Correspondence  |   May 2007
Lower Tidal Volumes and Positive End-expiratory Pressure Prevents Alveolar Coagulation in Patients without Lung Injury
Author Notes
  • University of Louisville, Louisville, Kentucky.
Article Information
Correspondence   |   May 2007
Lower Tidal Volumes and Positive End-expiratory Pressure Prevents Alveolar Coagulation in Patients without Lung Injury
Anesthesiology 5 2007, Vol.106, 1065-1066. doi:10.1097/01.anes.0000265178.21114.9d
Anesthesiology 5 2007, Vol.106, 1065-1066. doi:10.1097/01.anes.0000265178.21114.9d
To the Editor:—
I read with interest the excellent article by Choi et al.  1 about the preventive role of mechanical ventilation, with lower tidal volumes plus positive end-expiratory pressure (PEEP), on alveolar coagulation. They demonstrated that mechanical ventilation with lower tidal volumes and PEEP (10 cm H2O) decreases the procoagulant activity in the lungs of even otherwise healthy surgical patients. The observed procoagulant activity change was explained by mechanical ventilation with high tidal volume and no PEEP. In previous studies, the same researchers and others showed that there were similar pulmonary hemostasis disturbances in patients with adult respiratory distress syndrome and pneumonia. Although much is unknown about the topic, the authors gave a detailed discussion as to whether this procoagulant activity is a possible sign of repair or a further trigger of proinflammatory process in the lung.
If we exclude this important work by Choi et al.  , the recent literature provides conflicting evidence on the role of high-tidal volume with no PEEP in causing ventilator-associated lung injury in healthy human lungs.2–4 Possibly because of the short amount of time that mechanical ventilation is provided during general anesthesia, it was hard to see any clinical effects of potential lung stretch in relatively healthy human lungs. Another explanation would be that high-tidal-volume ventilation alone is not a sufficient trigger to cause lung injury in healthy human lungs. Two recent articles from Wrigge et al.  4,5 support the latter explanation. Accepting this, one can hypothesize that mechanical ventilation with high tidal volumes without PEEP does not initiate any tissue injury that can be monitored by proinflammatory cytokine response.
However, when we take the article by Choi et al.  into account and further consider the bidirectional relation between coagulation and inflammation in pathogenesis of vascular disease as well summarized previously by Levi et al.  ,6 we realize that there are different questions to be asked and various hypotheses to be made to fully understand the mechanism of ventilator-associated lung injury in previously healthy subjects. For example, what might be the absolute first trigger to initiate stretch injury in the lungs? As in the vascular pathophysiology, is it the direct stretch of mononuclear cells (in this case alveolar macrophages) that triggers the proinflammatory or procoagulant pathways? Is it a set of proinflammatory cytokines originating from the alveolar macrophages (or even epithelial cells) triggering the procoagulant process in the lungs? Can such processes be triggered by lung cellular stretch through the activation of integrin–mitogen-activated protein kinase–interleukin-8 pathway, which would lead to further chemokine responses?7,8 Or do any of the toll-like receptors play a triggering role in initiating transcriptional processes through nuclear factor κB to deliver proinflammatory pathways including tumor necrosis factor α or interleukin 1β? Can it be that high-tidal-volume, no-PEEP ventilation cancels the alveolar integrity and stability of alveolar macrophages maintained by transforming growth factor β?9 
The sequence of triggers would bring the real mechanisms behind the ventilator-associated lung injury and associated lung injury. Therefore, it is extremely important to understand the sequence of triggers and potential pathways. At this point, if Choi et al.  performed any other tests in the bronchoalveolar lavage samples, such as proinflammatory cytokines, chemokines, or any transcriptional pathway agents, simultaneously with their procoagulant tests, it would be valuable to share such data for further development of new hypotheses to test the bidirectional relation between coagulation and inflammation.
University of Louisville, Louisville, Kentucky.
The author thanks Nancy Alsip, Ph.D. (University of Louisville, Louisville, Kentucky), for editorial assistance.
Choi G, Wolthuis EK, Bresser P, Levi M, van der Poll T, Dzoljic M, Vroom MB, Schultz MJ: Mechanical ventilation with lower tidal volumes and positive end-expiratory pressure prevents alveolar coagulation in patients without lung injury. Anesthesiology 2006; 105:689–95Choi, G Wolthuis, EK Bresser, P Levi, M van der Poll, T Dzoljic, M Vroom, MB Schultz, MJ
Gajic O, Dara SI, Mendez JL, Adesanya AO, Festic E, Caples SM, Rana R, St Sauver JL, Lymp JF, Afessa B, Hubmayr RD: Ventilator-associated lung injury in patients without acute lung injury at the onset of mechanical ventilation. Crit Care Med 2004; 32:1817–24Gajic, O Dara, SI Mendez, JL Adesanya, AO Festic, E Caples, SM Rana, R St Sauver, JL Lymp, JF Afessa, B Hubmayr, RD
Bregeon F, Roch A, Delpierre S, Ghigo E, Autillo-Touati A, Kajikawa O, Martin TR, Pugin J, Portugal H, Auffray JP, Jammes Y: Conventional mechanical ventilation of healthy lungs induced pro-inflammatory cytokine gene transcription. Respir Physiol Neurobiol 2002; 132:191–203Bregeon, F Roch, A Delpierre, S Ghigo, E Autillo-Touati, A Kajikawa, O Martin, TR Pugin, J Portugal, H Auffray, JP Jammes, Y
Wrigge H, Uhlig U, Zinserling J, Behrends-Callsen E, Ottersbach G, Fischer M, Uhlig S, Putensen C: The effects of different ventilatory settings on pulmonary and systemic inflammatory responses during major surgery. Anesth Analg 2004; 98:775–81Wrigge, H Uhlig, U Zinserling, J Behrends-Callsen, E Ottersbach, G Fischer, M Uhlig, S Putensen, C
Wrigge H, Uhlig U, Baumgarten G, Menzenbach J, Zinserling J, Ernst M, Dromann D, Welz A, Uhlig S, Putensen C: Mechanical ventilation strategies and inflammatory responses to cardiac surgery: A prospective randomized clinical trial. Intensive Care Med 2005; 31:1379–87Wrigge, H Uhlig, U Baumgarten, G Menzenbach, J Zinserling, J Ernst, M Dromann, D Welz, A Uhlig, S Putensen, C
Levi M, van der Poll T, Buller HR: Bidirectional relation between inflammation and coagulation. Circulation 2004; 109:2698–704Levi, M van der Poll, T Buller, HR
Goodman RB, Pugin J, Lee JS, Matthay MA: Cytokine-mediated inflammation in acute lung injury. Cytokine Growth Factor Rev 2003; 14:523–35Goodman, RB Pugin, J Lee, JS Matthay, MA
Pugin J: Molecular mechanisms of lung cell activation induced by cyclic stretch. Crit Care Med 2003; 31:S200–6Pugin, J
Pittet JF, Griffiths MJ, Geiser T, Kaminski N, Dalton SL, Huang X, Brown LA, Gotwals PJ, Koteliansky VE, Matthay MA, Sheppard D: TGF-beta is a critical mediator of acute lung injury. J Clin Invest 2001; 107:1537–44Pittet, JF Griffiths, MJ Geiser, T Kaminski, N Dalton, SL Huang, X Brown, LA Gotwals, PJ Koteliansky, VE Matthay, MA Sheppard, D