1.
PATHOGENESIS AND
MANAGEMENT OF ARDS
PRESENTER: DR. MIDHUN MOHAN K
CHAIR: DR.JAYAPRAKASH B

2.
BERLIN DEFINITION:
Syndrome characterised by
Onset within 1 wk of clinical insult
B/L radio graphic opacities not explained by
pleural effusions, atelectasis or nodules
Respiratory failure not explained by cardiac
failure or overload
Poor systemic oxygenation PaO2/FiO2≤300
mmHG on PEEP ≥5 cm H2O

3.
3 categories of ARDS:
Mild ARDS 200< PaO2/FiO2> 300
mmHg
Moderate ARDS 100<
PaO2/FiO2>200 mmHg
Severe ARDS PaO2/FiO2 ≤ 100
mmHg

4.
• ARDS results primarily from an
increase in lung vascular permeability.
• Accumulation of fluid and protein
increases when the lung endothelial
and epithelial barriers are injured.
• Increased permeability pulmonary edema.

5.
ETIOLOGY
PULMONAR
Y
PNEUMONIA
ASPIRTION
SMOKE INHALATION
O2 TOXICITY
EMBOLI
CONTUSION
RADIATION
GOOD PAUSTER
NEAR DROWING
DRUGS
EXTRA PULMONARY
SEPSIS
BURNS
PANCREATITIS
TRAUMA
SHOCK
TRANSFUSIONS
DIC
NEUROGENIC
PREGNANCY RELATED
CARDIO PULMONARY -
BYPASS
ANAPHYLAXIS

6.
MECHANISM OF LUNG
INJURY
• Lung injury is caused by an imbalance of pro-
inflammatory and anti- inflammatory
mediators.
• Nuclear factor kB (NF-kBfactor) , a
transcription factor, whose activation shifts the
balance in favor of a pro inflammatory state.

7.
• As early as 30 minutes after an acute insult,
there is increased synthesis of IL-8, a potent
neutrophil chemotactic and activating agent, by
pulmonary macrophage.
• IL1 and TNF lead to endothelial activation and
pulmonary micro vascular sequestration and
activation of neutrophil.
• Activated neutrophils release- oxidants,
protease, PAF &Leukotriene . This leads to
tissue damage, accumulation of edema fluid,
surfactant inactivation, hyaline membrane
formation.

8.
• The destructive forces unleashed by the
neutrophils can be counteracted by endogenous
anti-protease, antioxidants and anti
inflammatory cytokines (IL-10).
• Coagulating pathway itself is a powerful pro
inflammatory signal. (Thrombin promotes
adhesion of neutrophils to endothelium).
• It is the balance between the destructive and
protective factors that determines the degree of
tissue injury and clinical severity of ARDS.

9.
RESOLUTION
• Macrophage removes the exudate and tissue
debris.
• Type 2 pneumocytes give rise to type 1 cells.
• Endothelial restoration occurs both by migration
from uninjured capillaries and marrow derived
progenitor cells.
• Macrophage release fibrogenic cytokines (TGF-
β, PDGF) which stimulates the fibroblast
growth and collagen deposition.

10.
EARLY AND LATE PHASE OF LUNG
INJURY
EARLY (EXUDATIVE PHASE)
• First few hours or days.
• Interstitial and alveolar edema,
• Capillary congestion,
• Intra-alveolar hemorrhage.
• Protein-rich pulmonary edema.
• Hyaline membranes containing condensed fibrin and
plasma proteins form over the next several days.
• Later,in the exudative phase, inflammatory cells become
more numerous within the lung interstitium.
• Extensive necrosis of type I alveolar epithelial cells
“Diffuse alveolar damage (DAD)”.

11.
• Alveolar edema and alveolar collapse, that is,
atelectasis due to loss of normal surfactant-
related stabilization of alveoli, interfere with
oxygenation.
• Surfactant is washed out of alveoli and
inactivated by the alveolar edema.

