Acute Respiratory Distress SyndromeThe Rational selection of Rescue Methods in 2015

Ram E. Rajagopalan,MBBS, AB (Int Med) AB (Crit Care)

Head, Department of Critical Care MedicineSUNDARAM MEDICAL FOUNDATION

Chennai

Pl. effusion

Homogeneous Disease with Heterogeneous Effects

Maunder et al. JAMA 1986; 255:2463-5.Gattinoni et al. Intensive Care Med. 1986; 12: 137-42.

“Preservation of normallung regions”

Pulmonary edema

Dependent collapse

Evidence for a low VtTidal 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;

Titrated based on compliance:Assess Crs by looking at DP for a level of PEEPNote effect on DP with change of PEEPTitrate PEEP to get lowest DPAJRCCM 2001; 163: 69-78

Recruitment May Help!Recruitment, the application of a high Ptp, can make the alveolar distension more homogeneous

1. Opens atelectasis; reduced shunt2. Allows decelerating PEEP titration3. Improves compliance4. Lowers PEEP requirement

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 ManeuversRecruitment 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

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)

RMs work very selectively

AJRCCM 2002; 165:165-70Anesthesiology 2002; 96: 795-802Crit Care Med 2003; 31: 411-8

Adverse Effects are SeenRecruitment Maneuver

Cardiovascular effects

Cerebral perfusionGI FunctionAlveolar/

Endothelialinjury

High pressures generated may lead to transient or sustained organ dysfunction

Recruited lung is not normal

AJRCCM 2009; 180: 415 - 23Regional heterogeneity may persist even after “opening” the lung

The Prone Position also Homogenizes!

Supine Prone

Deforming Pressures in ARDS

LungSuperimposed

Pressure

But….Superimposed pressureis altered by…..

Deforming Pressures in ARDS

Heart & Mediastinum

Abdominal contents & caudal diaphragm;

“Pincers”

Effect of Heart & Mediastinum

AJRCCM 2000;161:1660-5

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

Chest Wall Compliance

Mobile anterior chest wall allows preferential ventilation

of ventral lung

Restriction of anterior chest makes wall compliance

homogeneous

Supine Prone

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

Homogenizes ventilation & V/Q matching

AJRCCM 2000;161:1660-5AJRCCM1998; 157: 387-93AJRCCM 1998; 157: 1785-90

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

Rajagopalan et al; Ind. J. Crit. Care Med. 1999; 3(1): 73-5. 0

5 0

1 0 0

1 5 0

2 0 0

2 5 0

3 0 0

3 5 0

Pre P = 0.0232 Best Prone

83.8 + 27.3 torr 160.9 + 75.6 torr

PaO

2 / F

iO2 R

atio

Gattinoni: Prone Trial 2001n = 152/ 152; 6-hours prone/day; 10 daysP/F <200 on 5 PEEP; <300 on 10 PEEP

No effect of Prone Positioning (?)

SUPINE

PRONE

Gattinoni et alN Engl J Med 2001; 345:568-73

Mancebo; Long ProningRCT of 136 patients76 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 studySupine posture J mortality

AJRCCM 2006; 173: 1233-9.

2013: Prone Works!

N Engl J Med 2013doi: 10.1056/ NEJMoa1214103

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%)

Gas exchange in HFOV

Diffusive & convective changes mediated by oscillation determine CO2 elimination

Oxygenation is determined by mean Paw

Sustaining high mPaw

Conventional ventilation translates into higher and prolonged peak Paw which may be more detrimental to normal alveoli

Paw

Time

mPaw HFO

mPaw PCVRationale for

HFOV

High Frequency Oscillation

N Engl J Med 2013. DOI: 10.1056/NEJMoa1215554

N Engl J Med 2013. DOI: 10.1056/NEJMoa1215716

OSCILLATE

Outcomes with HFOV

OSCAR

OSCILLATE stopped p 548 ptsOSCAR n=795

Canadian CTG

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 aeratedPoor aerationNormalHyperinflated

2/3

1/3

AJRCCM 2007; 175: 160–166.

In patients withARDS (Vt 6ml / Kg);

1/3 show significanthyperinflation with Inspiration (tidal)

Tidal Hyperinflation: Predictors

AJRCCM 2007; 175: 160–166.

Tidal NoHyperinflation Hyperinflation

P plat: 28.9+0.9 25.5+0.9 p=0.006

P/F: 102+24 149+34 p=0.0008

Eins L Wt 1912+206 1541+386 p=0.008

% non-aerated 27+14.3 16.1+7.7 p=0.002

% normal 39.1+19.8 68.2+11.3 p=0.003

% hyperinflat 23.3+10.1 3.0+2.2 p=0.01

Tidal hyperinflation is an independent predictor of inflammation and ventilator-free days

Lowest tidal volume?

12 cc / kg

RIP

Mor

talit

y

Tidal volume

4cc/kg 6cc/kg 12cc/kg

If 6 cc/Kg J survival over 12 cc/Kg;would 0 cc/Kg result in immortality!!!

Pump-driven veno-venous ECMO

Lung “rested”:

Peak Paw = 20-25 cm H2OPEEP = 10-15 cm H2ORR = 10FiO2 = 0.3

CESAR trial

ECMO: The CESAR study90 randomized to transfer to ECMO site90 left on conventional Rx

Not ARDS only (~90%)

“Murray score” >3ph <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

“ECMO group” “Control”Survival: 82% vs. 59% vs. 54%

63% vs. 47% (p=0.03)

Lancet 2009; 374; 1351-63

CESAR; Other concerns

Lancet 2009; 374; 1351-63

No difference in rescue modalities

Poor conventional care

CESAR; Sensitivity Analysis

Lancet 2010; 375: 550-1

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 clearThe benefits of expert care is obvious

My Take on ECMOProbably a very effective rescue method if performed with low complicationsHigh-cost is a limitationBest if performed in selected large-volume referral centres (unlikely in India??)

Criteria for initiation:The Murray score is ineffectiveP/F ratio based (Berlin ARDS severity) or? In patients with non-reducible DP

PECLA; A Caution

A lot of abuse of “pumpless” systems is on the rise

They are effective for CO2 removal, not oxygenation

“Pumpless Extra-corporeal Lung Assist”

Thank you for your patient

listening!