Protective ventilation for ALL patients

Protective ventilation for 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 ppelosi@hotmail.com

Conflicts of Interest I declare NO conflicts of interest

PROtective VEntilation NETWORK To perform Large multicenter clinical studies, randomized controlled trials, and meta-analyses http://www.provenet.eu/

The ARDS Lung Lower lesion alveolar-capillary membrane ρ x g x h P= 5 cmh 2 O P = 10 cmh 2 O Higher lesion alveolar-capillary membrane PaO 2 /FiO 2 > 150 PaO 2 /FiO 2 < 150 LESS EDEMA-ATELECTASIS LOWER PEEP-LOWER MORTALITY HIGHER EDEMA-ATELECTASIS HIGHER PEEP-HIGHER MORTALITY

Ventilator Induced Lung Injury Slutsky AS & Ranieri VM N Engl J Med 2013;369:2126-36 BAROTRAUMA VOLUTRAUMA BIOTRAUMA

Use of Lower Tidal Volumes Benefits Patients with ARDS Putensen C. Ann Internal Med. 2009; 151:566 No Low V T at similar PEEP High V T at similar PEEP Odds ratio 1,297 patients with ARDS from 6 RCTs outcome: hospital death 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] No Low V T + high PEEP High V T + low PEEP 0.75 [0.58 0.96] 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]

LungSafe Practice of Ventilation in ICUs Worldwide Bellani G JAMA. 2016 Feb 23;315(8):788-800 international observational study 2,396 patients with mild, moderate or severe ARDS V T > 8 ml/kg in 40% of patients

Use of Lower Tidal Volumes Benefits Patients without ARDS Serpa Neto A. Intensive Care Med. 2014; 40:950 2,184 ICU patients without ARDS from 7 studies outcome: duration of ventilation [METANALYSIS]

Use of Lower Tidal Volumes Benefits Patients without ARDS Serpa Neto A. Crit Care Med. 2015; 43:4155 2,184 ICU patients without ARDS from 7 studies outcome: hospital stay and ARDS development [METANALYSIS]

Use of Lower Tidal Volumes Benefits Patients without ARDS Serpa Neto A. Crit Care Med. 2015; 43:4155 Peak pressure = 20-24 cmh 2 O Plateau pressure =16-19 cmh 2 O PEEP = 5-6 cmh 2 O PaO 2 /FiO 2 = 260 mmhg Volume controlled = 51% Pressure controlled = 49%

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: NCT02153294 Pts without moderate or severe ARDS: V T 4 6 vs. 8 10 ml/kg PBW Preventive Strategies in Acute Respiratory Distress Syndrome (ARDS) (EPALI) Corporacion Parc Tauli. NCT02070666 NLM Identifier: NCT02070666 Pts without ARDS: V T 6 vs. 8 ml/kg PBW A new ARDS Network trial

PRoVENT Practice of Ventilation in ICUs Worldwide Serpa-Neto A et al. Lancet Respir Med. 2016 Nov;4(11):882-893. international observational study 1,022 patients without ARDS 7.9 [6.8 9.1] ml/kg PBW V T > 8 ml/kg in 40% of patients

Experimental edema due to intermittent positive pressure ventilation with high inflation pressures Protection by PEEP Webb HH, Tierney DF Am Rev Respir Dis. 1974 Nov;110(5):556-65 Ventilator Induced Lung Injury Tidal Volume or PEEP? P = 14 cmh2o PEEP = 0 cmh2o P = 45 cmh2o PEEP = 10 cmh2o P = 45 cmh2o PEEP = 0 cmh2o Lower Tidal Volume & Higher PEEP Higher Tidal Volume & Lower PEEP

Use of Higher PEEP Benefits Patient with Moderate or Severe ARDS Briel M. et al. JAMA 2010; 303:865 2,299 ICU patients with ARDS from 3 investigations outcome: death [METANALYSIS]

Permissive atelectasis to minimize VILI Rocco PR et al. Curr Opin Anaesthesiol. 2012, 25(2):123-30 Cressoni M et al. Am J Respir Crit Care Med 2014,189(2):149 158 Cressoni M et al. Anesthesiology. 2016 Feb 12. [Epub ahead of print] Stress σ = ΔF/ΔS (P L )) Energy = ΔP 2 x (2 x Est) Strain ε = ΔL/L 0 (V T /EELV) Power = Energy / Time ΔP = V T /Cst,rs = V T /EELV Healthy lungs Intensity = Power/Area Higher Dishomogeneities Less VILI with Less Stress, Strain, P, Power, Intensity

Biological Impact of Transpulmonary Driving Pressure in Experimental Acute Respiratory Distress Syndrome Samary CS et al. Anesthesiology. 2015 Aug;123(2):423-33.

