Intensive Care Med (2008) 34:10021011

DOI 10.1007/s00134-008-1062-3 SYSTEMATIC REVIEW

Fekri Abroug
Lamia Ouanes-Besbes
The effect of prone positioning in acute
Souheil Elatrous respiratory distress syndrome or acute lung
Laurent Brochard
injury: a meta-analysis. Areas of uncertainty
and recommendations for research

Received: 2 August 2007
Accepted: 5 January 2008
Published online: 19 March 2008
Springer-Verlag 2008
F. Abroug (!) L. Ouanes-Besbes
CHU F. Bourguiba, Service de Ranimation selected randomised controlled trials
Polyvalente,
5000 Monastir, Tunisia
e-mail: f.abroug@rns.tn
S. Elatrous
CHU T. Sfar, Service de Ranimation
Mdicale,
Mahdia, Tunisia
L. Brochard
Hpital Henri Mondor, INSERM U 841,
Service de Ranimation Mdicale, AP-HP,
Crteil, France
Abstract Objective: To compare
the effects of ventilation in prone and not find a significant effect of prone
in supine position in patients with
acute lung injury/acute respiratory
distress syndrome (ALI/ARDS).
Design: Meta-analysis of randomised
controlled trials. Data sources:
BioMedCentral, PubMed, CINAHL,
and Embase (to November 2007), with
additional information from authors.
Measurements and results: From
comparing positioning in ALI/ARDS
we extracted data concerning study
design, disease severity, clinical out-
comes, and adverse events. Five trials
including 1,372 patients met the inclu-
sion criteria for mortality analysis; one
trial was added to assess the effects
on acquisition of ventilator-associated
pneumonia (VAP). The included trials
were significantly underpowered
and enrolled patients with varying
severity. Prone positioning duration
and mechanical ventilation strategy
were not standardised across studies.
Using a fixed-effects model, we did
positioning (proning) on mortality
(odds ratio 0.97, 95% confidence
interval 0.771.22). The PaO2 /FiO2
ratio increased significantly more with
proning (weighted means difference
25 mmHg, p < 0.00001). Proning
was associated with a non-significant
23% reduction in the odds of VAP
(p = 0.09), and with no increase
in major adverse airway complica-
tions: OR 1.01, 95% CI 0.711.43.
Length of intensive care unit stay
was marginally and not significantly
increased by proning. Conclusions:
Prone position is not associated with
a significant reduction in mortality
from ALI/ARDS despite a significant
increase in PaO2 /FiO2 , is safe, and
tends to decrease VAP. Published
studies exhibit substantial clinical
heterogeneity, suggesting that an
adequately sized study optimising
the duration of proning and ventila-
tion strategy is warranted to enable
definitive conclusions to be drawn.
Keywords ARDS ALI Mechanical
ventilation Prone positioning

Introduction ventilation in prone position improves arterial oxygena-

Acute respiratory distress syndrome (ARDS) and acute
lung injury (ALI) remain associated with unacceptably
high mortality despite recent advances in supportive
treatment [1]. Several open-label studies showed that
tion with few untoward effects, in 58100% of paediatric
and adult patients [211]. Prone position enhances
oxygenation via more even distribution of gravitational
gradient in pleural pressure [12, 13], better distribution
of ventilation to the dorsal areas of the lungs [1416],

