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ORIGINAL ARTICLE
Noninvasive Ventilation of Patients with Acute Respiratory
Distress Syndrome
Insights from the LUNG SAFE Study
Giacomo Bellani
1,2
, John G. Laffey
3,4,5,6,7,8
,T`ai Pham
9,10,11
, Fabiana Madotto
12
,EddyFan
8,13,14,15
,
Laurent Brochard
4,5,8,14
, Andres Esteban
16
, Luciano Gattinoni
17
, Vesna Bumbasirevic
18,19
,LisePiquilloud
20,21
,
Frank van Haren
22,23
, Anders Larsson
24
,DanielF.McAuley
25,26
,PhilippeR.Bauer
27
,YaseenM.Arabi
28,29
,
Marco Ranieri
30
, Massimo Antonelli
31
,GordonD.Rubenfeld
8,14,32
,B.TaylorThompson
33
, Hermann Wrigge
34
,
Arthur S. Slutsky
5,8,14
, and Antonio Pesenti
35,36
; on behalf of the LUNG SAFE Investigators and the ESICM Trials Group*
1
Department of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy;
2
Department of Emergency and Intensive Care, San
Gerardo Hospital, Monza, Italy;
3
Department of Anesthesia,
4
Department of Critical Care Medicine, and
5
Keenan Research Centre for Biomedical
Science, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Canada;
6
Department of Anesthesia,
7
Department of
Physiology,
8
Interdepartmental Div ision of Critical Care Medicine,
13
Institute of Health Policy, Management and Evaluation, and
14
Department of
Medicine, University of Toronto, Toronto, Canada;
9
Assistance Publique–H ˆopitaux de Paris, H ˆopital Tenon, Unit ´edeR´eanimation M ´edico-
Chirurgicale, P ˆole Thorax Voies A ´eriennes, Groupe Hospitalier des H ˆopitaux Universitaires de l’Est Parisien, Paris, France;
10
Unit ´eMixtede
Recherche 1153, Inserm, Sorbonne Paris Cit ´e, Epid ´emiologie Clinique et Statistiques, pour la Recherche en Sant ´e Team, Universit ´eParis
Diderot, Paris, France;
11
Sorbonne Universit ´es, Universit ´e Pierre et Marie Curie, Paris 06, France;
12
Research Centre on Public Health,
Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy;
15
Department of Medicine, University Health Network and Mount
Sinai Hospital, Toronto, Canada;
16
Hospital Universitario de Getafe, Centro de Investigaci ´on Biom ´edica en Red de Enfermedades Respiratorias,
Madrid, Spain;
17
Department of Anesthesiology, Emergency and Intensive Care Medicine, University Medical Center G ¨ottingen, G ¨ottingen,
Germany;
18
School of Medicine, University of Belgrade, Belgrade, Serbia;
19
Department of Anesthesia and Intensive Care, Emergency
Center, Clinical Center of Serbia, Belgrade, Serbia;
20
Adult Intensive Care and Burn Unit, University Hospital of Lausanne, Lausanne,
Switzerland;
21
Department of Medical Intensive Care, University Hospital of Angers, Angers, France;
22
Intensive Care Unit, The Canberra
Hospital, Canberra, Australia;
23
Australian National University, Canberra, Australia;
24
Section of Anesthesiology and Intensive Care,
Department of Surgical Sciences, Uppsala University, Uppsala, Sweden;
25
Centre for Experimental Medicine, Queen’s University of Belfast,
Wellcome-Wolfson Institute for Experimen tal Medicine, Belfast, U nited Kingdom;
26
Regional Intensive Care Unit, Royal Victoria Hospital, Belfast, United
Kingdom;
27
Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota;
28
King Saud Bin Abdulaziz University
for Health Sciences, Riyadh, Saudi Arabia;
29
King Abdullah International Medical Research Center, Riyadh, Saudi Arabia;
30
Dipartimento di
Anestesia e Rianimazione, Policlinico Umberto I, Sapienza Universit `a di Roma, Roma, Italy;
31
Istituto di Anestesiologia e Rianimazione,
Universit `a Cattolica del Sacro Cuore‐Fondazione Policlinico Universitario A. Gemelli, Roma, Italy;
32
Sunnybrook Health Sciences Center,
Toronto, Canada;
33
Division of Pulmonary and Critical Care, Department of Medicine, Massachusetts General Hospital, Harvard Medical School,
Boston, Massachusetts;
34
Department of Anesthesiology and Intensive Care Medicine, University of Leipzig, Leipzig, Germany;
35
Dipartimento di
Aneste sia, Rianimazio ne ed Emergenza Urgenza, Fondazione Istituto di ricovero e Cura a Carattere Scientifico C `a Granda-Ospedale Maggiore
Policlinico, Milan, Italy; and
36
Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Universit `a degli Studi di Milano, Milan, Italy
ORCID ID: 0000-0002-1246-9573 (J.G.L.).
