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Rich Kallet MS RRT FAARC FCCM Director of Quality Assurance

Respiratory Care Services UCSF at San Francisco General Hospital

¨  What is ARDS?: how our understanding changed over time

¨  What are the risk factors and major etiologies?

¨  How does MV exacerbate or attenuate lung injury?

¨  Ventilator managment of ARDS

¨  Prone Position

¨  How does asynchrony impact LPV and how should it be managed?

¨  Is there a role for NIV and HFNC in ARDS?

¨  1821: Rene Laennec: “idiopathic anasarca of the lungs w/o heart failure”.

¨  Universally fatal “Double PNA” ¨  1900: Osler: “uncontrolled septicemia leads to frothy

pulmonary edema that resembles serum, not the sanguinous transudative edema seen in congestive heart failure.”

¨  1918: Phosgene gas poisoning / Spanish Influenza ¨  WWII: Brewer/Burford: “persistent wet lung of trauma” in

battle casualties w/ severe brain, thoracic, abdominal & extremity trauma..most difficult to resuscitate, highest mortality.

¨  1948: Moon: “shock lung” following hemorrhage ¨  1959: Petersdorf: Asian influenza pandemic of 1956. ¨  1966: Vietnam War: “wet lung” ; “Da Nang Lung”

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¨  Sudden onset of respiratory distress w/o hx of pulm disease.

¨  Variety of insults (7 (~60%) Trauma, pancreatitis, viral PNA, Drug OD, Aspiration)

¨  Non-cardiogenic pulmonary edema* ¨  Diffuse opacities on CXR ¨  Diffuse inflammation interstitial fibrosis (late ARDS

autopsy) ¨  Low compliance ¨  Hypoxemia refractory to high FIO2

¨  Responsiveness to PEEP * 7/12 pts had evidence of fluid overload

LIS (1988) AECC (1994) Berlin (2012)

5 pt scoring system (0-4) 4 categories

CXR (0-4 quadrants) PaO2/FiO2*

(> 300: 0; < 100: 4)

Crs (> 80: 0; < 20: 4) PEEP (< 5: 0; > 15:4)

ARDS > 2.50

Acute Onset Bilateral Opacities

(Diffuse or patchy) Not explained by atelectasis, pleural effusions

P/F < 300: ALI P/F < 200: ARDS

Absence of LA HTN or Fluid Overload PAOP < 18 mmHg

Onset: < 7 days from insult.

Bilateral Opacities (Diffuse or patchy)

Not fully explained by atelectasis, pleural effusions,

Origin of Edema: Not fully explained by cardiac, fluids

Minimal PEEP > 5 Mild: 201-300

Mod: 101-200 Severe: < 100

Major Causes

¨  Pneumonia ¨  Sepsis ¨  Aspiration ¨  Trauma

¨  Lesser Causes

¨  Transfusions (TRALI) ¨  Pancreatitis ¨  Hemorrhagic Shock ¨  Inhalation Injury ¨  IV Drug ¨  Fat Embolism ¨  Near Drowning

Exotic / Unusual

¨  Protozoan: Malaria ¨  Fungal: Coccidiomycosis ¨  Hemorrhagic Fevers:

Marburg, Ebola ¨  Eclampsia ¨  Amniotic fluid embolism ¨  Inhalation of Fumes ¨  Reaction to Contrast ¨  Reaction to drugs

(Amantadine, Bleomycin, Amiodarone)

¨  Annual Incidence USA: 190,000 adult cases ¨  Overall Mortality: ~40% (1970-80s > 60%) ¨  Clinical Trials (ARDS Net): ↓ 39% to 22% ¨  Berlin Definition:

¡  Mild: 27% [24-30] ¡  Moderate: 32% [29-34] ¡  Severe: 45% [42-48]

¨  Impact of Comorbidities ¡  ESLD, BMTransplant: ~70% ¡  ARDS + Renal Failure (dialysis): ~67% ¡  SFGH Presence of Comorbidities (pre/post LPV): 78% vs.

