Documente Academic
Documente Profesional
Documente Cultură
BACKGROUND:
We used data from the B-type Natriuretic Peptide for the Fluid Management of
Weaning (BMW) randomized controlled trial performed in nine ICUs across Europe and
America. We compared the cumulative incidence of VAC and VAP between the biomarkerdriven, depletive fluid-management group and the usual-care group during the 14 days
following randomization, using specific competing-risk methods (the Fine and Gray model).
METHODS:
RESULTS: Among the 304 patients analyzed, 41 experienced VAP, including 27 (17.8%) in the
usual-care group vs 14 (9.2%) in the interventional group (P 5 .03). From the Fine and Gray
model, the probabilities of VAC and VAP occurrence were both significantly reduced with the
interventional strategy while adjusting for weaning outcome as a competing event (subhazard ratios [25th-75th percentiles], 0.44 [0.22-0.87], P 5 .02 and 0.50 [0.25-0.96], P 5 .03,
respectively).
Using proper competing risk analyses, we found that a depletive fluidmanagement strategy, when initiating the weaning process, has the potential for lowering VAP
risk in patients who are mechanically ventilated.
CONCLUSIONS:
TRIAL REGISTRY:
Campo), Hospital de Sant Pau, Barcelona, Spain; Service de Ranimation Mdicale (Dr Kouatchet), CHU dAngers, Angers, France; Departamento de Paciente Crtico (Dr Tomicic), Clinica Alemana, Santiago de
Chile, Chile; Service de Ranimation Mdicale and UPRES-EA 3830
(Dr Beduneau), CHU de Rouen, Rouen, France; Service de Ranimation
Mdicale et des Maladies Infectieuses (Dr Sonneville), AP-HP, CHU
Bichat-Claude Bernard, Univ Paris Diderot, Sorbonne Paris Cit, Paris,
France; Ranimation DAR B (Dr Jaber), CHU Saint Eloi, INSERM U1046,
Montpellier, France; Service de Ranimation Mdicale (Dr Darmon),
AP-HP, CHU Saint Louis, Paris, France; Service de Soins Intensifs
(Dr Castanares-Zapatero), Hpital Universitaire Saint-Luc, Bruxelles,
Belgium; Critical Care Department (Dr Brochard), St. Michaels Hospital,
Toronto, ON, Canada; and Interdepartmental Division of Critical Care
Medicine (Dr Brochard), University of Toronto, Toronto, ON, Canada.
58 Original Research
Downloaded From: http://journal.publications.chestnet.org/ by a Universita Studi Di Torino User on 07/21/2014
[ 146#1
C H E S T J U LY 2 0 1 4
FUNDING/SUPPORT:
journal.publications.chestnet.org
59
Acknowledgments
Author contributions: A. M. D. served as
principal author, 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. A. M. D., L. B., and C. B.-B.
contributed to study concept and design;
A. M. D., F. R.-C., A. K., V. T., G. B., R. S., S. J.,
M. D., and D. C.-Z. contributed to patient
recruitment; A. M. D., F. R.-C., A. K., V. T.,
G. B., R. S., S. J., M. D., and D. C.-Z. contributed to data collection; A. M. D., S. K., H. V.,
L. B., and C. B.-B. contributed to data
analysis and interpretation; A. M. D., S. K.,
L. B., and C. B.-B. contributed to the drafting
of the manuscript; and A. M. D., S. K., F. R.-C.,
H. V., A. K., V. T., G. B., R. S., S. J., M. D.,
D. C.-Z., L. B., and C. B.-B. contributed to
the review, revision, and approval of the final
version.
Financial/nonfinancial disclosures: The
authors have reported to CHEST the
following conflicts of interest: Dr Brochard
has been a consultant for Drger, and his
research laboratory has received research
grants from Covidien, General Electric,
Drger, and Vygon. The remaining authors
have reported that no potential conflicts of
interest exist with any companies/organizations whose products or services may be
discussed in this article.
Role of sponsors: The study sponsors had no
role in study design, data collection, data
analysis, data interpretation, or writing of the
report.
References
1. Melsen WG, Rovers MM, Koeman M,
Bonten MJ. Estimating the attributable mortality of ventilator-associated
pneumonia from randomized prevention studies. Crit Care Med.
2011;39(12):2736-2742.
2. Bekaert M, Timsit JF, Vansteelandt
S, et al; Outcomerea Study Group.
Attributable mortality of ventilatorassociated pneumonia: a reappraisal
using causal analysis. Am J Respir Crit
Care Med. 2011;184(10):1133-1139.
3. Chastre J, Fagon JY. Ventilator-associated
pneumonia. Am J Respir Crit Care Med.
2002;165(7):867-903.
4. Cook DJ, Walter SD, Cook RJ, et al.
Incidence of and risk factors for
ventilator-associated pneumonia in
critically ill patients. Ann Intern Med.
