what it is and what it is not ards

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Acute Respiratory Distress Syndrome (ARDS) -What it is and what it is not.- Andrew Bernard, M.D. Assistant Professor of Surgery Medical Director, Surgical Intensive Care Unit College of Medicine University of Kentucky

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Page 1: What It Is And What It Is Not  Ards

Acute Respiratory Distress Syndrome

(ARDS)

-What it is and what it is not.-Andrew Bernard, M.D.

Assistant Professor of SurgeryMedical Director, Surgical Intensive Care Unit

College of MedicineUniversity of Kentucky

Page 2: What It Is And What It Is Not  Ards

Objectives

1. Understand basic history, physiology and pathophysiology of acute lung injury and ARDS.

2. Outline the current evidence base for treatment for ARDS.

3. Speculate on future therapies for ARDS that are currently in development.

Page 3: What It Is And What It Is Not  Ards

Definitions

• ARDS-Acute respiratory distress syndrome

• ALI-Acute lung injury

ALI

ARDS

Page 4: What It Is And What It Is Not  Ards

History• Ashbaugh, 1967• Common pattern:

– Severe respiratory distress

– Refractory cyanosis– Loss of compliance– Diffuse alveolar

infiltrates

• Typical disorders:– Sepsis– Pneumonia– Aspiration– Major trauma

Ashbaugh et al. Lancet 1967.

Page 5: What It Is And What It Is Not  Ards

Synonyms

• Da Nang lung• Shock lung• Post-traumatic lung• Respirator lung

Bernard GR et al. Am J Resp Crit Care 2005.

Page 6: What It Is And What It Is Not  Ards

Progress?

• Definition vague• Inadequately powered trials• 1990-Mortality for ARDS still 67%• 1994- American-European Consensus

Conference on ARDS and ALI

• Current incidence: 200,000 cases/yr U.S.• Mortality: 40%

Page 7: What It Is And What It Is Not  Ards

Risk Factors for ARDS• Pulmonary

1. Pneumonia2. Aspiration3. Inhalation4. Pulmonary contusion5. Fat emboli6. Near-drowning7. Reperfusion

• Non-Pulmonary1. Sepsis2. Trauma + fractures3. Shock4. Pancreatitis5. Cardiopulmonary

bypass6. DIC7. Burns8. Head injury9. Transfusion

Page 8: What It Is And What It Is Not  Ards

Pathophysiology• Endothelial injury

– Endothelin-1, VWF• Epithelial injury• Neutrophil-mediated injury

– Near endothelium, retained, activated• Cytokines

– TNF, IL-1, IL-8• Oxidative injury• Ventilator-induced injury• Hypercoagulability• Fibrosis

Ware LB. Sem in Resp Crit Care Med 2006.

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Normal Lung

Ware LB. Sem in Resp Crit Care Med 2006.

Page 10: What It Is And What It Is Not  Ards

Increased permeability pulmonary edema

Ware LB. Sem in Resp Crit Care Med 2006.

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Diagnosis

• Onset: acute• Oxygenation: P/F ratio < 200• Radiographic: bilateral infiltrates• Volume status: PAWP ≤ 18 (no atrial HTN)

• ALI = ARDS with P/F 200-300

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Page 13: What It Is And What It Is Not  Ards

Mechanical VentilationTreatment or Harm?

• Critical to treatment of ARDS• BUT: Ventilation can both improve AND

propagate ARDS• High inspiratory volumes: ↑ edema• Edema is due to:

– microvascular injury and– ↑ capillary permeability

• Positive end expiratory pressure (PEEP) helps• Inspiratory volume is culprit• Lower volumes→↓ mortality (even if it means

permissive hypercapnea)

Hickling et al. Crit Care Med 1994.

Page 14: What It Is And What It Is Not  Ards

Macintyre N. Sem Resp Crit Care Med 2006.

Page 15: What It Is And What It Is Not  Ards

Major Breakthrough• ARDS Network• Sponsored by NHLBI

(NIH)• Multi-center phase III trial• High (12cc/kg) vs low

(6cc/kg) tidal volumes• Plateau pressures

< 30cm H20

ARDS Network. NEJM 2000.

Page 16: What It Is And What It Is Not  Ards

Major Breakthrough• ARDS Network• Sponsored by NHLBI

(NIH)• Multi-center phase III trial• High (12cc/kg) vs low

(6cc/kg) tidal volumes• Plateau pressures

< 30cm H20

NormalNormalPIPPIP

PPplatplat

NormalNormalPIPPIP

PPplatplat

ARDS Network. NEJM 2000.

Page 17: What It Is And What It Is Not  Ards

Major Breakthrough• ARDS Network• Sponsored by NHLBI

(NIH)• Multi-center phase III trial• High (12cc/kg) vs low

(6cc/kg) tidal volumes• Plateau pressures

< 30cm H20

• Mortality reduction: 41% → 30%

NormalNormalPIPPIP

PPplatplat

NormalNormalPIPPIP

PPplatplat

ARDS Network. NEJM 2000.

Page 18: What It Is And What It Is Not  Ards

Major Breakthrough• ARDS Network• Sponsored by NHLBI

(NIH)• Multi-center phase III trial• High (12cc/kg) vs low

(6cc/kg) tidal volumes• Plateau pressures

< 30cm H20

NormalNormalPIPPIP

PPplatplat

NormalNormalPIPPIP

PPplatplat

ARDS Network. NEJM 2000.

