Article

Association Between Use of Lung-Protective Ventilation With Lower Tidal Volumes and Clinical Outcomes Among Patients Without Acute Respiratory Distress Syndrome A Meta-analysis

Department of Critical Care Medicine, ABC Medical School, Santo André, São Paulo, Brazil.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 10/2012; 308(16):1651-9. DOI: 10.1001/jama.2012.13730
Source: PubMed
ABSTRACT
Lung-protective mechanical ventilation with the use of lower tidal volumes has been found to improve outcomes of patients with acute respiratory distress syndrome (ARDS). It has been suggested that use of lower tidal volumes also benefits patients who do not have ARDS.
To determine whether use of lower tidal volumes is associated with improved outcomes of patients receiving ventilation who do not have ARDS.
MEDLINE, CINAHL, Web of Science, and Cochrane Central Register of Controlled Trials up to August 2012.
Eligible studies evaluated use of lower vs higher tidal volumes in patients without ARDS at onset of mechanical ventilation and reported lung injury development, overall mortality, pulmonary infection, atelectasis, and biochemical alterations.
Three reviewers extracted data on study characteristics, methods, and outcomes. Disagreement was resolved by consensus.
Twenty articles (2822 participants) were included. Meta-analysis using a fixed-effects model showed a decrease in lung injury development (risk ratio [RR], 0.33; 95% CI, 0.23 to 0.47; I2, 0%; number needed to treat [NNT], 11), and mortality (RR, 0.64; 95% CI, 0.46 to 0.89; I2, 0%; NNT, 23) in patients receiving ventilation with lower tidal volumes. The results of lung injury development were similar when stratified by the type of study (randomized vs nonrandomized) and were significant only in randomized trials for pulmonary infection and only in nonrandomized trials for mortality. Meta-analysis using a random-effects model showed, in protective ventilation groups, a lower incidence of pulmonary infection (RR, 0.45; 95% CI, 0.22 to 0.92; I2, 32%; NNT, 26), lower mean (SD) hospital length of stay (6.91 [2.36] vs 8.87 [2.93] days, respectively; standardized mean difference [SMD], 0.51; 95% CI, 0.20 to 0.82; I2, 75%), higher mean (SD) PaCO2 levels (41.05 [3.79] vs 37.90 [4.19] mm Hg, respectively; SMD, -0.51; 95% CI, -0.70 to -0.32; I2, 54%), and lower mean (SD) pH values (7.37 [0.03] vs 7.40 [0.04], respectively; SMD, 1.16; 95% CI, 0.31 to 2.02; I2, 96%) but similar mean (SD) ratios of PaO2 to fraction of inspired oxygen (304.40 [65.7] vs 312.97 [68.13], respectively; SMD, 0.11; 95% CI, -0.06 to 0.27; I2, 60%). Tidal volume gradients between the 2 groups did not influence significantly the final results.
Among patients without ARDS, protective ventilation with lower tidal volumes was associated with better clinical outcomes. Some of the limitations of the meta-analysis were the mixed setting of mechanical ventilation (intensive care unit or operating room) and the duration of mechanical ventilation.

Full-text

Available from: Ary Serpa Neto, Jul 08, 2015
CARING FOR THE
CRITICALLY ILL PATIENT
Association Between Use of Lung-Protective
V entilation With Lower Tidal Vol umes
and Clinical Outcomes Among Patients
Without Acute Respiratory Distress Syndrome
A Meta-analysis
Ary Serpa Neto, MD, MSc
Se´rgio Oliveira Cardoso, MD
Jose´ Antoˆnio Manetta, MD
Victor Galva˜o Moura Pereira, MD
Daniel Crepaldi Espo´sito, MD
Manoela de Oliveira Prado
Pasqualucci, MD
Maria Cecı´lia Toledo
Damasceno, MD, PhD
Marcus J. Schultz, MD, PhD
M
ECHANICAL VENTILATION
is a life-saving strategy
in patients with acute
respiratory failure. How-
ever, unequivocal evidence suggests
that mechanical ventilation has the
potential to aggravate and precipitate
lung injury.
1
In acute respiratory dis-
tress syndrome (ARDS), and in a
milder form of ARDS formerly known
as acute lung injury (ALI),
2
mechani-
cal ventilation can cause ventilator-
associated lung injury. Ventilator-
associated lung injury is a frequent
complication in critically ill patients
receiving mechanical ventilation, and
its development increases morbidity
and mortality.
1
Higher tidal volume (V
T
) ventila-
tion causes the alveoli to overstretch
in a process called volutrauma, and
this overstretching is the main cause
of ventilator-associated lung injury.
3
The use of a lower V
T
was shown to
reduce morbidity and mortality in
For editorial comment see p 1689.
Author Affiliations: Department of Critical Care Medi-
cine, ABC Medical School, Santo Andre´, Sa˜ o Paulo,
Brazil (Drs Serpa Neto, Cardoso, Manetta, Pereira, Es-
po´ sito, and Damasceno); Department of Internal Medi-
cine, Hospital das Clı´nicas, University of Sa˜ o Paulo, Sa˜o
Paulo (Dr Damasceno); and Department of Intensive
Care Medicine and Laboratory of Experimental Inten-
sive Care and Anesthesiology, Academic Medical
Center, University of Amsterdam, Amsterdam, the
Netherlands (Dr Schultz).
Corresponding Author: Ary Serpa Neto, MD, MSc, Av-
enue Lauro Gomes, 2000 Sa˜ o Paulo, Brazil (aryserpa
@terra.com.br).
Caring for the Critically Ill Patient Section Editor: Derek
C. Angus, MD, MPH, Contributing Editor, JAMA
(angusdc@upmc.edu).
Context Lung-protective mechanical ventilation with the use of lower tidal volumes
has been found to improve outcomes of patients with acute respiratory distress syn-
drome (ARDS). It has been suggested that use of lower tidal volumes also benefits
patients who do not have ARDS.
Objective To determine whether use of lower tidal volumes is associated with im-
proved outcomes of patients receiving ventilation who do not have ARDS.
Data Sources MEDLINE, CINAHL, Web of Science, and Cochrane Central Register
of Controlled Trials up to August 2012.
