1. 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

2. Homogeneous Disease with Heterogeneous Effects
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:

3. Evidence for a low Vt Tidal Volume:
Low (6cc / Kg) vs. traditional (12 cc/Kg)
N Engl J Med 2000; 342:

4. Titrating PEEP to ‘Compliance’
Initiated based on oxygenation;
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
AJRCCM 2001; 163: 69-78

5. Recruitment May Help! Opens atelectasis; reduced shunt
Recruitment, the application of a high Ptp, can make the alveolar distension more homogeneous
Opens atelectasis; reduced shunt
Allows decelerating PEEP titration
Improves compliance
Lowers PEEP requirement

6. 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…

7. 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) _

8. Recruitment Maneuvers
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

9. RMs work very selectively
The effect on oxygenation is variable & un-sustained
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)
AJRCCM 2002; 165:165-70
Anesthesiology 2002; 96:
Crit Care Med 2003; 31: 411-8

10. Adverse Effects are Seen
Recruitment Maneuver
Cerebral perfusion
Alveolar/
Endothelial
injury
GI Function
Cardiovascular effects
High pressures generated may lead to transient or sustained organ dysfunction

11. Recruited lung is not normal
Regional heterogeneity may persist even after “opening” the lung
AJRCCM 2009; 180:

12. The Prone Position also Homogenizes!
Supine

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

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

15. 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

16. 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

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

18. 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:

19. 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”

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

21. 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

22. 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:

23. 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

24. Gas exchange in HFOV
Diffusive & convective changes mediated by oscillation determine CO2 elimination
Oxygenation is determined by mean Paw

25. 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

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

27. Outcomes with HFOV OSCILLATE stopped p 548 pts OSCAR n=795 OSCILLATE
Canadian CTG
OSCAR
OSCILLATE stopped p 548 pts
OSCAR n=795
Oxford

28. 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

29. 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

30. 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.

31. 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.

32. Lowest tidal volume? Mortality Tidal volume 12 cc / kg
RIP
Mortality
Tidal volume
12 cc / kg
If 6 cc/Kg J survival over cc/Kg;
would 0 cc/Kg result in immortality!!!
4cc/kg 6cc/kg 12cc/kg

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

34. 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;

35. 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”

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

37. 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

38. 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

39. 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

40. Thank you for your patient listening!