48%

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¨  Berlin Definition

¨  Mild: 5 days [2-11]

¨  Moderate: 7 days [4-11]

¨  Severe: 9 days [5-17]

¨  Attraction /migration/ activation of macrophages, platelets, neutrophils.

¨  Stimulation & Release of ROS,

¨  Hyaline membrane formationactivation of fibrin,leakage of plasma proteins,

¨  cellular debris (necrosis / apoptosis)

¨  Necrosis: Inability to reabsorb edema fluid via active ion pumps

¨  Lymphatic drainage capacity exceeded

Atelectrauma

Volutrauma

V

P

Overdistension: Excessive Strain

Shearing

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In severe ARDS ~ 1/3 of lung appears to be normally aerated ~ 300g of tissue =lung size of a 5 yo child (Vt ~ 150 mL) Traditional VT ventilation 12-15 mL/kg 68 kg adult 800-1000 mL Functionally: 36-45 mL/kg VT

Note: Strain-stress plays out in alveolar regions of different gas volumes: Stress Raisers “amplifiers”

0

0.5

1

1.5

2

2.5

2.5 1.8 0.6

1.16 1.22

1.67 1.32 1.44

2.33

Estimated Strain of a 6 vs. 12 mL/kg VT as FRC Decreases

Strain 6 mL/kg Strain 12 mL/kg

Injury Control Gajic et al Am J Respir Crit Care Med. 2002

PCV 15 PCV 35

40 mL/kg VT 6 mL/kg VT

N = 30 , ARDS Net Protocol: 6 mL/kg & Pplat < 30 cmH2O

More Protected: 53% normal aerated tissue 26% non-aerated tissue Pplat 26 cmH2O Crs: 26 mL/cmH2O

Less Protected: 53% normal aerated tissue 49% non-aerated tissue Pplat 29 cmH2O Crs: 26 mL/cmH2O ↑IL-6 TNFα stat sig only for hyperinflated tissue

CT HU Color Coding Red: Hyperiflated , Blue Normal, Yellow Poorly Aerated, Green Non Aerated

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¨  Hyperoxic Acute Lung Injury: 240 years of research ¨  Tissue injury & aging occurs through generation ROS

RNS ¨  Breathing a FIO2 > 0.80 for approximately 3-6 days

typically is fatal to most animals ¨  Pretreatment w/ hyperoxia prior to, or combining

hyperoxia with high-stretch ventilation significantly magnifies VILI.

¨  LPV + prolonged (17hrs) needless exposure to high FIO2 (> 0.70) → worsening oxygenation index at 48h & longer duration of MV.

¨  Dose dependent effect (i.e. still seen at FIO2 > 0.55

¨  Alveolar epithelial cell cultures exposed to both 48h of hyperoxia (0.8-0.9).

¨  Hyperoxia stiffens the cell membrane; increases its resistance to stretch.

¨  Alveolar cell cultures attached to an artificial basement membrane that was stretched resulted in substantial detachment of alveolar cells from its supporting matrix.

¨  Oxidative stress induced a loss of pliability within the alveolar epithelial cell membrane (relative to the basement membrane) inducing shear-injury that enhances stretch-induced injury.

Frequency distribution of 197 discreet measurements of lower inflection points from 16 clinical studies.

0 1 2 3 4 5 6 7 8 9 1011121314151617181920212223242526270

10

20

30

LIP (cm H2O)

Num

ber

of P

atie

nts

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Mild Moderate Severe

VT: 6-8 mL/kg FiO2 < 0.60 PEEP: 5-10 Pplat: < 26 Pplat-PEEP: < 15

VT: < 6 mL/kg FiO2 < 0.60 PEEP: 10-15 Pplat: 26 Pplat-PEEP: < 15 Prone?

