Acute lung injury (ALI) and Acute respiratory distress syndrome ...

Acute lung injury (ALI) and
Acute respiratory distress syndrome
(ARDS)
Arthur P. Wheeler, MD
Associate Professor of Medicine
Director, Medical ICU
Division of Allergy, Pulmonary and Critical Care Medicine
Vanderbilt University
Commercial disclosures: none
Research Support: NO1-HR-46054-64, NO1-16146-54

• 21 yo female WKU student
• Previously healthy
• Admitted with Gullian-Barre
• Day 5 aspiration-induced ARDS
• Ventilation
– Tidal volume 10 ml/kg
–FiO 2 0.8
– PEEP 15
– PIP 70 cm H 2 0
– Adjustments made to normalize blood gases

• Day 23 bilateral tension
pneumothoraces
– Multiple (4+3) chest tubes
– Large bilateral (R>L) cystic
areas
– Pneumomediastinum
– Interstitial emphysema

• Day 52 air-hunger, suddenly sat upright
– New seizure
– Livedo reticularis right hemi-thorax, hand, and face
– ECG: acute inferior myocardial infarction
– Head CT: multiple new infarcts
• Day 70 autopsy:
– Severe lung injury with prominent cystic changes,
extensive fibrosis and foci of infection
– Multiple myocardial infarcts, intact atrial septum
– Multiple CNS infarcts c/w emboli
Marini JJ Ann Intern Med 1989; 110: 699

Acute lung injury (ALI)
Acute respiratory distress syndrome
• Acute onset
• Profound hypoxemia
• Radiograph of
pulmonary edema
• No evidence of left
atrial hypertension
• “Stiff” or “small” lungs
• Predisposing cause
(ARDS)
Bernard GR. Am J Resp Crit Care 1994; 149: 818

Causes of ALI
Severe
sepsis
26%
Aspiration
15%
Trauma
Pneumonia
11%
35%
Other
13%
ARDS Network N Engl J Med 2000; 342:1301
Drowning
Pancreatitis
Reperfusion
Salicylate and narcotic OD
Fat / amniotic fluid embolism
Smoke / chemical inhalation

Mortality rate of ALI/ARDS
100
80
Mortality (%)
60
40
20
0
83 84 85 86 87 88 89 90 91 92 93
Milberg J JAMA 1995;273:306

Supportive care for all patients
• DVT prophylaxis
• Gastrointestinal bleeding prophylaxis
• Elevate HOB to 30 degrees
• Hand washing
• Catheters inserted using full barrier precautions with
chlorhexidine.
• Sedation and analgesia protocols.
• Reduction in transfusion thresholds.
• Standardized feeding protocols.
• Contrast nephropathy avoidance.
• Bedsore prevention program.

Causes of death
Multiple
organ failure
Severe
sepsis
Underlying
injury /
illness
Lung failure
Montgomery AB Am Rev Respir Dis. 1985;132:485

Epithelial injury
Protein rich
edema fluid
Inflammatoryhemorrhagic
infiltrate
Increased
vascular
permeability
Adapted from Ware LB, N Engl J Med. 2000; 342:1334
Activated
coagulation

ALI is heterogeneous
Near normal
Marginal
Non-functional
Maunder R, JAMA 1986; 255:2463

Major questions in ALI in the 1990’s
• What is the best way to ventilate the lung
• Does attenuating inflammation offer benefit
• What should be done with fluids

ARDSnet
Mass General
Washington
San Francisco
Philadelphia
Baltimore
NHLBI
Utah
Denver
Michigan
Vanderbillt
Cleveland
Duke
NIH NHLBI ARDS Clinical Trials Network

Ventilation

Airway pressures
Airway
Pressure
Peak inspiratory
pressure (PIP)
Plateau pressure
PEEP
Time

Mechanisms of ventilation induced
lung injury
• Healthy animals developed lung injury if ventilated
with PIP > 40 cm H 2 O “Barotrauma”
– Kolobow Am Rev Resp Dis 135:312, 1987
• Identical pressures did not cause injury if lung
expansion was restricted “Volutrauma”
– Hernandez J Appl Physiol 1989 66:2364
• PEEP attenuated the injury of high pressure
ventilation “Repetitive opening injury”
– Webb Am Rev Resp Dis 1974; 110: 556