and potentially lesser overdistension of airspace, reducing
thereby the occurrence of ventilator-induced lung in-
jury [1720]. It also improves lung mechanics and alveolar
ventilation [16].
In addition to a reduction in the intensity of ventilator
support (lower inspired oxygen concentration, lower
PEEP and mean airway pressure decreasing the ventilator-
associated lung injury), resulting hence in facilitated
patient recovery and earlier weaning from mechanical
ventilation, beneficial physiologic effects of prone posi-
tioning are expected to ensue in improved overall outcome
and especially in reduced mortality [21].
Two large randomised controlled trials (RCTs) and
two moderately sized RCTs comparing prone pos-
ition ventilation with supine ventilation in ARDS/ALI
patients failed to show an improved survival rate in such
patients [2225]. As a consequence of the accumulation
of published negative trials, recent surveys have recorded
a statistically significant decrease in the use of prone
positioning at any time from 13% of ARDS patients in
1998 to 7% in 2004 [26]. This phenomenon has been
recorded in the same intensive care units (ICUs) that were
surveyed in 1998. It seems that the lack of evidence of an
efficacy of prone positioning on a patient-centred outcome
(mortality) has been interpreted as evidence of the absence
of clinically relevant effect of prone positioning. This
was reinforced by the lack of information on the trade-off
between benefits and risks of prone positioning [increase
in PaO2 /FiO2 and reduced rate of ventilator-associated
pneumonia (VAP) on the one hand, and increased work-
load, accidental tracheal tube displacement, and pressure
sores on the other hand].
However, some of these RCTs were stopped before
the termination of patients inclusion, yielding studies
substantially underpowered to demonstrate potential
benefits of prone ventilation [22, 24, 25]. Additional
methodological limitations accrue from inclusion of
patients with different ARDS severity, patients in the late
stages of ARDS, absence of ventilation guidelines, and
the use of high tidal volumes. Moreover, these studies
highlighted the lack of general agreement on the duration
of prone position, both on a 24-h basis and throughout the
course of ARDS.
Of interest, the most recent RCT on prone positioning
showed in a multivariate analysis that prone ventilation
was an independent factor associated with improved sur-
vival in patients with severe ARDS [25]. This study, which
was prematurely stopped because of a slow inclusion rate,
had the peculiar design of targeting a prolonged prone pos-
ition (20 h per day).
Since none of the published RCTs was sufficiently
highly powered to enable definitive conclusions, we
undertook this meta-analysis to systematically review
the published randomised trials assessing the effect of
prone positioning on mortality of patients with ARDS/
ALI.
1003
Methods
Search strategy
Pertinent studies were independently searched in PubMed,
EMBASE, CINAHL, and BioMedCentral (updated
30 November 2007), by two trained investigators (F.A.,
L.O.-B.) using the following MeSH and keyword terms:
acute respiratory distress syndrome, acute lung injury,
acute respiratory failure, and prone position ventila-
tion. The literature search included both adult and paedi-
atric populations. No language restriction was imposed.
Study selection
Titles, abstracts, and citations were independently assessed
by both reviewers to assess the potential relevance for full
review. From the full text, both reviewers independently
assessed studies for inclusion based on the criteria for
population, intervention, study design, and outcomes. In-
cluded studies met the following criteria: (1) All study
participants, whether adults or children, had a clinical diag-
nosis of acute respiratory failure (ARF), acute respiratory
distress syndrome or acute lung injury. ARDS and ALI
were respectively defined by the radiographic evidence
of bilateral pulmonary infiltrates, the absence of clinical
evidence of left atrial hypertension, and a PaO2 /FiO2
ratio of 300 or less (characteristic of ALI), or 200 or less
(characteristic of ARDS). (2) Intervention: conventional
ventilation in supine position compared with ventilation
in prone position whatever its duration, on a 24-h basis,
and during the ICU stay. (3) Design: prospective RCTs.
(4) Outcomes: mortality rate, whether the ICU mortality
or 28-day mortality, was the main outcome of this meta-
analysis. It had to be clearly reported in the manuscript.
Secondary outcomes corresponded to the following: the
effect of prone positioning on PaO2 /FiO2 ratio. This
usually corresponded to the average change of PaO2 /FiO2
ratio during the duration of the technique implementation.
We also analysed the reported rate of VAP whatever its
diagnosis method. Analysis also encompassed the inci-
dence of procedure-related major airway complications.
These were defined by the occurrence of accidental extu-
bation, selective intubation, or accidental displacement of
tracheal tube. We also compared the length of ICU stay.
Excluded from the meta-analysis were: (1) non-
controlled studies; (2) studies that examined only the
physiologic effects of prone positioning. These studies
included either ARDS/ALI patients or patients with acute
exacerbation of COPD.
Data abstraction and study characteristics
We extracted study design (including patient selection and
randomisation), population, prone position duration on
1004

