ARDS

Dr
Muhammed Aslam

Objectives

Introduction
Definition
Etiology / Risk Factors
Pathology & Pathogenesis
Clinical presentation
Workup
Management of ALI/ARDS
Conclusion

Introduction
ARDS is a clinical devastating syndrome that affects
both medical and surgical patients.
Despite great advances in understanding the
pathogenesis of disease mortality rate is still high.
Even survivors of ARDS usually experience long ICU
stay, hospital stay and several co-morbidities.
Moreover survivors require prolonged rehabilitation time
till full recovery.

What is ARDS?

Asbaugh, Bigelow & Petty described ARDS as:

A syndrome of acute respiratory failure in adults
characterized by non-cardiogenic pulmonary
edema manifested by severe hypoxemia caused by right
to left shunting through collapsed or fluid-filled alveoli.

The Berlin Definition: An acute, diffuse,

inflammatory lung injury that leads to increased
pulmonary vascular permeability, increased lung weight,
and a loss of aerated tissue.
(The ARDS Definition Task Force. Acute Respiratory Distress Syndrome: The Berlin Definition.JAMA 2012; May 21,
2012:Epub ahead of print.)

Definition (older)
American-European Consensus Conference
An acute condition characterized by bilateral
pulmonary infiltrates and severe hypoxemia in
the absence of evidence for cardiogenic
pulmonary edema.
PaO2/FiO2* <300 = ALI
PaO2/FiO2 <200 = ARDS
Cardiogenic pulmonary edema must be
excluded either by clinical criteria or by a
pulmonary capillary wedge pressure (PCWP)
lower than 18 mm Hg

Limitations of Consensus Definitions

The chest radiograph is subject to
variability in interpretation
PaO2/FiO2 may vary according to
ventilator parameters, e.g., PEEP, and at
extremes of FiO2
Accuracy in excluding the presence of
heart failure may be influenced by
measurement methodology and timing

The Berlin Definition

JAMA. 2012;307:2526-2533

Acute lung injury no longer exists.

Under the Berlin definition, patients with PaO2/FiO2 200300 would now have mild ARDS.
Onset of ARDS (diagnosis) must be acute, as defined
as within 7 days of some defined event, which may be
sepsis, pneumonia, or simply a patients recognition of
worsening respiratory symptoms.

The Berlin Definition

continue.
Bilateral opacities consistent with pulmonary edema must be present
but may be detected on CT or chest X-ray. These opacities must not be
fully explained by pleural effusions, lobar collapse, lung collapse, or
pulmonary nodules.
There is no need to exclude heart failure in the new ARDS definition
The new criterion is that respiratory failure simply be not fully explained
by cardiac failure or fluid overload, in the physicians best estimation
using available information.
An objective assessment meaning an echocardiogram in most
cases should be performed if there is no clear risk factor present like
trauma or sepsis.

ARDS Severity
Mild
Moderate
Severe

PaO2/FiO2 ***
200 300
100 200
< 100

Mortality
27%
32%
45%

*** on ventilator with PEEP 5 cm H2O

Aetiology
Direct Precipitating Cause
Pneumonia
Aspiration
Pulmonary embolism
Pulmonary contusion
Inhalation injury
Reperfusion injury
Chest trauma with lung contusion
Near-drowning

Indirect (Systemic) Precipitating Cause

Sepsis
Blood transfusions with transfusion-related acute lung
injury (TRALI)
Trauma with multiple fractures and the fat-emboli
syndrome
Burns
Acute pancreatitis
Post-cardiopulmonary bypass
Toxic ingestions, e.g., aspirin, tricyclic antidepressants

 Over 60 possible causes have been identified but the

four most frequent causes include:

Sepsis (Most common cause )

Aspiration
Pneumonia
Severe Trauma

Factors Influencing Risk of ARDS

Chronic alcohol abuse,
Hypoproteinemia,
Advanced age,
Increased severity, and extent of injury or
illness as measured by injury severity
score (ISS) or APACHE score,
Hypertransfusion of blood products,
Cigarette smoking

Pathology and Pathophysiology

In normal, healthy lungs there is a small amount of fluid
that leaks into the interstitium. The lymphatic system
removes this fluid and returns it into the circulation
keeping the alveoli dry.

 ARDS is a consequence of an alveolar injury which

produces diffuse alveolar damage. The injury causes
the release of pro-inflammatory cytokines.
Cytokines recruit neutrophils to the lungs, where they
become activated and release toxic mediators (eg,
reactive oxygen species and proteases) that damage the
capillary endothelium and alveolar epithelium.

 Damage to the capillary endothelium and alveolar

epithelium allows protein to escape from the vascular
space.

 The oncotic gradient that favors resorption of fluid is lost

and fluid pours into the interstitium, overwhelming the
lymphatic system.