Ventilation can cause systemic
inflammation: “biotrauma”
1200
600
1000
500
BAL
TNF
(pg/ml)
800
600
400
BAL
IL-6
(pg/ml)
400
300
200
200
100
0
Control MVHP MVZP HVZP
0
Control MVHP MVZP HVZP
Tremblay J Clin Invest 1997; 99:944

Inadequate
Tidal Volume
or PEEP
Large
Tidal Volume
or Inadequate
PEEP
Consequences:
• Atelectasis
• Hypoxemia
• Hypercapnia
ALI
Before Ventilation
Consequences:
• V/Q mismatch
TNF
IL-6, etc
• Alveolar-capillary injury
• “Barotrauma”
• Inflammation

Tidal volume in practice
50
40
Percent of
responders
30
Normal
Recommended
20
10
0
< 5 5-9 10-13 14-17
Tidal volume mL/kg measured body weight
Carmichael L. J Crit Care 1996; 11: 9

Trials of lower tidal ventilation
Mortality (%) Pressure
Traditional “Protective” Limits
Stewart 1 (n = 120) 47 50 PIP=50
Brochard 2 (n = 116) 38 47 PIP=60
Brower 3 (n = 52) 46 50 Pplat 45-55
Amato 4 (n = 53) 71 38
1. NEJM 338:355-361, 1998 2. AJRCCM 158: 1831, 1998
3. CCM 27:1492, 1999 4. NEJM 339: 347, 1998

normal
Hypothesis:
In patients with ALI, ventilation with smaller tidal volumes
(6 mL/kg) will result in better clinical outcomes than
traditional tidal volumes (12 mL/kg) ventilation.
ARDS Network N Engl J Med 2000; 342:1301

Ventilator procedures
12 ml/kg Group
•Initial Vt = 12 ml/kg PBW
•If Pplat > 50 cmH 2 0, reduce Vt
•Minimum Vt = 4 ml/kg
6 ml/kg Group
•Initial Vt = 6 ml/kg PBW.
•If Pplat > 30 cmH 2 0, reduce Vt.
•Minimum Vt = 4 ml/kg
24
20
PEEP
16
12
8
4
0
0.3 0.4 0.4 0.5 0.5 0.6 0.7 0.7 0.8 0.9 0.9 0.9 1.0 1.0 1.0
FIO2
PaO 2 = 55 - 80 mmHg or SpO 2 = 88 - 95%
Standardized weaning protocol

Macro-barotrauma is not the
mechanism of injury
6ml/kg 12 ml/kg
p
Requiring
thoracostomy 13% 12% 0.932
Not requiring
thoracostomy 7% 9% 0.359
ARDS Network N Engl J Med 2000; 342:1301

Effects of lower tidal volume
14
Tidal volume
30
Total respiratory rate
Vt
(ml/kg
PBW)
12
10
8
6
6 ml/kg
12 ml/kg
Breaths per
minute
26
22
18
4
0 1 2 3 4
Study Day
14
0 1 2 3 4
Study Day
35
Plateau pressure
45
Arterial PaCO2
30
cm water
25
20
PaCO2 40
(mm Hg)
35
15
0 1 2 3 4
Study Day
ARDS Network N Engl J Med 2000; 342:1301
30
0 1 2 3 4
Study Day

PaO 2 / FiO 2
180
160
*
*
P/F
140
120
ARDS Network N Engl J Med 2000; 342:1301
6 ml/kg
12 ml/kg
0 1 2 3 4
Study Day

Median ventilator
free days
7 days p=0.005
Hospital mortality
9 % ARR p=0.0054
ARDS Network N Engl J Med 2000; 342:1301

Median organ failure free days
CNS
Hepatic
*
Cardiovascular
*
Coagulation
*
= 6 ml/kg
= 12 ml/kg
Renal
ARDS Network N Engl J Med 2000; 342:1301
0 7 14 21 28
Days
*

0
6 mL/kg 12 mL/kg
-20
Percent change
Day 0 to 3
-40
-60
-80
IL-6 IL-8 IL-10
-100
Crit Care Med. 2005;33:1
P=0.001 between groups

Tidal volume as a risk factor for ALI
Baseline Vt 2001 Risk of developing ALI
♂=10.4 mL/kg
♀=11.4 mL/kg
Gajic O. Crit Care Med 2004, 32:1817
OR 1.29 /mL Vt >6 PBW
(1.12-1.51)

