What did we learn
from the ARDS net ?
Antonio Anzueto MD
Professor Medicine
University of Texas San Antonio, Texas
Hemodynamics: • Hypotensive on
vasopressors. Oxygenation: • PaO2/FiO2 86 Ventilation: • PaCO2 76 • pH 7.1
ARDSnet Studies
• High vrs. Low tidal volume
• High vrs. Low PEEP
• Late steroids rescue
• Hemodynamic monitoring: CVP vrs PA
catheter.
• Fluid management
• Feeding: EDEN and OMEGA
• Albuterol
ARDSnet Studies
• High vrs. Low tidal volume
• High vrs. Low PEEP
• Late steroids rescue
• Hemodynamic monitoring: CVP vrs PA
catheter.
• Fluid management
• Feeding: EDEN and OMEGA
• Albuterol
ARDSNet Tidal Volume Study:
Ventilator Management
• Mode: Assist control
• Reduce VT to 6 mL/kg predicted body
weight
• Set rate to maintain baseline Ve (not >35)
• Keep Pplat <30 cm H2O
• Maintain SaO2 / SpO2 88%-95%
ARDSNet. N Engl J Med 2000;342:1301-8.
FIO2 .3 .4 .4 .5 .5 .6 .7 .7 .7 .8 .9 .9 .9 1.0
PEEP 5 5 8 8 10 10 10 12 14 14 14 16 18 20-24
ARDS - NIH TRIAL
DAY 1 High TV Low TV
PaO2/FiO2 176 ± 76 158 ± 73
PEEP 8.6 ± 3.6 9.4 ± 3.6
pH 7.41±0.07 7.38±0.08
PaCO2 35 ± 8 40 ± 10
ARDS NET et al NEJM 2000
Overall efficacy of low Vt
ventilation
0
10
20
30
40
50
60
70
Mortality Organ Failure Unassisted
Breathing
%
*P < 0.02 in all cases
23%
11% 19%
ARDS NET et al NEJM 2000
% P
atients
Tidal volume (ml / kg)
ARDS
20
15
10
5
0
20
15
10
5
0
8.9 1.9
1998
7.7 1.9
2004 2010
7.5 1.5
20
15
10
5
20
15
10
5
ARDS
4.6 2.4
1998
5.9 2.8
2004
PEEP (cm H2O)
9.4 3.9
2010
Plateau pressure (cm of water)
60
50
40
30
20
10
0
60
50
40
30
20
10
0 ARDS
21.9 4.1
1998
21.4 5.6
2004
23.9 5.6
2010
ICU HOSPITAL
COPD 21.4 % 25.9 %
Asthma 8.2 % 8.3 %
ARDS 47.3 % 53.5 %
Postoper. 15.3 % 19.8 %
CHF 24.8 % 33.8 %
C. Pneum. 32.4 % 40.3 %
Hosp. Pneum. 33.9 % 43.1 %
Sepsis 41.9 % 52.1 %
Trauma 19.3 % 22.8 %
Coma 27.8 % 38.8 %
MORTALITY
ARDSnet Studies
• High vrs. Low tidal volume
• High vrs. Low PEEP
• Late steroids rescue
• Hemodynamic monitoring: CVP vrs PA
catheter.
• Fluid management
• Feeding: EDEN and OMEGA
• Albuterol
ARDSnet: Late Steroid Rescue
Protocol (LaSRS)
• ARDS for 7 to 28 days.
• PaO2/FiO2 ration < 200.
• Randomized to:
– Placebo
– MMPS – bolus dose 2 mg/kg – followed
0.5mg/kg q 6hrs for 14 days, then q 12hrs for
7 days then taper.
• BAL study entry and 7 days
NEJM 2006; 354:1671
Days after randomization
Pro
port
ion o
f patients
0 10 20 30 40 50 60
00.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
Dead
On Vent
In Hospital, Off Vent
Discharged Home
PlaceboMethylprednisolone
Outcome
NEJM 2006; 354:1671
ARDSnet Studies
• High vrs. Low tidal volume
• High vrs. Low PEEP
• Late steroids rescue
• Hemodynamic monitoring: CVP vrs PA
catheter.