Abstract
Rationale: Noninvasive ventilation (NIV) is increasingly used in
patients with acute respiratory distress syndrome (ARDS). The evidence
supporting NIV use in patients with ARDS remains relatively sparse.
Objectives: To determine whether, during NIV, the categorization
of ARDS severity based on the Pa
O
2
/FI
O
2
Berlin criteria is useful.
Methods: The LUNG SAFE (Large Observational Study to Understand
the Global Impact of Severe Acute Respiratory Failure) study described
the management of patients with ARDS. This substudy examines the
current practice of NIV use in ARDS, the utility of the Pa
O
2
/FI
O
2
ratio in
classifying patients receiving NIV, and the impact of NIV on outcome.
Measurements and Main Results: Of 2,813 patients with ARDS, 436
(15.5%) were managed with NIV on Days 1 and 2 following fulfillment of
diagnostic criteria. Classification of ARDS severity based on Pa
O
2
/FI
O
2
ratio
was associated with an increase in intensity of ventilatory support, NIV
failure, and intensi ve care unit (ICU) mortality. NIV failure occurred in
22.2% of mild, 42.3% of moderate, and 47.1% of patients with severe
ARDS. Hospital mortality in patients with NIV success and failure was
16.1% and 45.4%, respectively. NIV use was independently associated
with increased ICU (hazard ratio, 1.446 [95% confidence interval,
1.159–1.805]), but not hospital, mortality. In a propensity matched
analysis, ICU mortality was higher in NIV than invasively ventilated
patients with a Pa
O
2
/FI
O
2
lower than 150 mm Hg.
Conclusions: NIV was used in 15% of patients with ARDS, irrespective
of severity category. NIV seems to be associated with higher ICU
mortality in patients with a Pa
O
2
/FI
O
2
lower than 150 mm Hg.
Clinical trial registered with www.clinicaltrials.gov (NCT 02010073).
Keywords: noninvasive ventilation; acute respiratory distress
syndrome
( Received in original form June 29, 2016; accepted in final form October 7, 2016 )
Am J Respir Crit Care Med Vol 195, Iss 1, pp 67–77, Jan 1, 2017
Copyright © 2017 by the American Thoracic Society
Originally Published in Press as DOI: 10.1164/rccm.201606-1306OC on October 18, 2016
Internet address: www.atsjournals.org
Bellani, Laffey, Pham, et al.: Noninvasive Ventilation of Patients with ARDS 67
Noninvasive ventilation (NIV) has become
an established approach in the
management of patients with acute
respiratory failure, with strong evidence for
its benefits in patients with acute
exacerbations of chronic obstructive
pulmonary disease (1–3) and cardiogenic
pulmonary edema (4). NIV is not
uncommonly used in the management of
patients with acute respiratory distress
syndrome (ARDS) (5–7), as evidenced by
its formal recognition in the Berlin criteria
for ARDS introduced in 2012 (8).