Breakdown of the alveolar epithelial barrier allows

the air spaces to fill with bloody, proteinaceous
edema fluid and debris from degenerating cells. In
addition, functional surfactant is lost, resulting in
alveolar collapse.

 Healthy lungs regulate the movement of fluid to maintain

a small amount of interstitial fluid and dry alveoli.
Lung injury interrupts this balance causing excess fluid in
both the interstitium and alveoli.

Results of the excess fluid include impaired gas exchange,

decreased compliance, and increased pulmonary arterial
pressure.

NORMAL ALVEOLUS

Type I cell
Alveolar
macrophage
Endothelial
Cell
RBCs

Type II
cell
Capillary

ACUTE PHASE OF ARDS

Type I cell
Alveolar
macrophage
Endothelial
Cell
RBCs

Type II
cell
Capillary
Neutrophils

 Three distinct stages (or phases) of the syndrome

including:
Exudative stage

Proliferative (or fibroproliferative) stage

Fibrotic stage

Exudative Stage (0-6 Days)

Characterized by:
Accumulation of excessive fluid in the lungs due to
exudation (leaking of fluids) and acute injury.
Hypoxemia is usually most severe during this phase of
acute injury, as is injury to the endothelium (lining
membrane) and epithelium (surface layer of cells).
Some individuals quickly recover from this first stage;
many others progress after about a week into the second
stage.

Proliferative Stage (7-10 Days)

Connective tissue and other structural elements in the
lungs proliferate in response to the initial injury, including
development of fibroblasts
The terms "stiff lung" and "shock lung" frequently used to
characterize this stage.
Abnormally enlarged air spaces and fibrotic tissue
(scarring) are increasingly apparent.

Fibrotic Stage ( >10-14 Days)

Inflammation resolves.
Oxygenation improves and extubation becomes
possible.
Lung function may continue to improve for as long as 6
to 12 months after onset of respiratory failure, depending
on the precipitating condition and severity of the initial
injury.
Varying levels of pulmonary fibrotic changes are
possible.

CLINICAL PRESENTATION
Development of acute dyspnea and hypoxemia within
hours to days of an inciting event
Tachypnea, tachycardia, and the need for a high fraction
of inspired oxygen (FIO2) to maintain oxygen saturation.
Febrile or hypothermic.
Sepsis-hypotension and peripheral vasoconstriction with
cold extremities
Bilateral rales
Manifestations of the underlying cause

 Because cardiogenic pulmonary

edema must be distinguished from
ARDS, carefully look for signs of
congestive heart failure or
intravascular volume overload,
including jugular venous distention,
cardiac murmurs and gallops,
hepatomegaly, and edema.

Approach to Clinical Diagnosis

Chest Radiograph -diffuse, bilateral alveolar infiltrates
consistent with pulmonary edema
Early in the course of the disorder, the infiltrates
associated with ARDS may be variable: mild or dense,
interstitial or alveolar, patchy or confluent
Initially, the infiltrates may have a patchy peripheral
distribution, but soon they progress to diffuse bilateral
involvement with ground glass changes or frank alveolar
infiltrates

Chest Radiograph
cardiogenic edema: increased heart size,
increased width of the vascular pedicle,
vascular redistribution toward upper lobes,
the presence of septal lines, or a perihilar
(bats wing) distribution of the edema
Lack of these findings, in conjunction with
patchy peripheral infiltrates that extend to
the lateral lung margins, suggests ARDS

Arterial blood gas analysis

PaO2/FiO2 Ratio
ARDS Severity
PaO2/FiO2
Mild
200 300
Moderate
100 200
Severe
< 100

ABG
In addition to hypoxemia, arterial blood gases often
initially show a respiratory alkalosis.
However, in ARDS occurring in the context of sepsis, a
metabolic acidosis with or without respiratory
compensation may be present.
As the condition progresses and the work of breathing
increases, the partial pressure of carbon dioxide (PCO2)
begins to rise and respiratory alkalosis gives way to
respiratory acidosis

To exclude cardiogenic pulmonary

edema
Echocardiogram -left ventricular ejection
fraction, wall motion, and valvular
abnormalities
plasma B-type natriuretic peptide (BNP)
value.

Hematologic
Septic patients -leukopenia or leukocytosis.
Thrombocytopenia (DIC).
Renal function Test - Acute tubular necrosis
Liver function Test - hepatocellular injury or cholestasis.
Von Willebrand factor (VWF) may be elevated in patients
at risk for ARDS and may be a marker of endothelial
injury
Cytokines - (IL)1, IL-6, and IL-8, are elevated

 Invasive HemodynamicMonitoring- pulmonary artery

wedge pressure (PCWP
Bronchoalveolar Lavage- to rule in or rule out acute
processes that may have specific therapies.(eg: acute
eosinophilic pneumonia, diffuse alveolar hemorrhage,