VT: < 6 mL/kg FiO2 < 0.60 PEEP: 15-20 Pplat: ? Pplat-PEEP: < 15 Prone

Balance: severity of lung injury vs. deleterious effects sedation /paralytics

18%

30%

52%

Gattinoni Anesthesiology 1991

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PP

Qs/Qt

PaO2 / Fi O2

PP

SP

PP SP

N Engl J Med 2013

Multi-center RCT N = 466: 90 Day mortality ↓ 41 to 24% Adjusted RR for mortality 0.48 (SOFA); ↑  VFD 4 & 14 (D-28,D-90) ↑  No difference in complication rates

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¨  VT ≈ Global Inspiratory Muscle Shortening

¨  Peak Flow/ Flow Pattern ≈ Velocity of Contraction

¨  Respiratory Drive → Corollary Discharge to Sensory

¨  Dyspnea: Efferent impulse/muscle tension > speed & magnitude of chest/lung displacement.

¨  Breathlessness: “Unpleasent urge to breathe” (excessive drive related in part to PCO2

¨  Pain & Dyspnea are processed in the same ancient brain structures

0

0 .2

0 .4

0 .6

0 .8

1

1.2

1.4

C MV 200 300 400 500

Simulated VT Demand

WOB

vent

(Jou

les/L)

VC-CF VC-DF PCV

0

0 .5

1

1.5

2

2 .5

3

200 300 400 500

Simulated VT Demand

WOB

sim

(Jou

les/L

)

UB VC-CF VC-DF PCV

100% VT Demand

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ΔP needed to keep VT ~ 6-7 mL/kg →↓ Peak Flow Capacity →↑ WOB ↑ VT

¨  Pmus: average in AMV ~ 15 cmH2O

¨  Distress: Pmus 25-40 cmH2O (PAOP 18-29)

¨  Magnifies hydrostatic ΔP capillary – interstitium →↑edema formation (↓ cardiac function)

¨  ↑O2 cost of breathing→↓ PVO2 → magnifies Qs/Qt

¨  Note: survival from ARDS depends upon the ability to clear pulmonary edema

¨  Loaded muscles→ instinct full relaxation → ↑ force of contraction

¨  Forced expiration: Counteracts PEEP

¨  VT mismatching cannot be treated without either matching VT or sedation

¨  ~ 20-30 sec on CPAP = PEEP on CMV ¨  Evaluate VT, peak flow, Ti: variability ¨  Compare to LPV goals vs. Sedation goals ¨  Severe , early ARDS: ↑ sedation, ? NMBA ¨  Milder ARDS: liberalize VT goals ¨  Trifecta of ARDS: shock, hypoxemia, acidosis! ¨  Pay attention to PAIN & ACIDOSIS

¨  NIV: ARDS is not short-term condition like COPD exacerbation / cardiogenic edema (5-7 vs. 0.5 -2 days) ¡  ~ 50-70% of ARDS patients fail a trial of NIV (related to

presence of shock, acidosis ¡  Failed NIV + Delayed Intubation →↑mortality 68 vs. 39%

predicted

¨  High-Flow Nasal O2 (FLORALI Study): ↓ need for MV compared to standard suppl O2 Rx for PNA-ARDS ¡  Contraindicated if PaCO2 > 45 mmHg, hemodynamic

instability. ¡  Poor methods prevent assessing efficacy to NIV (8hrs/d) ¡  Abandon w/in 30min if respiratory distress persists

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¨  190,000 cases/yr, Overall mortality ~ 40% ¨  New Berlin Definition Mild, Moderate & Severe based

on P/F (27, 32, 45% Mortality).

¨  3 Injuries: strain, shear, O2 toxicity

¨  Better P targets: Pplat 26, Pplat-PEEP < 15 ¨  Better PEEP: (Mil) 5-10, (Mod) 10-15, (Sev): 15-20

¨  Avoid prolonged exposure FiO2 > .80 (Goal < 0.60)

¨  Prone YES for severe ARDS (P/F < 150) ¨  Diagnostic CPAP to evaluate asynchrony

¨  Very cautious use of NIV, HFNC