Potential advantages of NIV in the
management of patients with ARDS are
mainly related to the avoidance of
complications linked to sedation, muscle
paralysis, and ventilator-associated
complications associated with endotracheal
intubation and invasive mechanical ventilation
(MV) (9). Initially, theuseofNIVinpatients
with ARDS focused on immunocompromised
patients, such as those with hematologic
malignancies (10–14). However, NIV has been
used in a broader selection of patients with
ARDS (7). Of concern, the evidence
supporting NIV use in patients with ARDS is
based on relatively small samples (5, 15).
Moreover, in most studies, patients treated
with NIV were compared with patients treated
with oxygen administration (16) or with
historical cohorts (17).
Several concerns exist regarding the use
of NIV in patients with ARDS. The
subgroup of ARDS most likely to benefit
from NIV remains unclear. Although some
literature suggests that NIV may best be
reserved for patients with mild ARDS
(i.e., patients with a Pa
O
2
/FI
O
2
ratio of
200–300 mm Hg) (5, 15, 18, 19), it is not
always the case in practice (20). Although
some factors leading to NIV failure in
patients with ARDS are better understood,
relatively few patients have been studied to
date (21, 22). The impact of NIV on
outcome in ARDS is therefore not well
understood. In particular, concerns have
been raised regarding the impact of
prolonged NIV in the absence of respiratory
status improvement, potentially delaying
tracheal intubation and invasive MV (20, 21,
23, 24). Finally, the recent Berlin definition
of ARDS does not specify whether patients
with ARDS managed with NIV should be all
classified as having “mild” ARDS or whether
the Pa
O
2
/FI
O
2
ratioseveritystratification is
more appropriate (25).
For these reasons, a key prespecified
secondary aim of the LUNG SAFE (Large
Observational Study to Understand the
Global Impact of Severe Acute Respiratory
Failure) (26) study was to describe the
current practice of the use of NIV in ARDS.
Our primary objective was to determine the
proportion of patients managed with NIV
on Days 1 and 2 following fulfillment of
diagnostic criteria for ARDS. Secondary
objectives included determining the utility
of the P a
O
2
/FI
O
2
ratio severity categories
in the classification of NIV patients,
characteristics of patients managed with
NIV, ventilatory settings used in these
patients, factors associated with NIV
failure, and the association between
NIV use and mortalit y in pati ents
with ARDS.
Methods
LUNG SAFE was a prospective,
observational, international multicenter
cohort study. Detailed methods have been
published elsewhere (26), and are also
available in the online supplement.
Patients, Study Design, and Data
Collection
Patients receiving invasive MV or NIV were
enrolled in the participating intensive care
units (ICUs) for 4 consecutive weeks.
Exclusion criteria were age less than 16 years
or inability to obtain informed consent.
Following enrollment, patients were
evaluated daily for acute hypoxemic
respiratory failure (AHRF), defined as
Pa
O
2
/FI
O
2
less than or equal to 300 mm Hg
while simultaneously receiving invasive MV
or NIV (depending on the patient group)
with end-expiratory pressure greater than
or equal to 5 cm H
2
O, and new radiologic
pulmonary parenchymal abnormalities. For
*A complete list of LUNG SAFE national coordinators, site investigators, and national societies endorsing the study may be found in the online supplement.
Supported by the European Society of Intensive Care Medicine (ESICM), Brussels, Belgium; by St. Michael’s Hospital, Toronto, Canada; and by the University
of Milan-Bicocca, Monza, Italy. The ESICM provided support in data collection and study coordination. ESICM, St. Michael’s Hospital, and University of Milan-
Bicocca had no role in the design and conduct of the study; management, analysis, and interpretation of the data; preparation, review, or approval of the
manuscript; or decision to submit the manuscript for publication.
Author Contributions: Conception and design, G.B., J.G.L., T.P., E.F., L.B., A.E., L.G., F.v.H., A.L., D.F.M., M.R., G.D.R., B.T.T., H.W., A.S.S., and A.P.
Analysis and interpretation, G.B., J.G.L., T.P., F.M., E.F., L.B., M.R., G.D.R., A.S.S., B.T.T., and A.P. Drafting manuscript for important intellectual content,
G.B., J.G.L., T.P., F.M., E.F., L.B., A.E., L.G., V.B., L.P., F.v.H., A.L., D.F.M., P.R.B., Y.M.A., M.R., M.A., G.D.R., B.T.T., H.W., A.S.S., and A.P.
