Pes to set PEEP-

The American Approach

Patient Engagement, Systems Science, and the Elimination of Preventable Harm

Daniel Talmor, MD, MPH

ARDS Patient

• Post traumatic ARDS

• 46 y/o male s/p MVC, fractured pelvis

• Compromise of circulation to the legs

• Anasarca and a tense abdominal wall

• Initial ventilator settings

– CMV

– TV= 535 cc

– Fi02= 1

– PEEP= 13

Animal Experiments Show That Adequate PEEPCan Reduce VILI

• Faridy et al. – Large volume mechanical ventilation increased surface tension

– At a given VT, effect attenuated by higher PEEP

• Wyszogrodski et al. – High volume ventilation inactivated surfactant in cats

– At a given VT, effect less with higher PEEP

• Webb and Tierney – High volume ventilation caused hemorrhagic edema and hyaline membranes in rats

– At constant peak pressure, effect less with higher PEEP

• Muscedere et al. – Even low volume ventilation in lavaged rat lungs caused histological damage.

– Effects were reduced or eliminated with higher PEEP.

• Chiumello et al. – Ventilation of injured rat lungs released inflammatory cytokines.

– At a given VT, effects were less with higher PEEP.

ALVEOLI Trial

• ALVEOLI- higher vs. lower levels of PEEP based on tables- Day 1 PEEP- 8.9 vs. 14.7 cm H2O .

• Stopped early for futility

• No benefit in rates of death before hospital discharge in either group

Lower PEEPHigher Fi02

Higher PEEPLower Fi02

Brower, NEJM 2004.

Further Trials

• Amato demonstrated a benefit to a low tidal volume

strategy combined with PEEP set by LIP of the PV

curve.

• ARIES trial seemed to confirm this

• LOVS trial showed no benefit.

• The EXPRESS trial which set PEEP based on the

airway plateau pressure showed mixed results

“The LOV study and the Express study not only should conclude the era of comparing PEEP levels in unselected populations with

ALI and ARDS, but also underscore the need for a new definition of ARDS aimed at

identifying patients with greater lung edema and larger recruitability …”

Gattinoni L, Caironi P; JAMA. 2008

Briel M, JAMA, 2010; 303: 865

Vent

PL = Pao - PPlPao

PPl

Lung

Chest Wall

PL is the pressure actually distending the lung.

This may be very different from the pressure measured at the airway.

PL May be more important then Pao

Vent

PL = Pao - PPlPao

PPl

Lung

Chest Wall

Titrating ventilation based on ventilator pressures does not allow us to take this variability into account

PL May be Very Different then Pao

Pleural Pressure MeasurementPulmonary vs Non-pulmonary ARDS

Gattinoni, AJRCCM 1998

Esophageal Pressure to Estimate Pleural Pressure

Mechanical ventilation: passive

Pes

Volume

Volume

0 25

P-V curveof passiveChest Wall

Pes (cmH2O)

Pressure transducing wafers implanted in dog lungs revealed differences in pleural pressure due to the gravitational effect of the dependant vs. non-dependant regions of the lung.

Pes Values Reflect High Pleural Pressures

-7

+4

Pes 0

Non-Dependant

Mid-Lung

Dependant

Pelosi AJRCCM 2001

In Humans

Talmor et al. CCM 2006

Pes Ranges Widely in Patients with ALI

Transpulmonary and Airway Pressure

Talmor et al. CCM 2006

Sample Data from Anesthetized Obese Subject

Paw

Pes

Vol.

Flow

31 sec

Threshold Paw

Expanded Time Scale

Paw

Pes

Vol.

Flow

6 sec.

PT 1 Initial Ventilator settings on PCV

Paw

-10

50

0

Pes

PL

50

040

Paw = 13 to 40

Pes = 20 to 33

Ptp = -8 to 6

Ventilator pressures:

PEEP 13 26

which raised

Pplateau 40 46

Pt 1 Strategy: Change ventilator pressures to optimize PL

Pt 1 After Ventilator Changes to Optimize PL

Paw

-10

50

0

Pes

PL

50

040

Paw = 26 to 46

Pes = 22 to 33

Ptp = 4 to 12

Ventilator pressures:

PEEP 13 26

Pplat 40 46

Driving pressure: 27 20

Pt 1 Strategy: Change Ventilator Pressures to Optimize PL

Talmor D, N Eng J Med, 2008; 359:2095

Talmor D, N Eng J Med, 2008; 359:2095

6- Month Survival

N001 Baseline

17 cmH2OPao

Flow

Pes

Ptp

28 cmH2O

-11 cmH2O

N001 Day 1

33 cmH2OPao

Flow

Pes

Ptp

34 cmH2O

-0.8 cmH2O

25 23 21 19 17 15 13 11 9 7 5

0

10

20

30

40

50

60

-10

-5

0

5

10

15

20

25

30

PEEP (cmH2O)

EIT

Co

lla

ps

e (%

)Baseline

EIT CollapsePtpE absolute

PtpE calculated Ptp

E (c

mH

2 O)

PL and EIT

Fumagalli, ATS 2016

25 23 21 19 17 15 13 11 9 7 5

0

10

20

30

40

50

60

-10

-5

0

5

10

15

20

25

30

PEEP (cmH2O)

EIT

Co

lla

ps

e (%

)Obese

EIT CollapsePtpE absolute

PtpE calculated Ptp

E (c

mH

2 O)

PL and EIT

Fumagalli, ATS 2016

Optimal Risk/Benefit of PEEP May Depend on Recruitability

0

10

20

30

P=0.566 ml/kg

6 ml/kg

Pplat

Driving Pressure

PEEP(cm H20)

6 ml/kgNon-

recruitable 6 ml/kgRecruitable

Injury >Benefit

Benefit>Injury

Lower PEEP

Higher PEEP

Pes to set PEEP-

The American Approach

Patient Engagement, Systems Science, and the Elimination of Preventable Harm

Daniel Talmor, MD, MPH