Transpulmonary Pressure

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

Daniel Talmor, MD, MPH

Disclosures

• Research funding

– NHLBI

– CMS

– Gordon and Betty Moore Foundation

• Advisor

– Intensix

– Medial

• In debt

– To many people, but in particular to Dr. Steve Loring

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

ARDS Mortality: What More Can We Do?

0.5

0.6

0.7

0.8

0.9

1

0 7 14 21 28

Proportion Surviving

Days after study entry

Vt = 12

Vt = 6

Slide courtesy BT Thompson

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.

Clinical Trials of Higher PEEP

• 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

• ALVEOLI trial stopped early for futility

• 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 Feb 13;299(6):691-3.

Briel M, JAMA, 2010; 303: 865

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

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

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 Am J Respir Crit Care Med 2001; 164:122-130

Relationship Between Transpulmonary and

Airway Pressure

Talmor et al. CCM 2006

Sample Data From Anesthetized Obese

Subject

Paw

Pes

Vol.

Flow

Threshold Paw

Expanded Time Scale

Paw

Pes

Vol.

Flow

6 sec.

In Humans

Gattinoni. Am J Respir Crit Care Med Vol 164. pp 1701–1711, 2001

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

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

N Eng J Med, 2008; 359:2095

6- Month Survival

N001 Baseline

17 cmH2O

Pao

Flow

Pes

Ptp

28 cmH2O

-11 cmH2O

N001 Day 1

33 cmH2O

Pao

Flow

Pes

Ptp

34 cmH2O

-0.8 cmH2O

Echocardiography

Hemodynamics

Sarge et al. ATS 2012

Mechanical ventilation: Passive

Pes

Volume

Volume

0 25

P-V curveof passiveChest Wall

Pes (cmH2O)

Elastance Derived Measurement of Transpulmonary Pressure

ECW = ΔPES/ VT

ERS = ΔPAO / VT

ΔPAO

PL= PAO * EL/ERS

ECW – based Method

Assumption: Measured slope

of chest wall P-V curve is

accurate, but

Ppl = 0 when Pao = 0

Pressure (cmH2O)V

olu

me

rela

tive

to

Ve

eo

(mL)

PL,eeo = Pao,eeo – Pes,eeo

PL,eio = Pao,eio – Pes,eio

Pressure (cmH2O)

Vo

lum

e re

lati

ve t

o V

eeo

(mL)

Pes – based Method

Assumption: Measured Pes is

approximately equal to Ppl

P-V CurvesRespiratory systemChest wall (Pes – based)Chest wall (ECW – based)

Maintain slope but shift chest wall P-V curve to pass through origin

PL,eio = Pao,eio – (Pao,eio ×

ECW/ERS)

Pressure (cmH2O)

Vo

lum

e re

lati

ve t

o V

eeo

(mL)

PL,eeo = Pao,eeo –(Pao,eeo × ECW/ERS)

Clinical Use of Elastance-Derived PL

Grasso S, Ranieri VM, Intensive Care Med, 2012

RCTs of Higher PEEP

Amato Villar

P=0.56

Vt

6Vt

12

PPlat

Driving

Pressure

PEEP

(cm H20)

Vt

7

ALVEOLI Express LOVS

Vt

10 Vt

6

Vt

6

Vt

6

Vt

6 Vt

6

Vt

6

Beneficial Non-Beneficial

EPVent

Vt

7

Vt

7

?

+RM +RM

Slide courtesy BT Thompson

EPVent II- Overall Concept

• A phase II prospective randomized controlled trial of ventilation directed by esophageal

pressure measurements.

• Enroll 200 patients with moderate to severe ARDS by the Berlin conference definition in 10

academic medical centers in North America.

• Randomized to EPVent group or empiric high-PEEP control group.

EPVent2 05-2015

Transpulmonary Pressure

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

Daniel Talmor, MD, MPH