Correspondence and requests for reprints should be addressed to John G. Laffey, M.D., Departments of Anesthesia and Critical Care Medicine, Keenan
Research Centre for Biomedical Science, St Michael’s Hospital, University of Toronto, Canada. E-mail: laffeyj@smh.ca
This article has an online supplement, which is accessible from this issue’s table of contents at www.atsjournals.org
At a Glance Commentary
Scientific Knowledge on the
Subject:
Noninvasive ventilation
(NIV) is used to treat patients with
acute respiratory distress syndrome
(ARDS). Current worldwide practice
in the use of this technique, its
implications for patient management,
and association with outcome are
poorly understood. The Berlin
definition of ARDS is unclear in regard
to the severity classification of patients
with NIV.
What This Study Adds to the
Field:
NIV is used in about 15% of
patients with ARDS, irrespective of the
severity of hypoxemia. Classification of
ARDS severity in patients with NIV
based on Pa
O
2
/FI
O
2
ratio had
management and prognostic
significance. Use of NIV, in
comparison with invasive ventilation,
has important implications for patient
management. Although mortality rate
was low in patients successfully
managed with NIV, patients who
failed NIV had a high mortality. NIV
may be associated with a worse
intensive care unit outcome than
invasive mechanical ventilation in
moderate to severe ARDS.
ORIGINAL ARTICLE
68 American Journal of Respiratory and Critical Care Medicine Volume 195 Number 1
|
January 1 2017
patients fulfilling AHRF criteria a more
detailed set of data was reco rded, to
determine whether the patient fulfilled the
Berlin criteria for ARDS.
Data on arterial blood gases, type of
ventilatory support/settings, and Sequential
Organ Failure Assessment (SOFA) score
were collected on selected days during the
ICU stay. Data were collected once per day,
as close as possible to 10:00
A.M.Data
on ventilatory settings were recorded
simultaneously with arterial blood gas
analysis. Decisions to withhold or withdraw
life-sustaining treatments and their timing
were recorded. ICU and hospital survival
were collected at the time of discharge,
censored at 90 days after enrollment.
We assessed clinician recognition of
ARDS at two time points: on Day 1 of study
entry, and when patients exited the study. ARDS
was deemed to have been clinician-recognized
if either question was answered positively.
NIV Patient Cohort and Definitions
We restricted analyses to the subset of
patients (93%) fulfilling ARDS criteria on Day 1
or 2 following the onset of AHRF. Patients were
classified as “NIV patients” if they received NIV
on Day 1 and 2 following fulfill ment of ARDS
criteria. In all NIV patients, arterial blood gas
measurements were taken while the patient was
receiving NIV. Patients were classified as
“invasive-MV patients” if they received invasive
MV on Day 1 and/or Day 2 of ARDS (see
Table E1 in the online supplement).
NIV definition encompassed all forms
of patient interface and ventilatory modes.
High-flow oxygen therapy was not included.
Because data were collected once per day and
the duration of NIV sessions was not
recorded, patients that were switched from
NIV to invasive-MV before the Day 2 data
collection (n = 75) were classified in the
invasive-MV group. We considered that, in
these patients, the NIV session may have
been too short to be meaningful.
NIV failure was defined as the need to
switch to invasive-MV after Day 1 and 2 of
NIV. We limited the comparison of NIV
“success” and “failure” groups to patients
without treatment limitation (whose definition
encompassed all forms of treatment limitation)
unless this occurred after institution of invasive
MV (see also S
TATISTICAL ANALYSIS).
Statistical Analysis
For continuous variables, we reported
median with inte rquartile range or
mean 6 SD, and for categorical variables,
we reported proportions. Student’s t test,
analysis of variance, Wilcoxon rank sum
test, or Kruskal-Wallis, chi-square, or
Fisher te sts were u sed when a pprop riate.