“Lung protective” ventilation
V
Add PEEP
o
l
u
m
e
12 ml/kg PBW
Pressure
Limit Distending
Pressure

Hypothesis:
In patients with ALI ventilated with 6 mL/kg, higher
levels of PEEP will result in better clinical outcomes
than lower levels of PEEP.
N Engl J Med 2004; 351:327

Ventilation strategy
PEEP
•All given 6 mL/kg PBW tidal volume
•Oxygenation: SpO 2 = 88 - 95% or PaO 2 = 55 - 80 mm Hg
•Standardized weaning
24
20
16
12
8
4
0
0.3 0.3 0.4 0.4 0.5 0.5 0.6 0.7 0.7 0.7 0.8 0.8 0.9 0.9 0.9 1.0 1.0 1.0 1.0
N Engl J Med 2004; 351:327
FIO2

Barotrauma
20
15
Low PEEP
High PEEP
P=0.51
Percent
10
5
267 270
0
New Barotrauma
N Engl J Med 2004; 351:327

Vt (ml/kg)
9
8
7
6
Physiology of higher / lower PEEP
Tidal volume
Low PEEP
High PEEP
Pplat (mm Hg)
28
27
26
25
24
Pplat
5
16
0 1 2 3 4 7
PEEP
23
0.65
0 1 2 3 4 7
FIO2
Low PEEP
PEEP
14
12
10
FIO2
0.60
0.55
0.50
0.45
High PEEP
8
0.40
6
0 1 2 3 4 7
0 1 2 3 4 7
Study day
0.35
N Engl J Med 2004; 351:327
Study day

Physiology of higher / lower PEEP
PaO2 / FIO2 ratio
PaCO2
210
50
190
45
P/F Ratio
170
PaCO2
40
150
35
Low PEEP
High PEEP
130
0 1 2 3 4 7
Study day
30
1 2 3 4 7
Study day
N Engl J Med 2004; 351:327

Hospital mortality
25% low vs 28% high p=0.48
Higher PEEP
Lower PEEP
Median ventilator free days
14.5 low vs 13.8 high p=0.51
N Engl J Med 2004; 351:327

Median organ failure free days
Renal
P=0.74
Coagulation
P=0.90
Hepatic
P=0.72
Cardiovascular
P=0.68
CNS
P=0.25
0 7 14 21 28
Low PEEP
High PEEP
N Engl J Med 2004; 351:327

“Lower tidal volume with 6 cc per kilo decreased mortality
from 40% to 31%. You twirl a knob, you’re ‘gonna save a
life..OK…”

Summary
• Lower tidal volumes reduce death rates compared to
“traditional” tidal volumes.
• Patients on higher tidal volumes look more comfortable
(until they die).
• In the range tested higher PEEP is not “better” or
“worse” than lower PEEP.
• Lower tidal volumes may prevent ALI development.

Treating inflammation

Ketoconazole for Early Treatment of Acute Lung Injury and Acute
Respiratory Distress Syndrome: A Randomized Controlled Trial
The NIH NHLBI ARDS Network
JAMA 2000;283:1995-2002.

Crit Care Med. 2002;30:1-6.

RCT of Steroids for persistent ARDS
• ARDS x 7 d with LIS > 2.5
• Randomized (2:1) to
steroids vs. placebo
– MPS 2 mg/kg load then
– 2 mg/kg/d x 14 d then
– 1 mg/kg/d x 7 d then
– 0.5 mg/kg/d x 7 d etc to 32 d
• Improvement = LIS by 1
• If no improvement at 10d,
crossed over
Placebo 8
2 died
2 improved
4 cross-overs
24 randomized
MPS 16
16
Meduri U. JAMA 1998; 280:159

Mortality outcomes
Placebo MPS p value
• Intention to Rx 5/8 (62%) 2/16 (12%) 0.03
• As treated 2/4 (50%) 5/20 (25%) NS
Meduri U. JAMA 1998; 280:159

• Randomized, blinded controlled trial of
methylprednisilone vs. placebo for ALI
persisting > 7 days
– 2 mg/kg/day x 14 days; then 1 mg/kg/day x 7
days then tapered over 4 days.
N Engl J Med. 2006 20;354:1671-84

Methylprednisilone vs. placebo results
N Engl J Med. 2006 20;354:1671

Summary
• With the exception of human recombinant
activated protein C for severe sepsis, no antiinflammatory
strategy has improved mortality
in ALI.