Low CLow CLLPIPPIP

PPplatplat

Low CLow CLLPIPPIP

PPplatplat

Page 19: What It Is And What It Is Not  Ards

Adjuncts to Improve Survival

• Daily spontaneous breathing trials• Daily discontinuation of sedation• Avoiding neuromuscular blocakde• DVT prophylaxis• HOB elevation• Stress ulcer prophylaxis• Enteral nutrition (when possible)

Page 20: What It Is And What It Is Not  Ards

PEEP• Improves oxygenation• Maintains recruitment (avoids reopening

alveoli with each inspiration)

• But:– Raises intra-thoracic pressure (impairing

cardiac filling)

• High PEEP vs low PEEP? No difference

Brower RG et al. NEJM 2004.

Page 21: What It Is And What It Is Not  Ards

Recruitment Maneuvers• High levels of PEEP for brief periods• ? Enhances recruitment• ? Increases PaO2/FIO2 ratio• ? Sustained effect

• ARDS Network: No good evidence of durability

• Others: May be diagnostic, allowing titrating of PEEP

Marin JJ. Crit Care Med 2003.

Page 22: What It Is And What It Is Not  Ards

Recruitment Maneuver-Example

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Pressure Control Ventilation• Usually combined with inverted I:E ratio• Basic premise: prolonged inspiration• Mechanism of benefit: prolonged diffusion

• Data are mixed• Potential problem:

– Vt depends upon compliance– Vt can thus change– May be difficult to maintain low tidal volumes

Marin JJ. Crit Care Med 2003.

Page 24: What It Is And What It Is Not  Ards

ECMO• Extracorporeal

membrane oxygenation

• First used in neonates• Has been used in

ARDS• Improves oxygenation• No change in mortality• Rescue Rx or on trial

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Glucocorticoids in ARDS• Date back to Ashbaugh in 1967• Premise: decrease lung inflammation• Disadvantage: myopathy and infection• Data are mixed

• NHLBI multi-center, randomized trial:– Improved oxygenation– Fewer ventilator days– Mortality unchanged

NHLBI ARDS Clinical Trial Network. NEJM 2006.

Page 26: What It Is And What It Is Not  Ards

Surfactant

• Surfactant dysfunction is part of ARDS• No defined role in adults • Established Rx in children

• Evidence base in children is marginal

Spragg RG et al. NEJM 2004.

Page 27: What It Is And What It Is Not  Ards

Inhaled Nitric Oxide (iNO)• Vasodilator• First reported in 1993• Mechanism-locally active (pulmonary bed)• Results:

– ↓ PA pressures– ↓ left to right intrapulmonary shunt– Improved oxygenation

• Large randomized trials:– No durable effects– Mortality unchanged

Rossaint R et al. NEJM 1993.

Page 28: What It Is And What It Is Not  Ards

Noninvasive Positive Pressure Breathing (NIPPV)

• CPAP or BiPAP• COPD and CHF• Avoids intubation• Fewer pneumonias• Less sinusitis• Less organ failure• Lower mortality

• Large studies needed

Ferrer M et al. Am J Resp Crit Care Med 2003.

Page 29: What It Is And What It Is Not  Ards

Prone Positioning• Redistributes

pulmonary blood flow• Decreases shunt• Improves

oxygenation• Improves compliance• Mortality?????• Revolutionary

technology

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Supine vs Prone

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HFOV• Benefit: lower pressure

oscillations• Disadvantage: technically

challenging

• Data are mixed• Oxygenation clearly

increased• Mortality benefit???• NHLBI phase II ongoing

Henderson-Smart DJ et al. Cochrane Database Syst Rev 2003.

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Partial Liquid Ventilation• Fill lungs with

perfluorocarbon• Mechanisms:

– Improved blood flow– Decreased inflammation– Safe in children and adults

• Randomized trial 311 patients:– More ventilator days– Trend toward ↑ mortality

Kacmarek RM et al. Am J Resp Crit Care Med 2006.

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Fluid Therapy in ARDS

• Fluid conservation appropriate– On a protocol– CVP < 4– PCWP < 8– Fewer vent days– More days out of ICU– No change: Shock, dialysis, mortality

Page 34: What It Is And What It Is Not  Ards

Is a Swan helpful in ARDS?

• PA Catheters are harmful (Connors et al, JAMA 1996)

• FACTT (Fluid and Catheter Treatment Trial)– 1000 patients– Randomized, vs CVC– More catheter-related complications in PAC

group– Primary endpoint (60-day mortality):

No difference Wheeler et al. NEJM 2006.

Page 35: What It Is And What It Is Not  Ards

Edwards ScvO2 Catheter

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Transfusion-Related Acute Lung Injury

• Respiratory distress, pulmonary edema, hypoxia, hypotension and fever

• Within 2 hours of transfusion (6 at most)• Mechanism

– Plasma in transfused product– HLA antibodies or granulocyte specific antibodies

• 1/5000?• 5-10% mortality• Diagnosis:

– Difficult to tease out– Isolation of antibodies

Popovsky et al. Guidelines for the management of TRALI. AABB 2003.

Page 37: What It Is And What It Is Not  Ards

Transfusion-Related Acute Lung Injury-Treatment

• Stop the transfusion• Treat pulmonary and cardiac dysfunction• Test the transfused units• Contact a reference lab for advice• Subsequent transfusions to that individual

not a problem

Popovsky et al. Guidelines for the management of TRALI. AABB 2003.

Page 38: What It Is And What It Is Not  Ards

Goals for Ventilation

• Oxygenate• Protect the lung• Tolerate PaO2 55• Don’t sweat hypercarbia!• Stay recruited• Avoid plateaus > 30

Page 39: What It Is And What It Is Not  Ards

Summary

• ARDS is NOT: a garbage can diagnosis

• ARDS is:– A real diagnosis– Major killer of the critically ill – Worthy of documentation– Best managed using evidence