Multivariate Cox proportional hazards
models were applied to investigate the
relationship between potential covariates and
outcomes (ICU and hospital mortality, NIV
failure). Propensity score matching method
was used to evaluate the possible different
treatment effects (invasive-MV and NIV) on
survival (see Table E2). Patients were matched
(1:1 match without replacement) using a
caliper of 0.2 SD of the logit of the propensity
score. For all tests, a two-sided a of 0.05 was
considered significant. The analyses were
performed using SAS (SAS Institute, Cary,
NC) and R (The R Foundation for Statistical
Computing, Vienna, Austria) software.
Results
Incidence of NIV Use
A total of 459 ICUs enrolled patients in the
study and 422 enrolled patients with ARDS. In
the ICUs enrolling patients with ARDS, 207
(49.1%) used NIV on Days 1 and 2 of ARDS, in
at least one patient. Of the 2,813 patients that
developed ARDS within 2 days of AHRF onset,
507 patients received NIV on Day 1 (18%).
Of these, 436 (15.5%) were managed with NIV
on Days 1 and 2, and constitute the study
population (Figure 1), whereas 75 patients
were managed with NIV on Day 1 and on
invasive MV on Day 2 (see Table E3).
Continuous positive airway pressure
was used in 28.2% of patients in the NIV group
(Table 1), whereas the remaining patients were
managed with pressure cycled modes.
Classification of NIV Patients
In patients with ARDS managed with NIV,
classification of severity into mild, moderate, and
severe categories according to the Pa
O
2
/FI
O
2
bands in the Berlin definition was associated
with a step-wise increase in positive end-
expiratory pressure (PEEP) and F
I
O
2
(Table 1).
Greater ARDS severity category was associated
with an increase in clinician recognition of
ARDS, and a worsening in outcomes, including
ICU length of stay, ICU mortality, and
nonsignificant increase in hospital mortality
(Table 2). Increasing ARDS severity category
was associated with a significant increase in
NIV failure in patients without preintubation
treatment limitations (from 22.2 to 42.3 to
47.1%; P = 0.008).
Of interest, the use of NIV did not vary
significantly with mild (14.3%), moderate
(17.3%), and severe (13.2%) ARDS severity
category (Table 1).
Baseline Characteristics of NIV
Patients
NIV patients were older and had lower
nonpulmonary SOFA scores, both in the
whole population and across the different
severity categories, compared with invasive-
MV patients (Table 1). NIV patients had a
higher prevalence of chronic renal failure,
congestive heart failure, and chronic
obstructive pulmonary disease than
invasive-MV patients (Table 1). The
prevalence of immunosuppression and/or
malignancies did not differ between the
two groups. Clinician recognition of
ARDS was significantly lower in N IV
patients com pared with invasive-MV
patients (Table 2). The use of NIV was
independently associated with a lower
recognition of ARDS by clinicians (odds
ratio, 0.585; 95% confidence interval,
0.45–0.76) (see Table E4). ARDS recognition
was increased in patients that failed NIV
(Table 3). There were no differe nces in
treatment limitation rates in NIV patients
versus invasive-MV patients.
Effect of NIV versus Invasive MV on
Ventilation and Gas Exchange
NIV patients had significantly lower levels
of PEEP, and higher respiratory rates than
invasive-MV patients. In NIV patients,
measured tidal volumes and minute
ventilation were greater than in invasive-
MV patients (Table 1). In contrast to
patients managed with invasive-MV, tidal
and minute ventilation did not change
significantly with greater ARDS severity
(Table 1).
At ARDS onset, Pa
O
2
/FI
O
2
ratio was not
different between the NIV and invasive-
MV patients (Table 1). Pa
O
2
/FI
O
2
ratios
improved more rapidly in the patients
treated with invasive-MV (Figure 2B; see
Figure E1). Baseline Pa
CO
2
did not differ
between the NIV and invasive-MV patients.