Study Selection Eligible studies evaluated use of lower vs higher tidal volumes in pa-
tients without ARDS at onset of mechanical ventilation and reported lung injury devel-
opment, overall mortality, pulmonary infection, atelectasis, and biochemical alterations.
Data Extraction Three reviewers extracted data on study characteristics, methods,
and outcomes. Disagreement was resolved by consensus.
Data Synthesis Twenty articles (2822 participants) were included. Meta-analysis using
a fixed-effects model showed a decrease in lung injury development (risk ratio [RR], 0.33;
95% CI, 0.23 to 0.47; I
2
, 0%; number needed to treat [NNT], 11), and mortality (RR,
0.64; 95% CI, 0.46 to 0.89; I
2
, 0%; NNT, 23) in patients receiving ventilation with lower
tidal volumes. The results of lung injury development were similar when stratified by
the type of study (randomized vs nonrandomized) and were significant only in random-
ized trials for pulmonary infection and only in nonrandomized trials for mortality. Meta-
analysis using a random-effects model showed, in protective ventilation groups, a lower
incidence of pulmonary infection (RR, 0.45; 95% CI, 0.22 to 0.92; I
2
, 32%; NNT, 26),
lower mean (SD) hospital length of stay (6.91 [2.36] vs 8.87 [2.93] days, respectively;
standardized mean difference [SMD], 0.51; 95% CI, 0.20 to 0.82; I
2
, 75%), higher mean
(SD) Pa
CO
2
levels (41.05 [3.79] vs 37.90 [4.19] mm Hg, respectively; SMD, −0.51; 95%
CI, −0.70 to −0.32; I
2
, 54%), and lower mean (SD) pH values (7.37 [0.03] vs 7.40 [0.04],
respectively; SMD, 1.16; 95% CI, 0.31 to 2.02; I
2
, 96%) but similar mean (SD) ratios of
Pa
O
2
to fraction of inspired oxygen (304.40 [65.7] vs 312.97 [68.13], respectively; SMD,
0.11; 95% CI, −0.06 to 0.27; I
2
, 60%). Tidal volume gradients between the 2 groups
did not influence significantly the final results.
Conclusions Among patients without ARDS, protective ventilation with lower tidal
volumes was associated with better clinical outcomes. Some of the limitations of the
meta-analysis were the mixed setting of mechanical ventilation (intensive care unit or
operating room) and the duration of mechanical ventilation.
JAMA. 2012;308(16):1651-1659 www.jama.com
©2012 American Medical Association. All rights reserved. JAMA, October 24/31, 2012—Vol 308, No. 16 1651
Page 1
patients with ARDS or ALI, thus jus-
tifying the progressive decrease in V
T
used by clinicians over the past
decades.
4-6
However, in critically ill
patients without ALI, there is little
evidence regarding the benefits of
ventilation with lower V
T
, partly
because of a lack of randomized con-
trolled trials evaluating the best ven-
tilator strategies in these patients.
7
Some observational studies have
suggested that use of higher V
T
in
patients without ARDS or ALI, at the
initiation of mechanical ventilation,
increases morbidity and mortality.
8-10
As suggested by the “biotrauma
hypothesis,” ventilation with higher
V
T
and peak pressures may lead to
recruitment of neutrophils and local
production and release of inflamma-
tory mediators.
11
We conducted a
meta-analysis to determine whether
conventional (higher) or protective
(lower) tidal volumes would be asso-
ciated with lung injury, mortality,
pulmonary infection, and atelectasis
in patients without lung injury
at the onset of mechanical ventila-
tion.
METHODS
Studies were identified by 2 authors
through a computerized blinded search
of MEDLINE (1966-2012), Cumula-
tive Index to Nursing and Allied Health
Literature (CINAHL), Web of Sci-
ence, and Cochrane Central Register of
Controlled Trials (CENTRAL) using a
sensitive search strategy combining the
following Medical Subject Headings and
keywords (protective ventilation [text
word] OR lower tidal volumes [text
word]). All reviewed articles and cross-
referenced studies from retrieved ar-
ticles were screened for pertinent in-
formation.
Selection of Studies
Articles were selected for inclusion in
the systematic review if they evalu-
ated 2 types of ventilation in patients
without ARDS or ALI at the onset of
mechanical ventilation. In 1 group of
the study, ventilation was protective
(lower V
T
). Then, this protective ven-
tilation group was compared with
another group using conventional
methods (higher V
T
). A study was
deemed eligible if it evaluated patients
who did not meet the consensus crite-
ria for ARDS or ALI at baseline.
12
We
included randomized trials as well as
observational studies (cohort, before/
after, and cross-sectional), with no
restrictions on language or scenario
(intensive care unit or operating
room). We excluded revisions and
studies that did not report the out-
comes of interest. When we found
duplicate reports of the same study in
preliminary abstracts and articles, we
analyzed data from the most complete
data set. When necessary, we con-
tacted the authors for additional
unpublished data.
Data Extraction
Data were independently extracted from
each report by 3 authors using a data
recording form developed for this pur-
pose. After extraction, data were re-
viewed and compared by the first au-
thor. Instances of disagreement between
the 2 other extractors were solved by a
consensus among the investigators.
Whenever needed, we obtained addi-
tional information about a specific study
by directly questioning the principal in-
vestigator.
Validity Assessment
In randomized trials, we assessed allo-
cation concealment, the baseline simi-
larity of groups (with regard to age, se-
verity of illness, and severity of lung
injury), and the early stopping of treat-
ment. We used the GRADE approach
to summarize the quality of evidence
for each outcome.
13
In this approach,
randomized trials begin as high-
quality evidence but can be rated down
for apparent risk of bias, imprecision,
inconsistency, indirectness, or suspi-
cion of a publication bias.
Definition of End Points
The primary end point was the devel-
opment of lung injury in each group of
the study. Secondary end points in-
cluded overall survival, incidence of
pulmonary infection and atelectasis, in-
tensive care unit (ICU) and hospital
length of stay, time to extubation,
change in Pa
CO
2
, arterial pH values, and
change in the ratio of PaO
2
to fraction
of inspired oxygen (F
IO
2
).
Statistical Analysis
We extracted data regarding the
study design, patient characteristics,
type of ventilation, mean change in
arterial blood gases, lung injury
development, ICU and hospital
length of stay, time to extubation,
overall survival, and incidence of
atelectasis. For the analysis of lung
injury development, mortality, pul-
monary infection, and atelectasis, we
used the most protracted follow-up
in each trial up to hospital discharge.