Fluid therapy and
monitoring catheters

Is a PA catheter harmful or helpful
• Prospective cohort study of the association
between PAC (inserted ICU day 1) and survival,
LOS, cost.
• “Propensity score” to adjust for covariates.
• PAC recipients matched with patients with same
disease category and propensity score who did
not get PAC.
Connors A, JAMA 1996; 276:889-897

Evidence the PAC may be harmful
Relative Hazard of Death:
Patients (n)
All (5735)
ARF (1789)
MOF (2480)
CHF (456)
Others* (1010)
Odds Ratio (95% CI)
1.21 (1.09-1.25)
1.30 (1.05-1.61)
1.32 (1.11-1.57)
1.02 (0.55-1.89)
1.06 (0.80-1.41)
p
< 0.001
< 0.001
< 0.001
ns
ns
* (severe COPD, cirrhosis, nontraumatic coma, etc)
Connors A. JAMA 1996; 276:889-897

Effectiveness of PAC in the initial care
of the critically ill
Mortality (30-day)
ICU LOS (days)
Total Costs
PAC (n=1008)
37.5%
14.8
$49,300
No PAC (n=1008)
32.8% p = 0.003
13.0 p < 0.001
$35,700 p < 0.001
Connors A. JAMA 1996; 276: 889-897

FACTT trial objectives
To evaluate the mortality and morbidity
effects of:
• PAC versus CVC management
and
• “Fluid conservative” vs. “fluid liberal”
management

FACTT: Factorial trial design
C
A
T
H
E
T
E
R
PAC
(n = 500)
CVC
(n = 500)
Fluid Management
“Conservative”
(n = 500)
“Liberal”
(n = 500)
250 patients 250 patients
250 patients 250 patients

FACTT: Treatment principles
• Evaluate MAP, UOP, CI, exam and CVP or PAOP <
every 4 hours
• Hypotension: correct as fast as possible using any
combination of any fluid and vasopressor.
• Oliguria treatment:
– Fluid - if CVP or PAOP low or low-normal
– Furosemide - if CVP or PAOP high/high-normal
• Ineffective circulation (low cardiac output) treatment:
– Fluid - if CVP or PAOP low or low-normal
– Dobutamine - if CVP or PAOP high/high-normal

FACTT: Treatment principles
• If hypotension, oliguria and ineffective circulation
are absent or resolved:
– and CVP or PAOP is abnormally high give
incremental furosemide.
– and CVP or PAOP is within the “normal range”
give fluid or diuretics to separate patients into
two “normal” pressure ranges (liberal and
conservative).

Intravascular
Pressure
(PAOP/CVP)
>> Normal
Low MAP
Acceptable MAP off vasopressors
Low UOP
low flow nl flow
Dobutamine
Lasix
Lasix
Acceptable UOP
low flow nl flow
Dobutamine
Lasix
Lasix
> Normal
High normal
Vasopressor
Fluids
Dobutamine
Fluid
Lasix
Fluid
Dobutamine
Fluid
Lasix
Cons.
Lasix
Low normal
Fluid
Fluid
Fluid
Liberal
Fluid

Conservative fluid strategy
Furosemide
UOP < 0.5 ml/kg/h &
CVP or PAOP low
MAP < 60 mmHg
Low flow by exam or CI

Liberal fluid strategy
Fluids
FiO2 > 0.7
CI > 4.5
LUNG
CVP 10-14
14
PAOP 14-18
18
Favors
Perfused
KIDNEY
(organs)

FACTT: outcome variables
Primary
Mortality prior to hospital discharge to day 60
Secondary (major)
Ventilator - free days to day 28
Organ - failure - free days to day 28

11,512 Met ALI Criteria
1,001 Randomized
1 Lost f/u
Exclusions:
•21% PAC
•16% MD refusal
•14% Chronic Lung Disease
•11% Lethal underlying Disease
•9% Dialysis
•8% Time window
•8% Severe liver Disease
1,000 Entered Trial
PAC Lib CVC Lib PAC Cons CVC Cons

N Engl J Med 2006; 354: 2213

Enrollment and outcomes
1001 Randomized
513 assigned to PAC
501 received PAC
12 not inserted
5 withdrew consent
5 exclusions discovered
1 died before placement
1 heart
0 Lost
block
to follow
during
up
insertion
488 assigned to CVC
487 received CVC
7 crossovers 1 day 0
2 day 1
1 day 2
1 withdrew 2 day consent 3
1 day 6
513 analyzed
487 analyzed