However, although baseline Pa
CO
2
in mild
ARDS was higher in NIV compared with
invasive-MV patients (48 6 18 vs. 41 6
10 mm Hg; P = 0.002), Pa
CO
2
in severe
ARDS was lower in NIV (43 6 14 vs. 52 6
18 mm Hg; P , 0.001) compared with
invasive-MV. In contrast to invasive-MV
patients, where Pa
CO
2
increased, the
Pa
CO
2
in the NIV group did not change
ORIGINAL ARTICLE
Bellani, Laffey, Pham, et al.: Noninvasive Ventilation of Patients with ARDS 69
(P = 0.134) with greater ARDS severity
(Table 1, Figure 2).
NIV Failure versus Success
Among the 349 NIV patients without
preintubation treatment limitations, 131
(37.5%) failed NIV (Table 3). A multivariate
Cox model revealed that higher
nonpulmonary SOFA score, lower
Pa
O
2
/FI
O
2
, and the percentage increase of
Pa
CO
2
over the first 2 days of treatment
were independently associated with NIV
failure within 28 days from AHRF onset
(see Table E5).
Effect of Intubation on Physiologic
Variables
Table E6 and Figure 2C show the
comparison, for physiologic variables,
between the last available recording of
NIV and the first available recording
during invasive-MV. After i ntubation,
both Pa
O
2
/FI
O
2
(152 6 68 vs. 182 6
95 mm Hg; P , 0.001) and Pa
CO
2
significantly increased. After initiation
of invasive-MV, patients were managed
with a higher PEEP and had lower
respiratory rates, and received lower
tidal and minute volumes compared
with preintubation values.
Outcomes in NIV Patients
Crude ICU and hospital mortalities were not
significantly different between the NIV and
the invasive-MV patients (Table 2; see
Figure E2).
Patients that failed NIV were more
severely ill (Table 3) and had significantly
worse ICU (42.7% vs. 10.6%; P , 0.001)
and hospital mortality compared with those
that were successfully managed with NIV
(Table 3).
In a multivariate Cox regression model
adjusting for covariates significantly
associated with outcome (see Table E7),
NIV use was independently associated with
increased ICU (but not hospital) mortality
rate (hazard ratio, 1.446 [95% confidence
interval, 1.159–1.805]). Furthermore, we
matched 353 NIV patients with invasive-
MV patients using propensity score (see
Table E2). The two matched populations
were homogeneous for demographic
characteristics, comorbidities, and severity
of organ failures (see Table E2). ICU and
hospital mortality rates did not differ
(Table 4). Kaplan-Meier survival estimates
for invasive-MV and NIV patients of the
matched samples were not significantly
different (Figure 3). In the subset of patients
with a Pa
O
2
/FI
O
2
ratio less than 150, ICU
mortality was 36.2% with NIV compared
with 24.7% with invasive-MV (P =0.033)
(Table 4). Figure 3 shows survival curves in
NIV and invasive-MV groups for matched
patients with a Pa
O
2
/FI
O
2
higher and lower
than 150 mm Hg.
Table E8 shows the comparison
between survivors and nonsurvivors at
hospital discharge in NIV patients.
Nonsurvivors were older, with a higher
prevalence of immunosuppression or
neoplastic disease, and had a higher
nonpulmonary SOFA score. Moreover,
nonsurvivors had, on the day of ARDS
diagnosis, a lower Pa
O
2
/FI
O
2
and higher
respiratory rate than survivors. A
multivariate Cox model performed on
baseline characteristics in the NIV group
showed that chronic heart failure, presence
of hematologic or neoplastic disease,
chronic liver failure, age, ARDS severity,
percentage decrease of Pa
O
2
/FI
O
2
ratio
between Days 1 and 2, total respiratory rate,
Patients with ARDS
3,022
Patients with ARDS after
2 days from AHRF onset
209 (6.9%)
Patients with ARDS within
2 days of AHRF onset
2,813 (93.1%)
Patients invasively ventilated*
2,377 (84.5%)
Patients non-invasively
ventilated on Day 1 and 2
436 (15.5%)
Non-survivors
§
462 (25.7%)
Survivors
§
1,337 (74.3%)
Survivors
§
71 (54.6%)
Survivors
§
183 (83.9%)
Survivors
§
25 (28.7%)
Survivors
§
79 (13.7%)
Non-survivors
§
499 (86.3%)
Non-survivors
§
59 (45.4%)
Non-survivors
§
35 (16.1%)
Non-survivors
§
62 (71.3%)
No limitation of care
†
1,799 (75.7%)
Limitation of care
†
578 (24.3%)
Limitation of care
†
87 (20.0%)
Failure
‡
131 (30.0%)
Non-failure
‡
218 (50.0%)
Severity at ARDS onset
Mild 714 (30.0%)
Moderate 1,106 (46.5%)
Severe 557 (23.4%)
Severity at ARDS onset
Mild 119 (27.3%)
Moderate 232 (53.2%)
Severe 85 (19.5%)
Figure 1. Flowchart of the study population. *Seventy-five patients received noninvasive ventilation on Day 1 and invasive ventilation at Day 2.
