Acute Lung Injury

and
ARDS

Andreas Crede
Emergency Medicine Registrar
 Overview
• Introduction
• Definition
• Pathophysiology
• Treatment
• New Stuff
• References
 Introduction
• 1st described 1967 (Ashbaugh et al)
• Incidence 1.5 -7.5/ 100000 population
• 28 day mortality 25 – 30%1
• Diagnosis clinical
 Definition
• Acute onset (<7days) respiratory failure/distress
• Diffuse, bilateral infiltrates on CXR
• Absent left atrial hypertension (PAOP
≤18mmHg)
• Or absent clinical evidence of left atrial
hypertension
• PaO2/ FiO2 <300mmHg (ALI)
• PaO2/ FiO2 <200mmHg (ARDS)2
 Risk Factors
• Alcoholism
• Genetic predisposition
 Causes
• Direct Injury1
• Pneumonia
• Aspiration
• Drowning
• Amniotic fluid and fat embolism
• Alveolar haemorrhage
• Smoke, toxic gas inhalation
• Reperfusion (incl rapid drainage pleural effusion)
• Unilateral lung re-implantation
 Causes
• Indirect Injury1
• Severe Sepsis
• Massive transfusion
• Shock
• Pancreatitis
• Salicylate/ narcotic overdose
• Anaphylaxis
• Cardiopulmonary bypass
 Differential
• LVF
• Fluid overload
• Mitral stenosis
• Lymphangitis carcinomatosis
• Interstitial lung disease1
 Physical/ chemical injury
Activation Innate
Inflammatory Cascade

Leakage Protein Rich Oedema Fluid

Inflammatory Cellular
Infiltrates

Diffusion Abnormalities
V/Q Mismatch

Hypoxia

Respiratory Failure
 Physical/ chemical injury
Activation Innate
Inflammatory Cascade

Cellular Infiltrate
Atelectasis
Oedema Fluid

Reduced Thoracic Compliance +

Vasoconstriction

Hypoxia

Respiratory Failure
Physical/ chemical injury
Activation Innate
Inflammatory Cascade

Small Vessel Thrombosis

Increased Dead Space

Hypoxia

Respiratory Failure
 Alveolar
Damage
Hypoxic Capillary
Vasoconstriction Damage

Leakage
↑Dead Space Oedema
Fluid
Hypoxia

Inflammatory
↓Thoracic
Cellular
Compliance
Infiltrates

V/Q
Atelectasis
Mismatch
 Respiratory Failure
Atelectasis/
Reduced Lung Compliance

↑ Dead Space Hypoxaemia

 Histologically
• Exudative Phase3
• Neutrophilic Infiltrate
• Alveolar Haemorrhage
• Proteinaceous Pulmonary Oedema
• Cytokines (TNF, IL1,8)
» ↑ Inflammation
» ↑ Oxidative Stress and Protease Activity
» ↓ Surfactant Activity
» Atelectasis
 Histologically
• Elastase- induced capillary and alveolar
damage3
• ↑ Alveolar flooding
• ↓ Fluid clearance
• Capillary thrombosis
• ↓ Anticoagulant proteins
• ↑ Procoagulant proteins (Tissue Factor)
• ↑ Anti- fibrinolytic Protein (Plasminogen Activator
Inhibitor)
 Post Acute Phase
• Fibroproliferative Phase3
– Variable time period
– Fibrosis
– Chronic Inflammation
– Neovascularisation

• Resolution3
– Improvement of hypoxaemia
– Improved dead space and lung compliance
– Resolution radiographic abnormalities
– Can take up to 1 year
– Residual restrictive or obstructive picture
 Long Term
• Chronic Respiratory Disease
• Muscle Fatigue
• Muscle Wasting
• Weakness
 Treatment
• Ventilation
• Fluid Management
• Steroids
• Other Stuff
 Ventilation
• Tidal Volumes
• PEEP
• Positioning
• Weaning Protocols
 Tidal Volume
• Recommended 4-6ml/kg4
• High tidal volumes4
• Overdistention of alveoli
• Local inflammatory response resulting in systemic
inflammation
• TNF, IL6, IL10,
 Tidal Volume4
• Low tidal volume ventilation
• Weight
• Predicted not actual
• Plateau Pressure
• ≤30cm H2O
• Resp Rate
• Titrated to pH 7.3-7.45
• PEEP and FiO2
• Adjusted to maintain saturation
• Low tidal volume may result in hypercarbia
• ARMA (Respiratory Management in ALI/ARDS Trial)
• NaHCO3 infusions/ hyperventilation to maintain pH
 Tidal Volumes
• Same sedation strategies
• No ↑ duration of ventilation
• High frequency oscillatory ventilation
shown no benefit over low tidal volume
ventilation
• 30 day mortality not statistically significant (37%
vs 52%, p=0.10)
• Earlier recovery from hypoxia
• Only ventilation strategy shown to
reduce mortality (40% - 31%)4
 PEEP
• Recommendation: lowest PEEP/ FiO2 to
maintain saturation
• Recruits collapsed alveoli
• In dependant regions
• Over-distends in non-dependant regions
• ↓ Repetitive opening/ closing of alveoli: ↓ airway
damage
• Endothelial/ epithelial stretch injury with
subsequent capillary injury
• Similar cytokine response as ↑tidal volume
PEEP
 PEEP
• ALVEOLI Trial4
• Higher PEEP = improved oxygenation
• In hospital mortality equal btw high and low PEEP
• Time on ventilator similar
• Duration non- pulmonary organ failure equal
 PEEP
Adverse effects of PEEP
•  Cardiac output
• Volutrauma
•  Lung water
•  High VA/Q
•  Dead space
•  Endothelial permeability
•  Epithelial permeability
•  Bronchial blood flow
Fessler, ARRD 1993
PEEP + Lung Perfusion