12.
LATE(PROLIFERATIVE PHASE)
• 7 to 10 days after initial injury.
• Type II alveolar cells, fibroblasts and
myofibroblasts proliferate.
• Increased dead-space fraction,
• High minute ventilation requirement,
• Pulmonary hypertension
• Further reduction in lung compliance.

13.
CLINICAL FEATURES
• Rapid course, occurring within 12 to 72 hours
of the predisposing event.
• Patient will be anxious, agitated, and dyspneic

14.
• Inflammatory changes→ decrease lung
compliance, ↑ WOB, tachypnea, ↓TV
• ABG → PaO2 ≤ 50 to 55 mm Hg & SPO2 <
85%

15.
• The hallmark of ARDS is hypoxemia that is
resistant to oxygen therapy
• Large right-to-left shunt.
• Initially compensate by hyperventilating
• Maintain an acceptable PaO2 with an acute
respiratory alkalosis.
• Deteriorate over several hours, requiring
endotracheal intubation and mechanical
ventilation.

16.
When large portions of the lung are
nonventilated due to alveo-
lar collapse or flooding (hatched area),
blood flow to these units with mixed
venous P O 2 (Pv O 2 ) of 40 mm Hg and
content of 15 vol. percent is effectively
“shunted” through the lungs without being
resaturated.
Thus, despite a high concentration of
supplemental oxygen (100% in this
example) and high alveolar P O 2 in
ventilated unit, these blood flows mix in
accord with their oxygen contents, that is,
the resulting left atrial blood has an oxygen
content that is the weighted mean of the
oxygen content of the shunted and
nonshunted blood. In this example of a
50% shunt, the left atrial and systemic
arteries have an arterial P O 2 of 60 mm Hg.
Ca O 2 , arterial oxygen content; C CO 2
capillaryoxygen content; Cv O 2 , mixed
venous oxygen content; P a , alveolar
pressure; Pa O 2 , arterial P O 2 ; Pv O 2 ,
partial pressure of oxygen in the mixed
venous blood.

17.
CHEST X RAY
• Diffuse, bilateral alveolar infiltrates.
• LACK OF:
1. increased heart size,
2.increased width of the vascular pedicle
3.vascular redistribution toward upper lobes
4.presence of septal lines,
5. perihilar (bat’s wing) distribution of the edema
Along with patchy peripheral infiltrates that
extend to the lateral lung margins, suggests ARDS.

18.
CT CHEST
• Ground-glass opacification
frequent pattern , although a
nonspecific sign
• A reticular pattern at follow-up is
the most common CT pattern in
ARDS survivors.

19.
LABORATORY STUDIES
1. ABG- To confirm the diagnosis.
Hallmark of ARDS – hypoxemia not
responding to O2 therapy.
EARLY STAGE: Respiratory alkalosis.
If respiratory muscle fatigue, then hypercapnea.
LATE STAGE: increased in minute ventilation
due to increased dead space fraction.

20.
2. CPK and TROP I
3.NT PRO –BNP
4.ECG and ECHO
5.Invasive Hemodynamic monitoring. (PA
catheterisation)
6. Bronchoalveolar lavage (BAL):
a) For the evaluation of patients
who have ARDS of unclear origin.
b) To rule in or rule out acute
processes that may have specific therapies.
C/I of BAL: a)Those with a very low Pa O 2
b)Those requiring high levels of PEEP.

21.
7. LUNG BIOPSY: For a highly selective group
of patients where alternative diagnoses are
possible and would significantly change
management and prognosis.

22.
Goals of Management of Patients
with ARDS
Treatment of respiratory system abnormalities
• Diagnose and treat the precipitating cause of
ARDS.
• Maintain oxygenation, preferably using non toxic
FiO2 (<0.7),PEEP, or mechanical ventilation.
• Prevent ventilator-induced lung injury (VILI) by
using a low tidal volume ventilatory strategy with
a limit (≤30 cm H2O) on plateau pressure

23.
• 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 pharmacologic paralysis.
• Wean from mechanical ventilation when
patient can breathe without assisted ventilation.