• Fluid management
• Feeding: EDEN and OMEGA
• Albuterol
Kaplan Meier estimates of survival and
unassisted breathing
Mortality to day 60
PAC 27.4% vs. CVC 26.3%
P=0.69 CI -4.4 to 6.6%
Ventilator-free days to day 28
PAC 13.2+0.5 vs. CVC 13.5+0.5
P=0.58
KIDNEY
Favors
Dry
LUNG
Conservative fluid strategy
CVP < 4
PAOP < 8
MAP < 60
Low flow by exam or CI <2.5
UOP < 0.5 ml/kg/h &
CVP or PAOP low
Furosemide
ARDSnet- NEJM 2006; 354:2213
Favors
Perfused
KIDNEY
(organs)
LUNG
Liberal fluid strategy
CVP 10-14
PAOP 14-18
CI > 4.5 FiO2 > 0.7
Fluids
ARDSnet- NEJM 2006; 354:2213
Probab Probability of Survival to
Hospital Discharge and
Breathing Without Assistance
during the First 60 Days after
Randomization
ARDSnet Studies
• High vrs. Low tidal volume
• High vrs. Low PEEP
• Late steroids rescue
• Hemodynamic monitoring: CVP vrs PA
catheter.
• Fluid management
• Feeding: EDEN and OMEGA
• Albuterol
Feeding: Survival and Hospital Stay
ARDS NET - JAMA. 2012;307:795-803
Diet supplement: Survival and Hospital Stay
ARDS Net - JAMA. 2011;306:1574-1581
Albuterol: Survival and Ventilator –free-days
ARDS Net – AJRCCM 2011
JAMA. 2012;307:2526-2533
The ARDS Definition Task Force: Ranieri, MD ,Gordon D. Rubenfeld,
MD, Taylor Thompson,MD; Niall D. Ferguson, MD,; Ellen Caldwell,
MS; Luigi Camporota, MD ; Arthur S. Slutsky, MD ; Massimo
Antonelli, MD ;Antonio Anzueto, MD; Richard Beale, MBBS ; Laurent
Brochard,MD ; Roy Brower, MD; Andres Esteban, MD, PhD ; Luciano
Gattinoni,MD ; Andrew Rhodes,MD; Andrew Bersten,MD; Antonio
Pesenti, MD
Mild Moderate Severe
Timing Acute onset within 1 week of a known clinical insult or
new/worsening respiratory symptoms
ARDS
JAMA. 2012;307:2526-2533
Mild Moderate Severe
Timing Acute onset within 1 week of a known clinical insult or
new/worsening respiratory symptoms
Hypoxemia PaO2/FiO2 201-300
with PEEP/CPAP ≥ 5
PaO2/FiO2 ≤ 200 with
PEEP ≥ 5
PaO2/FiO2 ≤ 100 with
PEEP ≥ 10
ARDS
JAMA. 2012;307:2526-2533
Mild Moderate Severe
Timing Acute onset within 1 week of a known clinical insult or
new/worsening respiratory symptoms
Hypoxemia PaO2/FiO2 201-300
with PEEP/CPAP ≥ 5
PaO2/FiO2 ≤ 200 with
PEEP ≥ 5
PaO2/FiO2 ≤ 100 with
PEEP ≥ 10
Origin of Edema
Respiratory failure associated to known risk factors and not fully
explained by cardiac failure or fluid overload. Need objective
assessment of cardiac failure or fluid overload if no risk factor are
present
ARDS
JAMA. 2012;307:2526-2533
Mild Moderate Severe
Timing Acute onset within 1 week of a known clinical insult or
new/worsening respiratory symptoms
Hypoxemia PaO2/FiO2 201-300
with PEEP/CPAP ≥ 5
PaO2/FiO2 ≤ 200 with
PEEP ≥ 5
PaO2/FiO2 ≤ 100 with
PEEP ≥ 10
Origin of Edema
Respiratory failure associated to known risk factors and not fully
explained by cardiac failure or fluid overload. Need objective
assessment of cardiac failure or fluid overload if no risk factor are
present
Radiological
Abnormalities Bilateral opacities*
Bilateral
opacities*
Opacities involving at
least 3 quadrants*
ARDS
JAMA. 2012;307:2526-2533
Mild Moderate Severe
