Acute Respiratory Distress Syndrome
Has management changed in the last Decade?
Ram E. Rajagopalan,
MBBS, AB (Int Med) AB (Crit Care)
Head, Department of Critical Care Medicine
SUNDARAM MEDICAL FOUNDATION
Chennai
X-Ray in Early ARDS
Homogeneous pulmonary
infiltrates
Non-central distribution
of oedema
Normal cardiac size
CT Ratio <.55
CT in Early ARDS
A thirty-year-old observation
“Preservation of normal
lung regions”
Pulmonary edema
Dependent collapse
Pl. effusion
Maunder et al. JAMA 1986; 255:2463-5.
Gattinoni et al. Intensive Care Med. 1986; 12: 137-42.
“It is Sponge Lung!!”
h
Lung
superimposed
pressure
“Sponge Lung”*
Gravity dependent
atelectasis
*Int Care Med 1986; 12: 137-42.
**AJRCCM 2002; 165: 1647–53.
Density x h
The “Baby lung”
ARDS Lung has “normal” &
unaerated / partially aerated alveoli
“Normal” segments inflate easily

Unaerated segments distend poorly
 High pressure
 Slow response

Normal lung segments may be
over-inflated when ventilated with
traditional tidal volumes

Tidal Volume in ARDS
Low (6cc / Kg) vs. ‘traditional’ (12 cc/Kg)
n = 432 vs. 429
N Engl J Med 2000; 342: 1301-8.
P-V relationship in ARDS
UIP
LIP
Pressure
Beside avoiding large Vt……
Alveolar Collapse
Pressure
“Volutrauma & Atelectrauma”
Non-dependent bullae are
probably due to alveolar
overdistension
Dependent bullae are due
to alternating opening &
closing of the airway
Gattinoni et al. AJRCCM 2001; 164: 1701-11.
Limiting Injury:
“Lung Protective Ventilation”
PEEP
LIMIT Pr. or Vol.
Pressure
ARDSnet: High vs. Low PEEP
LoPEEP
5
5
8-10
10
12-14
14
14-18
18-24
HiPEEP
14
14-16
15-18-20
20
20
20-22
22
22-24
NEJM 2004; 351: 327-36.
1.0
Survival
Probability
FiO2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
n = 549
0.5
0
Discharge
0
10
20
30
Days
40
50
60
Variability in Recruitable
Lung
N Engl J Med 2006;354:1775-86.
A
25
A
B
B
20
n
15
10
5
0
-5
0
5 10 15 20 25 30 35 40 45 50 55 60
Recruitable lung (% of total)
Supports prior
physiological studies* The “anatomical” (CT) extent of potentially
*AJRCCM 2005; 171: 1002-1008.
recruitable lung is very variable
Problems with ARDSnet
approach
Significant
“Recruitable”
Lung volume
Sparse
“Recruitable”
Lung volume
Identification of
PEEP
the potentially
Opens
alveoli
Hyperinflates
lung
recruitable ARDS
Benefits
patient
Harms
patient
lung becomes
important
No Effect; a l’ARDSnet
Heterogeneous effect of Paw
_
 Ptp (not Pairway ) correlates c EELV
 A uniform airway pressure causes
heterogeneous lung expansion
because of pleural pressure D
 The range of Ppleura
J with lung injury
 May result in significant
over-distension of the
ventral lung (A)
Homogenize the Lung!
If the alveolar distension is made more
homogeneous……
…K PEEP induced asymmetrical expansion
The Prone Position
Supine
Prone
Prone Position Improves Oxygenation
350
P
r
e
P
=
0
.
0
2
3
2
B
e
s
t
P
r
o
n
e
PaO2 / FiO2 Ratio
300
Rajagopalan et al;
Ind. J. Crit. Care Med.
1999; 3(1): 73-5.
250
200
150
100
50
8
3
.
8
+
2
7
.
3
t
o
r
r
0
1
6
0
.
9
+
7
5
.
6
t
o
r
r
Deforming Pressures in ARDS
Lung
Superimposed
Pressure
But….
Superimposed pressure
is altered by…..
Deforming Pressures in ARDS
Heart &
Mediastinum
Abdominal contents
& caudal diaphragm;
“Pincers”
Effect of Heart & Mediastinum
The weight of the heart and
mediastinum exaggerates the
gravitational collapse esp. on
the left lung

AJRCCM 2000;161:1660-5
In the prone position the
entire mass is supported on
the sternum and chest wall
with no intervening lung

Chest Wall Compliance
Supine
Prone
Mobile anterior chest wall
allows preferential ventilation
of ventral lung
Restriction of anterior chest
makes wall compliance
homogeneous
Uniform V/Q matching
Contrary to
popular belief,
pulmonary blood
flow may not be
gravity dependent
(“C”)
Prone Positioning
The Great Equalizer!
Decreases deforming forces
(abdominal ‘pincers’ &
heart)
Homogenizes chest wall
compliance
AJRCCM 2000;161:1660-5
AJRCCM1998; 157: 387-93
AJRCCM 1998; 157: 1785-90
Homogenizes
ventilation
& V/Q matching
Gattinoni: Prone Trial 2001
n = 152/ 152; 6-hours prone/day; 10 days
P/F <200 on 5 PEEP; <300 on 10 PEEP
SUPINE
PRONE
Gattinoni et al
N Engl J Med 2001; 345:568-73
No effect of Prone Positioning (?)
Mancebo; Long Proning
RCT of 136 patients
76 were in prone position
Aimed for 20 hrs/ day (obtained 17 hrs)
Average duration of 10 days
AJRCCM 2006; 173: 1233-9.
Mortality K 58% to 43% (p=0.12)
Multivariate analysis:
Higher SAPS II score,
Days ventilated before study
Supine posture J mortality
2013: Prone Works!
n = 466
P/F <150 (avg: 100)
Proned >16 hrs.
(averaged 17hrs.)
Mortality:
28 days: 16% (v. 32.8%)
90 days: 23.6% (v. 41%)
N Engl J Med 2013
doi: 10.1056/ NEJMoa1214103
Recruitment Homgenizes!
Recruitment, the application of a high Ptp, can
make the alveolar distension more homogeneous
Can K PEEP induced asymmetry of distension
Lung Recruitment
26 patients
AJRCCM 2006;174: 268 – 78.