a 24-h basis, ventilatory strategy (whether a pulmonary
protective strategy was used or not), and duration of
follow-up. We also made a post-hoc power analysis
corresponding to the power of the analysed study to detect
the relative risk of mortality actually observed in that
experiment. The primary end-point of our analysis was
to determine the effect of prone ventilation on the inci-
dence of ICU or 28-day mortality. Secondary end-points
included effects on oxygenation during the acute phase of
illness assessed by the PaO2 /FiO2 change, the incidence
of VAP and that of major airway adverse effects in relation
with prone position. We also analysed the duration of ICU
stay. We attempted to contact authors of included trials to
request additional data if necessary.
Internal validity assessment
The methodological quality of each trial was evaluated
using the 5-point scale (0 = worst and 5 = best) as de-
scribed by Jadad et al. [27]. This instrument assesses the
adequacy of randomisation, blinding, and the handling of
withdrawals and dropouts.
investigate the hypothesis that higher effect might be dis-
closed in more severely ill patients, we also sought for a re-
lation between the relative risk reduction recorded in each
study and the mortality rate in the corresponding control
(supine) group. The meta-analysis was conducted using
RevMan 4.2.10. This study was performed in compliance
with The Cochrane Collaboration and the Quality of
Reporting of Meta-Analyses (QUOROM) guidelines [29].
Results
Study characteristics
Figure 1 shows a flow chart of studies assessed and
excluded at various stages of the review. Finally, a total of
six prospective RCTs were selected. One of these studies
examined the effect of prone positioning on the prevention

Data analysis and synthesis

Our primary outcome was mortality in the ICU or at

28 days. Secondary end-points included respective effects
of prone and supine position on oxygenation during
the acute phase of illness (ranging from 4 to 10 days),
the incidence of VAP, and that of major airway adverse
complications (extubation, selective intubation) and
minor complications (pressure sores) in relation to prone
position. We also compared the duration of ICU stay.
Binary outcomes from individual studies were ana-
lysed according to the MantelHaenszel model to compute
individual odds ratios (ORs) with pertinent 95% confi-
dence intervals (CIs), and a pooled summary effect
estimate was calculated by means of a fixed-effects model.
Weighted mean differences (WMDs) and 95% CI were
computed for continuous variables. Statistical hetero-
geneity and inconsistency were measured by using Coch-
ran Q tests and I 2 , respectively [28]. Since the majority
of published studies were negative, the risk of publication
bias was assessed by using visual inspection of funnel plot.
Statistical significance is set at the two-tailed 0.05 level
for hypothesis testing and 0.10 for heterogeneity testing.
I 2 values around 25%, 50%, and 75% were considered
to represent low, moderate, and severe statistical incon-
sistency, respectively. Unadjusted P values are reported
throughout. The relationship between baseline PaO2 /FiO2
ratio (a surrogate for patients disease severity) or the
duration of prone positioning (a surrogate for treatment
intensity) on one hand, and the odds of mortality on the
other hand, were evaluated using Spearman correlation. To Fig. 1 Flow chart of the meta-analysis
 1005

of lung worsening in comatose patients [30]. It contributed

40%
20%
< 20%

< 10%
power
Study
only to the analysis of the effect of prone positioning on

the occurrence of VAP. The remaining five studies in-
cluded hypoxaemic patients with ARF with ARDS or ALI.

