2. WHAT IS ARDS?
It is a clinical syndrome of severe dyspnea of rapid
onset, hypoxemia, and diffuse pulmonary infiltrates
leading to respiratory failure.
A common condition with a complex pathophysiology
caused by many underlying medical and surgical
disorders.
3. Epidemiology
Incidence of ARDS varies widely
Annual incidence: 60/100,000
Approximately, 10% of ICU patients meet criteria for
ARDS
However, there is very little data regarding incidence of
ARDS in India.
Morbidity / Mortality
26-44%, most (80%) deaths attributed to non-pulmonary
4. Definition
ARDS syndrome with multiple risk factors that trigger
acute onset of respiratory insufficiency
Until recently, most accepted definition of ARDS for use
at bedside or to conduct clinical trials
American-European Consensus Conference (AECC)
definition published in 1994
5. AECC Definition
ARDS was defined as:
Acute onset of respiratory failure, bilateral infiltrates on
chest radiograph,
Hypoxemia (PaO2/FiO2 ratio ≤200 mmHg,) and
No evidence of left atrial hypertension or a pulmonary
capillary pressure <18 mmHg (if measured) to rule out
cardiogenic edema.
In addition, Acute Lung Injury (ALI), less severe form
of acute respiratory failure, different from ARDS
(hypoxemia, PaO2/FiO2 ≤300 mmHg)
6. AECC Definition Drawbacks
elatively low specificity
eliability of the chest radiographic criteria of ARDS
oderate with substantial interobserver variability
ypoxemia criterion (PaO2/FiO2 <200 mmHg) may
e affected by pts ventilator settings
Wedge pressure can be difficult to interpret and if a
atient with ARDS develops a high wedge pressure
7. Development of New Definition
European Society of Intensive Care
Medicine with endorsement from
American Thoracic Society and the
Society of Critical Care Medicine
Convened an international expert panel to
revise the ARDS definition panel met in
2011 in Berlin,
New definition was coined the Berlin
definition
9. ARDS Berlin definition :
Advantages
In Berlin definition there is no use of term Acute Lung
Injury (ALI) (committee felt term ALI was used
inappropriately in many contexts and hence was not
helpful )
ARDS was classified as mild, moderate and severe
according to the value of PaO2/FiO2 ratio
PaO2/FiO2 ratio value is considered only with a CPAP or
PEEP value of at least 5 cmH2O
Timing of acute onset of respiratory failure to make
diagnosis clearly defined in berlin definition
10.
11. GENETICS
More than 40 different genes associated with the
development or outcome of ARDS have been identified,
which include : ACE, SOD 3, MYLK, SFTPB, TNF, VEGF.
Amongst these, a gene with a strong association with
ARDS is ACE.
This association came to prominence during the SARS
pandemic, when the ACE2 Protein, which contributes to
regulation of pulmonary vascular permeability , was
identified as the receptor for the novel corona virus that
caused SARS.
12. Factors influencing risk of ARDS
INCREASED RISK OF ARDS WITH :
Chronic alcohol abuse
Cigarette smoking
Hypoproteinemia
Advanced age
Hypertransfusion of blood products
13. Interestingly , Diabetes Mellitus and pre
hospitalization antiplatelet therapy have been
found to decrease the risk of ARDS in
research studies.
Role of obesity as a risk factor has been
found to be doubtful.
19. Pathophysiology
3. ACM integrity is
lost, interstitial and
alveolus fills with
proteinaceous fluid,
surfactant can no
longer support
alveolus
.
20. Pathogenesis
Aspiration, trauma or sepsis can lead to insult or injury to
alveolar epithelium & capillary endothelium
Injury generally detected in both endothelium &
epithelium at time of diagnosis
Leads to leakage of plasma proteins through interstitial
compartment & into alveolar space
Many of these plasma proteins in turn activate procoagulant &
proinflammatory pathways that lead to fibrinous & purulent
exudates
21. Pathogenesis (Contd)
In response to direct lung injury or a systemic insult such
as endotoxin, in pulmonary or circulatory pro-
inflammatory cytokines occurs
Activated neutrophils secrete cytokines, such as tumor
necrosis factor-alpha and interleukins inflammatory
response
Neutrophils also produce oxygen radicals & proteases
that can injure capillary endothelium & alveolar
epithelium.
