LUNG protective mechanical ventilation strategies using low tidal volumes (VT
) of approximately 6 ml/kg predicted body weight and moderate or high positive end-expiatory pressures (PEEP) have been demonstrated to improve relevant outcome measures in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).1,2
Despite the fact that lowering VT
failed to improve outcomes in three other controlled trials investigating VT
in ALI and ARDS patients,3–5
there is unequivocal evidence that mechanical ventilation in critically ill patients has the potential to aggravate or, under certain circumstances, initiate lung injury.6,7
In addition to mechanical ventilation with lower VT
, patients with ALI and ARDS could benefit from strategies that avoid cyclic alveolar collapse and tidal recruitment, including the use of higher levels of PEEP. Meta-analysis suggest this approach can not only waive the need for rescue therapies as a result of life-threatening hypoxemia,7
it can also reduce mortality in patients with more severe ALI.8
It is still matter of discussion whether or not lung protective strategies could be beneficial in ventilated patients without ALI or ARDS as well. In this issue of Anesthesiology, Sundar et al.9
studied the use of low VT
ventilation on duration of postoperative mechanical ventilation among patients with normal lungs who underwent elective cardiac surgery.
Mechanical ventilation is often mandatory for patients who undergo surgery, especially cardiac surgery. Despite its life-saving necessity, mechanical ventilation adds mechanical stress to lung tissues and may cause damage on a cellular level. Potential mechanisms include: (1) stress failure of plasma membrane (necrosis, release of mediators and cytosol from damaged cells), (2) stress failure of endothelial and epithelial barriers (loss of compartmentalization, hemorrhage, accumulation of lung leukocytes), (3) damage of the extracellular matrix, (4) overdistension without tissue destruction, (5) effects on the vasculature independent of stretch and rupture (increased intraluminal pressure and shear stress).10,11
In contrast with results from small animal models—in which mechanical stress induced by high VT
and low (or no) PEEP has caused lung injury in normal lungs (and which have been recently seen in larger animals in the context of high VT)12
—effects of short-term perioperative mechanical ventilation on pulmonary integrity in patients are less well defined.13
Two retrospective analyses identified high airway pressures and VT
as independent risk factors for ALI and ARDS in critically ill patients who require mechanical ventilation for reasons other than ALI or ARDS.14,15
Studies on mechanical ventilation in perioperative settings often make use of small patient populations and focus at different (and not necessarily clinically relevant) outcomes, such as inflammatory mediators. Such studies have revealed inhomogeneous results.13
The impression is, however, that major surgery (e.g.
, cardiac surgery), which per se
causes a clinically relevant inflammatory response, makes the lungs more vulnerable to injury caused by mechanical stress.16–18
This effect might be explained by a two- or multiple-hit model. Accordingly, potentially injurious mechanical ventilation as a second hit requires preexisting injury caused by ALI/ARDS. Alternatively, it may also be a marked inflammatory response (e.g.
, triggered by major surgery) to cause or aggravate lung injury and/or systemic inflammation.16–18
Different studies on mechanical ventilation strategies during and/or after cardiac surgery are summarized in table 1
. The present study by Sundar et al.9
is the largest one in cardiac surgery patients and it focuses on clinically relevant outcomes. Although the authors failed to show a significant difference in time on mechanical ventilation, the number of patients still on mechanical ventilation at 6 and 8 h after surgery was significantly lower in the protective ventilation group.9
However, there are several limitations of this study: (1) it is a single-center study, thus its results cannot be generalized to other centers or other groups of patients; (2) obese patients were not included in the study; (3) the level of PEEP was selected according to a specific table and not via
individual physiologic parameters like gas-exchange, compliance, or oxygen delivery; and (4) weaning procedures were not specifically standardized.
In this study, PEEP levels in both study groups were approximately 5 cm H2
O. Low PEEP levels might increase regional shear stress and lung injury by causing opening and closing of lung units within a ventilatory cycle (atelectrauma), even in absence of high plateau pressures.19
Tidal recruitment and derecruitment can be minimized by using PEEP levels of 10 cm H2
O during anesthesia, at least in healthy nonobese patients.20
Although it is uncertain whether ventilation strategies that use higher levels of PEEP during the intraoperative period are beneficial to these patients,17,21
higher levels of PEEP could reduce intraoperative atelectasis, decreasing repetitive collapse and reexpansion of dependent lung parts, and thereby attenuating pulmonary inflammation and coagulation.22,23
Individual factors such as obesity, pneumoperitoneum, preexisting disease, and some surgical interventions may aggravate atelectasis formation.
