Optimizing Driving Pressure (ΔP) :

( Is Power relevant...? )

Marcelo B. P. Amato

University of São Paulo, Brazil

Toronto, November, 2018

I disclose the following financial relationships (all happening in the

last 5 years) with commercial entities that produce healthcare-

related products or services, relevant to the content I am

presenting:

Company Relationship Content Area

Medtronics Consultant Mechanical Ventilation

Orange Med Consultant Mechanical Ventilation

Philips / Dixtal Research grants E.I.T.

Timpel S.A. Research grants, minority shares E.I.T.

Conflict of Interest Disclosure

Marcelo B.P. Amato

0

0

Time

PA

ΔP

Volume control

Zero Flow

Pre

ssure

( cm

H2O

)F

low

(

L /

se

c)

VSET

Relative Risk of Death in the Hospital versus ΔP in the Combined Cohort after Multivariate Adjustment.

Amato MBP et al. N Engl J Med 2015;372:747-755

Figure 2b : Combined population of ARDS ( N = 3080 )

*: adjusted for age, APACHE/SAPS risk, arterial-pH, P/F ratio , and study-trial

low

-PP

PLA

T &

low

-DP

hig

h-P

PP

LA

T &

low

-DP

low

-PP

PLA

T &

hig

h-D

P

hig

h-P

PP

LA

T &

hig

h-D

P

Y D

ata

0.5

0.7

1.0

1.4

2.0

∆P ≤ 14 ∆P >14

PPLAT ≥ 30 PPLAT ≥ 30PPLAT < 30PPLAT < 30

P < 0.01

P < 0.001

P = 0.92

Mo

rtal

ity

ris

k (

adju

sted

*)

*: adjusted for study-trial, age, APACHE/SAPS risk, arterial-pH, P/F ratio

(N = 529)

(N = 882)

(N = 260)

(N = 1406)

Figure-2b

?@

? ?30

Worse!

Better!

P11P P12P P13PP11A P12A P13AGROUPS

Methods

P16A P15P

SHAM VILI(3-4 hours)

P16A

ARDSNET – after 48 hs OLA – after 48 hs

P11P P12P

P15P

P11A

P14A

vs.

2nd PET

Sagital

Coronal

Axial

Slice ViewHigh PEEP Group

2nd PET

Low PEEP Group

0.022

Ki (m

in-1

)

0.000

18F-FDG

uptake scale

PLATOOLA VS ARDSNET

TEMPO

BASAL POS VILI 0h 6h 12h 24h 36h FINAL

cm

H2

O

0

10

20

30

40

50 ARDSNET

OLA

Plateau Pressure

VILI

Extreme CyclicStress

Same Maximal

Stress !

DELTA DE PRESSÃOOLA VS ARDSNET

TEMPO

BASAL POS VILI 0h 6h 12h 24h 36h FINAL

cm

H2O

0

10

20

30

40

50ARDSNET

OLA

Driving Pressure

VILI

High

Cyclic Stress

Low Stress

Extreme CyclicStress

Anterior.

Posterior

RN

A co

llag

en

typ

e I

control VILI VILI +40hs prot.

P < 0.001

VILI +40hs OLALow Cyclic

StressHigh Cyclic

Stress

Before

1 monthafter ARDS

6 monthsafter ARDS

Toufen et al - submitted to ICM 2018

Risk factors for low FVC at 6 months

Driving pressure (cmH2O)

Vita

l c

ap

acity

-6 m

onth

s

Toufen et al - submitted to ICM 2018

∆P < 13 cmH2O(n = 9)

∆P ≥ 13 cmH2O(n = 9)

Toufen et al - submitted to ICM 2018

Anesthesia

Left-Lung

Ventilation

VT = 6 mL/kg

PPLAT = 29 cmH2O

PEEP = 0 cmH2O

P = 29 cmH2O !!!!!

Gattinoni et al. 2016

Anesthesiology 2016

DynamicStatic

vs.

dissipated

Amato et al.

1998

(N = 53)

Brochard et al.

Brower et al.

Stewart et al.

1998-1999

(N = 288)

ARDSnet2000

(N = 861)

Alveoli2004

(N = 545)

ExpressLOVSTalmor et al.

