Mounier - 2010
Mounier - 2010
Mounier - 2010
DOI: 10.1183/09031936.00057509
CopyrightßERS Journals Ltd 2010
ABSTRACT: The aim of the present study was to examine whether prone positioning (PP) affects AFFILIATIONS
ventilator associated-pneumonia (VAP) and mortality in patients with acute lung injury/adult A full list of the authors’ affiliations
and the OUTCOMEREA Study Group
respiratory distress syndrome. members can be found in the
2,409 prospectively included patients were admitted over 9 yrs (2000–2008) to 12 French Acknowledgements section.
intensive care units (ICUs) (OUTCOMEREA). The patients required invasive mechanical
CORRESPONDENCE
ventilation (MV) and had arterial oxygen tension/inspiratory oxygen fraction ratios ,300 during
J-F. Timsit
the first 48 h. Controls were matched to PP patients on the PP propensity score (¡10%), MV Medical ICU
duration longer than that in PP patients before the first turn prone, and centre. INSERM U823
VAP incidence was similar in the PP and control groups (24 versus 13 episodes?1,000 patient- Albert Michallon Teaching Hospital
days MV-1 respectively, p50.14). After adjustment, PP did not decrease VAP occurrence (HR 1.64 38043 Grenoble CEDEX 9
France
(95% CI 0.70–3.84); p50.25) but significantly delayed hospital mortality (HR 0.56 (95% CI 0.39– E-mail: [email protected]
0.79); p50.001), without decreasing 28-day mortality (37% in both groups). Post hoc analyses
indicated that PP did not protect against VAP but, when used for .1 day, might decrease mortality Received:
and benefit the sickest patients (Simplified Acute Physiology Score .50). April 06 2009
Accepted after revision:
In ICU patients with hypoxaemic acute respiratory failure, PP had no effect on the risk of VAP. Aug 24 2009
PP delayed mortality without decreasing 28-day mortality. PP .1 day might decrease mortality, First published online:
particularly in the sickest patients. Sept 09 2009
Day 0
Matched SP patients
Matching criteria
PP propensity score
Centre
MV duration before PP
Beginning of PP=Day 0
PP patients
Beginning of
endotracheal MV
FIGURE 1. Diagram of the matching process. The matching criteria (denoted in grey) are: propensity score ¡10% calculated over the first 48 h after intensive care unit
admission; centre; and mechanical ventilation (MV) duration before prone positioning (PP) in the PP group or on the corresponding day (day 0) in the supine positioning (SP)
group. We calculated the number of patients with ventilator-associated pneumonia (VAP) after day 0.
into account. We used Kaplan–Meier plots to evaluate the risk based on data in the literature [2] and OUTCOMEREA 1
of VAP and death in each group. database, were: male sex; pneumonia diagnosis at admission;
chronic respiratory failure; acute respiratory failure at admis-
Risk factors for VAP and parameters that were not balanced sion; septic shock at admission; use of vasoactive agents within
between the PP and SP groups were used to estimate the the first 48 h in the ICU; temperature; cardiac frequency (fC);
adjusted HR of VAP using a marginal Cox model for clustered Pa,O2/FI,O2 ratio; and the need for an arterial catheter.
data. This model takes into account both the censored nature of
the data and accounts for intra-cluster (intra-pair) dependence VAP occurred in 414 (19%) out of 2,208 SP patients and 90
using a robust sandwich covariance estimate [29]. Values of (45%) out of 201 PP patients. Median duration of PP use was 1
pf0.05 were considered significant. Analyses were computed day [1–3]. PP was significantly associated with longer MV
using the SAS 9.1 software package (SAS Institute, Cary, NC, duration compared to SP (19 (8–35) days versus 7 (4–13) days,
USA). Survival curves were drawn using R (R Foundation, p,0.0001), longer time in the ICU (25 (11–39) days versus 10 (5–
Vienna, Austria). 17) days, p,0.0001), and longer time in the hospital (41 (18–68)
versus 24 (12–43), p,0.0001). Mortality was higher in the PP
RESULTS group (95 (47%) versus 777 (35%) hospital deaths, p50.0006).
