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Editorial Views  |   February 2007
Recruitment in Pulmonary and Extrapulmonary Acute Respiratory Distress Syndrome: The End of a Myth?
Author Notes
  • Anesthesiology and Critical Care Medicine, University of Paris 6, Paris, France.
Article Information
Editorial Views / Critical Care / Respiratory System
Editorial Views   |   February 2007
Recruitment in Pulmonary and Extrapulmonary Acute Respiratory Distress Syndrome: The End of a Myth?
Anesthesiology 2 2007, Vol.106, 203-204. doi:
Anesthesiology 2 2007, Vol.106, 203-204. doi:
IN this issue of Anesthesiology, Thille and an international group of coworkers recognized for their expertise in acute respiratory distress syndrome (ARDS) bring convincing evidence that positive end-expiratory pressure-induced alveolar recruitment does not differ between patients with pulmonary and extrapulmonary ARDS.1 The authors recommend that the origin of ARDS should not influence selecting the appropriate positive end-expiratory pressure level: The recruitability of the lungs seems similar in pneumonia, aspiration, inhalation injury, alveolar hemorrhage, pulmonary contusion and secondary lung injury resulting from sepsis, acute pancreatitis, multiple trauma, cardiopulmonary bypass, and massive transfusion.
This multicenter study contradicts the classic and widespread belief that ARDS from primary pulmonary causes is less responsive to positive end-expiratory pressure, prone position, and recruitment maneuvers than ARDS from extrapulmonary causes2 and outlines some of the methodologic bias originally involved in generation of this belief. Initially, two studies suggested that lung recruitment obtained by increasing intrathoracic pressure resulting from prone positioning was substantially lower in patients with direct injury to the lung compared with patients with secondary lung injury.2,3 In both studies, recruitment was measured using the quasi-static compliance method, a method that entails a risk of underestimating alveolar recruitment and changes in respiratory mechanics, as pointed out by Thille et al.  1 In the second study reporting different arterial oxygen response to prone positioning between primary and secondary ARDS, the difference in arterial oxygenation, although statistically significant, was of small magnitude and of questionable clinical significance.3 In addition, questions can be raised regarding the statistical analysis.3 A third study, performed in five patients with ARDS caused by severe pneumonia and five patients with extrapulmonary ARDS, reported that lung recruitment after three consecutive sighs was considerably less in the former than in the latter.4 The method for measuring lung recruitment, however, could be questioned: End-expiratory lung volume was measured by the closed-circuit helium dilution method before and after sighs, and lung recruitment was computed as the sigh-induced change in end-expiratory lung volume, ignoring whether the increase in lung volume was related to (over)inflation of previously aerated lung or to lung recruitment. Another clinical study demonstrated different gas exchange response to nebulization of prostacyclin between primary and secondary ARDS.5 In six patients with severe pneumonia resulting from infection or aspiration, nebulized prostacyclin decreased arterial oxygenation without changing pulmonary arterial pressure. In contrast, in nine patients with lung injury resulting from extrapulmonary sepsis, necrotizing pancreatitis, or multiple trauma, it significantly improved arterial oxygenation and decreased mean pulmonary arterial pressure. Differences in gas exchange response, however, coincided with differences in lung morphology assessed by lung computed tomography. Primary ARDS had a diffuse loss of lung aeration, whereas secondary ARDS had a focal lung aeration predominating in the lower lobes and sparing the upper lobes. Differences in lung morphology rather than the cause of lung injury likely explain the difference found in gas exchange response because it has been clearly demonstrated that diffuse loss of lung aeration is not specific to pneumonia: Mild forms remain focally distributed, whereas severe forms affect lung tissue diffusely.6,7 
After the initial report putting forward the idea that pulmonary and extrapulmonary ARDS behave differently in terms of alveolar recruitment and should require specific clinical management,2 many contradictory studies were published.6,8–14 Although a higher incidence of lung consolidation and focal loss of aeration is observed in secondary ARDS,6,15 differences in lung morphology (focal vs.  diffuse loss of lung aeration) do not exactly coincide with the cause of lung injury.6,10 Several studies have reported that alveolar recruitment resulting from increases in positive end-expiratory pressure,9,12,13 recruitment maneuvers,8 and prone positioning11 were not influenced by the cause of lung injury at the early phase of ARDS. Interestingly, in all of these studies, lung recruitment was measured from static pressure-volume curves, and in their study, Thille et al.  1 elegantly demonstrate that the quasi-static compliance method is inappropriate for measuring recruitment. Finally, Gattinoni et al.  14 recently reported a series of 68 ARDS patients in whom computed tomography of the whole lung was performed at airway pressures of 5, 15, and 45 cm H2O. Contradicting their initial hypothesis,2 patients with primary ARDS had a higher percentage of recruitable lung than patients with secondary ARDS.