MANAGEMENT

Goals of Management of Patients with ARDS

Treatment of respiratory system abnormalities
Diagnose and treat the precipitating cause of ARDS
Maintain oxygenation
Prevent ventilator-induced lung injury (VILI) by using a
low tidal volume ventilatory strategy
Keep pH in normal range without compromising goal to
prevent VILI

 Enhance patient-ventilator synchrony and patient comfort

by use of sedation, amnesia, opioid analgesia, and
pharmacological paralysis, if necessary
Liberate or wean from mechanical ventilation when
patient can breathe without assisted ventilation
Treatment of non-respiratory system abnormalities
Support or treat other organ system dysfunction or failure
General critical care
Adequate early nutritional support
Prophylaxis against deep vein thrombosis (DVT) and
gastrointestinal (GI) bleeding

Maintaining Adequate Oxygenation

Positive end-expiratory pressure

(PEEP) is employed.
When utilized in sufficient
amounts PEEP allows FiO2 to be
lowered from high potentially toxic
concentrations
Whether maintenance of PEEP above a certain point improves
clinical outcome is unknown

Lung-Protective Mechanical Ventilation

Mechanical ventilation using limited tidal volumes
The goals of lung-protective ventilation are to avoid
injury due to overexpansion of alveoli during inspiration
(volu-trauma) and injury due to repetitive opening and
closing of alveoli during inspiration and expiration
(atelecta-trauma)

Tidal Volumes Over The Years..

1990s

2010s

Low Tidal Volume Ventilation (LTVV)

Initial Settings
Calculate Ideal Body Weight (IBW) in pounds
Males = 106 + [6 x (height in inches 60 in)]
Females = 105 + [5 x (height in inches 60 in)]
1 lb is equal to 0.45359237 kilogram.

 Set initial tidal volume to 8 ml/kg IBW

Reduce tidal volume to 7 ml/kg IBW
then 6 ml/kg IBW over the next 1-3
hours.
Set respiratory rate to < 35 bpm to
match baseline minute ventilation

Adjusting Settings
Adjustments to tidal volume are based on the Plateau
pressure reading.
Goal is to maintain Plateau pressure < 30cmH2O.
If Plateau pressure rises above 30 cmH2O, the tidal
volume setting is decreased by 1 ml/kg IBW increments
to a minimum of 4 ml/kg IBW.
Using LTVV when Plateau pressures are not high has
also shown benefit.

Adjuncts to Lung Protective Mechanical

Ventilation
Permissive Hypercapnia
Permissive hypercapnia is defined as clinician-allowed
hypercapnia during assisted ventilation, despite an ability
to achieve a level of minute ventilation sufficient to
maintain a normal

Adjuncts to Lung Protective Mechanical

Ventilation
Fluid Management
Distinction between primary ARDS due to aspiration,
pneumonia, or inhalational injury, which usually can be
treated with fluid restriction, from secondary ARDS due
to remote infection or inflammation that requires initial
fluid and potential vasoactive drug therapy is central in
directing initial treatments to stabilize the patient.

Hemodynamic Management

Adjuncts to Lung Protective Mechanical

Ventilation

Prone Positioning
About two-thirds of patients with ARDS improve
their oxygenation after being placed in a prone position.
Mechanisms that may explain the improvement include:
(1) increased functional residual capacity;
(2) change in regional diaphragmatic motion;
(3) perfusion redistribution;
(4) improved clearance of secretions.

Adjuncts to Lung Protective Mechanical

Ventilation

Inhaled NitricOxide
Inhaled prostacyclin
Tracheal Gas Insufflation
Extracorporeal Membrane Oxygenation (ECMO) or
ExtracorporealCO2 Removal (ECCO2R)

Adjuncts to Lung Protective Mechanical

Ventilation
Corticosteroids
The general consensus among intensivists is that
corticosteroids have little or no role to play in treating the
acute phase of ALI or ARDS.
However, the role of corticosteroids in later
phases of ALI or ARDS has been controversial.

Rescue or Salvage Interventions Used in ARDS and Resistant

to Conventional Mechanical Ventialation and PEEP

Corticosteroids
Extracorporeal CO2 removal (ECCO2R)
Extracorporeal membrane oxygenation (ECMO)
High frequency oscillatory ventilation (HFOV)
Inhaled nitric oxide (NO) or inhaled prostacyclin
(epoprostenol/iloprost)
Pressure controlled inverse ratio ventilation (PC-IRV)
Prone positioning
Recruitment maneuvers
Tracheal gas insufflation (TGI)

Conclusion
ARDS is a multisystem syndrome not a disease
Characterized by accumulation of excessive fluid in the
lungs with resulting hypoxemia and ultimately some
degree of fibrotic changes.
The most frequent causes of ARDS include sepsis,
aspiration, pneumonia and severe trauma
Treatment is primarily supportive and can non-traditional
types of ventilation and oxygenation strategies.
Many theoretical therapies

The best proven strategy to improve survival

is
low tidal volume ventilation

THANK YOU