Overall population of the database Risk factors for PP in the overall population of 2,409 patients
The study flow chart is shown in figure 2. Of the 2,409 included are listed in table 2. Predictors of PP at the final step of the
patients, 201 (8%) received PP. Risk factors for VAP, selected multivariate logistic model (table 3) were male sex, coma,
TABLE 1 Risk of ventilator-associated pneumonia (VAP) and death associated with prone positioning (PP)
After adjustment for confounding variables: imbalanced variables and Pneumonia 1.64 (0.70–3.84) 0.25
VAP risk factors#
After adjustment for confounding variables: imbalanced variables and Death 0.56 (0.39–0.79) 0.001
hospital risk factors"
#
: adjusted on the following: at admission, male sex, pneumonia, septic shock, acute respiratory failure and coma; within 48 h after intensive care unit (ICU) admission,
vasoactive drugs; and on the day before PP (or the corresponding day in the control group), antibiotic use, at least one catheter, Sepsis-related Organ Failure
Assessment (SOFA) score, and an arterial oxygen tension/inspiratory oxygen fraction (Pa,O2/FI,O2) ratio. ": adjusted on the following: at admission, Simplified Acute
Physiology Score, at least one chronic disease, pneumonia, septic shock, cardiac arrest, acute respiratory failure and coma; within 48 h after ICU admission, vasoactive
drugs; and on the first day of PP, antibiotic use, enteral or parenteral nutrition, catheter, SOFA score and Pa,O2/FI,O2 ratio.
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EUROPEAN RESPIRATORY JOURNAL VOLUME 35 NUMBER 4 797
CRITICAL CARE AND LUNG INJURY R. MOUNIER ET AL.
3145 patients pneumonia, septic shock, acute respiratory failure, coma and
with ALI/ARDS lowest Pa,O2/FI,O2 ratio; 2) during the first 48 h of MV, use of
Pa,O2/FI,O2<300 and MV vasoactive agents and use of at least one catheter; and 3) on the
on admission day before PP (or the corresponding day in the SP group), use
of antibiotics, use of at least one catheter, lowest Pa,O2/FI,O2
Exclusion criteria: ratio and SOFA score. The median time from ICU admission to
736 patients with ICU PP was 6 days [2–12]. The median time spent in the ICU after
stay ≤2 days or MV ≤1 day T0 was longer in the PP group than in the SP group (14 (6–29)
days versus 3 (1–8) days, p,0.0001).
TABLE 2 Risk factors for prone positioning (PP) in 2,409 TABLE 2 Continued
patients who received endotracheal mechanical
Variables SP PP p-value
ventilation (MV) within 48 h after intensive care
unit (ICU) admission, for o2 days, and who had Treatment during the first 48 h
arterial oxygen tension/inspiratory oxygen
Vasoactive drugs 1413 (64) 156 (77.6) 0.0001
fraction (Pa,O2/FI,O2) ratios ,300 during the first
Steroids 680 (30.8) 76 (37.8) 0.04
48 h on MV
Antibiotics 1753 (79.4) 169 (84.1) 0.11
Variables SP PP p-value Enteral nutrition 566 (25.6) 35 (17.4) 0.01
Parenteral nutrition 385 (17.4) 45 (22.4) 0.08
Procedures during the first 48 h
Patients n 2208 201
Arterial catheter 1119 (50.7) 126 (62.7) 0.001
Age yrs 66 (54–76) 65 (50–75) 0.04
Central catheter 1403 (63.5) 162 (80.6) 0.0001
Males 1411 (63.9) 150 (74.6) 0.002
Swan catheter 107 (4.8) 20 (10) 0.002
Transfer from ward 1055 (47.8) 112 (55.7) 0.03
At least one catheter 1482 (67.1) 170 (84.6) ,0.00014
Severity scores at admission
Laboratory variables in the
SAPS II 52 (40–64) 51 (40–65) 0.85
first 48 h
APACHE II score 20 (15–25) 20 (15–25) 0.64
Temperature max uC 38.2 (37.7–38.9) 38.6 (38–39.2) ,0.0001
SOFA score 7 (5–10) 7 (5–11) 0.79
fC max bpm 116 (100–135) 126 (108–144) ,0.0001
Immunosuppression
Prothrombin rate max % 69 (55–80) 61 (49–74) ,0.0001
Chemotherapy 138 (6.3) 10 (5) 0.47
Lowest Pa,O2/FI,O2 ratio 165.5 (112–220) 129 (85–193) ,0.0001
Steroid therapy .1 month or 82 (3.7) 11 (5.5) 0.22
Laboratory variables in the first
.2 mg?kg-1
48 h in categories
