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OPINION Intraoperative ventilatory strategies to prevent
postoperative pulmonary complications:
a meta-analysis
Sabrine N.T. Hemmes a,b, Ary Serpa Neto c,d, and Marcus J. Schultz a,e
Purpose of review
It is uncertain whether patients undergoing short-lasting mechanical ventilation for surgery benefit from lung-
protective intraoperative ventilatory settings including the use of lower tidal volumes, higher levels of positive
end-expiratory pressure (PEEP) and/or recruitment maneuvers. We meta-analyzed trials testing the effect of
lung-protective intraoperative ventilatory settings on the incidence of postoperative pulmonary complications.
Recent findings
Eight articles (1669 patients) were included. Meta-analysis showed a decrease in lung injury development
[risk ratio (RR) 0.40; 95% confidence interval (CI) 0.22–0.70; I2 0%; number needed to treat (NNT) 37],
pulmonary infection (RR 0.64; 95% CI 0.43–0.97; I2 0%; NNT 27) and atelectasis (RR 0.67; 95% CI
0.47–0.96; I2 48%; NNT 31) in patients receiving intraoperative mechanical ventilation with lower tidal
volumes. Meta-analysis also showed a decrease in lung injury development (RR 0.29; 95% CI 0.14–0.60;
I2 0%; NNT 29), pulmonary infection (RR 0.62; 95% CI 0.40–0.96; I2 15%; NNT 33) and atelectasis
(RR 0.61; 95% CI 0.41–0.91; I2 0%; NNT 29) in patients ventilated with higher levels of PEEP, with or
without recruitment maneuvers.
Summary
Lung-protective intraoperative ventilatory settings have the potential to protect against postoperative
pulmonary complications.
Keywords
intraoperative, mechanical ventilation, positive end-expiratory pressure, postoperative complications,
tidal volume
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Lung-protective intraoperative ventilatory settings Hemmes et al.
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Intensive care and resuscitation
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Table 1. Characteristics of the included studies and summary of continuous variables (mean SD)
Protective Conservative Protective conservative
Primary
Study (year) N VT PEEP RM N VT PEEP RM N Setting Design Follow-up (h) TMV (h) outcome
COH, cohort; CRO, cross-sectional; CT, computed tomography; ICULS, ICU length of stay; LI, lung injury; NS, not specified; OS, oncology surgery; RCT, randomized controlled trial; TMV, time of mechanical ventilation;
VT, tidal volume (ml/kg).
a
Median (interquartile range).
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Lung-protective intraoperative ventilatory settings Hemmes et al.
129
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Intensive care and resuscitation
Table 2. Synthesis of demographic, ventilatory and laboratorial characteristics of the patients in the final
follow-up (mean SD)
Protective ventilation (n ¼ 886) Conventional ventilation (n ¼ 783) P value
1.2.4 Atelectasis
Lin et al. 2008 [17] 3 20 2 20 3.2% 1.50 [0.28, 8.04] 2004
Cai et al. 2007 [16] 7 8 5 8 7.9% 1.40 [0.77, 2.54] 2007
Licker et al. 2009 [18] 28 558 47 533 76.2% 0.57 [0.36, 0.89] 2009
Weingarten et al. 2010 [19] 4 20 5 20 7.9% 0.80 [0.25, 2.55] 2010
Yang et al. 2011 [21] 1 50 3 50 4.8% 0.33 [0.04, 3.10] 2011
Subtotal (95% CI) 656 631 100.0% 0.67 [0.47, 0.96]
Total events 43 62
Heterogeneity: Chi2 = 7.67, df = 4 (P = 0.10); I2 = 48%
Test for overall effect: Z = 2.19 (P = 0.003)
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Lung-protective intraoperative ventilatory settings Hemmes et al.