24.
Treatment of nonrespiratory system
abnormalities
• Support or treat other organ system
dysfunction or failure
• General critical care (preventive and
homeostatic measures)
• Adequate early nutritional support

25.
 Face mask usually ineffective
 PEEP :CPAP/BiPAP/Mechanical ventilation
The effect of PEEP-induced improvement in arterial
oxygenation is attributed predominantly to
recruitment of collapsed alveoli.
• Application of PEEP may also mediate a
redistribution of alveolar fluid into the
interstitium and decrease the absolute magnitude
of shunt by reducing cardiac output.
• Also allow to lower FiO2 from high, potentially
MAINTAINING ADEQUATE
OXYGENATION

26.
LUNG PROTECTIVE
VENTILATION
GOAL :
To avoid volume truama and atelect truama.

27.
ARMA TRIAL
• Randomized trial
• Mid-to-late 1990s
• Hypothesis -low tidal volume ventilation, combined with
limited end-inspiratory (plateau) pressure, would lower
mortality and ventilator days among survivors of ARDS
compared with use of traditional tidal volumes.
• The trial included 861 subjects.
• The low tidal volume arm consisted of a tidal volume of 6
mL/kg predicted body weight, as long as the end-
inspiratory pressure (Pplat) was ≤30 cm H2O.
• The traditional tidal volume arm used a tidal volume of 12
mL/kg predicted body weight, as long as the Pplat
remained <50 cm H2O.

28.
ARMA TRIAL:
• Low tidal volume + low plateau
pressure ventilation will decreases
the mortality.
• P plat ≤30 cm of H2O is safe.

29.
ROLE OF HIGHER PEEP
• ALVEOLI; LOVS & EXRESS
TRIAL showed no mortality benefits
with high PEEP
• Meta analysis combining the data
from above three trial showed
mortality benefit in those with
PaO2/FiO2<200

30.
Lung protective ventilation
low tidal volume
High PEEP minimum of 5cm H2O
Plateau pressure <30cm h2o
Oxygenation goal
PaO2 55-80mmhg
Spo2 88-95%
P plateau goal
<30cm H2o
PH goal. 7.30-7.45
VENTILATION TARGETS

31.
SETTINGS
Calculate Predicted Body
Weight(PBW)
Males: PBW (kg) =
• 50 + 2.3[(height in inches) − 60]
Females: PBW (kg) =
• 45.5 + 2.3[(height in inches) − 60]

32.
VENTILATOR MODE:
• Low TV VCV is preferred.
• PCV is also preferred as it can limit Pplat and
Ppeak.
• Inverse ratio ventilation – giving more time for
inspiration, can improve oxygenation (salvage
mode ventilation)
• BIPAP and APRV modes that allows spontaneous
breathing during positive pressure ventilation

33.
• High frequency oscillatory ventilator -
Supported by rapid pressure oscillations that
generate small tidal volumes also called ultimate
low tidal volume ventilator.
Commonly used in RD in newborn.

34.
ADJUVANTS TO PROTECTIVE
MECHANICAL VENTILATION
• PERMISSIVE HYPERCAPNOEA – recommented as core
ventilator strategy.
C/I of permissive hypercapnoea:
1.Increased ICP
2. A/C stroke
3. A/C or C/C MI
4.Severe PAH
5. RVF
6. Uncontrolled metabolic acidosis
7. Sickle cell Anemia
8 TCA overdose
9 Pregnancy

35.
• FLUID AND
HEMODYNAMIC Mx
ARDSNet FACTT Trial
• Results of the study support the use
of a conservative fluid strategy in
managing patients with ARDS who
are not in shock.
• Based on the results, the FACTT
investigators also recommend using a
CVC to guide hemodynamic and
fluid management.