†
Limitation
of care before acute hypoxemic respiratory failure (AHRF) onset or within 28 days.
‡
Failure of noninvasive ventilation was evaluated within
28 days from AHRF onset.
x
We reported vital status at hospital discharge censored at Day 90 after AHRF onset. Vital status was unknown
for nine patients: eight invasively ventilated and one noninvasively ventilated within 48 hours from AHRF onset. ARDS = acute respiratory distress
syndrome.
ORIGINAL ARTICLE
70 American Journal of Respiratory and Critical Care Medicine Volume 195 Number 1
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January 1 2017
Table 1. Demographic and Clinic Characteristics of Study Population (Stratified by ARDS Severity and Ventilation) at Baseline (ARDS Onset)
ARDS, Mild ARDS, Moderate ARDS, Severe ARDS
P Value
within NIV
P Value
within
Invasive-MVNIV Invasive-MV NIV Invasive-MV NIV Invasive-MV NIV Invasive-MV
N 119 714 232 1,106 85 557 436 2,377 ——
% within ARDS severity 14.3 85.7 17.3 82.7 13.2 86.8 15.50 84.50 ——
Male, n (%) 58 (48.7) 439 (61.5)* 150 (64.7) 683 (61.8) 49 (57.6) 350 (62.8) 257 (58.9) 1,472 (61.9) 0.016 0.875
Age, yr, median (IQR) 71 (59 to 77) 64 (51 to 75)* 68 (56 to 79) 64 (52 to 74)* 64 (49 to 76) 58 (44 to 70)* 68 (54 to 78) 63 (50 to 73)* 0.110 ,0.001
Risk factors for ARDS, n (%) 0.478 ,0.001
None 19 (16.0) 69 (9.7)* 30 (12.9) 85 (7.7)* 13 (15.3) 36 (6.5)* 62 (14.2) 190 (8.0)*
Nonpulmonary 15 (12.6) 180 (25.2)* 28 (12.1) 219 (19.8)* 5 (5.9) 81 (14.5)* 48 (11.0) 480 (20.2)*
Pulmonary 85 (71.4) 465 (65.1) 174 (75.0) 802 (72.5) 67 (78.8) 440 (79.0) 326 (74.8) 1,707 (71.8)
Comorbidities, n (%)
Diabetes 28 (23.5) 153 (21.4) 52 (22.4) 253 (22.9) 18 (21.2) 109 (19.6) 98 (22.5) 515 (21.7) 0.924 0.298
Chronic renal failure 19 (16.0) 77 (10.8) 31 (13.4) 111 (10.0) 12 (14.1) 36 (6.5)* 62 (14.2) 224 (9.4)* 0.803 0.021
Heart failure 22 (18.5) 74 (10.4)* 34 (14.7) 105 (9.5)* 10 (11.8) 45 (8.1) 66 (15.1) 224 (9.4)* 0.400 0.382
Chronic liver failure 4 (3.4) 31 (4.3) 2 (0.9) 45 (4.1)* 3 (3.5) 27 (4.8) 9 (2.1) 103 (4.3)* 0.109 0.763
Neoplasm or
immunosuppression
20 (16.8) 147 (20.6) 62 (26.7) 209 (18.9)* 17 (20.0) 129 (23.2) 99 (22.7) 485 (20.4) 0.089 0.125
