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
Vasoconstriction

Capillary
Damage

Leakage
Oedema
Fluid

Dead Space

Hypoxia

Inflammatory
Cellular
Infiltrates

Thoracic
Compliance

Atelectasis

V/Q
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 Volume

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

Percent Flow

50

25

D
0

Dorsal

Mid

Supine

ND

Ventral Ventral

Mid

Prone

ND

Dorsal

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 protocol 4
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: 155365
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 FluidManagement 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