How ARDS should be treated in 2017

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How ARDS should be treated in 2017 2017, Ostrava Luciano Gattinoni, MD, FRCP Georg-August-Universität Göttingen Germany

ARDS 1. Keep the patient alive respiration circulation 2. Cure the disease leading to the syndrome 3. Don t add damage lung body 4. Provide the best environment for lung healing (???)

Aim of the respiratory support To buy time with minimal damage Damaging factors Lung Ventilator Baby lung size Homogeneity Recruitability Mechanical power

Small, inhomogeneous, recruitable lung VILI comes from

Acute Respiratory Distress Syndrome Timing Chest Imaging a Origin of Edema Within 1 week of a known clinical insult or new/worsening respiratory symptoms Bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules Respiratory failure not fully explained by cardiac failure or fluid overload; Need objective assessment (e.g., echocardiography) to exclude hydrostatic edema if no risk factor present Mild Moderate Severe 200<PaO 2 /FiO 2 < 300 Oxygenation b with PEEP or CPAP 5 cmh 2 O c 100<PaO 2 /FiO 2 <200 with PEEP 5 cmh 2 O PaO 2 /FiO2<100 with PEEP 5 cmh 2 O a Chest X-ray or CT Scan b If altitude higher than 1000m,correction factor should be made as follows: PaO 2 /FiO 2 x (barometric pressure/760) c This may be delivered non-invasively in the Mild ARDS group JAMA. 2012;307(23):doi:10.1001/jama.2012.5669

MILD MILD ARDS MODERATE 320 320 280 280 240 240 200 200 P/F 160 P/F 160 120 120 80 80 40 40 0 5 10 15 20 0 5 10 15 20 PEEP SEVERE PEEP 320 280 240 200 P/F 160 120 PEEP 5 cmh 2 O Clinical PEEP 80 40 0 5 10 15 20 PEEP Caironi, et al. CCM 2015

Caironi, et al. CCM 2015

Baby lung

Gattinoni L et al. Intensive Care Med (1986) 12:137-142

CT numbers frequency (%) Hyperinflated Baby Lung (1987) Normally aerated Poorly aerated Non aerated 50 Normal 40 ARDS 30 20 10 0-1000 -900-800 -700-600 -500-400 -300-200 -100 0 100 CT numbers (Hounsfield Units)

Inhomogeneity

Voxel Vgas Gas fraction = V gas0 /V voxel Weighted gas ratio = V gas1 /V gas0 * fraction of tissue

Average ratio in normal subjects : 1.37±0.15 Healthy subject Moderate ARDS Severe ARDS

Ki/lung inhomogeneity interaction and gas/tissue composition MILD MODERATE SEVERE

Recruitability

Morphological response (1986) 5 cm H 2 O PaO 2 : 97 mm Hg 10 cm H 2 O PaO 2 : 103 mm Hg 15 cm H 2 O PaO 2 : 104 mm Hg d. 59% d. 56% 5 cm H 2 O 10 cm H 2 O PaO 2 : 34 mm Hg PaO 2 : 49 mm Hg d. 53% 15 cm H 2 O PaO 2 : 121 mm Hg d. 70% d. 52% d. 32% Intensive Care Med. 1986;12(3):137-42.

Opening pressures (2001) 6 dogs, Oleic acid % 100 80 60 40 20 0 Potential for recruitment 100% inflation 0 20 40 60 80 recruitment Airway pressure [cmh 2 O] Pelosi et al. Am J Respir Crit Care Med. 2001 Jul 1;164(1):122-30.

Recruitment and inflation % 100 Inflation/Recruitment (2001) 5 patients, ALI / ARDS 80 60 Potential for recruitment 5% 40 20 Inflation % Recruitment % 0 0 5 10 15 20 25 30 35 40 45 50 Paw [cmh 2 O] Crotti et al. Am J Respir Crit Care Med 2001;

Frequency [no. of patients] Figure 1 Potential for lung recruitment 24 22 20 18 16 14 12 10 8 6 4 2 0 5 ± 4% (59 ± 51 grams) lower 21 ± 10% (374 ± 236 grams) higher ALI patients ARDS patients potential for lung recruitment [% total lung weight] Gattinoni L, Caironi P, Cressoni M, Chiumello D, Ranieri VM, Quintel M, Russo S, Cornejo R, Bugedo G, NEJM 2006, 354(17):1775-86

Recruited lung tissue (g) Opening Pressures 600 500 400 Mild ARDS (N=5) Moderate ARDS (N=19) Severe ARDS (N=19) Plateu pressure limit 300 200 100 0 0 5 10 15 20 25 30 35 40 45 Courtesy of dr. Cressoni M. Pressure (cmh 2 O)

Compartments (HU) -1000/-900-900/-800-800/-700-700/-600-600/-500-500/-400-400/-300-300/-200-200/-100 0/-100 >0 A: TISSUE 0 50 100 150 200 250 300 350 400 450 500 PEEP 5 PEEP 15 ** ** * Tissue (g) ** -1000/-900 ** -900/-800-800/-700-700/-600-600/-500-500/-400-400/-300-300/-200-200/-100 0/-100 >0 ** B: GAS 0 50 100 150 200 250 300 350 400 450 500 550 600 650 700 Gas (ml) ** ** Chiumello, et al. AJRCCM 2016

Aim of the respiratory support To buy time with minimal damage Damaging factors Lung Ventilator Baby lung size Homogeneity Recruitability Mechanical power

VILI comes from Excessive power

Time course of ventilator induced lung injury 600 3.0 Lung Weight (g) 500 400 300 200 100 0-100 2.5 2.0 1.5 1.0 Strain (Vt/FRC) -200 0 12 24 36 48 60 Hours of mechanical ventilation 0.5 Protti A. et al. Am J Respir Crit Care Med. 2011 Feb 4.