Ventilator-related causes of lung injury: The mechanical power Gattinoni L et al. Intensive Care Med 2016;42:1567 75 % Increase in Power TV Flow P RR Power rs = 0.098 * RR * V * (P peak ½ * P) PEEP % Increase in Equation Motion Components

Power and Biological Markers in Experimental ARDS Samary 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 than atelectrauma in experimental ARDS Guldner A et al. Crit Care Med. 2016 Sep;44(9):e854-65 V ml VOLUTRAUMA vs ATELECTRAUMA Comparable Tidal Volume and Driving Pressure * = C dyn UIP P 3ml/kg ATELECTRAUMA C dyn VOLUTRAUMA LIP 3ml/kg P 0 10 20 36 cm H 2 O P

Volutrauma leads to higher lung inflammation than atelectrauma in experimental ARDS Guldner A et al. Crit Care Med. 2016 Sep;44(9):e854-65 Static strain is more injurious than dynamic strain!

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

Recruitment (g) Aeration and Recruitment in ALI/ARDS at end- expiration and end-inspiration Gattinoni, Pelosi et al. Am J Respir Crit Care Med 1995; 151:1807 1814 14 12 10 8 6 4 2 0 21 ± 1.8 ** Plateau Pressure (cmh 2 O) 26 ± 1.4 End Expiration End Inspiration ** 31 ± 1.8 ** 0 5 10 15 20 PEEP (cmh 2 O) 38 ± 2.1 46 ± 3.2

PEEP of 15 cmh 2 O 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?

1. Increased capillary pressure 2. Impeded drainage (compression thoracic duct) PEEP RV LV PEEP PEEP P v plasma capillaries edema Lymph flow (thoracic duct) Courtesy Prof Hedenstierna

Impact of acute hypercapnia and augmented PEEP on right ventricle function in ARDS Dessap AM et al Intensive Care Med (2009) 35:1850 1858 Boufferace K et al. Current Opinion in Critical Care 2011,17:30 35

PEEP in ARDS The Lung Safe Study Bellani G et al. JAMA Feb 23 2016, 315 (8): 788-800 PEEP was relatively low (12 cmh 2 O or lower) independently from ARDS severity Hypoxemia was treated by increasing FiO 2 Severe ARDS 8.4 cm H 2 O

PEEP: High vs Low - RCTs 60-day mortality (%) 45 40 35 30 25 20 15 10 5 0 P = 0.29 ALVEOLI LOVS EXPRESS N = 545 N = 983 N = 767 Low PEEP P = 0.17 P = 0.22 High PEEP

Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With ARDS Costa Leme A et al. JAMA. 2017 Apr 11;317(14):1422-1432 PEEP 12 vs 16 cmh 2 O

The Funeral for Positive End-Expiratory Pressure better known as PEEP It was a dream for generations of anesthesiologists and intensivists PEEP 1967. Rest in Peace

Lung Recruitability Is Better Estimated According to the Berlin Definition of ARDS at Standard 5 cm H 2 O PEEP: A Retrospective Cohort Study Caironi P. et al. Crit Care Med 2015; 43:781 790 PEEP 5-8 cmh 2 O PEEP 8-12 cmh 2 O PEEP 12-15 cmh 2 O

Bedside Selection of PEEP in Mild, Moderate, and Severe Acute Respiratory Distress Syndrome Chiumello D. et al. Crit Care Med 2014; 42:252 264 SatO 2 88-95 PaO 2 55-80 mmhg No routine RMs!

Prone position homogenizes aeration and ventilation at low PEEP Supine 7 6 Lung inflation 5 4 3 2 1 0 0 20 40 60 80 100 Lung Height (%) Gattinoni, Pelosi et al. Anesthesiology 1991; 74(1):15-23 Prone PEEP = 10 cmh 2 O P/F<150 mmhg while on F I O 2 >0.60; Guerin C. et al. N Engl J Med. 2013 Jun 6;368(23):2159-68