We calculated a pooled estimate of
risk ratio (RR) in the individual stud-
ies using a fixed-effects model
according to Mantel and Haenszel
and graphically represented these
results using forest plot graphs.
We explored the following vari-
ables as potential modifiers: incorpo-
ration of “open lung” techniques (using
the authors’ definitions) into experi-
mental strategies, between-group gra-
dients in tidal volumes and plateau pres-
sures, and case mix effects. We reasoned
that each of these might influence the
effect of protective ventilation on out-
come. To explore whether these vari-
ables modified the outcome, we com-
pared pooled effects among studies with
and without them. For continuous vari-
ables, we used the standardized mean
difference (SMD), which is the differ-
ence in means divided by a standard
deviation.
The homogeneity assumption was
measured by the I
2
, which describes the
percentage of total variation across stud-
ies that is due to heterogeneity rather
than chance. I
2
was calculated from ba-
sic results obtained from a typical meta-
analysis as I
2
=100% (Qdf)/Q, where
Q is the Cochran heterogeneity statis-
tic. A value of 0% indicates no ob-
served heterogeneity, and larger val-
ues show increasing heterogeneity.
When heterogeneity was found
PROTECTIVE VENTILATION AND LOWER TIDAL VOLUMES
1652 JAMA, October 24/31, 2012—Vol 308, No. 16 ©2012 American Medical Association. All rights reserved.
Page 2
(I
2
25%) we presented the random-
effects model results as primary
analysis.
A sensitivity analysis was carried
out by recalculating pooled RR esti-
mates for different subgroups of stud-
ies based on relevant clinical features.
This analysis demonstrates whether
the overall results have been affected
by a change in the meta-analysis
selection criteria. Also, a sensitivity
analysis about the treatment effect
according to quality components of
the studies (concealed treatment allo-
cation, blinding of patients and care-
givers, blinded outcome assessment)
was conducted. A potential publica-
tion bias was assessed graphically
with funnel plots, as well as by a Begg
and Mazumdar rank correlation and
an Egger regression. Interrater reli-
ability was determined by comparing
the number of studies included by
one author with those of another
author in each stage of the search
using coefficients.
Parametric variables were pre-
sented as the mean and standard de-
viation, and nonparametric variables
were presented as the median and in-
terquartile range (IQR). All analyses
were conducted with Review Manager
version 5.1.1 (The Cochrane Collabo-
ration) and SPSS version 16.0.1 (IBM
SPSS). For all analyses, 2-sided P val-
ues less than .05 were considered sig-
nificant.
RESULTS
Our initial search yielded 2122 stud-
ies (458 from MEDLINE, 141 from
CENTRAL, 885 from CINAHL, and 638
from Web of Science). After removing
711 duplicate studies, we evaluated the
abstracts of 1411 studies. After evalu-
ating the abstract of each study, we ex-
cluded 1364 studies because they did
not meet inclusion criteria. Subse-
quently, we carefully read the full text
of each of the remaining 47 studies and
excluded 27 for the following reasons:
no data on outcome of interest in 20
studies and same cohort previously ana-
lyzed in 7. Twenty references (2822 par-
ticipants) were included in the final
analysis (F
IGURE 1 and TABLE 1). For
the comparisons of interrater reliabil-
ity in each stage of the search, the co-
efficient was 0.91 in the citation stage
(P=.004), 0.86 during the abstract re-
view (P=.03), and 0.90 in the full-text
stage (P=.006).
Study Characteristics
Table 1 summarizes the studies’ char-
acteristics. All but 5 studies
16,22,23,26,29
were randomized controlled trials, and
median follow-up time was 21.0 hours
(IQR, 6.28-54.60 hours). The median
time of per-protocol mechanical venti-
lation was 6.90 hours for protective
and 6.56 hours for conservative strat-
egy. The development of lung injury
was the primary outcome in 4 studies.
Eight studies evaluated the levels of
inflammatory mediators in bronchoal-
veolar lavage or blood. Tidal volume
was set to 6 mL/kg of ideal body
weight (IBW) in the protective group
of 13 studies; only in 1 study was the
tidal volume in the protective ventila-
tion group above 8 mL/kg IBW. Four
studies did not report what weight
was used to calculate the tidal vol-
ume,
14,15,21,25
1 study used the mea-
sured weight,
19
and 15 studies used
the predicted weight.
9,16-18,20,22-24,26-32
Of these, 7 used the ARDSnet formula
to calculated the predicted body
weight.
16,18,20,24,28-30
The tidal volume gradient between
protective and conventional ventila-
tion ranged from 2 to 6 mL/kg IBW,
with a mean (SD) of 4.15 (1.42)
mL/kg IBW. The tidal volume gradient
was less than 4 mL/kg IBW in 30.0%
of the studies, between 4 and 5 mL/kg
IBW in 40% of the studies, and above
5 mL/kg IBW in 30% of the studies. In
15 studies, the reason for intubation
was scheduled surgery,
9,15,17-22,24,25,29-32
and in 5, the reason was mixed (medi-
cal or surgery).
14,16,23,24,28
Lung injury
was diagnosed according to the
American-European Consensus Con-
ference definition in 6 of the 8 trials
that assessed this outcome.
16,23,26,27,31,32
The diagnosis of infection was
made by clinical assessment plus labo-
ratory, radiological, and microbiologi-
cal evaluation in 2 studies
14,26
; was
made by decrease in PaO
2
/FIO
2
plus
radiological assessment in 1 study
31
;
and was not specified in the last
study.
20
eTable 1 (available at http://www.jama
.com) summarizes study methods, high-
lighting features related to the risk of
bias. Randomization was concealed in
11 of 15 randomized controlled trials in-
cluded, and follow-up was excellent with
minimal loss. Limitations included a lack
of blinding (all trials), a lack of inten-
tion-to treat analysis (12 trials), and early
stopping for benefit (1 trial). Age, weight,
minute-volume (product of respira-
tory rate and tidal volume), and Pa
O
2
/
FIO
2
were all similar between the 2
groups analyzed (T
ABLE 2 and eTable 2).