2008

(N = 1811)

TOTAL2013

(N = 3562)

time1998 2012

Plateau Pressure

Relative Risk

0.75 1.00 1.25 1.50 1.75

1.08 [1.00-1.17]

1.33 [1.24-1.43]Driving Pressure

Tidal Volume

Respiratory Rate

PEEP

1.16 [1.09-1.24]POWER

UNIVARIATE

Plateau Pressure

Relative Risk

0.75 1.00 1.25 1.50 1.75

1.08 [1.00-1.17]

1.33 [1.24-1.43]

Plateau Pressure

Driving Pressure

Tidal Volume

Respiratory Rate

PEEP

MULTIVARIATE

POWER

Plateau Pressure

Relative Risk

0.75 1.00 1.25 1.50 1.75

1.08 [1.00-1.17]

1.33 [1.24-1.43]

Plateau Pressure

Driving Pressure

Tidal Volume

Respiratory Rate

PEEP

Static (PEEP component)

Dynamic (dynamic component)

P < 0.001 P = 0.178

5XN = 3562 Pts.

Is it worth to decrease VT or P by 20%,

at the expense of increasing RR by 20%?

Animal experiment: pigs with ARDS

randomization

6 mL/kg

RR = 28

4.5 mL/kg

RR = 80

Power = 15 J/min Power = 30 J/min

∆P ≥ 13

Power = 15 J/min

Low frequency - higher VT

∆P < 13

Power = 30 J/min

Higher frequency - lower VT

Is it worth to decrease VT or P by 20%,

at the expense of increasing RR by 20%?

YES !and forget about power !

keeping constant Alveolar Ventilation...

Respiratory Rate ∞

Ris

k of V

ILI

N = 3562 Pts.

5XN = 3562 Pts.

1. Power calculations do not add relevant

information

2. Better use Driving Pressure only

3. Increasing Respiratory rate may be dangerous

4. But Less dangerous than increasing P

4. Each patient has an optimum RR in which

P is minimized with minimum risks

5. This ideal RR is usually above 30

breaths/min

Thank you!!!!

keeping constant Alveolar Ventilation...

Respiratory Rate

Tid

al V

olu

me

∞

Dead Space

VA = RR x ( VT – VD )

keeping constant Alveolar Ventilation...

Respiratory Rate

Drivin

g

Pre

ssu

re

∞

Minimum P

VA = RR x ( VT – VD )

keeping constant Alveolar Ventilation...

Respiratory Rate

RR

re

late

d d

am

ag

e

∞

keeping constant Alveolar Ventilation...

Respiratory Rate

Tid

al V

olu

me

∞

Dead Space

VA = RR x ( VT – VD )

keeping constant Alveolar Ventilation...

Respiratory Rate ∞

Ris

k of V

ILI

Reducing P∆P = constant,

but RR increases !

keeping constant Alveolar Ventilation...

Respiratory Rate ∞

VT / VD

?

Ris

k of V

ILI

keeping constant Alveolar Ventilation...

Respiratory Rate ∞

VT / VD

Ris

k of V

ILI

keeping constant Alveolar Ventilation...

Respiratory Rate ∞

VT / VD

Ris

k of V

ILI

keeping constant Alveolar Ventilation...

Respiratory Rate ∞

VT / VD

60 ?

Ris

k of V

ILI

Methods

• Target: PaCO2 of 57 – 63 mmHg

– PEEP: ARDSnet PEEP table

– MODE: VCV square wave flow

81

* = P < 0.05 vs VT = 6 mL/kg

7.5

Tid

al V

olu

me

( m

L / k

g )

6.1

5.24.6

4.3

3.8

2.8

I____I

14

22

15 1312

13

Drivin

g

pre

ssure

(c

mH

2O

)

keeping constant Alveolar Ventilation...

Respiratory Rate ∞

VT / VD

60 ?

Ris

k of V

ILI

Thank you!!!!

A B C

Lun

g V

olu

me

Airway Pressure

PPLATPEEP PPeak

EELV

VT

A = Static / PEEP componentB = Dynamic / Elastic componentC = Resistive component

Model E

Model D

P = 0.089 P = 0.369 P < 0.001

P < 0.001 P = 0.178

P or PL ?

( PAW - Pesoph )

Transpulmonary Driving Pressure (∆PL)

Airw

ay

Drivin

g P

ressure

(∆

P)

Thank you!!!!

Mental Experiment….( Einstein’s elevator )

Effects of Gravity on the space around:

PPLAT = 14

PEEP = 0

PPLAT = 45

PEEP = 10

PPLAT = 45

PEEP = 0

Webb & Tierney 1974; Am Rev Respir Dis;110:556

N = 3080

?

N = 3080

?

How much you are concerned?

