1. 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

2. X-Ray in Early ARDS Homogeneous pulmonary infiltrates
CT Ratio <.55
Homogeneous pulmonary
infiltrates
Non-central distribution
of oedema
Normal cardiac size

3. Gattinoni et al. Intensive Care Med. 1986; 12: 137-42.
CT in Early ARDS
A thirty-year-old observation
Pl. effusion
“Preservation of normal
lung regions”
Pulmonary edema
Dependent collapse
Maunder et al. JAMA 1986; 255:
Gattinoni et al. Intensive Care Med. 1986; 12:

4. “It is Sponge Lung!!” Lung superimposed h pressure Density x h
Gravity dependent atelectasis
Density x h
*Int Care Med 1986; 12:
**AJRCCM 2002; 165: 1647–53.

5. 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

6. Tidal Volume in ARDS Low (6cc / Kg) vs. ‘traditional’ (12 cc/Kg)
n = 432 vs. 429
N Engl J Med 2000; 342:

7. P-V relationship in ARDS
Pressure
Volume
UIP
LIP
Beside avoiding large Vt……

8. Alveolar Collapse
Pressure
Volume

9. “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:

10. Limiting Injury: “Lung Protective Ventilation”
Pressure
Volume
PEEP
LIMIT Pr. or Vol.

11. ARDSnet: High vs. Low PEEP
NEJM 2004; 351:

12. Variability in Recruitable Lung
Recruitable lung (% of total)
N Engl J Med 2006;354:
Supports prior
physiological studies*
The “anatomical” (CT) extent of potentially
recruitable lung is very variable
*AJRCCM 2005; 171:

13. Problems with ARDSnet approach
Significant
“Recruitable”
Lung volume
Sparse
“Recruitable”
Lung volume
Identification of
the potentially
recruitable ARDS
lung becomes
important
PEEP
Opens alveoli
Benefits patient
Hyperinflates lung
Harms patient
No Effect; a l’ARDSnet

14. 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) _

15. …K PEEP induced asymmetrical expansion
Homogenize the Lung!
If the alveolar distension is made more homogeneous……
…K PEEP induced asymmetrical expansion

16. The Prone Position
Prone
Supine

17. Prone Position Improves Oxygenation
PaO2 / FiO2 Ratio
Rajagopalan et al;
Ind. J. Crit. Care Med.
1999; 3(1): 73-5.

18. Deforming Pressures in ARDS
Lung
Superimposed
Pressure
But….
Superimposed pressure
is altered by…..

19. Deforming Pressures in ARDS
Heart & Mediastinum
Abdominal contents & caudal diaphragm; “Pincers”

20. Effect of Heart & Mediastinum
The weight of the heart and mediastinum exaggerates the gravitational collapse esp. on the left lung
In the prone position the entire mass is supported on the sternum and chest wall with no intervening lung
AJRCCM 2000;161:1660-5

21. Restriction of anterior chest makes wall compliance homogeneous
Chest Wall Compliance
Supine Prone
Mobile anterior chest wall allows preferential ventilation of ventral lung
Restriction of anterior chest makes wall compliance homogeneous

22. Uniform V/Q matching
Contrary to popular belief, pulmonary blood flow may not be gravity dependent (“C”)

23. Prone Positioning The Great Equalizer!
Decreases deforming forces (abdominal ‘pincers’ & heart)
Homogenizes chest wall compliance
Homogenizes ventilation & V/Q matching
AJRCCM 2000;161:1660-5
AJRCCM1998; 157:
AJRCCM 1998; 157:

24. Gattinoni: Prone Trial 2001
n = 152/ 152; 6-hours prone/day; 10 days
P/F <200 on 5 PEEP; <300 on 10 PEEP
No effect of Prone Positioning (?)
SUPINE
PRONE
Gattinoni et al
N Engl J Med 2001; 345:568-73

25. 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
Mortality K 58% to 43% (p=0.12)
Multivariate analysis:
Higher SAPS II score,
Days ventilated before study
Supine posture J mortality
AJRCCM 2006; 173:

26. 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: / NEJMoa

27. Recruitment Homgenizes!
Recruitment, the application of a high Ptp, can make the alveolar distension more homogeneous
Can K PEEP induced asymmetry of distension

28. Lung Recruitment 60 cm recruitment PEEP + 25
26 patients
60 cm recruitment PEEP + 25
40 cm recruitment + PEEP above LIP
No recruitment PEEP + 5
AJRCCM 2006;174: 268 – 78.