Ventilation in Intensive Care Unit patients with Uninjured Lungs Ventilation in Intensive Care Unit patients with the Acute Respiratory Distress Syndrome (ARDS) mild ARDS moderate and severe ARDS Protective ventilation includes: Protective ventilation includes: Protective ventilation includes: Protective ventilation includes: Tidal volume size 6 ml/kg predicted body weight Tidal volume size 6 8 ml/kg predicted body weight Tidal volume size 6 8 ml/kg predicted body weight 2 RCTs [31,32], and 1 3 meta analyses meta analysis [17,18,33]* and 2 IPD meta analyses [17,18,33]* evidence 2 RCTs comes [4] and from 1 meta analysis 2 RCTs [4] and [5] 1 meta analysis [5] evidence 2 RCTs comes [4] and from 1 meta analysis 2 RCTs [4] and [5] 1 meta analysis [5] Level of PEEP 5 10 cm H 2 O Level of PEEP 10 cm H 2 O but < 15cmH 2 O 3 RCTs [7,8,9] and 1 IPD meta analysis [10] 4 RCTs [7,8,9] and 1 IPD meta analysis [10]

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 Serpa Neto A et al. Ann Intensive Care. 2016 Dec;6(1):109 MD <0 favors strategy A (Low V T /Low PEEP)

Associations between PEEP and outcome of patients without ARDS at onset of ventilation:a systematic review and meta-analysis of randomized controlled trials Serpa Neto et al. Ann. Intensive Care (2016) 6:109 Low PEEP = 2.0 ± 2.8 cmh 2 O High PEEP = 9.7 ± 4.0 cmh 2 O High PEEP: No effect on duration of MV Lower rate of ARDS (high I 2 )

Ventilation During General Anesthesia for Surgery Ventilation in Intensive Care Unit patients with Uninjured Lungs Ventilation in Intensive Care Unit patients with the Acute Respiratory Distress Syndrome (ARDS) mild ARDS moderate and severe ARDS Protective ventilation includes: Protective ventilation includes: Protective ventilation includes: Protective ventilation includes: Tidal volume size 6 ml/kg predicted body weight Tidal volume size 6 8 ml/kg predicted body weight Tidal volume size 6 8 ml/kg predicted body weight 2 RCTs [31,32], and 1 3 meta analyses meta analysis [17,18,33]* and 2 IPD meta analyses [17,18,33]* evidence 2 RCTs comes [4] and from 1 meta analysis 2 RCTs [4] and [5] 1 meta analysis [5] evidence 2 RCTs comes [4] and from 1 meta analysis 2 RCTs [4] and [5] 1 meta analysis [5] Level of PEEP (<10 cmh 2 O)?? Level of PEEP 5 10 cm H 2 O Level of PEEP 10 cm H 2 O but < 15cmH 2 O Convincing RCT evidence is lacking 1 meta analysis 3 RCTs [7,8,9] and 1 IPD meta analysis [10] 3 RCTs [7,8,9] and 1 IPD meta analysis [10]

Driving Pressure ( P,rs) Bluth T et al. Curr Opin Anaesthesiol. 2016 Jun;29(3):421-9. V'aw ml/s Vol 750 500 250 0-250 -500-750 0 5 10 15 20 25 700 600 500 ml P = Pplat,rs 400 300 PEEP = V 200 T /Cst = V T /EELV 100 0-100 0 5 10 15 20 25 Paw cmh2o 35 30 25 20 15 10 5 0 PEEPtot Pplat 0 5 10 15 20 25 Time (s) P,rs

Driving pressure and survival in the ARDS c Amato MBP, et al. N Engl J Med 2015;372:747-55

LungSafe Practice of Ventilation in ICUs Worldwide Bellani G JAMA. 2016 Feb 23;315(8):788-800 2,396 pts with mild, moderate or severe ARDS

IPD Metaanalysis of studies in ARDS patients Receiving ELS Serpa-Neto A et al Intensive Care Med. 2016 Nov;42(11):1672-1684 c 653 patients from 12 studies RR for hospital death median settings in the first 3 days V T, ml/kg PBW PEEP, cm H 2 O Pplat, cm H 2 O ΔP, cm H 2 O ALL N = 653 ECMO N = 545 RR [95% CI] (p value) for hospital death 0.97 [0.87 1.08] (p = 0.602) 0.97 [0.92 1.02] (p = 0.249) 1.03 [0.97 1.09] (p = 0.298) 1.07 [1.02 1.12] (p = 0.004) 0.94 [0.83 1.06] (p = 0.294) 0.97 [0.91 1.03] (p = 0.323) 1.03 [0.97 1.10] (p = 0.308) 1.06 [1.01 1.12] (p = 0.029) ECCO 2 R N = 108 1.03 [0.80 1.32] (p = 0.817) 0.92 [0.83 1.02] (p = 0.125) 0.94 [0.81 1.10] (p = 0.454) 1.19 [1.04 1.35] (p = 0.009) adjusted for risk of death, age and severity of ARDS [METANALYSIS]