1998;129(6):433-440.
5. Magill SS, Klompas M, Balk R, et al.
Developing a new, national approach
to surveillance for ventilator-associated
events: executive summary. Chest.
2013;144(5):1448-1452.
journal.publications.chestnet.org
65
TABLE 1
] Baseline Characteristics
Characteristics
Age, y
Sex, No. (% male)
SAPS II at ICU admission
P Value
66 (55-76)
.18
93 (61.2)
.28
43 (34-54)
Immunosuppressiona
.66
.64
4 (2.7)
7 (4.9)
Hematologic malignancy
8 (5.5)
6 (4.2)
AIDS
3 (2.1)
5 (3.5)
Cardiopulmonary disease
.79
COPD
38 (25.0)
41 (27.0)
LVD
24 (15.8)
20 (13.2)
Neither
90 (59.2)
91 (59.9)
.38
Coma
22 (14.5)
15 (9.9)
Septic shock
18 (11.8)
21 (13.8)
COPD exacerbation
10 (6.6)
15 (9.9)
19 (12.5)
14 (9.2)
Pneumonia
40 (26.3)
50 (32.9)
Cardiac arrest
10 (6.6)
Surgery
19 (12.5)
Other
14 (9.2)
6 (3.9)
23 (15.1)
8 (5.3)
61 (40.1)
70 (46.1)
.30
Ventilator-associated pneumonia
32 (21.1)
25 (16.4)
.30
ARDSb
55 (36.2)
53 (34.9)
.81
35 (23.0)
32 (21.1)
.68
Steroid treatment
53 (34.9)
60 (39.5)
.41
4.4 (2.7-7.8)
5.0 (3.0-9.1)
.25
14 (10-15)
13 (10-15)
.96
5 (5-8)
218 (176-266)
4 (2-6)
2.0 (2.0-4.0)
37.0 (36.5-37.8)
5 (5-6)
225 (174-297)
4 (3-5)
2.0 (2.0-3.0)
37.1 (36.6-37.6)
.42
.40
.67
.39
.96
Data given as No. (%) or median (interquartile range) unless otherwise indicated. LVD 5 left ventricular systolic dysfunction; PEEP 5 positive endexpiratory pressure; SAPS 5 Simplied Acute Physiology Score; SOFA 5 Sequential Organ Failure Assessment.
aData were missing for 14 patients (six and eight cases in the usual-care group and in the interventional group, respectively).
bAt admission or later during the ICU stay.
Discussion
Previous studies of goal-directed fluid management in
critically ill patients who are mechanically ventilated
have shown beneficial respiratory effects of interventions aimed at lowering fluid balance.19-22 However,
none of these studies reported on VAP rate. To our
journal.publications.chestnet.org
61
TABLE 2
] Main Outcomes of the B-type Natriuretic Peptide for the Fluid Management of Weaning Study
Measure
P Value
Median (IQR)
47.7 (22.9-124.8)
39.8 (20.0-72.4)
.019
Mean (SD)
92.8 (110.2)
70.6 (106.8)
58.6 (23.3-139.8)
42.4 (20.8-107.5)
112.2 (147.1)
86.2 (127.9)
.034
74.4 (31.7-160.5)
134.3 (187.6)
49.3 (21.9-140.6)
107.1 (141.0)
.051
9.7 (2.3-12.9)
Mean (SD)
8.2 (5.2)
12.0 (6.5-13.1)
9.3 (4.9)
.026
23.3 (14.7-26.7)
25.9 (19.3-27.1)
Mean (SD)
18.9 (10.4)
20.3 (10.4)
Median (IQR)
54.9 (38.7-58.3)
57.9 (50.4-59.1)
Mean (SD)
42.8 (23.7)
45.7 (22.7)
.038
8.0 (4.0-13.0)
8.0 (4.0-14.0)
11.6 (12.3)
11.4 (11.2)
Median (IQR)
20.0 (12.0-33.0)
20.0 (13.0-33.0)
Mean (SD)
27.3 (37.3)
24.0 (14.2)
.995
ICU mortality
19 (12.5%)
18 (11.8%)
.861
Hospital mortality
25 (16.4%)
20 (13.2%)
.433
Day-60 mortality
28 (18.4%)
21 (13.8%)
.275
62 Original Research
Downloaded From: http://journal.publications.chestnet.org/ by a Universita Studi Di Torino User on 07/21/2014
[ 146#1
C H E S T J U LY 2 0 1 4
TABLE 3
Pathogen
Usual Care
Group (n 5 27)
Interventional
Group (n 5 14)
Staphylococcus species
2 (7.4)
1 (7.1)
Streptococcus species
4 (14.8)
1 (7.1)
Enterobacteriaceae
10 (37.0)
6 (42.9)
Nonfermentative
gram-negative bacilli
13 (48.1)
5 (35.7)
Other gram-negative
bacteria
0 (0.0)
1 (7.1)
Polymicrobiala
7 (25.9)
6 (42.9)
Figure 1 Cumulative incidence function of successful extubation (bold lines) and VAP (dotted lines) during the first 14 d following randomization
in patients managed according to the interventional fluid-management strategy (red) or according to usual care (black). BNP 5 B-type natriuretic
peptide; VAP 5 ventilator-associated pneumonia.
