Acute Respiratory Distress Syndrome
The Rational selection of Rescue Methods in 2015
Ram E. Rajagopalan,
MBBS, AB (Int Med) AB (Crit Care)
Head, Department of Critical Care Medicine
SUNDARAM MEDICAL FOUNDATION
Chennai
Homogeneous Disease with
Heterogeneous Effects
“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.
Evidence for a low Vt
Tidal Volume:
Low (6cc / Kg) vs. traditional (12 cc/Kg)
N Engl J Med 2000; 342: 1301-8.
Titrating PEEP to ‘Compliance’
Initiated based on oxygenation;
AJRCCM 2001; 163: 69-78
Titrated based on compliance:
Assess Crs by looking at DP for a level of PEEP
Note effect on DP with change of PEEP
Titrate PEEP to get lowest DP
Recruitment May Help!
Recruitment, the application of a high Ptp, can
make the alveolar distension more homogeneous
Opens atelectasis; reduced shunt
2. Allows decelerating PEEP titration
3. Improves compliance
4. Lowers PEEP requirement
1.
If…..
Oxygenation remains poor:
P/F ratio <100 (e.g. pO2 60 torr on 60% FiO2)
Lung Compliance remains poor?
Pplat >30; DP remains high
(Despite Vt <6cc/kg; post-PEEP titration/
recruitment)
It’s time to consider
RESCUE
THERAPIES…
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)
Recruitment Maneuvers
Recruitment Maneuver =
Transient / intermittent application of a
high trans-pulmonary pressure
intended to J End Exp. Lung Volume
(& open up unaerated lung)
An intentional over-distension of the lung
RMs work very selectively
The effect on oxygenation is variable & unsustained
AJRCCM 2002; 165:165-70
Anesthesiology 2002; 96: 795-802
Crit Care Med 2003; 31: 411-8
Preferred use in patients with:
Early ARDS (~ 24 hours) ; avoid if >7 days
Extra-pulmonary ARDS; avoid in pneumonia
 Low prior Vt and PEEP
…(post intubation, suction, disconnection)
Adverse Effects are Seen
Recruitment Maneuver
Alveolar/
Endothelial
injury
Cardiovascular
effects
GI Function
Cerebral
perfusion
High pressures generated may lead to transient
or sustained organ dysfunction
Recruited lung is not normal
AJRCCM 2009; 180: 415 - 23
Regional heterogeneity may persist even after
“opening” the lung
The Prone Position
also Homogenizes!
Supine
Prone
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
Recruitment vs. Prone
Recruitment is the “forceful compulsion”
of the ARDS lung to become uniformly
compliant
While Prone positioning removes
deforming forces to allow the lung to
normalize; “a permissive process”
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
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
Gas exchange in HFOV
Diffusive & convective changes mediated by
oscillation determine CO2 elimination
Oxygenation is determined by mean Paw
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
High Frequency Oscillation
N Engl J Med 2013. DOI: 10.1056/NEJMoa1215554
N Engl J Med 2013. DOI: 10.1056/NEJMoa1215716
Outcomes with HFOV
Canadian CTG
OSCILLATE
OSCILLATE stopped p 548 pts
OSCAR n=795
OSCAR
Oxford
Is HFOV ineffective?
The patients were sick enough; P/F ratio <200
 Delayed inclusion to 1 week confounds
 HFOV requires skill; adequacy in trial?


OSCAR (no difference)


Poor control ventilation (J Paw; J Vt) could have
annulled benefits of conventional Rx
OSCILLATE (HFOV worse)


Good conventional vent. may have made it beneficial
High Paw in HFOV; assoc. HD D & vasoactive Rx
The Arbitrary Choice of Paw
In both trials the selection of Paw was
arbitrary:
OSCAR: 5 cm above plateau (no recruitment)
OSCILLATE: 30 cm H2O after 40/40 CPAP RM
Not titrated to individual lung compliance
Subsequent D based on FiO2 Table
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
Lowest tidal volume?
If 6 cc/Kg
J survival over
12 cc/Kg;
would 0 cc/Kg result
in immortality!!!
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
My Take on ECMO
Probably a very effective rescue method if
performed with low complications
High-cost is a limitation
Best if performed in selected large-volume
referral centres (unlikely in India??)
Criteria for initiation:
The Murray score is ineffective
P/F ratio based (Berlin ARDS severity) or
? In patients with non-reducible DP
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
Thank you
for your
patient
listening!