Ventilation in Intensive Care Unit patients with Uninjured Lungs Ventilation in Intensive Care Unit patients with the Acute Respiratory Distress Syndrome (ARDS) mild ARDS moderate and severe ARDS Protective ventilation includes: Protective ventilation includes: Protective ventilation includes: Protective ventilation includes: Tidal volume size 6 ml/kg predicted body weight Tidal volume size 6 8 ml/kg predicted body weight Tidal volume size 6 8 ml/kg predicted body weight 2 RCTs [31,32], and 1 3 meta analyses meta analysis [17,18,33]* and 2 IPD meta analyses [17,18,33]* evidence 2 RCTs comes [4] and from 1 meta analysis 2 RCTs [4] and [5] 1 meta analysis [5] evidence 2 RCTs comes [4] and from 1 meta analysis 2 RCTs [4] and [5] 1 meta analysis [5] Level of PEEP (< 10 cmh 2 O)?? Level of PEEP 5 10 cm H 2 O Level of PEEP 10 cm H 2 O but < 15cmH 2 O Convincing RCT evidence is lacking 1 meta analysis 3 RCTs [7,8,9] and 1 IPD meta analysis [10] 3 RCTs [7,8,9] and 1 IPD meta analysis [10] Low driving pressure (< 13cmH 2 O) Low driving pressure (< 13cmH 2 O) suggestion comes from several studies and 1 IPD meta analysis [10] suggestion comes from several studies and 1 IPD meta analysis [10]

PRoVENT Practice of Ventilation in ICUs Worldwide Serpa-Neto A et al. Lancet Respir Med. 2016 Nov;4(11):882-893. international observational study 1,022 patients without ARDS P 10.0 [6.0-13] cm H 2 O P > 12 cmh 2 O in 30-40% of patients

Ventilation in Intensive Care Unit patients with Uninjured Lungs Ventilation in Intensive Care Unit patients with the Acute Respiratory Distress Syndrome (ARDS) mild ARDS moderate and severe ARDS Protective ventilation includes: Protective ventilation includes: Protective ventilation includes: Protective ventilation includes: Tidal volume size 6 ml/kg predicted body weight Tidal volume size 6 8 ml/kg predicted body weight Tidal volume size 6 8 ml/kg predicted body weight 2 RCTs [31,32], and 1 3 meta analyses [17,18,33]* and 2 IPD meta analyses [17,18,33]* evidence 2 RCTs comes [4] and from 1 meta analysis 2 RCTs [4] and [5] 1 meta analysis [5] evidence 2 RCTs comes [4] and from 1 meta analysis 2 RCTs [4] and [5] 1 meta analysis [5] Level of PEEP (<10 cmh 2 O)?? Level of PEEP 5 10 cm H 2 O Level of PEEP 10 cm H 2 O but < 15cmH 2 O Convincing RCT evidence is lacking 1 meta analysis 3 RCTs [7,8,9] and 1 IPD meta analysis [10] 3 RCTs [7,8,9] and 1 IPD meta analysis [10] Driving pressure (< 13cmH 2 O) studies are lacking Low driving pressure (< 13cmH 2 O) suggestion comes from several studies and 1 IPD meta analysis [10] Low driving pressure (< 13cmH 2 O) suggestion comes from several studies and 1 IPD meta analysis [10]

LungSafe Practice of Ventilation in ICUs Worldwide Bellani G JAMA. 2016 Feb 23;315(8):788-800 Pplat and Mortality in ARDS international observational study 2,396 patients with mild, moderate or severe ARDS

Plateau pressure or Driving Pressure and Survival in the ARDS Villar J et al. Crit Care Med. 2017 Mar 1 [Epub ahead of print]

LungSafe Practice of Ventilation in ICUs Worldwide Bellani G JAMA. 2016 Feb 23;315(8):788-800 2,396 pts with mild, moderate or severe ARDS

LungSafe Potentially modifiable factors contributing to outcome from ARDS Laffey GC et al. Intensive Care Med 2016 (Epub Ahead of Print) 2,396 pts with mild, moderate or severe ARDS Higher PEEP, lower plateau and driving P, & lower respiratory rate are associated with better survival from ARDS

