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