Permutt, JAP 1961

 PEEP
• Some Endpoints
• Best PaO2
• Lowest Shunt
• Best O2 delivery
• Best lung perfusion
• Plateau Pressure ≤30cm H2O
• Optimise aeration on CT
• Pressure/ volume curve becomes concave
 Positioning
• Prone positioning1,4
• Redistribution of blood & ventilation to least
affected areas of lung
• Secretion clearance
• Shifts mediastinum anteriorly – assists recruitment
of atelectatic areas
• ? reduce lung injury
• Reduced lung compression by abdominal contents
 Supine Ventilation

• ± 40% lung volume under lung, especially

patients with large hearts
Prone Ventilation
 Effect of Blood Flow in Prone
Positioning7
50
Percent Flow

25

D Mid ND D Mi ND
0 d
Dorsal Ventral Ventral Dorsal
Supine Prone
 Positioning
• Prone position4
• Transient improvement PaO2/FiO2
• No improvement: survival/ time on ventilator/ time
in ICU
• Role:
» High FiO2
» High plateau pressures
 Weaning Protocols
• Reduce duration of mechanical ventilation
vs patients managed by IMV protocol4
• Daily spontaneous breathing trial4
• 30-120 mins unassisted ventilation
• 4 Criteria before commencement
– Some reversal of underlying cause
– PEEP ≤8cm H2O/ FiO2 ≤50%
– Haemodynamic stability
– Ability to initiate inspiratory effort
Fluid Management
 Fluid Management
• Fluid movement regulated by:
• Starling equation
• Vessel wall
– Ability to filter fluid
– Selective permeability to proteins
Fluid Management
 Fluid Management
• Study of conservative vs liberal fluid
management5
• 60 day mortality: 25.5 vs 28.4% p=0.30
• 1st 28 days ventilator free: 14.6 vs 12.1 p<0.001
• 1st 28 days ICU free: 13.4 vs 11.2 p<0.001
• Difference in organ failure and need for dialysis not
statistically significant
• No specific mention of CVP/ PAOP levels which to
aim for
• Conservative = 4mmHg Liberal = 10-14mmHg
CVP
 Steroids
• Theoretical use to ↓inflammatory response
associated with ARDS6
• 2006 study6
• No ↓60 day mortality (28.6% vs 29.2% p= 0.10)
• Use of steroids 14+ days post onset: ↑ mortality
• ↓ need for vasopressors
• ↑ ventilator and shock free days
• ↑ neuromuscular weakness
• Short term improvement in oxygenation
 Other stuff
• Extracorporeal membrane oxygenation
• Improvement in oygenation
• No ↑ long term survival
• Vasodilators
• Improved oygenation
• No ↑ long term survival
• Ketoconazole
• Pentoxyfilline
• Nutritional modification
• Antioxidants
• Surfactant
• B2 stimulants1
 Emergency Department
Summary
• PREVENT!
• Low tidal volume ventilation
• Restrict PEEP
• Restrict Fluids (if possible)
• Initiate Weaning Protocol
• Supine Ventilation
 Conclusion
• Many theoretical therapies
• Only proven strategy to improve survival is
low tidal volume ventilation
• Therapies to reduce number of days
needing scarce resources valuable in our
setting
Thank You
 References
• 1. Wheeler, A.P. and Bernard, G.R. 2007,Acute Lung Injury and the Acute
Respiratory Distress Syndrome: A Clinical Review. Lancet; 369: 1553–65
• 2. The Acute Respiratory Distress Syndrome Network. 2000, Ventilation
With Lower Tidal Volumes as Compared with Traditional Tidal Volumes for
Acute Lung Injury and the Acute Respiratory Distress Syndrome. N Engl J
Med; 342:1301-08
• 3 Plantadosi, C.A and Schwartz, D.A. 2004, The Acute Respiratory Distress
Syndrome. Ann Intern Med; 141:460-470.
• 4. Girard, T>D> and Bernard,G.R. 2007, Mechanical Ventilation in ARDS: A
State-of-the-Art Review. Chest; 131;921-929
• 5. The National Heart, Lung and Blood Institue Acute Respiratory Distress
Syndrome Clinical Trials Network. 2006, Comparison of Two Fluid-
Management Strategies in Acute Lung Injury. N Engl J Med; 354:2564-75
• 6. The National Heart, Lung and Blood Institue Acute Respiratory Distress
Syndrome Clinical Trials Network. 2006, Efficacy and Safety of
Corticosteroids for Persistent Acute Respiratory Distress Syndrome. N Engl
J Med; 354:1671-84
• 7. www.slideshare.net