Baseline demographics
Characteristic
Age
Female (%)
Primary lung injury (%)
– Pneumonia
– Severe sepsis
– Aspiration
– Trauma
– Other
Medical ICU (%)
N Engl J Med 2006; 354: 2213
PAC
CVC p value
50+1 50+1 0.81
46 47 0.89
0.81
48 46
23 24
15 15
8 7
7 8
66 66 0.91

Baseline severity of illness
Characteristic
APACHE III
Shock (%)
Pre-study fluid intake (L/24 h)
PAC
CVC p value
95+1 94+1 0.55
37 32 0.06
4.9+0.2 4.9+0.2 0.99
Tidal volume (ml/kg PBW)
PEEP (cm H 2 O)
PaO 2 /FIO 2
Plateau pressure (cm H 2 0)
7.4+0.1 7.4+0.1 0.88
9.3+0.2 9.7+0.2 0.09
159+3 151+3 0.10
26.2+0.4 26.2+0.4 0.93
N Engl J Med 2006; 354: 2213

Timing of protocol initiation
Time to first protocol
instruction (hours)
ICU admission
ALI qualification
Randomization
PAC CVC p value
44.4+2 40.8+3 0.23
25.2+0.7 23.0+0.6 0.02
3.5+0.1 2.2+0.1

Instructions and compliance
PAC
CVC p value
Instructions per day
Instructions followed (%)
4.8+0.1 4.4+0.1 0.03
91+1 88+1 0.12
N Engl J Med 2006; 354: 2213

Catheter use and complications
Complications per catheter
0.1
0.05
0
3
2
1
0.08
P=0.35
0.06
PAC
CVC
Total catheters per patient
2.47
P

42 7

Positive blood cultures
20
15
p=0.43
Percent of
patients
10
5
PAC
CVC
0
Any 1 2 >2
Number of positive cultures
N Engl J Med 2006; 354: 2213

No differences between PAC and CVC in:
• Blood pressure
• Heart rate
• CVP
• Net fluid balance
• Vasopressor use
• Tidal volume
• PEEP
• Plateau pressure
• Oxygenation measures
N Engl J Med 2006; 354: 2213

Proportion of assessments in shock after
0.50
entry
0.40
0.30
PAC
CVC
0.20
0.10
0.00
Shock Free
Shock
Engl J Med 2006; 354: 2213-2224
Baseline shock status

1.6
Creatinine
(mg/dL)
1.2
0.8
0.4
Renal replacement therapy
PAC 14 % vs. CVC 11% p=0.15
Blood urea
nitrogen
(mg/dL)
35
30
25
PAC
CVC
N Engl J Med 2006; 354: 2213
20
0 1 2 3 4 5 6 7
Study Day

11.0
Hemoglobin
(gm/dL)
10.5
10.0
9.5
PAC
CVC
9.0
0 1 2 3 4 5 6 7
Study Day
Patients
transfused to day 7
(percent)
Percent
40
30
20
38
P

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

Organ failure free days to day 28
Renal
Hepatic
Coagulation
CNS
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
PAC CVC N Engl J Med 2006; 354: 2213

Summary
• Using the data from a PAC compared to that
from a CVC in an explicit protocol:
– Did not alter survival.
– Did not improve organ function.
– Did not change outcomes for patients entering in
shock compared to those without shock.
• PAC use resulted in more non-fatal
complications, mostly arrhythmias.
N Engl J Med 2006; 354: 2213

SICU mortality and PAC use
40
1
Percent PAC use
35
30
25
20
15
10
5
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
PAC Use
O/E mortality
0
0
'98 '99 '00 '01 '02 '03 '04 '05 '06
Brunswold M Crit Care Med 2007;34:A55

N Engl J Med. 2006;354:2564

Frequency of diuretic and fluid bolus
therapies
0.5
P

Cumulative furosemide dose
1200
1000
Liberal
Conservative
800
mg
600
400
200
0
0 1 2 3 4 5 6 7
N Engl J Med. 2006;354:2564
Study Day

8000
Net fluid balance
ml of fluid
6000
4000
2000
0
-2000
40
0 1 2 3 4 5 6 7
Vasopressor use
N Engl J Med. 2006;354:2564
P=0.25
Percent
30
20
10
0
Prerand
Prefluid
1 2 3 4 5 6 7
Study Day
Liberal
Conservative