Premature
One multicentre study included paediatric patients [24].
Four studies included only adult patients (one including

stop
Yes

Yes

Yes
No

No
No
only severe ARDS patients [25], two including patients
suffering either from ALI or ARDS [22, 31], and one
including all patients suffering from ARF [23]). Although

28-day mortality
28-day mortality

28-day mortality

Increase in lung
ICU mortality
ICU mortality
inclusion criteria corresponded not only to ALI/ARDS

injury score
patients in the latter study, analysis concerned all included

score outcome
Jadad Primary
patients without stratification according to ARF aetiology.
Following personal contact, the authors reported that
mortality rates were fairly similar across ARF aetiologies.
One of the studies included patients with post-traumatic
ALI/ARDS [31]. Table 1 gives details of the studies

3
3
3

3
3
characteristics. There was total agreement between the
two independent reviewers on inclusion of studies and the

Crossover
allowed
Jadad study quality grading.
Data for 1,372 patients were available for analysis

Yes

Yes
Yes

No
No
No
of the primary outcome, namely mortality; 713 patients
were ventilated in prone position, and 659 were ventilated

Duration prone
in supine position. All eligible reports were described

8 (7.7;9.8)
(hours/day)
as RCTs. They were published between 2001 and 2006.

7 1.8

11 5 h
In the most recently published studies, patients were

18 4
ventilated using a lung-protective ventilation strategy

17
4
corresponding to a limited tidal volume (68 ml/kg of
body weight) and a plateau pressure not exceeding 35 cm
H2 O [24, 25, 31]. The remaining two studies did not use supine (n)
Patients

such a ventilator strategy [22, 23]. In these five studies,

19
50

26
378

60
duration of ventilation in prone position varied from 7 h 152
to 18 h a day (mean duration per day 12 5 h). It lasted
prone (n)

between 4 days and the whole duration of hospitalisation.

Patients

Three studies allowed crossover from one study arm

76
152
413

21
51

25
to another [22, 23, 25] . This usually corresponded to
patients in the supine position who were subsequently
ventilated in prone position because of the persistence of
PaO2 /FiO2
Table 1 Characteristics of trials included in the meta-analysis

(mmHg)

severe hypoxaemia. In these studies, analysis was made

99.5

146
127

221
152

> 300

on intention-to-treat basis. The main outcome evaluated in

these studies was mortality reduction (either ICU mortal-
ity, or 28-day mortality) by ventilation in prone position
in comparison with supine ventilation. Three studies were
51 Comatose without

prematurely stopped because of a slow inclusion rate [22,

136 severe ARDS
304 ARDS/ALI

24, 25]. Calculation of studies power showed that all

40 ARDS/ALI

positive studies were underpowered (< 10%40%) to

lung injury
Number of

detect a statistical significance of the observed mortality

791 ARF
101 ALI
patients

reduction by prone positioning (Table 1).

Quantitative data synthesis

Voggenreiter 2005

Effects on mortality
Gattinoni 2001

Mancebo 2006
Guerin 2004
Curley 2005

Beuret 2002

When we pooled all studies, ventilation in prone position

was associated with a non-significant 3% reduction of the
Trial

odds of mortality [249 of 713 patients (34.9%) in the prone

1006

ventilation group versus 234 of 659 patients (35.5%) in
the supine position: OR 0.97, 95% CI 0.771.22, p for ef-
fect = 0.79, p for heterogeneity = 0.35; I 2 = 9.3%; Fig. 2].
The funnel plot of standard error versus OR for mortal-
ity did not suggest publication bias, with the effects of the
largest studies closer to the non-effect line (Fig. 3). No cor-
relation was found between the odds of mortality and ei-
ther the PaO2 /FiO2 ratio or the length of daily prone po-
sition in each of the included studies. Also, no correlation
was found between the relative risk reduction of mortality
and the corresponding mortality rate in the supine group.
I 2 , an alternative test for heterogeneity, was 9.3%, indi-
cating low heterogeneity. However, there was substantial
clinical heterogeneity in the included studies, with differ-
ent patient populations (adult and paediatric populations;
trauma and non-trauma patients; severe ARDS patients and
mixed ALI/ARDS patients; ARF from other than ARDS/
ALI origin), prone duration on 24-h basis, standardised
lung protective ventilation or non-protective ventilation.
Secondary outcome measures