As expected, V
T
and plateau pressure
were lower and positive end-expira-
tory pressure (PEEP) and respiratory rate
were higher in the protective group.
Pa
CO
2
was higher in the protective group
Figure 1. Literature Search Strategy
20 Articles included in meta-analysis
(2822 study participants)
47 Full-text articles assessed
for eligibility
1411 Potentially relevant articles
screened based on abstracts
2122 Articles identified
458 From MEDLINE
141 From CENTRAL
885 From CINAHL
638 From Web of Science
27 Excluded
20 No data on outcome
of interest
7 Same cohort previously
analyzed
711 Excluded (duplicate studies)
1364 Excluded
576 ARDS/ALI at onset of
mechanical ventilation
487 Reviews
227 Experimental studies
33 Secondary analysis
21 Older version of a study
20 Other
ALI indicates acute lung injury; ARDS, acute respira-
tory distress syndrome; CENTRAL, Cochrane Central
Register of Controlled Trials; CINAHL, Cumulative In-
dex to Nursing and Allied Health Literature.
PROTECTIVE VENTILATION AND LOWER TIDAL VOLUMES
©2012 American Medical Association. All rights reserved. JAMA, October 24/31, 2012—Vol 308, No. 16 1653
Page 3
but remained within normal limits
(35-45 mm Hg). Acidosis (pH 7.35)
was found in the protective group in 3
studies, and the pH level in the protec-
tive group was similar to that of the con-
ventional group. The mechanical ven-
tilation settings for each study are
provided in eTable 3.
Primary Outcome
Forty-seven of 1113 patients (4.22%)
assigned to protective ventilation and
138 of 1090 patients (12.66%) as-
signed to conventional ventilation de-
veloped lung injury during follow-up
(RR, 0.33; 95% CI, 0.23-0.47; number
needed to treat [NNT], 11). The re-
sult of the overall test for heteroge-
neity was not statistically significant,
and the I
2
was 0% (no sign of hetero-
geneity) (F
IGURE 2). When stratified by
the tidal volume gradient between the
2 groups, the RR for lung injury de-
creased from 0.35 (95% CI, 0.23-
0.51) in the group with less than 4
Table 1. Characteristics of the Included Studies and Summary of Continuous Variables
Source
a
No. of
Patients
Protective
Conservative
Setting
Follow-up,
h
Duration of MV,
Mean (SD), h
Primary
Outcome
Jadad
Score
V
T
,
mL/kg No.
V
T
,
mL/kg No. Protective Conservative
Lee et al,
14
1999
103 6 47 12 56 SICU 168 2.30 (0.5) 3.90 (0.8) Duration of MV 3
Chaney et al,
15
2000
25 6 12 12 13 CABG Dis ST 1ST 1 Pulmonary
mechanics
2
Gajic et al,
16
2004
166 9 66 12 100 ICU NS NS LI
Koner et al,
17
2004
44 6 15 10 29 CABG 12 9.90 (1.0) 10.0 (1.4) Cytokines in
blood
1
Wrigge et al,
9
2004
62 6 30 12 32 Surgical 3 NS NS Cytokines in
BAL
3
Wrigge et al,
18
2005
44 6 22 12 22 CABG Dis 16.1 (10.2) 12.9 (4.4) Cytokines in
BAL
1
Zupancich et
al,
19
2005
40 8 20 10 20 CS 6 NS NS Cytokines in
BAL
1
Michelet et al,
20
2006
52 5 26 9 26 OS 18 7.06 (1.81) 7.76 (1.85) Cytokines in
blood
3
Cai et al,
21
2007 16 6 8 10 8 Neurosurgery 7.15 6.90 (2.2) 7.4 (3.1) CT atelectasis 2
Wolthuis et al,
22
2007
36 8 23 10 13 ICU NS NS Sedative use
Yilmaz et al,
23
2007
375 8 163 11 212 ICU NS NS LI
Determann et
al,
24
2008
40 6 21 12 19 Surgical 5 ST ST Cytokines in
BAL
3
Lin et al,
25
2008 40 5 20 9 20 OS 24 4.33 (0.9) 4.23 (0.71) Cytokines in
blood
1
Licker et al,
26
2009
1091 6 558 9 533 OS 2.93 (1.2) 2.76 (1.0) LI
Determann et
al,
27
2010
150 6 76 10 74 ICU 672 NS NS Cytokines in
BAL
3
de Oliveira et
al,
28
2010
20 6 10 12 10 SICU 672 168.0 72.0 Cytokines in
BAL
3
Fernandez-
Bustamante
et al,
29
2011
229 8 154 10 75 Surgical NS NS Duration of MV;
ICULS;
mortality
Sundar et al,
30
2011
149 6 75 10 74 CS 672 7.50 10.71 Duration of MV 3
Yang et al,
31
2011
100 6 50 10 50 OS 168 2.00 (0.68) 2.11 (0.8) LI 3
Weingarten et
al,
32
2012
40 6 20 10 20 Surgical Dis 5.13 (1.86) 5.73 (1.71) Oxygenation 3
Total, Mean
(SD)
2822 6.45
(1.09)
1416 10.60
(1.14)
1406 21.0
(6.28-54.6)
b
6.90
(2.93-9.90)
b
6.56
(3.61-10.17)
b
2.33
(0.89)
Abbreviations: BAL, bronchoalveolar lavage; CABG, coronary artery bypass graft surgery; CS, cardiac surgery; CT, computed tomography; Dis, until patient’s discharge; ICU, intensive
care unit; ICULS, ICU length of stay; LI, lung injury; MV, mechanical ventilation; NS, not specified; OS, oncology surgery; SICU, surgical intensive care unit; ST, surgery time; V
T
, tidal
volume.
a
Most of the studies were randomized controlled trials. The exceptions are as follows: Gajic et al,
16
Yilmaz et al,
23
and Licker et al,
26
were cohort studies; Wolthuis et al
22
had a before-
and-after design; and Bustamante et al
29
had a cross-sectional design.
b
Median (interquartile range).
PROTECTIVE VENTILATION AND LOWER TIDAL VOLUMES
1654 JAMA, October 24/31, 2012—Vol 308, No. 16 ©2012 American Medical Association. All rights reserved.
Page 4
mL/kg IBW to 0.26 (95% CI, 0.10-
0.66) in the group with 4 to 5 mL/kg
IBW (eFigure 1). The RR for the de-
velopment of lung injury with conven-
tional ventilation, analyzing only ran-
domized controlled trials, was 0.26
(95% CI, 0.10-0.66; NNT, 10).
