Protective ventilation for ALL patients...Cressoni M et al. Am J Respir Crit Care Med...

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Protective ventilationfor ALL patients

PAOLO PELOSI, MD, FERS

Department of Surgical Sciences and Integrated Diagnostics (DISC), San

Martino Policlinico Hospital– IRCCS for Oncology, University of Genoa, Italy

Conflicts of Interest

I declareNO conflicts of interest

Pelosi P for the PROVE Network (www.provenet.eu)

http://www.provenet.eu/

To performLarge multicenter clinical

studies, randomizedcontrolled trials, and

meta-analyses

PROtective VEntilation NETWORK


ρ x g x h

P = 5 cmH2O P = 10 cmH2O

LESS EDEMA-ATELECTASISLOWER PEEP-LOWER MORTALITY

HIGHER EDEMA-ATELECTASISHIGHER PEEP-HIGHER MORTALITY

The ARDS LungH

igherlesionalveolar-capillary

mem

braneLo

wer

lesi

onal

veol

ar-c

apill

ary

mem

bran

e

PaO2/FiO2 > 150 PaO2/FiO2 < 150

Ventilator‐Induced Lung InjurySlutsky AS & Ranieri VM N Engl J Med 2013;369:2126-36


• BAROTRAUMA• VOLUTRAUMA • BIOTRAUMA

Putensen C. Ann Internal Med. 2009; 151:566

• 1,297 patients with ARDS from 6 RCTs

• outcome: hospital death

No Low VT atsimilar PEEP

High VT at similar PEEP Odds ratio

Brochard 116 – –

Brower 52 13/26 12/26 1.17 [0.39 – 3.47]

Brower 861 134/342 171/429 0.68 [0.51 – 0.90]

Stewart 120 30/60 28/60 1.14 [0.56 – 2.34]

0.75 [0.58 – 0.96]

No Low VT +high PEEP

High VT + low PEEP Odds ratio

Amato 53 13/29 17/24 0.33 [0.11 – 1.05]

Villar 95 17/50 24/45 0.41 [0.18 – 0.94]

0.38 [0.20 – 0.75]

[METANALYSIS]

Use of Lower Tidal VolumesBenefits Patients with ARDS


• international observational study

• 2,396 patients with mild, moderate or severe ARDS

Bellani G JAMA. 2016 Feb 23;315(8):788-800

LungSafe – Practice of Ventilation in ICUs Worldwide


• VT > 8 ml/Kg in 40% of patients

Ventilation in Intensive Care Unit–patients with the Acute Respiratory

Distress Syndrome (ARDS)

Ventilation in Intensive Care Unit–patients with

Uninjured Lungs

mild ARDS moderate and severe ARDS

Protective ventilation includes:



Tidal volume size6–8 ml/kg predicted body weight

evidence comes from2 RCTs [4] and

1 meta–analysis [5]












• 2,184 ICU patients without ARDS from 7 studies

• outcome: duration of ventilation

Use of Lower Tidal VolumesBenefits Patients without ARDS

Serpa Neto A. Intensive Care Med. 2014; 40:950

[METANALYSIS]


• 2,184 ICU patients without ARDS from 7 studies

• outcome: hospital stay and ARDS development


[METANALYSIS]

Serpa Neto A. Crit Care Med. 2015; 43:4155



Peak pressure = 20-24 cmH2OPlateau pressure =16-19 cmH2O PEEP = 5-6 cmH2OPaO2/FiO2 = 260 mmHg

Volume controlled = 51%Pressure controlled = 49%

Serpa Neto A. Crit Care Med. 2015; 43:4155


RANDOMIZED CONTROLLED TRIALS PRotective VENTilation in Patients Not Fulfilling the Consensus

Definition for Moderate or Severe ARDS (PReVENT-NL)Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA). NCT02153294 NLM Identifier: NCT02153294Pts without moderate or severe ARDS:VT 4–6 vs. 8–10 ml/kg PBW

Preventive Strategies in Acute Respiratory Distress Syndrome (ARDS) (EPALI)

Corporacion Parc Tauli. NCT02070666 NLM Identifier: NCT02070666Pts without ARDS: VT ≤ 6 vs. 8 ml/kg PBW


A new ARDS Network trial


• 1,022 patients without ARDS

• 7.9 [6.8–9.1] mL/kg PBW

• VT > 8 ml/Kg in 40% of patients

PRoVENT – Practice of Ventilation in ICUs Worldwide

Serpa-Neto A et al. Lancet Respir Med. 2016 Nov;4(11):882-893.