Furthermore, although some positive clinical indication on ventilation-free hours or reduced reintubation rate were observed, clinical decisions regarding patient need for reintubation (or any other intervention) were made by these teams based on their clinical assessments. The rate of intubation was determined mainly by bleeding, arrhythmia, and pancreatitis not specifically related to ventilation management.
Inflammatory responses to cardiac surgery are variable and may depend on individual patient factors, such as comorbidities, genetic predisposition, previous tissue injury (e.g.
, cardiac shock), or surgical trauma depending on type of surgery, amount of ischemia-reperfusion injury, and blood loss. Because high-risk patients are usually not included in studies on perioperative ventilation, the issue of protective mechanical ventilation may be even more relevant in daily practice when one treats these patients. Despite an accurately performed sample size calculation in the study by Sundar et al.
the number of patients undergoing routine elective cardiac surgery to be studied might be higher to see differences in relevant outcomes depending on mechanical ventilation strategy.
When using lung protective mechanical ventilation more extensively in patients without ALI/ARDS, adverse effects such as hypercapnia, atelectasis formation, and increased requirements for higher fractional inspired oxygen tension and PEEP should be considered. Increased fluid administration or even use of catecholamines might be necessary when treating potential cardiovascular impairment as a result of decreased venous return as associated with higher PEEP. In fact, it is often required when using lower VT
. Balancing the risks and benefits of protective mechanical ventilation during anesthesia should include an assessment of preoperative patient status and expected amount and duration of surgical trauma, among other individual factors. There is an increasing body of evidence from relatively small studies directly or indirectly suggesting a potential benefit of protective ventilatory strategies for patients without lung injury. This finding is especially true for patients during cardiac and thoracic surgery (e.g.
, esophagectomy, which is often associated with a clinically relevant systemic inflammatory response to surgical procedures). Systematic patient scoring methodologies may be useful in assisting clinicians identify patients at risk of postoperative complications.24
Future studies might consider stratifying patients to include those with more severe illness or injury. This stratification, however, assumes that the more ill a patient is, the more relevant a protective ventilatory strategy may be.
Hermann Wrigge, M.D.,*
Paolo Pelosi, M.D.†
*Department of Anesthesiology and Intensive Care Medicine, University of Leipzig, Germany. firstname.lastname@example.org. †Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Italy.
1. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med 2000; 342:1301–8
2. Parsons PE, Eisner MD, Thompson BT, Matthay MA, Ancukiewicz M, Bernard GR, Wheeler AP, NHLBI Acute Respiratory Distress Syndrome Clinical Trials Network: Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury. Crit Care Med 2005; 33:1–6
3. Stewart TE, Meade MO, Cook DJ, Granton JT, Hodder RV, Lapinsky SE, Mazer CD, McLean RF, Rogovein TS, Schouten BD, Todd TR, Slutsky AS: Evaluation of a ventilation strategy to prevent barotrauma in patients at high risk for acute respiratory distress syndrome. Pressure- and Volume-Limited Ventilation Strategy Group. N Engl J Med 1998; 338:355–61
4. Brochard L, Roudot-Thoraval F, Roupie E, Delclaux C, Chastre J, Fernandez-Mondéjar E, Clémenti E, Mancebo J, Factor P, Matamis D, Ranieri M, Blanch L, Rodi G, Mentec H, Dreyfuss D, Ferrer M, Brun-Buisson C, Tobin M, Lemaire F: Tidal volume reduction for prevention of ventilator-induced lung injury in acute respiratory distress syndrome. The Multicenter Trail Group on Tidal Volume reduction in ARDS. Am J Respir Crit Care Med 1998; 158:1831–8