Secondary Outcomes
Overall mortality was lower in pa-
tients receiving protective ventilation
(RR, 0.64; 95% CI, 0.46 to 0.89; NNT,
23). The incidence of pulmonary in-
fection (using the authors’ definition)
and atelectasis were lower in the group
receiving ventilation with a lower V
T
(RR [random-effect], 0.45; 95% CI, 0.22
to 0.92; NNT, 26; and RR, 0.62; 95%
CI, 0.41 to 0.95, respectively)
(Figure 2). The I
2
test indicated mod-
erate heterogeneity only in the analy-
sis of pulmonary infection (32%). Pro-
tective ventilation was associated with
a shorter mean (SD) hospital stay (6.91
[2.36] vs 8.87 [2.93] days, respec-
tively; SMD, 0.51; 95% CI, 0.20 to 0.82),
and showed no difference in ICU stay
(3.63 [2.43] vs 4.64 [3.29] days, re-
spectively; SMD, 0.37; 95% CI, −0.53
to 1.27) and time of mechanical ven-
tilation (51.07 [58.08] vs 47.12 [45.00]
hours, respectively; SMD, 0.48; 95% CI,
−0.27 to 1.23).
Mean (SD) levels of Pa
CO
2
were
higher in the protective ventilation
group (41.05 [3.79] vs 37.90 [4.19]
mm Hg, respectively; SMD, −0.51; 95%
CI, −0.70 to −0.32), and mean (SD) pH
levels were lower (7.37 [0.03] vs 7.40
[0.03], respectively; SMD, 1.16; 95% CI,
0.31 to 2.02). The mean (SD) Pa
O
2
/
FIO
2
ratio was similar between the
groups (304.40 [65.70] vs 312.97
[68.13], respectively; SMD, 0.11; 95%
CI, −0.06 to 0.27). All these analyses
yield significant heterogeneity and were
analyzed by random-effects model (I
2
for hospital stay, ICU stay, time of me-
chanical ventilation, Pa
CO
2
, pH, and
Pa
O
2
/FIO
2
of 75%, 95%, 92%, 54%, 96%,
and 60%, respectively) (eFigures 2, 3,
4, 5, 6, and 7 and eTable 4).
In eTable 5, the GRADE evidence
profile is provided. This profile evalu-
ates the effect of protective ventilation
in patients without ARDS or ALI, only
from a systematic review and a meta-
analysis of randomized controlled trials.
The findings for lung injury, mortal-
ity, and pulmonary infection were con-
sidered moderate, high, and low qual-
ity, respectively, by the GRADE profile.
Sensitivity analyses according to qual-
ity components of each study are shown
in eTable 6.
In addition, we excluded each trial
one at a time and assessed the results.
In lung injury and pulmonary infec-
tion analyses, the results were always
significant despite the exclusion of any
trial. After we excluded the trial by
Yilmaz et al,
23
the analysis of mortality
was no longer significant.
Sensitivity Analysis
To explore these results, we per-
formed a stratified analysis across a
number of key study characteristics and
clinical factors, and this analysis is
shown in T
ABLE 3. Protection from lung
injury, in the protective group, was
more pronounced in studies that were
not randomized controlled trials per-
formed in the ICU. These trials did not
incorporate recruitment maneuvers,
had a higher plateau pressure gradi-
ent, and a smaller tidal volume gradi-
ent. In the survival analysis, we found
significant changes in studies without
recruitment maneuvers, in studies that
were not randomized trials, and in stud-
ies performed in the ICU with a lower
tidal volume gradient.
For pulmonary infections, we
found no statistically significant asso-
ciation in studies that were not ran-
domized trials, a tidal volume gradi-
ent less than 4 mL/kg IBW, and the
use of recruitment maneuvers. A tidal
volume gradient from 4 to 5 mL/kg
IBW and a randomized controlled
trial performed in surgical patients
were each associated with a signifi-
cant reduction in pulmonary infec-
tions in the protective group.
Publication Bias
Funnel-plot graphical analysis (eFig-
ure 8), Begg and Mazumdar rank cor-
relation, and Egger regression did not
suggest a significant publication bias for
the analyses conducted in Figure 2
(Kendall =0.17, P=.63; Egger regres-
sion intercept=0.24, P=.68).
COMMENT
We found evidence that a ventilation
strategy using lower tidal volumes is as-
sociated with a lower risk for develop-
ing ARDS. Furthermore, the strategy
was associated with lower mortality,
fewer pulmonary infections, and less at-
electasis when compared with higher
tidal volume ventilation in patients
without lung injury at the onset of me-
Table 2. Demographic, Ventilation, and Laboratory Characteristics of the Patients at the Final
Follow-up Visit
Mean (SD)
P
Value
Protective
Ventilation
(n = 1416)
Conventional
Ventilation
(n = 1406)
Age, y 59.97 (7.92) 60.22 (7.36) .93
Weight, kg 72.71 (12.34) 72.13 (12.16) .93
Tidal volume, mL/kg IBW
a
6.45 (1.09) 10.60 (1.14) .001
PEEP, cm H
2
O
a
6.40 (2.39) 3.41 (2.79) .01
Plateau pressure, cm H
2
O
a
16.63 (2.58) 21.35 (3.61) .006
Respiratory rate,
breaths/min
a
18.02 (4.14) 13.20 (4.43) .01
Minute-volume, L/min
a,b
8.46 (2.90) 9.13 (2.70) .72
Pa
O
2
/FIO
2
a
304.41 (65.74) 312.97 (68.13) .51
Pa
CO
2
,mmHg
a
41.05 (3.79) 37.90 (4.19) .003
pH
a
7.37 (0.03) 7.40 (0.03) .11
Abbreviations: FIO
2
, fraction of inspired oxygen; IBW, ideal body weight; PEEP, positive end-expiratory pressure.
a
At the final follow-up visit.
b
Minute-volume is the product of respiratory rate and tidal volume.