22. Pathogenesis (Contd)
Some patients achieve complete resolution of lung
injury before progressing into fibroproliferative stage,
whereas others progress directly to develop fibrosis
The extent of fibrosis may be determined by :
Severity of initial injury,
Ongoing orrepetitious lung injury,
Toxic oxygen effects, and
Vventilator-associated lung injury.
Piantadosi CA, Schwartz DA. The acute respiratory distress syndrome. Ann Intern Med 2004;141:460-
23. Pathogenesis (Contd)
Epithelial & endothelial damage, in turn leads to
permeability
Leads to subsequent influx of protein-rich fluid into
alveolar space
In addition to these structural changes, there is evidence
of impaired fibrinolysis in ARDS that leads to capillary
thrombosis and microinfarction.
24. Clinical Course and
Pathophysiology
The natural history of ARDS is marked by three phases –
EXUDATIVE
PROLIFERATIVE
FIBROTIC
Each phase have characteristic clinical and
pathological features.
25. Exudative phase ( 0-7 days )
In this phase, alveolar capillary endothelial cells and type 1
pneumocytes ( alveolar epithelial cells ) are injured, and tight
alveolar barrier is damaged giving away the entry to fluid and
macromolecules.
The protein rich fluid accumulates in the interstitial and
alveolar spaces.
Pro – inflammatory cytokines are increased in this acute
phase, leading to recruitment of leukocytes( especially
neutrophils) into pulmomary interstitium and alveoli .
26. There is plasma protein aggregation in air spaces with
cellular debris and dysfunctional pulmonary surfactant to
form hyaline membrane whorls .
Collapse of large sections of dependant lung can
contribute to decreased lung compliance.
35. Pathophysiology
Impaired Gas Exchange
V/Q mismatch
Related to filling of alveoli
Shunting causes hypoxemia
Increased dead space
Related to capillary dead space and V/Q mismatch
Impairs carbon dioxide elimination
Results in high minute ventilation
37. Basis of explanation of hypoxia
When large portions of the lung are non-ventilated due to
alveolar collapse or flooding, the blood flow to these units
is effectively shunted through the lungs without being
resaturated.
Thus, despite a high concentration of supplemental oxygen
and high alveolar Po2 in ventilated lung unit ( “ referred to
as a baby lung “) , these blood flows mix in accord with
their o2 contents, that is, the resultant left atrium receives
blood which has weighted mean oxygen content of both
shunted and non shunted blood.
38. Pathophysiology
Decreased Compliance
Hallmark of ARDS
Consequence of stiffness of poorly or non-aerated lung
Fluid filled lung becomes stiff/boggy
Requires increased pressure to deliver Vt
39. Pathophysiology
Pulmonary Arterial Pressure
Occurs in up to 25% of ARDS patients
Results from hypoxic vasoconstriction
Positive airway pressure causing vascular compression
Can result in right ventricular failure.
40. Role of RAS
In addition to classical views of ARDS including role of
cellular & humoral mediators :
Role of Renin-Angiotensin System (RAS) has been
highlighted
RAS thought to contribute to pathophysiology of ARDS
vascular permeability
Angiotensin-converting enzyme (ACE) key
enzyme of RAS that converts inactive angiotensin I
to vasoactive & aldosterone-stimulating peptide
angiotensin II
41. Role of RAS
ACE also metabolizes kinins along with many other
biologically active peptides
ACE found in varying levels on surface of lung
epithelial & endothelial cells
Angiotensin II induces :
Apoptosis of lung epithelial & endothelial cells and is a
potent fibrogenic factor
Based on these biological properties of ACE there
is considerable interest in its potential involvement in
ARDS
43. Physiology of ventilator induced
lung injury
Volutrauma : delivering too much pressure leads to
overdistention of alveoli . Because the compliance of the
ARDS lung is heterogenous, the same airway pressure
may cause underdistention of a more affected lung region
with low compliance and overdistention of a less affected
region.
Atlectrauma : allowing alveoli to collapse completely
during each breath cycle with too little airway pressure
44. Biotrauma :
The physical force and trauma of ventilation leads
to release of mediators that sustain inflammation
and translocation of proinflammatory products and
bacteria through already permeable barriers,
causing systemic damage.