Another confusing factor is the difficulty of classifying ARDS in one or the other category. In the study by Thille et al.  ,1 physicians well known for their expertise in ARDS were unable to classify 37% of the patients. The reasons are multiple. Lung infection rapidly complicates the course of mechanical ventilation, inducing a direct injury to the lung. In anesthetized and ventilated animals, disseminated foci of bronchopneumonia are found only a few hours after the initiation of mechanical ventilation.16,17 In the study of Thille et al.  , 45% of the patients were included at a late phase of ARDS, a condition that complicates classification. Over time with mechanical ventilation, the risk of lung superinfection rapidly increases and extensive fibrosis may occur, contributing to the mixing of pulmonary and extrapulmonary lung injuries. Conversely, a focal bronchopneumonia, initially limited to the lung parenchyma, may induce secondary septic shock and extrapulmonary lung injury. In patients with multiple trauma, it is not easy to discriminate pulmonary contusion from lung injury resulting from hemorrhagic shock and massive transfusion. Finally, as previously reported,7 it can be difficult to discriminate pulmonary and extrapulmonary ARDS because both of them may coexist in the same patient.
The “primary/secondary ARDS story” illustrates the critical importance of using adequate methodology in physiologic human studies. Inaccurate methodology may lead to incorrect interpretation of the data and false theories. When, in addition, the theory flatters and coincides with good sense—it appears quite logical that a consolidated infected lung recruits less than a lung with alveolar-interstitial edema—then, despite numerous studies unable to confirm the theory, the belief persists for a long time. One should always remember what Mahatma K. Gandhi said in 1921: “An error does not become truth by reason of multiplied propagation, nor does truth become error because nobody will see it.”18 
Anesthesiology and Critical Care Medicine, University of Paris 6, Paris, France.
References
Thille AW, Richard J-C, Maggiore SM, Ranieri VM, Brochard L: Alveolar recruitment in pulmonary and extrapulmonary acute respiratory distress syndrome: Comparison using pressure-volume curve or static compliance. Anesthesiology 2007; 106:212–7Thille, AW Richard, J-C Maggiore, SM Ranieri, VM Brochard, L
Gattinoni L, Pelosi P, Suter PM, Pedoto A, Vercedi P, Lissoni A: Acute respiratory distress syndrome caused by pulmonary and extrapulmonary disease: Different syndromes? Am J Respir Crit Care Med 1998; 158:3–11Gattinoni, L Pelosi, P Suter, PM Pedoto, A Vercedi, P Lissoni, A
Lim CM, Kim EK, Lee JS, Shim TS, Lee SD, Koh Y, Kim WS, Kim DS, Kim WD: Comparison to prone position between pulmonary and extrapulmonary acute respiratory distress syndrome. Int Care Med 2001; 27:477–85Lim, CM Kim, EK Lee, JS Shim, TS Lee, SD Koh, Y Kim, WS Kim, DS Kim, WD
Pelosi P, Cardrinhen P, Bottino N, Panigada M, Carrieri F, Riva E, Lissoni A, Gattinoni L: Sigh in acute respiratory distress syndrome. Am J Respir Crit Care Med 1999; 159:872–80Pelosi, P Cardrinhen, P Bottino, N Panigada, M Carrieri, F Riva, E Lissoni, A Gattinoni, L
Domenighetti G, Stricker H, Waldispuehl B: Nebulized prostacyclin (PGI2) in acute respiratory distress syndrome: Impact of primary (pulmonary injury) and secondary (extrapulmonary injury) disease on gas exchange response. Crit Care Med 2001; 29:57–62Domenighetti, G Stricker, H Waldispuehl, B