PROTECTIVE VENTILATION AND LOWER TIDAL VOLUMES
©2012 American Medical Association. All rights reserved. JAMA, October 24/31, 2012—Vol 308, No. 16 1655
Page 5
chanical ventilation. These benefits
were associated with a shorter hospi-
tal length of stay. Protective ventila-
tion was associated with higher Pa
CO
2
levels and lower pH values, but no dif-
ference in the incidence of acidosis was
found. In all studies, although the pri-
mary goal of the investigators was to
compare 2 different tidal volumes, other
ventilator strategy elements were asso-
ciated with the use of lower tidal vol-
umes. Notably, differences in the lev-
els of PEEP and plateau pressure did not
influence the final results of the meta-
analysis.
Previously, Esteban et al
33
showed
plateau pressures above 35 cm H
2
Oto
be associated with an increased risk of
death in ICU patients. Although not de-
finitive, this study at least suggested that
higher V
T
has the ability to exaggerate
lung injury and maybe even cause death
in patients who require mechanical ven-
tilation for days. Fernández-Pérez et al
34
showed higher V
T
to be associated with
postoperative respiratory failure in pa-
tients receiving ventilation for only a
few hours in the operating room. In
light of this information, over the past
decade, V
T
has progressively de-
Figure 2. Effect of Ventilation With Smaller Tidal Volume in Patients With Healthy Lungs at the End of the Follow-up Period for Each Study
Favors Low V
T
Favors High V
T
0.01 101.0 1000.1
RR (95% CI)
High V
T
, No.
Events Total
Low V
T
, No.
Events Total
Lung injury
RR (95% CI)Weight, %
32 100 12 66Gajic et al,
16
2004 0.47 (0.22-1.00)18.1
626 326Michelet et al,
20
2006 0.43 (0.10-1.97)4.6
60 212 17 163Yilmaz et al,
23
2007 0.29 (0.16-0.53)40.7
20 533 5 558Licker et al,
26
2009 0.23 (0.09-0.62)17.7
10 74 2 76Determann et al,
27
2010 0.17 (0.04-0.82)8.6
450 150Yang et al,
31
2011 0.23 (0.03-2.18)3.4
5 75 7 154Fernandez-Bustamante et al,
29
2011 0.67 (0.20-2.17)5.6
120 020Weingarten et al,
32
2012 0.32 (0.01-8.26)1.3
1090 1113Subtotal (95% CI) 0.33 (0.23-0.47)100.0
138 47Total events
Heterogeneity: χ
2
7
=
3.74; P
=
.81, I
2
=
0%
Test for overall effect: z
=
6.06; P<.001
0.01 101.0 1000.1
RR (95% CI)
Mortality
126 226Michelet et al,
20
2006 2.08 (0.18-24.51)1.0
213 323Wolthuis et al,
22
2007 0.82 (0.12-5.71)2.5
69 212 27 163Yilmaz et al,
23
2007 0.41 (0.25-0.68)55.7
15 533 13 558Licker et al,
26
2009 0.82 (0.39-1.75)16.7
23 74 24 76Determann et al,
27
2010 1.02 (0.51-2.04)17.7
1 75 3 154Fernandez-Bustamante et al,
29
2011 1.47 (0.15-14.38)1.5
274 175Sundar et al,
30
2011 0.49 (0.04-5.48)2.2
150 050Yang et al,
31
2011 0.33 (0.01-8.21)1.7
120 120Weingarten et al,
32
2012 1.00 (0.06-17.18)1.1
1077 1145Subtotal (95% CI) 0.64 (0.46-0.86)100.0
115 74Total events
Heterogeneity: χ
2
8
=
6.94; P
=
.54, I
2
=
0%
Test for overall effect: z
=
2.68; P
=
.007
0.01 101.0 1000.1
RR (95% CI)
Atelectasis
220 320Lin et al,
25
2008 1.59 (0.24-10.70)3.1
58 78Cai et al,
21
2007 4.20 (0.33-53.12)1.1
47 533 28 558Licker et al,
26
2009 0.55 (0.34-0.89)83.1
350 150Yang et al,
31
2011 0.32 (0.03-3.18)5.4
520 420Weingarten et al,
32
2012 0.75 (0.17-3.33)7.3
631 656Subtotal (95% CI) 0.62 (0.41-0.95)100.0
62 43Total events
Heterogeneity: χ
2
4
=
3.76; P
=
.44, I
2
=
0%
Test for overall effect: z
=
2.18; P
=
.03
RR (95% CI)
0.01 101.0 1000.1
Pulmonary infection
10 56 2 47Lee et al,
14
1999 0.20 (0.04-0.99)16.6
10 26 6 26Michelet et al,
20
2006 0.48 (0.14-1.60)14.6
30 533 23 558Licker et al,
26
2009 0.72 (0.41-1.26)55.8
750 150Yang et al,
31
2011 0.13 (0.01-1.06)13.0
665 681Subtotal (95% CI) 0.52 (0.33-0.82)100.0
57 32Total events
Heterogeneity: χ
2
3
=
4.39; P
=
.22, I
2
=
32%
Test for overall effect: z
=
2.79; P
=
.005
A pooled estimate of risk ratio (RR) was calculated in the individual studies using a fixed-effects model according to Mantel and Haenszel. The size of the data markers
indicates the weight of the study in the final analyses. V
T
indicates tidal volume.
PROTECTIVE VENTILATION AND LOWER TIDAL VOLUMES
1656 JAMA, October 24/31, 2012—Vol 308, No. 16 ©2012 American Medical Association. All rights reserved.
Page 6
creased from greater than 12 to 15
mL/kg IBW to less than 9 mL/kg
IBW.
6,35
The results of the present meta-
analysis support this change in venti-
lation practice. Our results may even
suggest that V
T
should be further re-
duced.
Protective ventilation in patients
with ALI or ARDS is already well
established; however, physicians do
not always adhere to such guidelines.
Mikkelsen et al
36
reported that ap-
proximately one-third of the pa-
tients were receiving protective ven-
tilation at 48 hours, and the main
reason for poor adherence was the
uncertainty about the diagnosis of
ARDS. Another possible reason is
that 82% of the patients who never
received protective ventilation had a
plateau pressure below 30 cm H
2
O.
However, it is well established that
reducing the V
T
in patients with pla-
teau pressures below 30 cm H
2
Ois
associated with a survival benefit.
