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
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.
Definitions
• ARDS-Acute respiratory distress syndrome
• ALI-Acute lung injury
ALI
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.
Synonyms
• Da Nang lung• Shock lung• Post-traumatic lung• Respirator lung
Bernard GR et al. Am J Resp Crit Care 2005.
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%
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
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.
Normal Lung
Ware LB. Sem in Resp Crit Care Med 2006.
Increased permeability pulmonary edema
Ware LB. Sem in Resp Crit Care Med 2006.
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
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.
Macintyre N. Sem Resp Crit Care Med 2006.
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.
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.
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.
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
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)
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.
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.
Recruitment Maneuver-Example
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.
ECMO• Extracorporeal
membrane oxygenation
• First used in neonates• Has been used in
ARDS• Improves oxygenation• No change in mortality• Rescue Rx or on trial
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.
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.
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.
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.
Prone Positioning• Redistributes
pulmonary blood flow• Decreases shunt• Improves
oxygenation• Improves compliance• Mortality?????• Revolutionary
technology
Supine vs Prone
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.
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.
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
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.
Edwards ScvO2 Catheter
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.
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.
Goals for Ventilation
• Oxygenate• Protect the lung• Tolerate PaO2 55• Don’t sweat hypercarbia!• Stay recruited• Avoid plateaus > 30
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