Cumulative fluid balance
ml of fluid
8000
6000
4000
2000
Liberal
Conservative
6 ml TV (1996-1999)
PEEP (1999-2002)
0
0 1 2 3 4 5 6 7
-2000
N Engl J Med. 2006;354:2564
Study Day

Cumulative fluid balance at day 7:
Baseline shock vs. no shock
12000
ml of fluid
9000
6000
3000
Liberal
Conservative
6863 ml
7234 ml
0
-3000
N Engl J Med. 2006;354:2564
Shock free
Baseline
Shock

CVP separation
13
12
11
10
9
8
Liberal
Conservative
Prerand
Prefluid
1 2 3 4 5 6 7
Study Day
N Engl J Med. 2006;354:2564

PAOP separation
17
16
PAC Liberal
PAC Conservative
PAOP
15
14
13
12
Prefluid
N Engl J Med. 2006;354:2564.
1 2 3 4 5 6 7
Study Day

Proportion of assessments in shock after
entry
0.50
0.40
Liberal
Conservative
0.30
0.20
0.10
0.00
Shock Free
Shock
N Engl J Med. 2006;354:2564
Baseline shock status

Tidal volume
(mL/kg PBW)
8.00
7.00
6.00
5.00
Conservative
Liberal
PEEP
(cm H 2 O)
N Engl J Med. 2006;354:2564
4.00
10.0
9.0
8.0
7.0
6.0
0 1 2 3 4 7
p=0.008
0 1 2 3 4 7
Study Day

200
190
Conservative
Liberal
PaO 2 / FiO 2
14
12
Oxygenation index
180
170
10
160
150
P=0.07
0 1 2 3 4 7
8
6
P=0.003
1 2 3 4 7
On study plateau pressure
Murray lung injury score
27
26
P=0.002
2.75
2.50
P < 0.001
25
2.25
24
2.00
23
0 1 2 3 4 7
1.75
0 1 2 3 4 7
Study Day
Study Day

Respiratory rate
PaCO2
30
48
46
28
44
26
42
24
Liberal
Conservative
1 2 3 4 7
40
38
0 1 2 3 4 7
13
Minute ventilation
7.43
pH
12
7.41
11
7.39
7.37
10
1 2 3 4 7
Study Day
7.35
0 1 2 3 4 7
Study Day

Survival to hospital discharge and breathing
without assistance to day 60
Mortality: Liberal 28.4% vs.
Conservative 25.5% p = 0.30
Median ventilator free days
Liberal 14.6 vs. Conservative 12.1
p = 0.002

ICU free days to day 28
Conservative
13.4
P

Organ failure free days to day 28
Renal
Hepatic
Coagulation
CNS
P=0.025
0 4 8 12 16 20 24 28
Conservative
Liberal
N Engl J Med. 2006;354:2564

Dialysis to Day 60
Renal support
Conservative Liberal P value
Patients (%) 10 14 0.06
Days 11.0 + 1.7 10.9 + 1.4 0.96
N Engl J Med. 2006;354:2564

Hemoglobin
(gm/dL)
11.0
10.5
10.0
9.5
9.0
Liberal
Conservative
0 1 2 3 4 5 6 7
Study Day
P

Frequency of metabolic abnormalities
Abnormality
K < 3.0
K < 2.5
Na > 150
Na increase > 10
HCO 3 > 40
Conservative Liberal p value
(Percent of patients)
26 22 < 0.001
4 3 0.23
25 18 0.0088
28 23 0.0810
6 2 0.0005

Summary
• Conservative patients had better lung injury scores,
oxygenation index and lower PEEP and plateau pressures.
• Conservative patients had lower MAP, SV, and CI.
• No difference in heart rate, SvO 2 , proportion of protocol
reassessments in shock, percentage receiving
vasopressors.
• The conservative strategy had higher BUN, but there was
no difference in creatinine, renal failure free days, dialysis
use or duration.
N Engl J Med. 2006;354:2564

Conclusions
• Use a normal tidal volume.
• Use a level of PEEP you like.
• Corticosteroids improve oxygenation not survival.
• Routine use of a PAC should be avoided.
• Application of a fluid conservative protocol after
shock resolution improves physiology and
shortens time on ventilator.

ARDSnet
FACTT: Acknowledgements