journal.publications.chestnet.org
63
TABLE 4
Yes (n 5 41)
P Value
Outcomes
43.9 (20.7-117.3)
141.6 (49.1-330.9)
, .0001
11.9 (6.9-13.1)
1.4 (0.0-11.2)
, .0001
7.0 (4.0-14.0)
15.0 (9.0-47.0)
, .0001
7.0 (4.0-12.5)
15.0 (9.0-51.5)
, .0001
22.5 (13.8-43.0)
48.0 (17.0-60.0)
.003
23.0 (14.0-46.0)
59.0 (21.5-60.0)
.001
30 (11.4)
7 (17.1)
.31
39 (14.8)
7 (17.1)
.71
Data are given as median (IQR) unless otherwise indicated. VAP 5 ventilator-associated pneumonia. See Table 2 legend for expansion of other
abbreviation.
aPatients still in ICU or in hospital at last follow-up (day 60) were attributed a 60-d length of stay in ICU or hospital, respectively.
bMortality analyses are unadjusted for dierences in acuity or mortality risk.
in guidelines for VAP prevention.30 Whether incorporating a depletive fluid-management strategy into a
bundle of preventive measures may favorably alter
patients outcomes needs further research.
Our study has some limitations. First, we recorded VAP
episodes occurring during weaning from mechanical
ventilation, which started after a median of 5 days
following intubation. Therefore, we could not assess the
effect of fluid-balance management on early-onset VAP.
Second, the generalizability of our study (ie, its external
validity) may be limited by the specific inclusion and
exclusion criteria used in the BMW trial, especially the
exclusion of patients with renal failure because of the
influence of renal function on BNP levels. Third, we
could not control for implementation of VAP preventive measures in both groups, but the study was ran-
64 Original Research
Downloaded From: http://journal.publications.chestnet.org/ by a Universita Studi Di Torino User on 07/21/2014
[ 146#1
C H E S T J U LY 2 0 1 4
Acknowledgments
Author contributions: A. M. D. served as
principal author, 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. A. M. D., L. B., and C. B.-B.
contributed to study concept and design;
A. M. D., F. R.-C., A. K., V. T., G. B., R. S., S. J.,
M. D., and D. C.-Z. contributed to patient
recruitment; A. M. D., F. R.-C., A. K., V. T.,
G. B., R. S., S. J., M. D., and D. C.-Z. contributed to data collection; A. M. D., S. K., H. V.,
L. B., and C. B.-B. contributed to data
analysis and interpretation; A. M. D., S. K.,
L. B., and C. B.-B. contributed to the drafting
of the manuscript; and A. M. D., S. K., F. R.-C.,
H. V., A. K., V. T., G. B., R. S., S. J., M. D.,
D. C.-Z., L. B., and C. B.-B. contributed to
the review, revision, and approval of the final
version.
Financial/nonfinancial disclosures: The
authors have reported to CHEST the
following conflicts of interest: Dr Brochard
has been a consultant for Drger, and his
research laboratory has received research
grants from Covidien, General Electric,
Drger, and Vygon. The remaining authors
have reported that no potential conflicts of
interest exist with any companies/organizations whose products or services may be
discussed in this article.
Role of sponsors: The study sponsors had no
role in study design, data collection, data
analysis, data interpretation, or writing of the
report.
References
1. Melsen WG, Rovers MM, Koeman M,
Bonten MJ. Estimating the attributable mortality of ventilator-associated
pneumonia from randomized prevention studies. Crit Care Med.
2011;39(12):2736-2742.
2. Bekaert M, Timsit JF, Vansteelandt
S, et al; Outcomerea Study Group.
Attributable mortality of ventilatorassociated pneumonia: a reappraisal
using causal analysis. Am J Respir Crit
Care Med. 2011;184(10):1133-1139.
3. Chastre J, Fagon JY. Ventilator-associated
pneumonia. Am J Respir Crit Care Med.
2002;165(7):867-903.
4. Cook DJ, Walter SD, Cook RJ, et al.
Incidence of and risk factors for
ventilator-associated pneumonia in
critically ill patients. Ann Intern Med.
1998;129(6):433-440.
5. Magill SS, Klompas M, Balk R, et al.
Developing a new, national approach
to surveillance for ventilator-associated
events: executive summary. Chest.
2013;144(5):1448-1452.
journal.publications.chestnet.org
65