47. Physiological effects of Prone
Ventilation
Improves gas exchange by :
1. Ameliorating the ventral dorsal transpulmonary pressure
difference
2. Reducing dorsal compression
3. Improving lung perfusion
48. Ventral- Dorsal transpulmonary
pressure ( Ptp)
The distending pressure across the lung is estimated by
transpulmonary pressure.
Defined as airway pressure(Paw ) and pleural pressure
(Ppl)difference. [ Ptp= Paw – Ppl]
In a supine patient, the dorsal pleural pressure is greater
than ventral pleural pressure. Hence, Ventral Ptp is greater
than dorsal Ptp and there is greater expansion of ventral
alveoli than the dorsal alveoli ( leading to their collapse).
This difference is favourable reduced by prone positioning.
49. Reduction of dorsal compression
by prone ventilation
In prone position, the heart becomes dependant lying on
the sternum, potentially decreasing posterior and medial
lung compression.
In addition, the diaphragm is displaced caudally ,
decreasing the compression of posterior caudal lung
parenchyma.
These effects improve ventilation and oxygenation.
50. Imroved lung perfusion in prone
positioning
Improved v/q mismatch as the previously dependant
alveoli begin to reopen in prone position.
52. CLINICAL PRESENTATION
The development of ARDS usually follows a rapid course
, occuring most often between 12 to 72 hours of the
predisposing event.
At its onset, patient usually becomes anxious, agitated,
and dyspneic .
Inflammatory changes in lung decrease lung compliance,
which in turn leads to increased work of breathing, small
tidal volumes, and tachypnea.
53. CLINICAL PRESENTATION
The hallmark of ARDS is hypoxemia resistant to oxygen
therapy because of the large right to left shunt .
Initially, patients may be able to compensate by
hyperventilating , thereby maintaining an acceptable
PaO2 with an acute respiratory alkalosis.
Typically, patients deteriorate over several hours,
requiring endotracheal intubation and mechanical
ventilation.
58. Diagnosis
A/c Berlin definition
Within 1 week of a known clinical insult or new or
worsening respiratory symptoms
Bilateral opacities — not fully explained by effusions,
lobar/lung collapse, or nodules on Chest X ray
Edema d/t Respiratory failure not fully explained by
cardiac failure or fluid overload
59. Diagnostic evaluation
No lab findings are specific for ARDS other than the
diagnostic criteria.
Blood Gas Analysis :
o In early phase : hypoxemia and respiratory alkalosis
due to shunt or low ventilation – perfusion ratio.
o In the late phase : increased dead space ventilation and
work of breathing , reduced CO2 elimination : Respiratory
Acidosis
60. Diagnostic evaluation( contd)
Hematological abnormalities : such as anemia ,
leucocytosis/ leucopenia, thrombocytopenia due to
systemic inflammation and endothelial injury.
Acute phase reactants : increased ceruloplasmin,
decreased albumin.
Pro inflammatory cytokines : Increased TNF alpha and IL-
1 ,6,8
Imaging : in form of chest xray and CT scan.
61. Diagnostic evaluation( contd)
BAL : Testing is helpful in ruling out the differentials of
ARDS. Eg:
o High eosinophils(> 15-20%) : possibilities of
eosinophilic pneumonia.
o High erythrocytes and hemosiderin laden macrophages
: diffuse alveolar hemorrhage( seen in Goodpasture
syndrome, granulomatosis with polyangitis, SLE, APLA)
o High lymphocytes : hypersensitivity pneumonitis,
sarcoidosis , cryptogenic organizing pneumonia.
62. Lung biopsy :
o Routine lung biopsy is not recommended in patients with
ARDS.
o Should be reserved for highly selective group of patients
where alternative diagnosis are possible and would
significantly change management and prognosis.
64. PREDICTING ARDS
LUNG INJURY PREDICTION SCORE( LIPS)
Generated in a multicentre cohort, LIPS is aimed at
identifying those at highest risk of developing ARDS.
It includes 2 broad categories for scoring :
Pre disposing conditions: 9 included
Risk modifiers : 6 included.
65. References
Harrisons principles of internal medicine , 20th edition
Fishman’s textbook of pulmonary medicine , 6th edition
Robbins and cotran textbook of pathology , 19th edition
Uptodate