10
In this context, the adoption of pro-
tective ventilation in patients without
lung injury may be even more diffi-
cult.
It is possible that the beneficial ef-
fects of protective ventilation, regard-
ing the development of lung injury, are
even greater than what is suggested by
the current analysis. Mechanical ven-
tilation can damage the lung, cause in-
flammation, and release cytokines into
the systemic circulation.
20,25
This pro-
cess may cause fever, leukocytosis, and
new pulmonary infiltrates, which could
be interpreted as ventilator-associated
pneumonia instead of ventilator-
associated lung injury. The absence of
strict criteria for the diagnosis of pneu-
monia, such as microbiological identi-
fication in blood and bronchoalveolar
lavage, in the studies evaluated may lead
to an incorrect diagnosis. Ventilator-
associated lung injury may be incor-
rectly diagnosed as pneumonia in many
cases, underestimating the true inci-
dence of lung injury. It is difficult to di-
agnose pneumonia in the presence of
ARDS or ALI, with a quoted sensitiv-
ity using conventional clinical criteria
of less than 50%.
37
Table 3. Summary of Stratified Analyses of Pooled Relative Risks
Stratified Analysis
No. of
Trials
No. of
Patients
Risk Ratio
(95% CI)
P
Value
Heterogeneity,
Q
Acute Lung Injury
Recruitment maneuvers
Yes 1 1091 0.23 (0.09-0.62) .004
No 7 1112 0.35 (0.24-0.52) .001 0.80
Tidal volume gradient, mL/kg IBW
4 4 1861 0.35 (0.23-0.51) .001 0.43
4-5 4 342 0.26 (0.10-0.66) .004 .87
Randomized
Yes 4 342 0.26 (0.10-0.66) .004 0.87
No 4 1861 0.35 (0.23-0.51) .001 0.43
Setting
Operation room 5 1512 0.34 (0.18-0.63) .001 0.73
ICU 3 691 0.33 (0.21-0.51) .001 0.43
Plateau pressure gradient, cm H
2
O
4 3 368 0.38 (0.21-0.71) .002 0.52
4-8 1 1091 0.23 (0.09-0.62) .004
Diagnosis
AECCD 6 1922 0.30 (0.21-0.45) .001 0.83
Other 2 281 0.56 (0.22-1.41) .22 0.66
Mortality
Recruitment maneuvers
Yes 1 1091 0.82 (0.39-1.75) .61
No 8 1131 0.60 (0.42-0.87) .006 0.49
Tidal volume gradient, mL/kg IBW
4 4 1731 0.54 (0.36-0.79) .002 0.35
4-5 5 491 0.97 (0.53-1.78) .92 0.89
Randomized
Yes 5 491 0.97 (0.53-1.78) .92 0.89
No 4 1731 0.54 (0.36-0.79) .002 0.35
Setting
Operation room 6 1661 0.86 (0.46-1.60) .63 0.94
ICU 3 561 0.57 (0.38-0.84) .005 0.10
Plateau pressure gradient, cm H
2
O
4 3 351 1.02 (0.54-1.92) .95 0.71
4-8 1 1091 0.82 (0.39-1.75) .61
Pulmonary Infection
Recruitment maneuvers
Yes 1 1091 0.72 (0.41-1.26) .25
No 3 255 0.27 (0.12-0.64) .003 .48
Tidal volume gradient, mL/kg IBW
4 1 1091 0.72 (0.41-1.26) .25
4-5 2 152 0.31 (0.11-0.86) .02 0.28
5 1 103 0.20 (0.04-0.99) .05
Randomized
Yes 3 255 0.27 (0.12-0.64) .003 0.48
No 1 1091 0.72 (0.41-1.26) .25
Setting
Operation room 3 1243 0.59 (0.36-0.95) .03 0.27
ICU 1 103 0.20 (0.04-0.99) .05
Plateau pressure gradient, cm H
2
O
4 2 155 0.33 (0.13-0.85) .02 0.40
4-8 1 1091 0.72 (0.41-1.26) .25
Infection diagnosis
Not specified 1 52 0.48 (0.14-1.60) .23
Specified 3 1294 0.53 (0.32-0.87) .01 0.11
CLCXR 2 1194 0.60 (0.36-1.01) .05 0.14
PaO
2
/FIO
2
x-ray 1 100 0.13 (0.01-1.06) .06
Abbreviations: AECCD, American-European Consensus Conference definition; CLCXR, clinical laboratory culture x-
ray; F
IO
2
, fraction of inspired oxygen; IBW, ideal body weight; ICU, intensive care unit.
PROTECTIVE VENTILATION AND LOWER TIDAL VOLUMES
©2012 American Medical Association. All rights reserved. JAMA, October 24/31, 2012—Vol 308, No. 16 1657
Page 7
Our findings are in line with a re-
cently published retrospective study of
cardiac surgery patients.
38
Although it
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.
23
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
2
=0%).
Pulmonary infection yielded moder-
ate heterogeneity (I
2
=32%), but the
analysis with a random-effects model
showed similar results. However, all the
continuous analyses showed signifi-
cant heterogeneity (all I
2
60%) and
with the use of a random-effects model
only differences in pH level, Pa
CO
2
level,
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
data analysis.
Study concept and design: Serpa Neto, Cardoso,
Manetta, Pereira, Espo´ sito, Schultz.
Acquisition of data: Serpa Neto, Pereira, Espo´ sito,
Pasqualucci.
Analysis and interpretation of data: Serpa Neto,
Cardoso, Manetta, Pereira, Espo´ sito, Damasceno,
Schultz.
Drafting of the manuscript: Serpa Neto, Pereira,
Damasceno, Schultz.
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,
Schultz.
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-
ported.
Online-Only Material: The eTables and eFigures are
available at http://www.jama.com.