Uninjured Lungs

Tidal volume size6 ml/kg predicted body weight

evidence comes from2 RCTs [31,32], 1

meta–analysis and 2IPD meta–analyses [17,18,33]*























P = 14 cmH2OPEEP = 0 cmH2O



Experimental edema due to intermittent positive pressure ventilation with high inflation pressures

Protection by PEEPWebb HH, Tierney DF Am Rev Respir Dis. 1974 Nov;110(5):556-65


Lower Tidal Volume&

Higher PEEP

Higher Tidal Volume&

Lower PEEP

Ventilator Induced Lung InjuryTidal Volume or PEEP?

Use of Higher PEEP Benefits Patient with Moderate or Severe ARDS

• 2,299 ICU patients with ARDS from 3 investigations

• outcome: death

Briel M. et al. JAMA 2010; 303:865

[METANALYSIS]


Permissive atelectasis to minimize VILI

Healthy lungs

Stressσ =ΔF/ΔS(PL))

Strainε =ΔL/L0(VT/EELV)

ΔP =VT/Cst,rs =VT/EELV

Rocco PR et al. Curr Opin Anaesthesiol. 2012, 25(2):123-30

Energy =ΔP2 x(2xEst)

Power =Energy/Time

Intensity =Power/Area

Cressoni M et al. Am J Respir Crit Care Med 2014,189(2):149–158Cressoni M et al. Anesthesiology. 2016 Feb 12. [Epub ahead of print]

Higher DishomogeneitiesLess VILI with Less Stress, Strain, ∆P, Power, Intensity


Biological Impact of Transpulmonary Driving Pressurein Experimental Acute Respiratory Distress Syndrome

Samary CS et al. Anesthesiology. 2015 Aug;123(2):423-33.


% Increase

in Power

% Increase in Equation Motion Components

TVFlow∆ P

RR

PEEP

Ventilator-related causes of lung injury:The mechanical power

Gattinoni L et al. Intensive Care Med 2016;42:1567–75

Powerrs = 0.098 * RR * ∆V * (Ppeak – ½ * ∆P)


Power and Biological Markers in Experimental ARDSSamary CS et al. Anesthesiology. 2016 Nov;125(5):1070-1071


The Biological Effects of Higher and Lower PEEP in Pulmonary and Extrapulmonary ALI with IAH

Santos CL et al. Crit Care. 2014 Jun 13;18(3):R121


Volutrauma leads to higher lung inflammation thanatelectrauma in experimental ARDS

3 ml/kg

P

V

LIP

Cdyn

0 36

Cdyn

P

UIP P3 ml/kg=

2010

ml

cm H2 O

*

Comparable Tidal Volume and Driving PressureVOLUTRAUMA vs ATELECTRAUMA

ATELECTRAUMA VOLUTRAUMA

Guldner A et al. Crit Care Med. 2016 Sep;44(9):e854-65


Volutrauma leads to higher lung inflammation thanatelectrauma in experimental ARDS

Guldner A et al. Crit Care Med. 2016 Sep;44(9):e854-65

Static strain is more injuriousthan dynamic strain !


PEEP and Lymphatic drainagePelosi P, Rocco PRM, de Abreu MG (Crit Care 2018 – in press)


10

12

14

8

6

4

2

00 5 10 15 20

PEEP (cmH2O)

End ExpirationEnd Inspiration

Plateau Pressure (cmH2O)

**

31 ± 1.821 ± 1.8

**

26 ± 1.4

**

46 ± 3.238 ± 2.1

Rec

ruit

men

t (g

)Gattinoni, Pelosi et al. Am J Respir Crit Care Med 1995; 151:1807–1814

Aeration and Recruitment in ALI/ARDSat end- expiration and end-inspiration


PEEP of 15 cmH2O does not reduce lung inhomogeneities in ARDS

Cressoni M et al. Intensive Care Med. 2017 Mar 10. [Epub ahead of print]

The clinical question is:Atelectrauma is less harmful than

volutrauma due to a further increase of PEEP?Pelosi P for the PROVE Network (www.provenet.eu)

Pv plasma

capillaries

PEEP PEEP

Lymph flow(thoracic duct)