29. Effects in Clinical Trials
Systematic review of clinical trials of RM
Average effects of RM on oxygenation is +ve Inadequate data on sustenance of effect
Sustained mPaw is important
AJRCCM 2008; 178:

30. Sustaining high mPaw Rationale for HFOV
Time
mPaw
HFO
PCV
Rationale for HFOV
Conventional ventilation translates into higher and prolonged peak Paw which may be more detrimental to normal alveoli

31. Gas exchange in HFOV
Oxygenation is determined by mean Paw

32. High Frequency Oscillation
N Engl J Med DOI: /NEJMoa
N Engl J Med DOI: /NEJMoa

33. Outcomes with HFOV OSCILLATE stopped p 548 pts OSCAR n=795 OSCILLATE

34. 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
Or too late; delayed inclusion in study
Greater need for sedation & HD issues
Study-related issues may account for the negative results, or…

35. ‘Baby lung’ & Recruited lung They are not ‘normal’
Regional heterogeneity will persist even after “opening” the lung
AJRCCM 2009; 180:

36. Vt: How low… do we go? 2/3 1/3 In patients with ARDS (Vt 6ml / Kg);
Non aerated
Poor aeration
Normal
Hyperinflated
In patients with
ARDS (Vt 6ml / Kg);
1/3 show significant
hyperinflation with
Inspiration (tidal)
1/3
AJRCCM 2007; 175: 160–166.

37. Tidal Hyperinflation: Predictors
Tidal No
Hyperinflation Hyperinflation
P plat: p=0.006
P/F: p=0.0008
Eins L Wt p=0.008
% non-aerated p=0.002
% normal p=0.003
% hyperinflat p=0.01
Tidal hyperinflation is an independent predictor of
inflammation and ventilator-free days
AJRCCM 2007; 175: 160–166.

38. Optimal tidal volumes Mortality Tidal volume 12 cc / kg
RIP
Mortality
Tidal volume
RIP
12 cc / kg
4cc/kg 6cc/kg 12cc/kg

39. Pump-driven veno-venous ECMO
Lung “rested”:
Peak Paw = cm H2O
PEEP = cm H2O
RR = 10
FiO2 = 0.3
CESAR trial

40. 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;

41. ECMO: The CESAR study 63% vs. 47% (p=0.03)
Lancet 2009; 374;
Survival: 82% vs % vs. 54%
63% vs. 47% (p=0.03)
“ECMO group”
“Control”

42. CESAR; Other concerns No difference in rescue modalities
Poor conventional care
Lancet 2009; 374;

43. 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
Conclusion: The benefits of ECMO not clear
The benefits of expert care is obvious
Lancet 2010; 375: 550-1

44. 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

45. Eicosanoid Metabolism
W-6
W-3
W-3 fatty acids
produce
eicosanoids
with lower
inflammatory
potential

46. The Formula

47. W-3 Fatty Acids in ARDS 3 RCTs included (author’s own paper too)
K Mortality OR: 0.40 ( )
ventilation SMD: 0.56 ( )
new organ failure OR: 0.17 ( )
ICU stay SMD: 0.51 ( )
Establishes efficacy of specific formula
(Oxepa ®)
JPEN 2008; 32:

48. ARDSnet: W-3 Fatty Acids
JAMA 2011; 306:

49. W-3 FA Supplement
n=272
(stopped for futility)
W-3 supplements trending to worse outcome compared to low-fat, high-CHO feed
JAMA 2011; 306:

50. Thank you for your patient listening!