1.9.4 Atelectasis
Lin et al. 2008 [17] 3 20 2 20 3.4% 1.50 [0.28, 8.04] 2004
Licker et al. 2009 [18] 28 558 47 533 82.8% 0.57 [0.36, 0.89] 2009
Weingarten et al. 2010 [19] 4 20 5 20 8.6% 0.80 [0.25, 2.55] 2010
Yang et al. 2011 [21] 1 50 3 50 5.2% 0.33 [0.04, 3.10] 2011
Subtotal (95% CI) 648 623 100.0% 0.61 [0.41, 0.91]
Total events 36 57
Heterogeneity: Chi2 = 1.69, df = 3 (P = 0.64); I2 = 0%
Test for overall effect: Z = 2.43 (P = 0.01)
0.02 0.1 1 10 50
Higher PEEP Lower PEEP
Test for subgroup differences: Chi2 = 3.55, df = 2 (P = 0.17), I2 = 43.7%
FIGURE 3. Effect of intraoperative ventilation with higher levels of positive end expiratory pressure (PEEP).
to benefit from ventilation with lower tidal volumes could increase cyclic alveolar collapse
volumes [5,6]. One recent randomized controlled of dependent lung regions, raising the risk of
trial shows a lower tidal volume strategy to protect atelectrauma. Application of PEEP is an easy inter-
against lung injury in patients without ARDS at vention that may counteract this side-effect of
onset of mechanical ventilation in the ICU [7]. lower tidal volume ventilation. Lower tidal volume
Notably, a recent observational study in patients ventilation could also lead to hypercapnia and
undergoing short-term postoperative mechanical hypercapnic acidosis. Notably, so-called permissive
ventilation after cardiac surgery shows mechanical hypercapnia is thought to have lung-protective
ventilation with tidal volumes more than 10 ml/kg qualities, even though the exact clinical implica-
to be associated with prolonged mechanical venti- tions are not entirely clear [35].
lation, hemodynamic instability, multiple organ Prescription of PEEP in critically ill patients
failure, and prolonged stay in the ICU, compared has also changed over the last decades. PEEP is
with mechanical ventilation with lower tidal progressively more frequently applied in intubated
volumes. In this study, women and obese patients and mechanically ventilated patients in the ICU,
are found to be particularly at risk of receiving with an increase in use of PEEP levels more than
&
ventilation with too large tidal volumes [33 ]. 10 cmH2O from 28% in the late 1990s [28,29] to 40%
These results confirm, at least in part, findings in a more recent survey across ICUs in Europe and
from another recent study that identifies female the Americas [36]. Particularly in patients with ARDS
sex, overweight and underweight as independent higher levels of PEEP are being applied, even though
factors for mechanical ventilation with too large the benefits of higher PEEP levels with or without
tidal volumes [34]. recruitment maneuver are not unequivocally
Mechanical ventilation with lower tidal volumes demonstrated [28,29,36]. Use of higher levels of
may not come without challenges. Use of lower tidal PEEP and recruitment maneuver could benefit
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Intensive care and resuscitation
patients with severe ARDS, though [4,37]. Trials ICU patients receiving long-term mechanical venti-
investigating the effects of higher levels of PEEP lation. Intraoperative use of lower tidal volumes
in critically ill patients without ARDS are lacking. could reduce the incidence of postoperative lung
The results of the present meta-analysis are in line injury, pulmonary infections and atelectasis. Intra-
with results from a previous systematic review operative use of higher levels of PEEP and recruit-
suggesting higher levels of PEEP to reduce post- ment maneuvers also reduces the incidence of these
operative atelectasis [38]. complications. It is difficult if not impossible to
None of the trials included in our meta-analysis separate the beneficial effects of lower tidal volumes
analyzed the effect of recruitment maneuver separate from that of higher levels of PEEP and recruitment
from the use of higher levels of PEEP. However, one maneuver. To better establish the effect of lung–
recent randomized controlled trial of cardiac surgery protective intraoperative ventilatory settings we are
patients shows decrease of alveolar dead-space and an also in need of well-powered randomized clinical
increase in arterial oxygenation during surgery when trials. Presently, one large multicenter trial is con-
recruitment maneuver are performed [39]. ducted to identify the effect of intraoperative use of
An adversity of use of higher levels of PEEP, with higher levels of PEEP and recruitment maneuver on
or without the use of recruitment maneuver, may be the incidence of postoperative complications in
due to an increase in right ventricular afterload adult surgical patients [41].
as well as a decrease in right ventricular preload.