2. Impeded drainage(compression thoracic duct)

1. Increased capillary pressure

edema

RVLV

PEEP

Courtesy Prof Hedenstierna

Impact of acute hypercapnia and augmentedPEEP on right ventricle function in ARDS

Dessap AM et al Intensive Care Med (2009) 35:1850–1858Boufferace K et al. Current Opinion in Critical Care 2011,17:30–35


8.4 cmH2O

Bellani G et al. JAMA Feb 23 2016, 315 (8): 788-800

PEEP in ARDS – The Lung Safe Study

Severe ARDS

PEEP was relatively low (12 cmH2O or lower) independently from ARDS severity

Hypoxemia was treated by increasing FiO2


PEEP: High vs Low - RCTs

Low PEEP High PEEP

60-d

ay

mor

talit

y (%

)

05

1015202530354045

N = 545ALVEOLI LOVS EXPRESS

N = 983 N = 767

P = 0.29

P = 0.17 P = 0.22


Costa Leme A et al. JAMA. 2017 Apr 11;317(14):1422-1432

Effect of Lung Recruitment and Titrated PositiveEnd-Expiratory Pressure (PEEP) vs Low PEEP

on Mortality in Patients With ARDS


PEEP 12 vs 16 cmH2O

PEEP1967…….

Restin

Peace

The Funeral for Positive End-ExpiratoryPressure …better known as PEEP

“It was a dream for generations of anesthesiologists and intensivists”


Caironi P. et al. Crit Care Med 2015; 43:781–790

Lung Recruitability Is Better Estimated Accordingto the Berlin Definition of ARDS at Standard

5 cm H2O PEEP: A Retrospective Cohort Study

PEEP12-15 cmH2O

PEEP5-8 cmH2O

PEEP8-12 cmH2O


Chiumello D. et al. Crit Care Med 2014; 42:252–264

Bedside Selection of PEEP in Mild, Moderate, and Severe Acute Respiratory Distress Syndrome

No routine RMs !

SatO2 88-95PaO2 55-80 mmHg


Supine

Prone

Gattinoni, Pelosi et al. Anesthesiology 1991; 74(1):15-23Lung Height (%)

0 20 806040 1001

567

432

0

Lung inflation

Guerin C. et al. N Engl J Med. 2013 Jun 6;368(23):2159-68

P/F<150 mmHg while on FIO2>0.60;

PEEP = 10 cmH2O

Prone position homogenizes aeration and ventilation at low PEEP




Uninjured Lungs


evidence comes from2 RCTs [31,32] and

3 meta–analyses [17,18,33]*






































Level of PEEP5–10 cm H2O

evidence comes from3 RCTs [7,8,9] and

1 IPD meta–analysis [10]




Level of PEEP≥ 10 cm H2O but < 15cmH2O








In non ARDS patients lower VT + lower PEEP are associated with a shorter length of ICU stay

Guo L et al. Critical Care (2016) 20:226

MD <0 favors strategy A (Low VT/Low PEEP)

Serpa Neto A et al. Ann Intensive Care. 2016 Dec;6(1):109


Associations between PEEP and outcomeof patients without ARDS at onset of ventilation:a systematic review and

meta-analysis of randomized controlled trialsSerpa Neto et al. Ann. Intensive Care (2016) 6:109

High PEEP: No effect on duration of MV – Lower rate of ARDS (high I2)

Low PEEP = 2.0 ± 2.8 cmH2O High PEEP = 9.7 ± 4.0 cmH2O




• PEEP > 5 cmH2Oin 60-40% of patients







Uninjured Lungs

Ventilation During General Anesthesia

for Surgery










































Level of PEEP (<10 cmH2O)??

Convincing RCTevidence is lacking1 meta‐analysis

















-750-500-250

0250500750

0 5 10 15 20 25

-1000

100200300400500600700

0 5 10 15 20 25

05

101520253035

0 5 10 15 20 25

PplatPEEPtot

V'aw ml/s

Volml

PawcmH2O

Time (s)

Driving Pressure (△P,rs)Bluth T et al. Curr Opin Anaesthesiol. 2016 Jun;29(3):421-9.