Rouby JJ, Puybasset L, Cluzel P, Richecoeur J, Lu Q, Coriat P, the CT scan ARDS study group: Regional distribution of gas and tissue in acute respiratory distress syndrome: II. Physiological correlations and definition of an ARDS Severity Score. Int Care Med 2000; 26:1046–56Rouby, JJ Puybasset, L Cluzel, P Richecoeur, J Lu, Q Coriat, P the CT scan ARDS study group,
Callister MEJ, Evans TW: Pulmonary versus  extrapulmonary acute respiratory distress syndrome: Different diseases or just a useful concept? Curr Opinion Crit Care 2002; 8:21–5Callister, MEJ Evans, TW
Jonson B, Richard JC, Strauss C, Mancebo J, Lemaire F, Brochard L: Pressure-volume curves and compliance in acute lung injury: Evidence of recruitment above the lower inflection point. Am J Respir Crit Care Med 1999; 159:1172–8Jonson, B Richard, JC Strauss, C Mancebo, J Lemaire, F Brochard, L
Puybasset L, Gusman P, Muller JC, Cluzel P, Coriat P, Rouby JJ, the CT scan ARDS study group: Regional distribution of gas and tissue in acute respiratory distress syndrome: III. Consequences for the effects of positive end-expiratory pressure. Int Care Med 2000; 26:1215–27Puybasset, L Gusman, P Muller, JC Cluzel, P Coriat, P Rouby, JJ the CT scan ARDS study group,
Desai SR, Wells AU, Suntharalingam G, Rubens MB, Evans TW, Hansell DM: Acute respiratory distress syndrome caused by pulmonary and extrapulmonary injury: A comparative CT study. Radiology 2001; 218:689–93Desai, SR Wells, AU Suntharalingam, G Rubens, MB Evans, TW Hansell, DM
Rialp G, Betbessé AJ, Pérez-Marquez M, Mancebo J: Short-term effects of inhaled nitric oxide and prone position in pulmonary and extrapulmonary acute respiratory distress syndrome. Am J Respir Crit Care Med 2001; 164:243–9Rialp, G Betbessé, AJ Pérez-Marquez, M Mancebo, J
Albaiceta GM, Taboada F, Parra D, Luyando LH, Calvo J, Menendez Otero J: Tomographic study of the inflection points of the pressure-volume curve in acute lung injury. Am J Respir Crit Care Med 2004; 170:1066–72Albaiceta, GM Taboada, F Parra, D Luyando, LH Calvo, J Menendez Otero, J
Grasso S, Fanelli V, Cafarelli A, Anaclerio R, Amabile M, Ancona G, Fiore T: Effects of high versus  low positive end-expiratory pressures in acute respiratory distress syndrome. Am J Respir Crit Care Med 2005; 171:1002–8Grasso, S Fanelli, V Cafarelli, A Anaclerio, R Amabile, M Ancona, G Fiore, T
Gattinoni L, Caironi P, Cressoni M, Chiumello D, Ranieri VM, Quintel M, Russo S, Patroniti N, Cornejo R, Bugedo G: Lung recruitment in patients with the acute respiratory distress syndrome. N Engl J Med 2006; 354:1775–86Gattinoni, L Caironi, P Cressoni, M Chiumello, D Ranieri, VM Quintel, M Russo, S Patroniti, N Cornejo, R Bugedo, G
Goodman LR, Fumagalli R, Tagliabue P, Tagliabue M, Gattinoni L, Pesenti P: Adult respiratory distress syndrome due to pulmonary and extrapulmonary causes: CT, clinical and functional correlations. Radiology 1999; 213:545–52Goodman, LR Fumagalli, R Tagliabue, P Tagliabue, M Gattinoni, L Pesenti, P
Marquette CH, Wermert D, Wallet F, Copin MC, Tonnel AB: Characterization of an animal model of ventilator-acquired pneumonia. Chest 1999;115:200–9Marquette, CH Wermert, D Wallet, F Copin, MC Tonnel, AB
Sartorius A, Qin L, Tonnellier M, Lenaour J, Goldstein I, Rouby JJ: Mechanical ventilation and lung infection in the genesis of airspace enlargement. Crit Care 2006; (in press)
Gandhi MK: Quotes of Gandhi Compiled by Shalu Bhalla UBS Publishers' Distributors Pvt. Ltd. New Delhi, India, p 22