Effects on oxygenation: During the acute phase of the ill-

Assessment of heterogeneity ness (which was assessed between the 4th and the 10th day
of procedure implementation), both ventilation in prone
Regarding the meta-analysis results, using the Q statistic position and ventilation in supine position were associ-
test, we did not find statistical heterogeneity (p = 0.35). ated with an increase of the PaO2 /FiO2 ratio. However,

Fig. 2 Effect of ventilation in prone position on mortality. Weight is the relative contribution of each study to the overall estimate of
treatment effect on a log scale assuming a fixed effects model

Fig. 3 Funnel plot for outcome

of mortality in trials of prone
ventilation in ALI/ARDS. Each
point represents one trial

ventilation in prone position improved the PaO2 /FiO2 sig-
nificantly more (WMD by fixed effects model 25 mmHg,
95% CI 1535, p for effect < 0.00001, p for heterogene-
ity = 0.06, I 2 = 56% corresponding to a moderate hetero-
geneity; Fig. 4).
Effects on incidence of VAP: Data on the effects of
prone positioning on VAP rate were available in only
three of the former analysed studies for mortality rate and
PaO2 /FiO2 change. The results of the study by Beuret
et al. [30] were added and contributed only to the analysis
of this outcome. Accordingly, pooling data corresponded
Fig. 4 Effects of prone positioning on the PaO2 /FiO2 ratio
Fig. 5 Effects on the incidence of ventilator-associated pneumonia
Fig. 6 Incidence of major airway complications
1007
to those of 535 patients allocated to prone positioning
and 482 patients ventilated in supine position. Pooled
results show a reduction of the incidence of VAP by prone
positioning (OR 0.77, 95% CI 0.571.04). This difference
did not achieve statistical significance (p = 0.09) and there
was a moderate heterogeneity among included studies
(I 2 = 48.2%; Fig. 5).
Adverse effects of prone positioning: Major adverse air-
ways events (defined as displacement of tracheal tube, se-
lective intubation, or accidental extubation) occurred with
similar frequency in prone ventilation and in supine venti-
1008
Fig. 7 Pooled estimates of ICU stay (days)
lation: 75 of 713 patients (10.5%) in the prone ventilation
group versus 69 of 659 patients (10.4%) in the supine posi-
tion group: OR 1.01, 95% CI 0.711.43, p for effect = 0.95,
p for heterogeneity = 0.61, I 2 = 0%; Fig. 6).
Pressure sores and facial oedema were reported more
frequently with prone positioning: in 296 (41%) out of 719
patients in the prone group and in 225 (34.1%) of 659 pa-
tients in the supine group (OR 1.35, 95% CI 1.081.69,
p = 0.007).
Data on the effects of prone positioning on the length
of ICU stay were reported in two studies only [23, 24].
Following personal contact we obtained data concerning
the study by Mancebo et al. [25]. Overall, data concerned
540 patients in the prone group and 488 patients in the
supine group. Ventilation in prone position was associated
with a non-significant prolongation of the ICU length of
stay (WMD = 0.96 days, 95% CI 1.11 to 3.02, p for ef-
fect = 0.36, p for heterogeneity = 0.96, I 2 = 0%; Fig. 7).
Discussion
The current meta-analysis pooled data from 1,372 patients
included in RCTs evaluating the effect of prone position-
ing in ALI/ARDS patients. It showed a substantial addi-