P,rs

∆P = Pplat,rs – PEEP = VT/Cst = VT/EELV

Amato MBP, et al. N Engl J Med 2015;372:747-55c

Driving pressure and survivalin the ARDS


• 2,396 pts with mild, moderate or severe ARDS




• 653 patients from 12 studies

• RR for hospital death

• median settings in the first 3 days

ALLN = 653

ECMON = 545

ECCO2RN = 108

RR [95%–CI] (p–value) for hospital death

VT,ml/kg PBW

0.97[0.87–1.08](p = 0.602)

0.94[0.83–1.06](p = 0.294)

1.03[0.80–1.32](p = 0.817)

PEEP, cm H2O

0.97[0.92–1.02](p = 0.249)

0.97[0.91–1.03](p = 0.323)

0.92[0.83–1.02](p = 0.125)

Pplat, cm H2O

1.03[0.97–1.09](p = 0.298)

1.03[0.97–1.10](p = 0.308)

0.94[0.81–1.10](p = 0.454)

ΔP,cm H2O

1.07[1.02–1.12](p = 0.004)

1.06[1.01–1.12](p = 0.029)

1.19[1.04–1.35](p = 0.009)

adjusted for risk of death, age and severity of ARDS

[METANALYSIS]

IPD Metaanalysis of studies in ARDS–patients Receiving ELS

c

Serpa-Neto A et al Intensive Care Med. 2016 Nov;42(11):1672-1684





Uninjured Lungs










































Level of PEEP (< 10 cmH2O)??
















Low driving pressure(< 13cmH2O)

suggestion comes fromseveral studies and















• Driving pressure associated with mortality






• P 10.0 [6.0-13] cm H2O

• P > 12 cmH2O in 30-40% of patients







Uninjured Lungs


























meta–analyses and 2IPD meta–analyses [17,18,33]*



meta–analyses and 2IPD meta–analyses [17,18,33]*









































Driving pressure(< 13cmH2O)

studies are lacking


studies are lacking




• 2,396 patients with mild, moderate or severe ARDS




Pplat and Mortality in ARDS

Villar J et al. Crit Care Med. 2017 Mar 1 [Epub ahead of print]

Plateau pressure or Driving Pressure and Survival in the ARDS



• Higher PEEP, lowerplateau and driving P, & lower respiratoryrate are associatedwith better survivalfrom ARDS

LungSafe – Potentially modifiable factorscontributing to outcome from ARDS

Laffey GC et al. Intensive Care Med 2016 (Epub Ahead of Print)





Uninjured Lungs



























































studies are lacking


studies are lacking


Pplat (< 25‐27 cmH2O)

















Sutherasan Y et al. Crit Care. 2015 May 8;19:215

Factors associated with ARDS

1) Higher (> 17 cmH2O) plateau pressure (odds ratio 1.12, 95% CI interval 1.04 to 1.21)

Factors associated with ICU acquired pneumonia

1) Higher tidal volume (odds ratio 1.003, 95% CI 1.0003 to 1.01)

2) Higher (>5 cmH2O) applied PEEP levels(odds ratio 0.89, 95% CI 0.80 to 0.99)

Management and Outcome of Mechanically Ventilated in Patients after Cardiac Arrest




• Pplat 15.0 [13.0-20.0] cm H2O

• Pplat > 17 cmH2O in 30-40% of patients







Uninjured Lungs

Ventilation During General Anesthesia

for Surgery


























































Plateau pressure (< 17 cmH2O)??

studies are lacking


Plateau pressure (< 17 cmH2O)??

studies are lacking

Driving pressure (< 15 cmH2O)Pplat (< 25‐27 cmH2O)














Practice of Ventilation in ARDS



Practice of Ventilation in ICUsSerpa-Neto A et al. Lancet Respir Med. 2016 Nov;4(11):882-893.


“Permissive Atelectasis” in ALL MV patientsPelosi P, Rocco PRM, de Abreu MG (Crit Care 2018 – in press)

InspirationExpiration


Permissive Atelectasis !

VT / P Pplat

PEEPEnergyPower

Energy = (∆P)2 / (2 x Est)

Power = Energy / Time (RR)


“Less is More”

Regional Intensity = Power / Surface

Permissive Atelectasis !

VT/ P Pplat

PEEPEnergyPower

Energy = (∆P)2 / (2 x Est)

Power = Energy / Time (RR)


“Less is More”

Regional Intensity = Power / Surface

In ARDS patientsPEEP based on lower PaO2/FiO2 Table

PRONE POSITION !

Protective Mechanical VentilationIn ALL patients

LOWER IS BETTER...ALSO PEEP in severe ARDS !

JUST DO IT !

Protective ventilation for ALL patients...Cressoni M et al. Am J Respir Crit Care Med...

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