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Acute Respiratory Distress Syndrome – What Works and 

What Does NotIlya Berim, MD

Dept. of Pulmonary, Critical Care and Sleep MedicineCreighton University

Disclosure

• I have no conflicts of interest pertinent to this presentation.

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Objectives

• Define acute respiratory distress syndrome (ARDS)• Ventilator induced lung injury• Driving pressure• Prone positioning • Pharmacologic therapy of ARDS• Therapies that did not work

Ventilator Induced Lung Injury (VILI)

• Barotrauma• Volutrauma• Atelectrauma• Biotrauma

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Berlin definition of ARDS

• Exclusion of alternative causes of bilateral pulmonary edema• Cardiogenic pulmonary edema• Interstitial lung disease• Diffuse alveolar hemorrhage

• New or worsening respiratory symptoms within 1 week of known insult• Bilateral opacities not fully explained by pleural effusions, lung collapse

or heart failure

Berlin definition of ARDS

• Severity• Mild: 200 mm Hg < PaO2/FiO2 ≤ 300 mm Hg• Moderate: 100 mm Hg < PaO2/FiO2 ≤ 200 mm Hg• Severe: PaO2/FiO2 ≤ 100 mm Hg

• Prognosis:• Mild: 27% mortality (95% CI 24 – 30%), 5 days on ventilator (IQR 2 – 11)• Moderate: 32% mortality (95% CI 29 – 34%), 7 days on ventilator (IQR 4 – 14)• Severe: 45% mortality (95% CI 42 – 48%), 9 days on ventilator (IQR 5-17)

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Therapy

• Lung protective ventilation / prone positioning• Treat the underlying cause

Lung protective ventilation

• Tidal volume of 6ml / kg of predicted body weight• Plateau pressure of 30 cm H2O or less• Reduce tidal volume to 4 – 6 ml / kg of predicted body weight if

unable to keep plateau pressure < 30 cm H20• Higher levels of PEEP supported

Brower RG N Engl J Med. 2000; 342(18): 1301–8 Laffey JG Intensive Care Med. 2016; 42(12): 1865–76

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ARDSNet website

Driving pressure (Dp)

• Difference between plateau pressure and PEEP• Might be a better estimate of relationship between tidal volume

administered by ventilator and patient specific volume of aerated lung

• Strongest mortality predictor• Tv, PEEP, Pplat, RR

• Dp of > 14 cm H2O results in steeper mortality increase with Dpincrease

Amato MB. N Engl J Med 2015; 372: 747-755

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Prone positioning

• Optimizes blood flow to the dependent lung• Reduces atelectasis• Facilitates secretion drainage• Increases FRC• Reduces plateau pressure

• In severe ARDS (PaO2/FiO2 < 150 mm Hg) reduces mortality (16% vs. 32.8%)

• Has to be done for > 12 hrs / 24 hr period

Gattinoni L Lancet. 1997; 350(9080): 815

Prone positioning

• Indications:• PaO2 / FiO2 < 150 mm Hg • FiO2 > 0.6, PEEP > 5 cm H2O• ARDS

• Contraindications• Shock• Massive hemoptysis• Fractures / spinal instability• Elevated ICP (> 30mm Hg) or CPP < 60 mm Hg• Tracheal surgery or sternotomy in the past 2 weeks• Pregnancy

Guerin C. et al. N Engl J Med. 2013;368(23):2159-2168.

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Proning video

Proning bed

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Cisatracurium

• Improves ventilator synchrony

• Reduces VILI

• Possible decrease in systemic inflammation

Forel JM. Crit Care Med 2006;34:2749-57

Cisatracurium

• Early administration (within 48 hrs of onset)• Severe ARDS (PaO2 / FiO2 < 150 mm Hg)• Neuromuscular blockade for 48 hrs

• 28 day mortality decrease• 23.7% vs. 33.3%

• Increase in ventilator – free days and days outside of ICU

Papazian L. N Engl J Med. 2010; 363(12): 1107–16

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Recruitment maneuvers

• Lung inflation with high pressure for a period of time• 35 – 50 cm H2O• Usually 30 – 45 seconds• Up to 4 times daily

• Improve oxygenation• Increase hypotension episodes and transient desaturation• No effect on mortality

Fan E. Am J Respir Crit Care Med. 2008;178(11):1156-1163

Recruitment maneuvers

• Recruitment maneuver followed by decremental PEEP guided by lung compliance

• ARDS, PaO2 / FiO2 < 200 mm Hg

• Resulted in increased 28 and 60 day mortality

Cavalcanti AB. JAMA. 2017;318(14):1335-1345

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Extracorporeal CO2 removal (ECCO2R)

• Low flow VV or AV device to facilitate CO2 removal but not oxygenation

• Allows for ultraprotective lung ventilation strategy (3ml/kg PBW Tv)• In severe ARDS, PaO2/FiO2 < 150 mm Hg, results in more ventilator

free days• No difference in mortality

• More studies en route.

Morelli A. Intensive Care Med. 2017;43(4):519-530 Bein T. Intensive Care Med 2013; 39: 847-856

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Airway Pressure Release Ventilation

• Theoretically improves oxygenation, controls lung injury and maximizes lung recruitment

• When used early (<48 hrs post dx) in ARDS with PaO2/FiO2 < 250 mm Hg, increases number of ventilator free days and requires less proning, paralysis or recruitment maneuvers

Zhou Y. Intensive Care Med. 2017; 43(11): 1648–1659

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High frequency oscillation ventilation (HFOV)

• Theoretically ideal ventilation mode in ARDS• Extremely small Tv• High “PEEP”• Limited airway pressures

• Mortality increased in large RCT causing early trial stop. • Potentially d/t effect on hemodynamics

• May be used as rescue strategy in very severe ARDS. (PaO2/FiO2 < 64 mm Hg

Meade MO. Am J Respir Crit Care Med 2017;196(6):727-733 Ferguson ND. N Engl J Med. 2013;368(9):795-805

More therapies that do not work

• Aspirin (325mg loading dose followed by 81mg for 7 days)• Inhaled NO• Beta 2 agonists• Keratinocyte growth factor• Statins• Stem cells• Interferon beta – 1a

Kor DJ et al. JAMA 2016 Jun 14;315(22):2406-14

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Fan E. JAMA. 2018;319(7):698-710

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Thank you!