tional increase in the PaO2 /FiO2 ratio in comparison to that
evoked during ventilation in supine position, and a non-
significant 3% reduction in mortality. Prone positioning
was associated with a statistically non-significant 23% re-
duction of the risk of VAP, and did not increase the rate
of major respiratory adverse events although specific unto-
ward effects of prone positioning (pressure sores) were sig-
nificantly more frequent. A marginal and non-significant
increase of 0.96 days in the ICU length of stay was associ-
ated with prone positioning.
The optimal indication for a meta-analysis is pooling
the results of trials with variable size but with similar
design, in particular assessing the same outcomes related
to a particular therapeutic tool in a well-delineated disease.
Accordingly, one may wonder whether a meta-analysis is
actually suitable for the evaluation of a technique such as
prone positioning in a spectrum of disease like ALI/ARDS
or ARF. Neither the intervention nor the disease spectrum
is standardised. The included studies exhibited large
variations in the intensity of the intervention (prone
positioning was performed for between 7 h and 17 h per
day, for 4 days or up to the whole length of stay), and
there were substantial differences among studies in the
stage of illness. Nevertheless, among other objectives,
meta-analyses allow identification of heterogeneity effects
among multiple studies. They also help identify data gaps
in the knowledge base and may suggest direction for fu-
ture research. Regarding prone positioning in ALI/ARDS
patients, there is a gap between what published research
actually says and the knowledge base of potential users.
This is illustrated by the significant decline in the use of
prone positioning, which was underscored in the recent
international survey on the use of mechanical ventila-
tion [26]. In this report, two consecutive surveys were
conducted 5 years apart in the same ICUs belonging to 23
countries (and presumably among the same physicians),
and were separated only by landmark publications on
the effects of prone positioning in ALI/ARDS patients.
Although knowledge translation to clinical practice may
be delayed [32], in this particular setting, negative studies
have rapidly been interpreted as definitively negative.
These changes in patterns suggest that a scientifically
sound approach like prone positioning, with a solid phys-
iologic rationale, may be abandoned if nothing is done
to rectify the impact of these publications and critically
appraise their conclusions [33]. Careful analysis of the
lower and higher boundaries of the CI around the point
estimate of the odds of mortality, shows that obviously
our meta-analysis does not rule out the possibility of
an increase by 22% of mortality by prone positioning.
Nonetheless, this meta-analysis does not also exclude
a mortality reduction by 23%. In addition, this analysis
shows that this strategy does not cause harm and might
even have beneficial effects on the occurrence of VAP.
Hence, an adequately powered RCT standardising the
procedure of prone ventilation (prone positioning duration
and use of lung-protective ventilation) is warranted in
order to enable definitive conclusions on the benefits of
this technique.