No cm
40
60
recruitment
recruitment
PEEP
+ PEEP
PEEP
+ 5 + 25
above LIP
Effects in Clinical Trials
Systematic review
of clinical trials of
RM
AJRCCM 2008; 178: 1156-63
Average effects of RM on oxygenation is +ve
Inadequate data on sustenance of effect
Sustained mPaw is important
Sustaining high mPaw
Paw
mPaw
HFO
Rationale for
HFOV
mPaw
PCV
Time
Conventional ventilation translates into higher
and prolonged peak Paw which may be more
detrimental to normal alveoli
Gas exchange in HFOV
Oxygenation
is determined
by mean Paw
High Frequency Oscillation
N Engl J Med 2013. DOI: 10.1056/NEJMoa1215554
N Engl J Med 2013. DOI: 10.1056/NEJMoa1215716
Outcomes with HFOV
OSCILLATE
OSCILLATE stopped p 548 pts
OSCAR n=795
OSCAR
Is HFOV ineffective?
One-size fits all approach
 No scope for titration in OSCILLATE
 No accounting of D in recruitability
 No prior recruitment in OSCAR

Were the patients ill enough to benefit?
 P/F ratio <200 for inclusion

Study-related issues
may account for the
negative results, or…

Or too late; delayed inclusion in study

Greater need for sedation & HD issues
‘Baby lung’ & Recruited lung
They are not ‘normal’
AJRCCM 2009; 180: 415 - 23
Regional heterogeneity will persist even after
“opening” the lung
Vt: How low… do we go?
Non aerated
Poor aeration
Normal
Hyperinflated
2/3
In patients with
ARDS (Vt 6ml / Kg);
1/3 show significant
hyperinflation with
Inspiration (tidal)
AJRCCM 2007; 175: 160–166.
1/3
Tidal Hyperinflation:
Predictors
Tidal
No
Hyperinflation Hyperinflation
P plat:
P/F:
Eins L Wt
28.9+0.9
102+24
1912+206
% non-aerated 27+14.3
% normal
39.1+19.8
% hyperinflat 23.3+10.1
AJRCCM 2007; 175: 160–166.
25.5+0.9 p=0.006
149+34 p=0.0008
1541+386 p=0.008
16.1+7.7 p=0.002
68.2+11.3 p=0.003
3.0+2.2 p=0.01
Tidal hyperinflation is an independent predictor of
inflammation and ventilator-free days
Optimal tidal volumes
Mortality
12 cc / kg
4cc/kg
6cc/kg
Tidal volume
12cc/kg
Pump-driven veno-venous ECMO
Lung “rested”:
Peak Paw = 20-25 cm H2O
PEEP = 10-15 cm H2O
RR = 10
FiO2 = 0.3
CESAR trial
ECMO: The CESAR study
90 randomized to transfer to ECMO site
90 left on conventional Rx
Not ARDS only (~90%)
“Murray score” >3
ph <7.20 (J CO2)
Death or severe
disability at 6 months
Power adjustments
made post-hoc; reduced
n from 240 to 180!
Lancet 2009; 374; 1351-63
ECMO: The CESAR study
Lancet 2009; 374; 1351-63
Survival: 82% vs.
59%
“ECMO group”
63%
vs. 54%
“Control”
vs.
47% (p=0.03)
CESAR; Other concerns
No difference in
rescue modalities
Poor conventional
care
Lancet 2009; 374; 1351-63
CESAR; Sensitivity Analysis
Considering poor baseline care even a
small J in survival in the conventionally
treated patients would “annul” benefits
of ECMO
2 less deaths would make results NS
Lancet 2010; 375: 550-1
Conclusion: The benefits of ECMO not clear
The benefits of expert care is obvious
PECLA; A Caution
“Pumpless Extra-corporeal Lung Assist”
A lot of abuse
of “pumpless”
systems is on
the rise
They are
effective for CO2
removal, not
oxygenation
Eicosanoid Metabolism
W-6
W-3
- linolenic acid (ALA)
C18:3-3
linoleic acid (LA)
C18:2-6
arachidonic acid (AA)
C20:4-6
W-3 fatty acids
produce
eicosanoids
with lower
inflammatory
potential
eicosapentanoic acid (EPA)
C20:5-3
docosahexanoic acid (DHA)
C22:6-3
cyclic endoperoxids
TXA2
TXA3
PGI2
LTA4 LTA5
PGI3
LTB4
LTB5
LTC4
LTC5
The Formula
W-3 Fatty Acids in ARDS
3 RCTs included (author’s own paper too)

K Mortality
K ventilation
K new organ failure
K ICU stay
JPEN 2008; 32: 596-605
OR: 0.40 (0.24-0.68)
SMD: 0.56 (0.32-0.79)
OR: 0.17 (0.08-0.34)
SMD: 0.51 (0.27-0.74)
Establishes efficacy of specific formula
(Oxepa ®)
ARDSnet: W-3 Fatty Acids
JAMA 2011; 306: 1574-81
W-3 FA Supplement
n=272
(stopped for futility)
JAMA 2011; 306: 1574-81
W-3 supplements trending to worse outcome
compared to low-fat, high-CHO feed
Thank you
for your
patient
listening!