%Total Lung Capacity Resting Biotrauma Stress at rupture Strain 2.0 1.5 100 90 80 1.0 70 60 Specific Lung Elastance 12 (cmh 2 O) 0.5 0.0 50 1 2 3 40 0 4 8 12 16 20 24 28 32 36 40 Transpulmonary pressure (PL cmh 2 O) Agostoni, Mead, Weibel, Gattinoni

Stress-strain curve of healthy pigs Stress (PL, cmh2o) 55 50 45 40 35 30 25 20 15 10 5 0 Specific Lung Elastance 5.8 cmh 2 O 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 Strain (dvgas/vgas0) Protti A. et al. Am J Respir Crit Care Med. 2011 Feb 4.

Lung Volume TLC FRC VT 100% V PEEP 0% VT 75% V PEEP 25% VT 50% V PEEP 50% VT 25% V PEEP 75% Protti et al. Crit Care Med. 2013 Feb 4.

Mechanical ventilation and VILI 1.Volume 2.Pressure 3.Respiratory Rate 4.Flow 5.Or???

ZEEP 600 Total Inspiratory Volume Volume 400 200 EXAPLES OF ENERGY COMPUTATIONS AT DIFFERENT PRESSURES 0 ZEEP Peak Pressure 0 10 20 30 Pressure 1200 1000 Total Inspiratory Volume LOW PEEP 1200 1000 Total Inspiratory Volume HIGH PEEP 800 800 PEEP Volume Volume 600 PEEP Volume Volume 600 400 400 200 200 0 PEEP Peak Pressure 0 PEEP Peak Pressure 0 10 20 30 40 50 60 Pressure 0 10 20 30 40 Pressure

Motion equation Total pressure = (E rs V) + (R aw F) + PEEP Distend the lung Move the gas Keep open

Mechanical Power Total pressure V RR = Power rs = 0,098 RR V 2 1 2 E rs + RR 1 + I: E 60 I: E R aw + V PEEP Distend the lung Move the gas Keep open TIME ENERGY

Percent increase power Contributions to Power generation 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% Baseline values RR 20 TV (L) 0,400 Ers 25 I:E 0,5 Raw 10 PEEP 10 Power rs 14,90 RR TV Peep Driving Press 0% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Percent increase variable

Summary TV Power 2 P aw Power 2 RR Power 1.6 PEEP Power 1

Interaction

Small, inhomogeneous, recruitable lung VILI comes from Excessive power

Chest wall elastance Stiff Soft Soft Stiff EL L Ew EL L Ew 25 5 cmh 2 O 15 15 E tot E tot

Transpulmonary plateau pressue (cmh 2 O) Slope P L /P aw = E w /E tot [0.2-0.8] A Surgical control group Medical control group B ALI patients ARDS patients 60 60 50 50 40 40 30 30 20 20 10 10 0 0 10 20 30 40 50 60 0 0 10 20 30 40 50 60 Airway plateau pressure (cmh 2 O) Airway plateau pressure (cmh 2 O) Chiumello et al, Am J Respir Crit Care Med. 2008

Always consider: V T Baby lung size

The ARDS lung is small and not stiff Normal V T FRC = 500 ml 2500 ml = 0.2 ARDS V T FRC = 500 ml 500 ml = 1

Always consider: The lung inhomogeneity Stress raisers Atelectrauma

Lung expansion/gas-free state Mead J J Appl Physiol. 1970 May;28(5):596-608. V 10 V V 1 V STRESS RAISER=(10/1) 2/3 = 4.64

Lung dishomogeneity and ARDS Mild (N=82) Moderate (N=71) Severe (N=12) P Dishomogeneity 1.49 ± 0.17 1.58 ± 0.29 1.75 ± 0.41 0.03 Dishomogeneity 2/3 1.30 ± 0.31 1.36 ± 0.44 1.45 ± 0.55 Extent 0.3 ± 0.1 0.36 ± 0.16 0.46 ± 0.18 0.01 Intensity 2.69 ± 0.27 2.76 ± 0.27 2.84 ± 0.41 0.31 Intensity 2/3 1.93 ± 0.42 1.97 ± 0.42 2.01 ± 0.55 Am J Respir Crit Care Med. 2014 Jan 15;189(2):149-58

Gas / Tissue Ratio The gas/tissue ratio as a function of lung height 7 6 5 4 3 2 1 0 Normal Supine Normal Prone ARDS Supine ARDS Prone 0 20 40 60 80 100 Lung Height (%) Gattinoni L et al. In: Tobin MJ (ed) New York

Guerin C. et al. N Engl J Med. 2013 Jun 6;368(23):2159-68 Gattinoni L. et al. Minerva Anestesiol. 2010 Jun;76(6):448-54

Atelectrauma

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

Recruited tissue Recruitment-Pressure curve Opening-closing Exp. Exp. 5 15 25 35 Pressure

Lung protective strategy Less energy + More homogeneous lung