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    • "Whether this unfavorable prognosis was more related to cardiac or noncardiac complications (e.g., infections, septic shock, and pulmonary complications of MV) we could not determine. In fact, a cause-and-effect relationship between invasive MV and clinical outcomes could not be established, and our findings might have been influenced by complications of invasive MV such as ventilator-associated pneumonia, delirium and acute respiratory distress syndrome [15,16,17,18]. Importantly, compared to patients treated without MV, the use of cardiovascular pharmacotherapy was less common in the invasive MV subgroup and reperfusion therapy was less common in both, invasive and non-invasive MV subgroups. "
    [Show abstract] [Hide abstract] ABSTRACT: Purpose: Patients with acute myocardial infarction (AMI) and respiratory impairment may be treated with either invasive or non-invasive mechanical ventilation (MV). However, there has been little testing of non-invasive MV in the setting of AMI. Our objective was to evaluate the incidence and associated clinical outcomes of patients with AMI who were treated with non-invasive or invasive MV. Methods: This was a retrospective observational study in which consecutive patients with AMI (n = 1610) were enrolled. The association between exclusively non-invasive MV, invasive MV and outcomes was assessed by multivariable models. Results: Mechanical ventilation was used in 293 patients (54% invasive and 46% exclusively non-invasive). In-hospital mortality rates for patients without MV, with exclusively non-invasive MV, and with invasive MV were 4.0%, 8.8%, and 39.5%, respectively (P<0.001). The median lengths of hospital stay were 6 (5.8-6.2), 13 (11.2-4.7), and 28 (18.0-37.9) days, respectively (P<0.001). Exclusively non-invasive MV was not associated with in-hospital death (adjusted HR = 0.90, 95% CI 0.40-1.99, P = 0.79). Invasive MV was strongly associated with a higher risk of in-hospital death (adjusted HR = 3.07, 95% CI 1.79-5.26, P<0.001). Conclusions: In AMI setting, 18% of the patients required MV. Almost half of these patients were treated with exclusively non-invasive strategies with a favorable prognosis, while patients who needed to be treated invasively had a three-fold increase in the risk of death. Future prospective randomized trials are needed to compare the effectiveness of invasive and non-invasive MV for the initial approach of respiratory failure in AMI patients.
    Full-text · Article · Mar 2016 · PLoS ONE
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    • "It is unclear how patients under GA for EST are optimally ventilated. Principally, there is no reason not to apply customary lung-protective ventilation to these patients [61]. Pathophysiological considerations support providing normoxemia and adequate (or adequately enhanced) perfusion via collaterals to the ischemic penumbra. "
    [Show abstract] [Hide abstract] ABSTRACT: Opinion statement: The acute treatment of major ischemic stroke has been revolutionized by strong and consistent evidence from multiple randomized trials. Endovascular treatment by mechanical thrombectomy will be increasingly chosen as an adjunctive or alternative to intravenous thrombolysis. To apply this form of stroke treatment is associated with the challenge of optimal periinterventional treatment. The patient has to be identified, counselled, prepared, monitored, cardiovascularly stabilized, possibly sedated and ventilated, and postprocedurally treated in the optimal way. However, most aspects of periinterventional treatment have as yet not been clarified and require prospective research. Among these, the question of general anesthesia vs conscious sedation has received most attention and may be the most crucial one. Based on a great amount of retrospective data, it appears reasonable to start the intervention under conscious sedation of the non-intubated patient with standby measures for emergent intubation, until prospective randomized trials have clarified that issue. Periinterventional management will significantly affect the success of recanalization.
    Preview · Article · Sep 2015 · Current Treatment Options in Neurology
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    • "The diagnosis of ARDS is important even when resources are limited because two of the management strategies demonstrated to improve mortality in ARDS – lung protective ventilation and proning [20, 21] – are cheap and potentially feasible to implement in a range of settings. While some evidence supports more liberal use of lung protective ventilation in respiratory failure [22], understanding the prevalence of ARDS is one element in a necessary effort to improve detection and treatment of respiratory diseases and critical illness in low-resource settings globally [23][24][25][26][27]. Our study offers several strengths. "
    [Show abstract] [Hide abstract] ABSTRACT: In low-resource settings it is not always possible to acquire the information required to diagnose acute respiratory distress syndrome (ARDS). Ultrasound and pulse oximetry, however, may be available in these settings. This study was designed to test whether pulmonary ultrasound and pulse oximetry could be used in place of traditional radiographic and oxygenation evaluation for ARDS. This study was a prospective, single-center study in the ICU of Harborview Medical Center, a referral hospital in Seattle, Washington, USA. Bedside pulmonary ultrasound was performed on ICU patients receiving invasive mechanical ventilation. Pulse oximetric oxygen saturation (SpO2), partial pressure of oxygen (PaO2), fraction of inspired oxygen (FiO2), provider diagnoses, and chest radiograph closest to time of ultrasound were recorded or interpreted. One hundred and twenty three ultrasound assessments were performed on 77 consecutively enrolled patients with respiratory failure. Oxygenation and radiographic criteria for ARDS were met in 35 assessments. Where SpO2 ≤ 97 %, the Spearman rank correlation coefficient between SpO2/FiO2 and PaO2/FiO2 was 0.83, p < 0.0001. The sensitivity and specificity of the previously reported threshold of SpO2/FiO2 ≤ 315 for PaO2/FiO2 ≤ 300 was 83 % (95 % confidence interval (CI) 68-93), and 50 % (95 % CI 1-99), respectively. Sensitivity and specificity of SpO2/FiO2 ≤ 235 for PaO2/FiO2 ≤ 200 was 70 % (95 % CI 47-87), and 90 % (95 % CI 68-99), respectively. For pulmonary ultrasound assessments interpreted by the study physician, the sensitivity and specificity of ultrasound interstitial syndrome bilaterally and involving at least three lung fields were 80 % (95 % CI 63-92) and 62 % (95 % CI 49-74) for radiographic criteria for ARDS. Combining SpO2/FiO2 with ultrasound to determine oxygenation and radiographic criteria for ARDS, the sensitivity was 83 % (95 % CI 52-98) and specificity was 62 % (95 % CI 38-82). For moderate-severe ARDS criteria (PaO2/FiO2 ≤ 200), sensitivity was 64 % (95 % CI 31-89) and specificity was 86 % (95 % CI 65-97). Excluding repeat assessments and independent interpretation of ultrasound images did not significantly alter the sensitivity measures. Pulse oximetry and pulmonary ultrasound may be useful tools to screen for, or rule out, impaired oxygenation or lung abnormalities consistent with ARDS in under-resourced settings where arterial blood gas testing and chest radiography are not readily available.
    Full-text · Article · Sep 2015 · Critical care (London, England)
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