This could cause a decrease in left ventricular
Acknowledgements
preload and reduction in left ventricular stroke
volume [40]. It is uncertain whether this causes We are indebted to Sérgio Oliveira Cardoso, M.D., José
problems in patients undergoing surgery. Antônio Manetta, M.D., Victor Galvão Moura Pereira,
Our study knows several shortcomings. First, it M.D., Daniel Crepaldi Espósito, M.D., Manoela de
is difficult if not impossible to differentiate between Oliveira Prado Pasqualucci, M.D., Maria Cecı´lia Toledo
the beneficial effect from lower tidal volumes and Damasceno, M.D., Ph.D., of the Department of Critical
that from higher levels of PEEP with or without Care Medicine, ABC Medical School, Santo André, São
recruitment maneuver. Most trials included in this Paulo, Brazil for their support and contribution to the
meta-analysis compared ‘conventional ventilation’ meta-analysis.
with higher tidal volumes and low levels of PEEP
with a ‘lung-protective’ mechanical ventilation Conflicts of interest
strategy with lower tidal volume ventilation and There are no conflicts of interest.
higher levels of PEEP (Table 1). As a result all trials
included in the meta-analysis assessing the effect of
higher levels of PEEP and recruitment maneuver is REFERENCES AND RECOMMENDED
also part of the meta-analysis analyzing the effect of READING
Papers of particular interest, published within the annual period of review, have
lower tidal volumes. Second, the incidence of lung been highlighted as:
& of special interest
injury could very well be higher than calculated in && of outstanding interest
this meta-analysis, as the clinical picture of ARDS Additional references related to this topic can also be found in the Current
World Literature section in this issue (p. 245).
often resembles ‘suspected’ pulmonary infection.
ARDS as well as pulmonary infection may present 1. Slutsky AS. Lung injury caused by mechanical ventilation. Chest 1999;
116:9S–15S.
with leucocytosis, fever and pulmonary infiltrates 2. Mead J, Takishima T, Leith D. Stress distribution in lungs: a model of
on the chest radiograph. Thus, it could be that ARDS pulmonary elasticity. J Appl Physiol 1970; 28:596–608.
3. Gattinoni L, Carlesso E, Caironi P. Stress and strain within the lung. Curr Opin
is mistakenly diagnosed as pulmonary infection Crit Care 2012; 18:42–47.
in some cases. Finally, when interpreting the results 4. Putensen C, Theuerkauf N, Zinserling J, et al. Meta-analysis: ventilation
strategies and outcomes of the acute respiratory distress syndrome and
of this meta-analysis, the possible occurrence of acute lung injury. Ann Intern Med 2009; 151:566–576.
positive publication bias should be taken into 5. Gajic O, Dara SI, Mendez JL, et al. Ventilator-associated lung injury in patients
without acute lung injury at the onset of mechanical ventilation. Crit Care Med
account. Furthermore, the use of funnel plots has 2004; 32:1817–1824.
a limited role, as test for bias when the number of 6. Gajic O, Frutos-Vivar F, Esteban A, et al. Ventilator settings as a risk factor for
acute respiratory distress syndrome in mechanically ventilated patients.
studies included in the analysis is small. Despite Intensive Care Med 2005; 31:922–926.
these limitations, our meta-analysis provides inter- 7. Determann RM, Royakkers A, Wolthuis EK, et al. Ventilation with lower tidal
volumes as compared with conventional tidal volumes for patients without
esting information which needs further exploration. acute lung injury: a preventive randomized controlled trial. Crit Care 2010;
14:R1.