COPD 46 (38.7) 132 (18.5)* 70 (30.2) 239 (21.6)* 19 (22.4) 101 (18.1) 135 (31.0) 472 (19.9)* 0.043 0.134
Home ventilation 8 (6.7) 13 (1.8)* 10 (4.3) 20 (1.8)* 3 (3.5) 5 (0.9) 21 (4.8) 38 (1.6)* 0.502 0.321
Parameters at day of ARDS
onset, mean 6 SD
Pa
O
2
, mm Hg 109.4 6 42.1 118.2 6 46.6 80.7 6 21.7 90.7 6 28.3* 67.7 6 14.0 66.3 6 15.2 86.0 6 31.6 93.2 6 37.9* ,0.001 ,0.001
F
I
O
2
0.45 6 0.18 0.48 6 0.19* 0.57 6 0.16 0.62 6 0.19* 0.88 6 0.13 0.90 6 0.15* 0.60 6 0.22 0.65 6 0.24* ,0.001 ,0.001
Pa
O
2
/FI
O
2
, mm Hg 243 6 29 246 6 28 146 6 29 149 6 28 79 6 17 75 6 17 160 6 63 161 6 68 ,0.001 ,0.001
pH 7.37 6 0.09 7.36 6 0.10 7.37 6 0.10 7.33 6 0.12* 7.41 6 0.09 7.27 6 0.14* 7.38 6 0.10 7.33 6 0.12* 0.007 ,0.001
Pa
CO
2
,mmHg 486 18 41 6 10* 47 6 18 46 6 15 43 6 14 52 6 18* 46 6 17 46 6 15 0.134 ,0.001
Base excess, mmol/L 1.49 6 7.50 21.93 6 6.23* 0.42 6 6.53 22.23 6 6.85* 1.18 6 5.99 22.74 6 8.11* 0.86 6 6.72 22.26 6 6.99* 0.181 0.009
PEEP, cm H
2
O76 276 376 286 3* 7 6 2106 4* 7 6 286 3* 0.042 ,0.001
Total respiratory rate,
breaths/min
24 6 7196 6* 27 6 7216 6* 27 6 6236 14* 26 6 7216 9* ,0.001 ,0.001
Minute ventilation, L/min 12.19 6 5.24 9.13 6 2.93* 13.63 6 5.74 9.50 6 3.10* 13.29 6 4.90 9.91 6 3.15* 13.18 6 5.47 9.49 6 3.07* 0.057 ,0.001
Tidal volume, ml/kg PBW 8.73 6 2.85 7.76 6 1.77* 8.37 6 2.84 7.60 6 1.92* 7.98 6 2.62 7.46 6 1.93* 8.39 6 2.81 7.61 6 1.88* 0.348 0.007
Nonpulmonary SOFA score
adjusted
3 6 376 4* 3 6 376 4* 3 6 376 4* 3 6 376 4* 0.548 0.370
Use of vasopressors, n (%) 16 (14.4) 342 (51.8)* 37 (17.6) 575 (55.2)* 9 (11.8) 325 (61.2)* 62 (15.6) 1,242 (55.6)* 0.453 0.005
Use of CPAP, n (%) 35 (29.4) — 65 (28.0)
— 23 (27.0) — 123 (28.2) — 0.930 —
Definition of abbreviations: ARDS = acute respiratory distress syndrome; COPD = chronic obstructive pulmonary disease; CPAP = continuous positive airway pressure; IQR = interquartile
range; MV = mechanical ventilation; NIV = noninvasive ventilation; PBW = predicted body weight; PEEP = positive end-expiratory pressure; SOFA = Sequential Organ Failure Assessment.
*P , 0.05, comparison versus NIV group with same ARDS severity.
ORIGINAL ARTICLE
Bellani, Laffey, Pham, et al.: Noninvasive Ventilation of Patients with ARDS 71