Situation 1:

VT = 8.2 mL/kg

PPLAT = 22 cmH2O

PEEP = 10 cmH2O

Situation 2:

VT = 6.0 mL/kg

PPLAT = 28 cmH2O

PEEP = 5 cmH2O

X

A Quasi-Experimental, Before-After Trial Examining the Impact of an Emergency

Department Mechanical Ventilator Protocol on Clinical Outcomes and Lung-Protective

Ventilation in Acute Respiratory Distress Syndrome.

Critical care medicine, Feb 2017

Brian M Fuller; Ian T Ferguson; and 11 more

DOI: 10.1097/CCM.0000000000002268

P = 12 cmH2O P = 23 cmH2O !!!!

Relative Risk of Death in the Hospital versus ΔP in the Combined Cohort after Multivariate Adjustment.

Amato MBP et al. N Engl J Med 2015;372:747-755

Transpulmonary Driving Pressure (∆PL)

Airw

ay

Drivin

g P

ressure

(∆

P)

Patients submitted to risky anesthesia ( N =1783)

*: adjusted for age, APACHE/SAPS risk, arterial-pH, P/F ratio , and study-trial

JAMA. 2016;315(8):788-800

Epidemiology, Patterns of Care, and

Mortality for Patients With Acute

Respiratory Distress Syndrome in

Intensive Care Units in 50 Countries

N = 12.906

Relative Risk of Death in the Hospital versus ΔP in the Combined Cohort after Multivariate Adjustment.

Amato MBP et al. N Engl J Med 2015;372:747-755

Spontaneous effort ‘magnify’ overall PL

….And the same happens with ∆P

PL = Pplat – Ppl

PL : transpulmonary pressure

PＡＯ : alveolar pressure

Ppl : pleural pressure

PL = 30 – (+8)

PL : transpulmonary pressure

= 22

PL = Pplat– Ppl

PL = 30 – (-4) = 34

Controlled Spontaneous

VT = 360 mL VT = 550 mL

CRS = 18 mL/cmH2O

∆P = 20 cmH2O

PEEP = 10 PEEP = 10

∆P = ??

CRS = 18 mL/cmH2O

550/18 = 30.5= ??

keeping constant Alveolar Ventilation...

Respiratory Rate ∞

Ris

k of V

ILI

N = 3562 Pts.

keeping constant Alveolar Ventilation...

Respiratory Rate ∞

Ris

k of V

ILI

Reducing

P

∆P = constant,

but RR increases !

PEEP

PLAT

Role of Strain Rate in the Pathogenesis of Ventilator-Induced Lung Edema*.Protti, Alessandro; Maraffi, Tommaso; Milesi, Marta; Votta, Emiliano; Santini, Alessandro; Pugni, Paola; Andreis, Davide; Nicosia, Francesco; Zannin, Emanuela; Gatti, Stefano; Vaira, Valentina; MD, PhD; Ferrero, Stefano; Gattinoni, Luciano; MD, FRCP

Critical Care Medicine. 44(9):e838-e845, September 2016.DOI: 10.1097/CCM.0000000000001718

Flow Rate

4

Role of Strain Rate in the Pathogenesis of Ventilator-Induced Lung Edema*.Protti, Alessandro; Maraffi, Tommaso; Milesi, Marta; Votta, Emiliano; Santini, Alessandro; Pugni, Paola; Andreis, Davide; Nicosia, Francesco; Zannin, Emanuela; Gatti, Stefano; Vaira, Valentina; MD, PhD; Ferrero, Stefano; Gattinoni, Luciano; MD, FRCP

Critical Care Medicine. 44(9):e838-e845, September 2016.DOI: 10.1097/CCM.0000000000001718

PsycologicalBarrier?

Gattinoni et al. 2016

Gattinoni et al. 2016

A B C

Lun

g V

olu

me

Airway Pressure

PPLATPEEP PPeak

EELV

VT

A = Static / PEEP componentB = Dynamic / Elastic componentC = Resistive component

Gattinoni et al. 2016

RR x V x PEEP

“Potential Energy”(???????)

RR x V x P

Gattinoni et al. 2016

Energy Dissipated in Large Airways

(???????)

Plateau Pressure

Calculated Terms

Relative Risk

0.75 1.00 1.25 1.50 1.75

Driving Pressure (x5) & RR (x1)…………………….

1.33 [1.24-1.43]

1.36 [1.27-1.45]

∆P ≥ 13

∆P < 13

∆P ≥ 13

∆P < 13

keeping constant Alveolar Ventilation...