AIDS 45 (2) 2 (1) 0.31
Temperature o38.2uC 1146 (51.9) 144 (71.6) ,0.0001
Bone marrow aplasia 33 (1.5) 4 (2) 0.59
fC o120 bpm 1027 (46.5) 128 (63.7) ,0.0001
Diagnosis at admission
Prothrombin rate f65% 917 (41.5) 117 (58.2) ,0.0001
Pneumonia 450 (20.4) 63 (31.3) 0.0003
Pa,O2/FI,O2 ratio
Septic shock 249 (11.3) 31 (15.4) 0.08
,100 436 (19.7) 73 (36.3) ,0.0001
Cardiac arrest 181 (8.2) 4 (2) 0.002
100–159 600 (27.2) 57 (28.4)
Acute respiratory failure 130 (5.9) 24 (11.9) 0.001
160–219 614 (27.8) 39 (19.4)
Stroke 124 (5.6) 7 (3.5) 0.20
220–299 558 (25.3) 32 (15.9)
Acute renal failure 94 (4.3) 3 (1.5) 0.06
COPD exacerbation 78 (3.5) 5 (2.5) 0.44
Cardiogenic pulmonary oedema 66 (3) 5 (2.5) 0.69 Data are presented as n (%) or median (interquartile range), unless otherwise
Multiple organ failure 34 (1.5) 7 (3.5) 0.04 stated. SP: supine position; SAPS II: Simplified Acute Physiology Score II;
Admission category# APACHE II: Acute Physiology and Chronic Health Evaluation II; SOFA:
Medical 1562 (71) 135 (67.5) Sequential Organ Failure Assessment; COPD: chronic obstructive pulmonary
# "
Emergency surgery 406 (18.4) 36 (18) 0.23 disease; fC: cardiac frequency. : data are missing for eight patients; :
Scheduled surgery 233 (10.6) 29 (14.5) evaluated using the APACHE II score (Knaus criteria). Variables within the first
Previous health status (McCabe) 48 h in the ICU were obtained as follows: in patients who received PP on the first
Not fatal 1267 (57.4) 118 (58.7) ICU day, we only used the worst data collected on day 0; in patients who
Fatal within 5 yrs 730 (33.1) 69 (34.3) 0.48 received MV on the second ICU day (day 1), we used the worst data collected
Fatal within 1 yr 211 (9.6) 14 (7) on day 1; and in patients who received MV on the first ICU day (day 0), we used
Comorbidities" the worst data collected between day 0 and day 1.
Immunosuppression 274 (12.4) 29 (14.4) 0.41
Respiratory failure 383 (17.3) 42 (20.9) 0.21
Cardiovascular failure 344 (15.6) 26 (12.9) 0.32
Cirrhosis 143 (6.5) 21 (10.4) 0.03 adjustment on imbalances between groups and risk factors for
Renal failure 103 (4.7) 9 (4.5) 0.90 events, PP was associated neither with VAP (HR 0.69 (95% CI
At least one chronic disease 962 (43.6) 99 (49.3) 0.12 0.19–2.52), p50.57) nor with death (HR 0.56 (95% CI 0.29–1.09),
Main symptom at admission p50.09).
Acute respiratory failure 623 (28.2) 71 (35.3) 0.03
Among 114 patients with SAPS II score values .50 on the day
Coma 520 (23.6) 17 (8.5) ,0.0001
of the first turn prone (or the corresponding day in controls),
Septic shock 407 (18.4) 40 (19.9) 0.61
64 received PP and 50 were controls. VAP occurred in 11 (17%)
Multiple organ failure 73 (3.3) 11 (5.5) 0.11
PP patients and one (2%) control. Of the PP patients, 41 (64%)
Cardiogenic shock 101 (4.6) 6 (3) 0.30
died, compared to 39 (78%) of the controls. After adjustment
Haemorrhagic shock 89 (4) 20 (10) 0.0001
Monitoring and scheduled surgery 202 (9.1) 15 (7.5) 0.42
on imbalances between groups and risk factors for events, PP
COPD exacerbation 53 (2.4) 8 (4) 0.17
was not associated with VAP (HR 4.33 (95% CI 0.70–26.65),
Acute renal failure 34 (1.5) 6 (3) 0.12
p50.11) but was significantly and negatively associated with
hospital death (HR 0.44 (95% CI 0.29–0.69), p50.0003) (tables 5
Trauma 21 (1) 3 (1.5) 0.46
and 6).
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EUROPEAN RESPIRATORY JOURNAL VOLUME 35 NUMBER 4 799
CRITICAL CARE AND LUNG INJURY R. MOUNIER ET AL.
1.0
consensus regarding the criteria for using PP or the optimal
0.9 duration of PP. In addition, a possible centre effect was taken
into account by including the centre in the propensity score.
0.8 In conclusion, our prospective multicentre cohort study
suggests that the use of PP is not superior to SP to prevent
0.7 VAP. However, PP may improve survival in longer PP use and
in the sickest patients.
