiumello D, Chiurazzi C et al (2016) Lung inhomogeneities, inflation and [18F]2-fluoro-2-deoxy-D-glucose uptake rate in acute respiratory distress syndrome. Eur Respir J 47(1):233–242CrossRefPubMedGoogle Scholar
  17. 17.
    Cressoni M, Gotti M, Chiurazzi C et al (2016) Mechanical power and development of ventilator-induced lung injury. Anesthesiology 124(5):1100–1106. CrossRefPubMedGoogle Scholar
  18. 18.
    Cressoni M, Chiumello D, Algieri I et al (2017) Opening pressures and atelectrauma in acute respiratory distress syndrome. Intensive Care Med 43(5):603–611CrossRefPubMedGoogle Scholar
  19. 19.
    Dreyfuss D, Saumon G (1998) Ventilator-induced lung injury: lessons from experimental studies. Am J Respir Crit Care Med 157(1):294–323CrossRefPubMedGoogle Scholar
  20. 20.
    Gattinoni L, Pelosi P, Vitale G et al (1991) Body position changes redistribute lung computed-tomographic density in patients with acute respiratory failure. Anesthesiology 74(1):15–23CrossRefPubMedGoogle Scholar
  21. 21.
    Gattinoni L, D’Andrea L, Pelosi P et al (1993) Regional effects and mechanism of positive end-expiratory pressure in early adult respiratory distress syndrome. JAMA 269(16):2122–2127CrossRefPubMedGoogle Scholar
  22. 22.
    Gattinoni L, Caironi P, Cressoni M et al (2006) Lung recruitment in patients with the acute respiratory distress syndrome. N Engl J Med 354(17):1775–1786CrossRefPubMedGoogle Scholar
  23. 23.
    Ghadiali SN, Gaver DP (2008) Biomechanics of liquid-epithelium interactions in pulmonary airways. Respir Physiol Neurobiol 163(1–3):232–243CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Goligher EC, Kavanagh BP, Rubenfeld GD et al (2014) Oxygenation response to positive end-expiratory pressure predicts mortality in acute respiratory distress syndrome. A secondary analysis of the LOVS and ExPress trials. Am J Respir Crit Care Med 190(1):70–76CrossRefPubMedGoogle Scholar
  25. 25.
    Grasso S, Terragni P, Mascia L et al (2004) Airway pressure-time curve profile (stress index) detects tidal recruitment/hyperinflation in experimental acute lung injury. Crit Care Med 32(4):1018–1027CrossRefPubMedGoogle Scholar
  26. 26.
    Kolobow T, Moretti MP, Fumagalli R et al (1987) Severe impairment in lung function induced by high peak airway pressure during mechanical ventilation. An experimental study. Am Rev Respir Dis 135(2):312–315PubMedGoogle Scholar
  27. 27.
    Mead J, Takishima T, Leith D (1970) Stress distribution in lungs: a model of pulmonary elasticity. J Appl Physiol 28(5):596–608CrossRefPubMedGoogle Scholar
  28. 28.
    Meade MO, Cook DJ, Guyatt GH et al (2008) Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA 299(6):637–645CrossRefPubMedGoogle Scholar
  29. 29.
    Meduri GU, Tolley EA, Chinn A, Stentz F, Postlethwaite A (1998) Procollagen types I and III aminoterminal propeptide levels during acute respiratory distress syndrome and in response to methylprednisolone treatment. Am J Respir Crit Care Med 158(5 Pt 1):1432–1441CrossRefPubMedGoogle Scholar
  30. 30.
    Mercat A, J‑CM R, Vielle B et al (2008) Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA 299(6):646–655CrossRefPubMedGoogle Scholar
  31. 31.
    Monnet X, Anguel N, Osman D et al (2007) Assessing pulmonary permeability by transpulmonary thermodilution allows differentiation of hydrostatic pulmonary edema from ALI/ARDS. Intensive Care Med 33(3):448–453CrossRefPubMedGoogle Scholar
  32. 32.
    Muscedere JG, Mullen JB, Gan K, Slutsky AS (1994) Tidal ventilation at low airway pressures can augment lung injury. Am J Respir Crit Care Med 149(5):1327–1334CrossRefPubMedGoogle Scholar
  33. 33.
    Pelosi P, D’Andrea L, Vitale G, Pesenti A, Gattinoni L (1994) Vertical gradient of regional lung inflation in adult respiratory distress syndrome. Am J Respir Crit Care Med 149(1):8–13CrossRefPubMedGoogle Scholar
  34. 34.
    Ranieri VM, Suter PM, Tortorella C et al (1999) Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial. JAMA 282(1):54–61CrossRefPubMedGoogle Scholar
  35. 35.
    Talmor D, Sarge T, Malhotra A et al (2008) Mechanical ventilation guided by esophageal pressure in acute lung injury. N Engl J Med 359(20):2095–2104CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    The Acute Respiratory Distress Syndrome Network (2000) 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 342(18):1301–1308CrossRefGoogle Scholar
  37. 37.
    Thille AW, Esteban A, Fernández-Segoviano P et al (2013) Comparison of the Berlin definition for acute respiratory distress syndrome with autopsy. Am J Respir Crit Care Med 187(7):761–767CrossRefPubMedGoogle Scholar
  38. 38.
    Thompson BT, Chambers RC, Liu KD (2017) Acute respiratory distress syndrome. N Engl J Med 377(6):562–572CrossRefPubMedGoogle Scholar
  39. 39.
    Vieillard-Baron A, Matthay M, Teboul JL et al (2016) Experts’ opinion on management of hemodynamics in ARDS patients: focus on the effects of mechanical ventilation. Intensive Care Med 42(5):739–749CrossRefPubMedGoogle Scholar
  40. 40.
    Villar J, Kacmarek RM, Pérez-Méndez L, Aguirre-Jaime A (2006) A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: a randomized, controlled trial. Crit Care Med 34(5):1311–1318CrossRefPubMedGoogle Scholar
  41. 41.
    Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) Investigators (2017) Effect of lung recruitment and titrated positive end-expiratory pressure (peep) vs low peep on mortality in patients with acute respiratory distress syndrome: A randomized clinical trial. JAMA. Google Scholar

Copyright information

© Springer Medizin Verlag GmbH 2017

Authors and Affiliations

  • M. Cressoni
    • 1
    Email author
  • C. Chiurazzi
    • 2
  • D. Chiumello
    • 1
    • 3
  • L. Gattinoni
    • 4
  1. 1.Dipartimento di Scienze della SaluteUniversità degli Studi di MilanoMilanoItaly
  2. 2.Department of Anesthesiology and Intensive Care MedicineHumanitas Clinical and Research CenterRozzano, MilanoItaly
  3. 3.SC Anestesia e RianimazioneASST Santi Paolo e CarloMilanItaly
  4. 4.Department of Anesthesiology, Emergency and Intensive Care MedicineUniversity of GöttingenGöttingenGermany

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