Respiratory Rate

Tid

al V

olu

me

∞

Dead Space

VA = RR x ( VT – VD )

RESPIRATORY RATE

30 60 90 120 150 300

TID

AL

V

OL

UM

E

( m

L /

iB

W )

0

2

4

6

8

RR vs VT/ibw

RR vs REAL DATA

HFOV

keeping constant Alveolar Ventilation...

Respiratory Rate ∞

VT / VD

60 ?

Ris

k of V

ILI

P or PL ?

( PAW - Pesoph )

Transpulmonary Driving Pressure (∆PL)

Airw

ay

Drivin

g P

ressure

(∆

P)

Transpulmonary Driving Pressure (∆PL)

Airw

ay

Drivin

g P

ressure

(∆

P)

Airway Driving Pressure (∆P) cmH2O

Tra

nspulm

onary

Drivin

g P

ressure

(∆

PL)

Time

Pre

ssure

20

22

24

26

28

30

32

34

36

Col 2

Col 1

Peak Airway pressure

Peak Alveolar pressure

Plateau Pressure

after long pause

0 0

0 1 2 3 4 5 6 7 8 9 10

Time (seconds)

Pre

ssure

(cm

H2O

)

Airway pressures

Alveolar pressures (estimated by MLR)

SR

SR : Stress relaxation

P1

Tpause ≤ 0.5 sec.

Panel B Panel C

Panel A

Ki (m

l/m

in/m

l) Borges & Hedenstierna 2017

One week later…

LIM 09 - HCFMUSP

Grafico driving pressure

LIM 09 - HCFMUSP

Grafico driving pressure

Cyclic Strain)

Cyc

lic

Str

ess

Eduardo Costa, Marcelo Amato, Arthur Slutsky (unpublished data)

UnadjustedAdjusted for Confounders

P<0.001

P<0.001

P=0.01

P=0.28

Ris

ko

fD

eat

h(l

og

od

ds)

Ris

ko

fD

eat

h(l

og

od

ds)

Driving Pressure Driving Pressure

Plateau Pressure Plateau Pressure

JAMA. 2016;315(8):788-800

Epidemiology, Patterns of Care, and

Mortality for Patients With Acute

Respiratory Distress Syndrome in

Intensive Care Units in 50 Countries

N = 12.906

P = 0.004

Results: …”among 545 patients……

…Driving Pressure was the only ventilatory

parameter during ECMO that showed an

independent association with in-hospital

mortality”… (ajusted HR = 1.06 [1.03-1.10])

Association between ventilatory settings and development of acute

respiratory distress syndrome in mechanically ventilated patients due to

brain injury

Eva Tejerina, MD, PhD; Paolo Pelosi, MD, PhD; Alfonso Muriel, MSc, PhD; Oscar Peñuelas, MD; Yuda Sutherasan, MD;

Fernando Frutos-Vivar, MD; Nicolás Nin, MD; Andrew R. Davies, MD; Fernando Rios, MD; Damian A. Violi, MD; Konstantinos

Raymondos, MD; Javier Hurtado, MD; Marco González, MD; Bin Du, MD; Pravin Amin, MD; Salvatore M. Maggiore, MD;

PhD; Arnaud W. Thille, MD; Marco Antonio Soares, MD; Manuel Jibaja, MD; Asisclo J. Villagomez, MD; Michael A. Kuiper,

MD; Younsuck Koh, MD; Rui P.Moreno, MD, PhD; Amine Ali Zeggwagh, MD; Dimitrios Matamis, MD Antonio Anzueto, MD;

Niall D. Ferguson, MD, MSc; Andrés Esteban, MD, PhD. for VENTILA group

ARDS No-ARDS

Driving Pressure

DELTA DE PRESSÃOOLA VS ARDSNET

TEMPO

BASAL POS VILI 0h 6h 12h 24h 36h FINAL

cm

H2O

0

10

20

30

40

50ARDSNET

OLA

Driving Pressure

VILI

High

Cyclic Stress

Low Stress

Extreme CyclicStress

PLATOOLA VS ARDSNET

TEMPO

BASAL POS VILI 0h 6h 12h 24h 36h FINAL

cm

H2

O

0

10

20

30

40

50 ARDSNET

OLA

Plateau Pressure

VILI

Extreme CyclicStress

Same Maximal

Stress !

Anterior.

Posterior

RN

A co

llag

en

typ

e I

control VILI VILI +40hs prot.

P < 0.001

VILI +40hs OLALow Cyclic

StressHigh Cyclic

Stress