Ventilation in prone position is primarily used to
increase oxygenation in patients with ARF through an
improvement in ventilation perfusion matching, even
distribution of gravitational gradient in pleural pressure,
and a favourable modification of transpleural pressure
gradients with a decrease of ventilator-induced lung
injury [1215, 1720]. Compression of lung segments
by the heart is also reduced [34]. Small non-controlled
clinical studies evaluating prone position ventilation
with or without additional therapeutic modalities such
as nitric oxide or high-frequency oscillatory ventila-
tion showed beneficial effects of prone positioning on
oxygenation [29]. However, prospective randomised
trials focusing on patient-centred outcomes did not find
evidence of beneficial effect of prone positioning on
mortality [2225, 31]. That improvement in physiologic
parameters or surrogate end-points do not translate to
clinically relevant benefit is not infrequent in critically ill
patients [35, 36]. In addition, there are several possible
reasons why improved oxygenation does not translate to
improved mortality rate. First, improvement in oxygena-
tion seems to have no impact on survival in ALI/ARDS
patients [1]. Second, multiple organ failure rather than
refractory oxygenation accounts for the majority of
deaths related to ARDS [37]. Third, the protective ex-
perimental effect of the prone position could only be
temporary [8, 17, 18]. Accordingly, if prone positioning
merely postpones lung injury, it is crucial to take advan-
tage of the window of opportunity associated with prone
positioning.
In addition to these physiologic explanations, method-
ological weaknesses in many of published studies on
prone positioning deserve consideration. Three studies
were prematurely stopped because of a slow inclusion rate
and lacked therefore adequate power to detect a statistical
significance of the observed reduction in the mortality
rate [22, 24, 25].
Along with a type II error, it is very important to con-
sider to what extent the issue of case-mix might have con-
tributed to the lack of evidence of prone position efficacy.
ARDS is indeed at the severe end of the ALI spectrum, and
published RCTs included patients suffering from various
degrees of severity of ALI. This was consistently observed
in the two largest studies evaluating prone positioning in
a controlled and randomised design [22, 23]. Guerin et al.
even included patients suffering ARF from other origins
than ARD or ALI [23]. Of note, the study by Mancebo
et al., which demonstrated a positive effect of prone pos-
itioning in the multivariate analysis, included only patients
with severe ARDS [25]. These findings are consistent with
those of Gattinoni et al., who showed in a post-hoc analy-
sis that prone ventilation was more effective in the most
severely ill patients (SAPS II > 49). Case-mix might also
pertain to the age of ARDS. In Mancebo et al.s study pa-
tients were included within 48 h of meeting inclusion cri-
teria, while in Gattinonis study inclusion of a substantial
1009
sample of the population occurred even late in the course
of ARDS [22, 25].
Another explanation stems from the lack of standardi-
sation of the prone procedure and that of ventilation strat-
egy. Indeed, duration of prone positioning varied from 7 h
to 17 h on a 24-h basis in the five studies included in the
meta-analysis. The study by Mancebo et al. [25], which ap-
plied the longest prone duration (17 h/24 h) and found po-
tential benefit from this procedure in the multivariate ana-
lysis, suggests that prone positioning should be applied for
the longest time (more than 20 h) during the 24-h period.
Along with this inference, it has been shown that the time
course of alveolar recruitment during prone position is not
consistent and in fact differs markedly from one patient
to another [38]. In some patients, the plateau of complete
alveolar recruitment may not be reached even after 8 h of
prone positioning [38]. Accordingly, it has been suggested
that the duration of prone positioning should be tailored on
an individual basis by repeated measurements of alveolar
recruitment. Future studies evaluating prone position ven-
tilation in ARDS should probably apply a prone position
duration closer to that of Mancebo et al. [25] than to that
of Gattinonis study [22].
Standardisation of the ventilation strategy is also
to consider. Three of the five studies included in this
meta-analysis were conducted prior to the generalisation
of protective lung ventilation in ARDS [22, 23, 31].
Protective lung strategy could indeed be synergistic with
the effects of prone position.
Compliance with assigned treatment is another con-
cern raised by open-label studies assessing ventilatory
techniques such as prone positioning. Indeed, Gattinoni
et al. planned to use prone position for at least 6 h per
day [22]. However, 27% of the patients allocated to prone
positioning were ventilated prone for fewer hours than
expected. A similar proportion of patients (25%) ran-
domised to prone ventilation in the study by Guerin et al.
were actually ventilated in prone position for a shorter
time than the scheduled 8 h [23]. In addition, a large
number of patients assigned in both studies to supine
ventilation actually crossed over to prone ventilation
because of a worsening in arterial oxygenation. Therefore,
ascertainment bias, inherent to every unblinded trial, and
limited compliance with the scheduled prone position
sessions might have seriously compromised the accuracy
of reported results of RCTs on prone position ventilation
in ARDS/ALI patients.
Obviously, the involvement of the aforementioned
limitations in published studies would make the drawing
of definitive conclusions a matter of great difficulty. Given
the difficulties in properly applying the results of RCTs in
the real world, individualised care should definitively not
be abandoned based on negative RCTs [39]. Despite the
lack of strong evidence for the efficacy of prone position
ventilation in reducing mortality in ARDS patients, and
the fact that prone positioning has relatively lost ground,
1010
this technique remains in more than only exceptional use
in most ICUs, and our study shows no sign of any harmful
effect. From a pragmatic standpoint, physicians prefer to
deal with a patient who is well oxygenated and requiring
the lowest FiO2 . Meanwhile, the optimal randomised
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