5. Brower RG, Shanholtz CB, Fessler HE, Shade DM, White P Jr, Wiener CM, Teeter JG, Dodd-o JM, Almog Y, Piantadosi S: Prospective, randomized, controlled clinical trial comparing traditional versus reduced tidal volume ventilation in acute respiratory distress syndrome patients. Crit Care Med 1999; 27:1492–8
6. Tremblay LN, Slutsky AS: Ventilator-induced injury: From barotrauma to biotrauma. Proc Assoc Am Physicians 1998; 110:482–8
7. Putensen C, Theuerkauf N, Zinserling J, Wrigge H, Pelosi P: Meta-analysis: Ventilation strategies and outcomes of the acute respiratory distress syndrome and acute lung injury. Ann Intern Med 2009; 151:566–76
8. Briel M, Meade M, Mercat A, Brower RG, Talmor D, Walter SD, Slutsky AS, Pullenayegum E, Zhou Q, Cook D, Brochard L, Richard JC, Lamontagne F, Bhatnagar N, Stewart TE, Guyatt G: Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: Systematic review and meta-analysis. JAMA 2010; 303:865–73
9. Sundar S, Novack V, Jervis K, Bender SP, Lerner A, Panzica P, Mahmood F, Malhotra A, Talmor D: Influence of low tidal volume ventilation on time to extubation in cardiac surgical patients. Anesthesiology 2011; 114:1102–10
10. Uhlig S: Ventilation-induced lung injury and mechanotransduction: Stretching it too far? Am J Physiol Lung Cell Mol Physiol 2002; 282:L892–6
11. Pelosi P, Negrini D: Extracellular matrix and mechanical ventilation in healthy lungs: Back to baro/volotrauma? Curr Opin Crit Care 2008; 14:16–21
12. 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 [Epub ahead of print Feb. 4]
13. Schultz MJ, Haitsma JJ, Slutsky AS, Gajic O: What tidal volumes should be used in patients without acute lung injury? Anesthesiology 2007; 106:1226–31
14. 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; 32:1817–24
15. Gajic O, Frutos-Vivar F, Esteban A, Hubmayr RD, Anzueto A: Ventilator settings as a risk factor for acute respiratory distress syndrome in mechanically ventilated patients. Intensive Care Med 2005; 31:922–6
16. Zupancich E, Paparella D, Turani F, Munch C, Rossi A, Massaccesi S, Ranieri VM: Mechanical ventilation affects inflammatory mediators in patients undergoing cardiopulmonary bypass for cardiac surgery: A randomized clinical trial. J Thorac Cardiovasc Surg 2005; 130:378–83
17. Wrigge H, Uhlig U, Baumgarten G, Menzenbach J, Zinserling J, Ernst M, Drömann 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; 31:1379–87
18. Reis Miranda D, Gommers D, Struijs A, Dekker R, Mekel J, Feelders R, Lachmann B, Bogers AJ: Ventilation according to the open lung concept attenuates pulmonary inflammatory response in cardiac surgery. Eur J Cardiothorac Surg 2005; 28:889–95
19. Mols G, Priebe HJ, Guttmann J: Alveolar recruitment in acute lung injury. Br J Anaesth 2006; 96:156–66
20. Neumann P, Rothen HU, Berglund JE, Valtysson J, Magnusson A, Hedenstierna G: Positive end-expiratory pressure prevents atelectasis during general anaesthesia even in the presence of a high inspired oxygen concentration. Acta Anaesthesiol Scand 1999; 43:295–301
21. 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; 98:775–81
22. 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; 105:689–95
23. Wolthuis EK, Choi G, Dessing MC, Bresser P, Lutter R, Dzoljic M, van der Poll T, Vroom MB, Hollmann M, Schultz MJ: Mechanical ventilation with lower tidal volumes and positive end-expiratory pressure prevents pulmonary inflammation in patients without preexisting lung injury. Anesthesiology 2008; 108:46–54
24. Canet J, Gallart L, Gomar C, Paluzie G, Vallès J, Castillo J, Sabaté S, Mazo V, Briones Z, Sanchis J, ARISCAT Group: Prediction of postoperative pulmonary complications in a population-based surgical cohort. Anesthesiology 2010; 113:1338–50
25. Chaney MA, Nikolov MP, Blakeman BP, Bakhos M: Protective ventilation attenuates postoperative pulmonary dysfunction in patients undergoing cardiopulmonary bypass. J Cardiothorac Vasc Anesth 2000; 14:514–8
26. Koner O, Celebi S, Balci H, Cetin G, Karaoglu K, Cakar N: Effects of protective and conventional mechanical ventilation on pulmonary function and systemic cytokine release after cardiopulmonary bypass. Intensive Care Med 2004; 30:620–6
© 2011 American Society of Anesthesiologists, Inc.