0.6
STATEMENT OF INTEREST
0.5 Statements of interest for A.T. Dinh-Xuan and E. Azoulay can be found
at www.erj.ersjournals.com/misc/statements.dtl
0 5 10 15 20 25 30
Time since the start of prone position days
ACKNOWLEDGEMENTS
The authors’ affiliations are as follows. R. Mounier: Assistance
FIGURE 4. Kaplan–Meier estimates of 28-day hospital survival in the group Publique-Hôpitaux de Paris, Louis Mourier Hospital, Medical ICU,
kept in the supine position (–––––) and in the group treated with prone positioning Colombes, France. C. Adrie and A.T. Dinh-Xuan: Assistance Publique-
(????????). HR 0.56, 95% CI 0.39–0.79; p50.001. Hôpitaux de Paris, Cochin hospital, University of René Descartes,
Physiology Dept, Paris, France. A. Français: INSERM U823, Albert
subgroup was defined by Pa,O2/FI,O2 f88 mmHg, SAPS II.49, Bonniot Research Center, team 11, Outcome of cancers and critical
and tidal volume of 12 mL?kg-1. In our study, PP for .2 days illnesses, La Tronche, France. M. Garrouste-Orgeas: Medical-Surgical
ICU, Saint Joseph Hospital, Paris, France. C. Cheval: Medical-Surgical
was associated with significantly lower hospital mortality in
ICU, Hyères Hospital, Hyères, France. B. Allaouchiche: Surgical ICU,
patients with SAPS II .50 on the first day of PP. There was also Edouard Heriot Hospital, Lyon, France. S. Jamali: Medical-Surgical
a trend toward a decreased mortality in with Pa,O2/FI,O2 ICU, Dourdan Hospital, Dourdan, France. D. Goldgran-Toledano:
,120 mmHg (tables 5 and 6) corresponding to the quartile of Medical-Surgical ICU, Gonesse Hospital, Gonesse, France. Y. Cohen:
patients with the lowest values in the initial study group Medical-Surgical ICU, Avicenne Teaching Hospital, Bobigny, France.
(table 4). We did not study tidal volume because high volumes E. Azoulay: Medical ICU, Saint-Louis Teaching Hospital, Paris, France.
such as those reported by GATTINONI et al. [15] have not been J-F. Timsit: INSERM U823, Albert Bonniot Research Center, team 11,
used in our ICUs for over 10 yrs. Altogether, these data suggest Outcome of cancers and critical illnesses, La Tronche and Medical ICU,
Albert Michallon Teaching Hospital, Grenoble, France. J-D. Ricard:
that PP may be helpful in patients whose acute illness is very
Assistance Publique-Hôpitaux de Paris, Louis Mourier Hospital,
severe. Furthermore, they are consistent with a recently Medical ICU, Colombes and INSERM U722, UFR of Medicine,
published meta-analysis showing that beyond the increase of University of Bichat, Paris, France.
Pa,O2/FI,O2 PP may improve survival in patients with greater
severity of the acute illness [44] through other mechanisms. The members of the OUTCOMEREA Study Group are as follows.
Scientific committee: J-F. Timsit (Hôpital Albert Michallon and
Furthermore, the fact that PP decreased mortality in this group
INSERM U823, Grenoble, France); P. Moine (Surgical ICU, Dept of
may also suggest that we should use it for a longer period of
Anesthesiology, University of Colorado, Denver, CO, USA); A. de
time independently on the effect of its beneficial effect on gas Lassence (ICU, Hôpital Louis Mourier, Colombes, France); E. Azoulay
exchange. (Medical ICU, Hôpital Saint Louis, Paris, France); Y. Cohen (ICU,
Hôpital Avicenne, Bobigny, France); M. Garrouste-Orgeas (ICU
Our study has several limitations. The presence or absence of Hôpital Saint-Joseph, Paris, France); L. Soufir (ICU, Hôpital Saint-
radiographic pulmonary infiltrates was not specifically Joseph, Paris, France); J-R. Zahar (Dept of Microbiology, Hôpital
recorded in the database. However, we performed a survey Necker, Paris, France); C. Adrie (Dept of Physiology, Hôpital Cochin,
of all 12 participating centres to ensure that they all use this France); A. Benali (Microbiology and Infectious Diseases, Hôpital
TABLE 5 Post hoc analyses of the effects of prone positioning (PP) on the occurrence of ventilator-associated pneumonia (VAP)
Data are presented as n or n (%), unless otherwise stated. Pa,O2/FI,O2: arterial oxygen tension/inspiratory oxygen fraction ratio; SAPS II: Simplified Acute Physiology Score.
The marginal Cox model was used to compute the hazard ratio (HR) adjusted on imbalances between groups and risk factors for events.
TABLE 6 Post hoc analyses of the effects of prone positioning (PP) on the occurrence of death
Data are presented as n (%), unless otherwise stated. Pa,O2/FI,O2: arterial oxygen tension/inspiratory oxygen fraction ratio; SAPS II: Simplified Acute Physiology Score. The
marginal Cox model was used to compute the hazard ratio (HR) adjusted on imbalances between groups and risk factors for events.
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