8. Schultz MJ, Haitsma JJ, Slutsky AS, et al. What tidal volumes should be used
in patients without acute lung injury? Anesthesiology 2007; 106:1226–
CONCLUSION 1231.
9. Dreyfuss D, Saumon G. Ventilator-induced lung injury: lessons
Lower tidal volumes, higher levels of PEEP and from experimental studies. Am J Respir Crit Care Med 1998; 157:294–
recruitment maneuver are increasingly used in 323.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Lung-protective intraoperative ventilatory settings Hemmes et al.
10. Wolthuis EK, Vlaar AP, Choi G, et al. Mechanical ventilation using noninjurious 25. ClinicalTrials.gov. (last accession date: December 17, 2012) Local Assessment
ventilation settings causes lung injury in the absence of preexisting lung of Ventilatory Management During General Anesthesia for Surgery (LAS
injury in healthy mice. Crit Care 2009; 13:R1. VEGAS), NCT01601223 http://clinicaltrials.gov/ct2/show/NCT01601223?
11. Duggan M, Kavanagh BP. Pulmonary atelectasis: a pathogenic perioperative term=las+vegas&rank=1 [Accessed on 17 December 2012]
entity. Anesthesiology 2005; 102:838–854. 26. Suter PM, Fairley B, Isenberg MD. Optimum end-expiratory airway pressure
12. Smetana GW, Lawrence VA, Cornell JE. Preoperative pulmonary risk in patients with acute pulmonary failure. N Engl J Med 1975; 292:284–289.
stratification for noncardiothoracic surgery: systematic review for the 27. Jardin F, Farcot JC, Boisante L, et al. Influence of positive end-expiratory
American College of Physicians. Ann Intern Med 2006; 144:581–595. pressure on left ventricular performance. N Engl J Med 1981; 304:387–392.
13. Canet J, Gallart L, Gomar C, et al. Prediction of postoperative pulmonary 28. Esteban A, Anzueto A, Alia I, et al. How is mechanical ventilation employed
complications in a population-based surgical cohort. Anesthesiology 2010; in the intensive care unit? an international utilization review. Am J Respir Crit
113:1338–1350. Care Med 2000; 161:1450–1458.
14. Serpa Neto A, Cardoso SO, Manetta JA, et al. Association between use of 29. Esteban A, Anzueto A, Frutos F, et al. Characteristics and outcomes in
&& lung-protective ventilation with lower tidal volumes and clinical outcomes adult patients receiving mechanical ventilation: a 28-day international study.
among patients without acute respiratory distress syndrome: a meta-analysis. JAMA 2002; 287:345–355.
Jama 2012; 308:1651–1659. 30. Brun-Buisson C, Minelli C, Bertolini G, et al. Epidemiology and outcome of
This meta-analysis shows that preventive use of lower tidal volume ventilation in acute lung injury in European intensive care units. Results from the ALIVE
patients without ARDS attenuates development of lung injury, pulmonary infection study. Intensive Care Med 2004; 30:51–61.
and mortality. 31. Sakr Y, Vincent JL, Reinhart K, et al. High tidal volume and positive fluid
15. Michelet P, D’Journo XB, Roch A, et al. Protective ventilation influences balance are associated with worse outcome in acute lung injury. Chest 2005;
systemic inflammation after esophagectomy: a randomized controlled study. 128:3098–3108.
Anesthesiology 2006; 105:911–919. 32. Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign:
16. Cai H, Gong H, Zhang L, et al. Effect of low tidal volume ventilation on international guidelines for management of severe sepsis and septic shock:.
atelectasis in patients during general anesthesia: a computed tomographic Crit Care Med 2008; 36:296–327.
scan. J Clin Anesth 2007; 19:125–129. 33. Lellouche F, Dionne S, Simard S, et al. High tidal volumes in mechanically
17. Lin WQ, Lu XY, Cao LH, et al. Effects of the lung protective ventilatory strategy & ventilated patients increase organ dysfunction after cardiac surgery.
on proinflammatory cytokine release during one-lung ventilation. Ai Zheng Anesthesiology 2012; 116:1072–1082.
