Our findings are in line with a re-
cently published retrospective study of
cardiac surgery patients.
should be noted that the lower tidal vol-
umes in that study were much higher
than those used in the protective groups
of the studies analyzed in this meta-
analysis, a tidal volume of more than
10 mL/kg was found as a risk factor for
organ failure and prolonged ICU stay
after cardiac surgery.
The results of this meta-analysis
should be interpreted within the con-
text of the included studies. System-
atic reviews are subject to publication
bias, which may exaggerate the study’s
conclusion if publication is related to
the strength of the results. Addition-
ally, it may be important to distin-
guish between mechanical ventilation
performed in the operating room and
that performed in the ICU. Patients in
the operating room receive mechanical
ventilation for a much shorter time
than those in the ICU. Both surgical
patients and critically ill patients are at
risk for several causes of lung injury.
However, these may not be the same
for both patient groups, and mechani-
cal ventilation may have different
effects on both groups. In addition,
although our meta-analysis found
decreased mortality rate with protec-
tive ventilation, the interpretation of
this finding should be considered cau-
tiously because it was discovered only
after the addition of the study by
Yilmaz et al.
Also, one important
limitation is that the patients received
ventilation for a relatively short time
in most studies, which complicates the
extrapolation of the results for patients
receiving ventilation for long periods
in the ICU. For the lung injury analy-
sis, 4 of 8 studies (accounting for
85.4% and 87.2% of the events in the
conservative and protective groups,
respectively) were not randomized
controlled trials, and the randomized
controlled trials were of moderate
quality. Furthermore, funnel plots are
limited as a test for publication bias
for a small number of studies.
All the dichotomous analyses yielded
significant results, and with the excep-
tion of pulmonary infection, all the re-
sults showed no heterogeneity (I
Pulmonary infection yielded moder-
ate heterogeneity (I
=32%), but the
analysis with a random-effects model
showed similar results. However, all the
continuous analyses showed signifi-
cant heterogeneity (all I
with the use of a random-effects model
only differences in pH level, Pa
and hospital length of stay showed sig-
nificant results. Therefore, continu-
ous analyses need to be interpreted with
caution because of the heterogeneity.
In conclusion, our meta-analysis sug-
gests that among patients without lung
injury, protective ventilation with use
of lower tidal volumes at onset of me-
chanical ventilation may be associated
with better clinical outcomes. We be-
lieve that clinical trials are needed to
compare higher vs lower tidal vol-
umes in a heterogeneous group of pa-
tients receiving mechanical ventila-
tion for longer periods.
Author Contributions: Dr Serpa Neto had full access
to all of the data in the study and takes responsibility
for the integrity of the data and the accuracy of the
Study concept and design: Serpa Neto, Cardoso,
Manetta, Pereira, Espo´ sito, Schultz.
Acquisition of data: Serpa Neto, Pereira, Espo´ sito,
Analysis and interpretation of data: Serpa Neto,
Cardoso, Manetta, Pereira, Espo´ sito, Damasceno,
Drafting of the manuscript: Serpa Neto, Pereira,
Critical revision of the manuscript for important in-
tellectual content: Serpa Neto, Cardoso, Manetta,
Pereira, Espo´ sito, Pasqualucci, Damasceno, Schultz.
Statistical analysis: Serpa Neto, Pereira.
Administrative, technical, or material support:
Cardoso, Manetta, Espo´ sito, Pasqualucci, Damasceno,
Study supervision: Damasceno, Schultz.
Conflict of Interest Disclosures: All authors have com-
pleted and submitted the ICMJE Form for Disclosure
of Potential Conflicts of Interest and none were re-
Online-Only Material: The eTables and eFigures are
available at http://www.jama.com.
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1658 JAMA, October 24/31, 2012—Vol 308, No. 16 ©2012 American Medical Association. All rights reserved.