Ventilation in Intensive Care Unit patients with Uninjured Lungs Ventilation in Intensive Care Unit patients with the Acute Respiratory Distress Syndrome (ARDS) mild ARDS moderate and severe ARDS Protective ventilation includes: Protective ventilation includes: Protective ventilation includes: Protective ventilation includes: Tidal volume size 6 ml/kg predicted body weight Tidal volume size 6 8 ml/kg predicted body weight Tidal volume size 6 8 ml/kg predicted body weight 2 RCTs [31,32], and 1 3 meta analyses meta analysis [17,18,33]* and 2 IPD meta analyses [17,18,33]* evidence 2 RCTs comes [4] and from 1 meta analysis 2 RCTs [4] and [5] 1 meta analysis [5] evidence 2 RCTs comes [4] and from 1 meta analysis 2 RCTs [4] and [5] 1 meta analysis [5] Level of PEEP (< 6 cmh 2 O)?? Level of PEEP 5 10 cm H 2 O Level of PEEP 10 cm H 2 O but < 15cmH 2 O Convincing RCT evidence is lacking 1 meta analysis 3 RCTs [7,8,9] and 1 IPD meta analysis [10] 3 RCTs [7,8,9] and 1 IPD meta analysis [10] Driving pressure (< 13cmH 2 O) studies are lacking Driving pressure (< 13cmH 2 O) Pplat (< 25 27 cmh 2 O) suggestion comes from several studies and 1 IPD meta analysis [10] Driving pressure (< 13cmH 2 O) Pplat (< 25 27 cmh 2 O) suggestion comes from several studies and 1 IPD meta analysis [10]

Management and Outcome of Mechanically Ventilated in Patients after Cardiac Arrest Sutherasan Y et al. Crit Care. 2015 May 8;19:215 Factors associated with ARDS 1) Higher (> 17 cmh 2 O) 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 cmh 2 O) applied PEEP levels (odds ratio 0.89, 95% CI 0.80 to 0.99)

PRoVENT Practice of Ventilation in ICUs Worldwide Serpa-Neto A et al. Lancet Respir Med. 2016 Nov;4(11):882-893. international observational study 1,022 patients without ARDS Pplat 15.0 [13.0-20.0] cm H 2 O Pplat > 17 cmh 2 O in 30-40% of patients

Ventilation During General Anesthesia for Surgery Ventilation in Intensive Care Unit patients with Uninjured Lungs Ventilation in Intensive Care Unit patients with the Acute Respiratory Distress Syndrome (ARDS) mild ARDS moderate and severe ARDS Protective ventilation includes: Protective ventilation includes: Protective ventilation includes: Protective ventilation includes: Tidal volume size 6 ml/kg predicted body weight Tidal volume size 6 8 ml/kg predicted body weight Tidal volume size 6 8 ml/kg predicted body weight 2 RCTs [31,32], and 1 3 meta analyses meta analysis [17,18,33]* and 2 IPD meta analyses [17,18,33]* evidence 2 RCTs comes [4] and from 1 meta analysis 2 RCTs [4] and [5] 1 meta analysis [5] evidence 2 RCTs comes [4] and from 1 meta analysis 2 RCTs [4] and [5] 1 meta analysis [5] Level of PEEP (< 6 cmh 2 O)?? Level of PEEP 5 10 cm H 2 O Level of PEEP 10 cm H 2 O but < 15cmH 2 O Convincing RCT evidence is lacking 1 meta analysis 3 RCTs [7,8,9] and 1 IPD meta analysis [10] 3 RCTs [7,8,9] and 1 IPD meta analysis [10] Driving pressure (< 13cmH 2 O) Plateau pressure (< 17 cmh 2 O)?? studies are lacking Driving pressure (< 15 cmh 2 O) Pplat (< 25 27 cmh 2 O) suggestion comes from several studies and 1 IPD meta analysis [10] Driving pressure (< 15 cmh 2 O) Pplat (< 25 27 cmh 2 O) suggestion comes from several studies and 1 IPD meta analysis [10]

Practice of Ventilation in ARDS Bellani G JAMA. 2016 Feb 23;315(8):788-800

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

Permissive Atelectasis in ALL MV patients Pelosi P, Rocco PRM, de Abreu MG (Crit Care 2018 in press) Expiration Inspiration

Permissive Atelectasis! Less is More P = Pplat,rs PEEP = V T /Cst = V T /EELV V T / P Energy = ( P) 2 / (2 x Est) Pplat Energy Power Power = Energy / Time (RR) PEEP Regional Intensity = Power / Surface

Permissive Atelectasis! Less is More P = Pplat,rs PEEP = V T /Cst = V T /EELV V T / P Energy = ( P) 2 / (2 x Est) Pplat Energy Power In ARDS patients PEEP based on lower PaO 2 /FiO 2 Table PRONE POSITION! PEEP Power = Energy / Time (RR) Regional Intensity = Power / Surface

JUST DO IT! Protective Mechanical Ventilation In ALL patients LOWER IS BETTER...ALSO PEEP in severe ARDS!