2008; 27:870–873. This large observational prospective study of cardiac surgery patients shows that
18. Licker M, Diaper J, Villiger Y, et al. Impact of intraoperative lung-protective postoperative use of high tidal volumes increases the risk of prolonged duration of
interventions in patients undergoing lung cancer surgery. Crit Care 2009; postoperative mechanical ventilation, prolonged stay in the ICU, and organ failure.
13:R41. 34. Jaber S, Coisel Y, Chanques G, et al. A multicentre observational study
19. Weingarten TN, Whalen FX, Warner DO, et al. Comparison of two ventilatory of intra-operative ventilatory management during general anaesthesia: tidal
strategies in elderly patients undergoing major abdominal surgery. Br J volumes and relation to body weight. Anaesthesia 2012; 67:999–1008.
Anaesth 2010; 104:16–22. 35. Ismaiel NM, Henzler D. Effects of hypercapnia and hypercapnic acidosis on
20. Fernandez-Bustamante A, Wood CL, Tran ZV, et al. Intraoperative ventilation: attenuation of ventilator-associated lung injury. Minerva Anestesiol 2011;
incidence and risk factors for receiving large tidal volumes during general 77:723–733.
anesthesia. BMC Anesthesiol 2011; 11:22. 36. Esteban A, Ferguson ND, Meade MO, et al. Evolution of mechanical
21. Yang M, Ahn HJ, Kim K, et al. Does a protective ventilation strategy reduce the ventilation in response to clinical research. Am J Respir Crit Care Med
risk of pulmonary complications after lung cancer surgery?: a randomized 2008; 177:170–177.
controlled trial. Chest 2011; 139:530–537. 37. Gattinoni L, Caironi P. Refining ventilatory treatment for acute lung injury and
22. Treschan TA, Kaisers W, Schaefer MS, et al. Ventilation with low tidal acute respiratory distress syndrome. JAMA 2008; 299:691–693.
& volumes during upper abdominal surgery does not improve postoperative 38. Imberger G, McIlroy D, Pace NL, et al. Positive end-expiratory
lung function. Br J Anaesth 2012; 109:263–271. pressure (PEEP) during anaesthesia for the prevention of mortality and
This randomized controlled trial comparing the effect of intraoperative use of lower postoperative pulmonary complications. Cochrane Database Syst Rev.
tidal volumes versus higher tidal volumes shows an increase in postoperative 2010; 9:CD007922.
atelectasis but not need for supplemental oxygen in patients receiving intraopera- 39. Unzueta C, Tusman G, Suarez-Sipmann F, et al. Alveolar recruitment improves
tive mechanical ventilation with lower tidal volumes. ventilation during thoracic surgery: a randomized controlled trial. Br J Anaesth
23. Weiser TG, Regenbogen SE, Thompson KD, et al. An estimation of the global 2012; 108:517–524.
volume of surgery: a modelling strategy based on available data. Lancet 2008; 40. Luecke T, Pelosi P. Clinical review: positive end-expiratory pressure and
372:139–144. cardiac output. Crit Care 2005; 9:607–621.
24. Pearse RM, Moreno RP, Bauer P, et al. Mortality after surgery in Europe: 41. Hemmes SN, Severgnini P, Jaber S, et al. Rationale and study design
& a 7 day cohort study. Lancet; 380: 1059–1065. of PROVHILO: a worldwide multicenter randomized controlled trial on
This very large international prospective trial documented a much higher incidence protective ventilation during general anesthesia for open abdominal surgery.
of postoperative mortality than previously assumed. Trials 2011; 12:111.
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