Timing Acute onset within 1 week of a known clinical insult or
new/worsening respiratory symptoms
Hypoxemia PaO2/FiO2 201-300
with PEEP/CPAP ≥ 5
PaO2/FiO2 ≤ 200 with
PEEP ≥ 5
PaO2/FiO2 ≤ 100 with
PEEP ≥ 10
Origin of Edema
Respiratory failure associated to known risk factors and not fully
explained by cardiac failure or fluid overload. Need objective
assessment of cardiac failure or fluid overload if no risk factor are
present
Radiological
Abnormalities Bilateral opacities*
Bilateral
opacities*
Opacities involving at
least 3 quadrants*
Additional
Physiological
Derangement
N/A N/A
VE Corr > 10 L/min
or
CRS<40 ml/cmH2O
*Not fully explained by effusions, nodules, masses, or lobar/lung collapse; use training set of CXRs; VE Corr =
VE x PaCO2/40 (corrected for Body Surface Area)
ARDS
JAMA. 2012;307:2526-2533
Validation Berlin Definition
JAMA. 2012;307:2526-2533
300 250 200 150 100 50
PaO2/FiO2
Increasing Severity of Lung Injury
Mild ARDS Moderate ARDS Severe ARDS Inc
reasin
g In
ten
sit
y o
f In
terv
en
tio
n
16.8 (3.6)
32.6 (4.9)31.9 (4.8)
53.3 (4.9)
0
30
60
Lower Vt Traditional Vt
Mild Severe
Percent Mortality
at 60 days
(+/- SD)
Mortality in Lower Vt trial
Mild vs Severe (by P/F quartiles)
Mild P/F > 192
Severe P/F < 103
p=0.814 for interaction of P/F and Rx
Britos et al CCM 2010
300 250 200 150 100 50
Low Tidal Volume Ventilation and Conservative Fluid Rx
PaO2/FiO2
Increasing Severity of Lung Injury
Mild ARDS Moderate ARDS Severe ARDS Inc
reasin
g In
ten
sit
y o
f In
terv
en
tio
n
Briel et al.
P/F </= 200
300 250 200 150 100 50
Low Tidal Volume Ventilation and Conservative Fluid Rx
Higher PEEP
Low – Moderate PEEP
PaO2/FiO2
Increasing Severity of Lung Injury
Mild ARDS Moderate ARDS Severe ARDS Inc
reasin
g In
ten
sit
y o
f In
terv
en
tio
n
P/F 100-200 P/F < 100
300 250 200 150 100 50
Low Tidal Volume Ventilation and Conservative Fluid Rx
Higher PEEP
Low – Moderate PEEP
PaO2/FiO2
Increasing Severity of Lung Injury
Mild ARDS Moderate ARDS Severe ARDS Inc
reasin
g In
ten
sit
y o
f In
terv
en
tio
n
Prone Positioning
N = 340 subjects with P/F < 150
300 250 200 150 100 50
Low Tidal Volume Ventilation and Conservative Fluid Rx
Higher PEEP
Low – Moderate PEEP
PaO2/FiO2
Increasing Severity of Lung Injury
Mild ARDS Moderate ARDS Severe ARDS Inc
reasin
g In
ten
sit
y o
f In
terv
en
tio
n
Neuromuscular
Blockade
Prone Positioning
300 250 200 150 100 50
Low Tidal Volume Ventilation and Conservative Fluid Rx
Higher PEEP
Low – Moderate PEEP
PaO2/FiO2
Increasing Severity of Lung Injury
Mild ARDS Moderate ARDS Severe ARDS Inc
reasin
g In
ten
sit
y o
f In
terv
en
tio
n
HFO
ECMO
Neuromuscular
Blockade
ECCO2-R
iNO
NIV
Prone Positioning
ARDSnet Studies
• High vrs. Low tidal volume
• High vrs. Low PEEP
• Late steroids rescue
• Hemodynamic monitoring: CVP vrs PA
catheter.
• Fluid management
• Feeding: EDEN and OMEGA
• Albuterol
“Success is defined as
moving from failure to
failure with undiminished
enthusiasm “
Sir W. Churchill
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