36.
PRONE POSITIONING
• Improve the O2 by ;
Increase FRC
Change in diaphragmatic motion
Perfusion redistribution
Increase clearance of secretion.

37.
DISADVANTAGES
• Accidental extubation
• Pressure sores
• Increase requirement forsedation
• Retinal ischemia in hypotensive
patients
• Cardiac arrythmia/hemodynamic
instability

38.
• Unresponsive cerebral hypertension
• Unstable bone fractures
• Left heart failure
• Hemodynamic instability
• Active intra abdominal pathology
CONTRA
INDICATIONS

39.
• RECRUITMENT MANEUVER
Application of CPAP to recruit or
open partially or totally collapsed alveoli using
high level of PEEP
CPAP at 35-40 cm of H2O for 30 sec.

40.
• INHALED NITRIC OXIDE
Vasodilation of pulmonary capillaries or
arterioles.
Divert blood flow to alveoli and away from
shunt (by lowering pul.artery pressure and pul.
Vas. resist).

41.
• Improves oxygenation
• Rapidly inactivated by hemoglobin
• Requires continuous delivery
• No improvement in mortality
• costly
• Only used as a salvage therapy

42.
INHALED
PROSTACYCLIN
• Epoprostenol/Iloprost
• Less cost
• Improve oxygenation to the same
degree

43.
TRACHEAL GAS INSUFFLATION (TGI)
• Delivering fresh gas through modified
endotracheal tube at point just above carina.
• Removes CO2 from trachea and small airways.
• Reduce anatomical dead space.
As a salvage intervention for patients
with high levels of PaCO2 (e.g., >100
mm Hg)

44.
• EXTRACORPORAL LIFE SUPPORT
External artificial membrane and a
mechanical pump to provide gas exchange and
systemic perfusion.

45.
• CORTICOSTEROIDS
Little role in treatment of ARDS
High dose benificial during proliferative
phase of ARDS, it prevents lungs scarring

46.
NEUROMUSCULAR BLOCKING AGENTS
• To improve ventilator synchrony and improve
oxygenation.
• Associated with prolonged
neuromuscular weakness in survivors
of ARDS.
• May be useful for short term use in
severe ARDS

47.
• OTHER THERAPIES
Statin
Beta agonist
Macrolides

48.
CLINICAL COURSE AND
DURATION
• The median duration of mechanical
ventilation is approximately 5 days, 7 days,
and 9 days for mild, moderate, and severe
ARDS, respectively.
• Most ARDS-related deaths occur within the
first 2 weeks, with one-third occurring by
day 7, two-thirds by day 14, and three-
fourths to four-fifths by day 28.
• The mortality rate of patients on

49.
CAUSES OF DEATH
• Underlying disease or injury
• Most common cause is SEPSIS
associated with multiple organ
system failure
• Only a relatively small fraction of
patients – 10% to 20% of all
patients with ARDS – die a
respiratory death due to irreversible

50.
PULMONARY SEQUELAE
• In the Toronto ARDS Outcomes study,
spirometry and lung volumes improved rapidly
among survivors, reaching normal in most
subjects by 6 months
• Diffusion capacity is mildly impaired in many
patients after ARDS, but it may return to
normal by 2 to 5 years among survivors.

51.
PHYSICALAND
NEUROMUSCULAR
SEQUELAE
• Low exercise capacity, weakness, and
decreased physical quality of life as far as
5 years after their acute illness.
• Risk factors for these findings
–multiorgan dysfunction in the ICU
– prolonged duration of ARDS
– treatment with corticosteroids during
the ICU stay

52.
• Critical illness polyneuropathy,
• ICU-acquired myopathy (critical
illness myopathy)
• Entrapment neuropathy
• Heterotopic ossification

53.
COGNITIVE AND
PSYCHOLOGICAL
SEQUELAE
• Impaired memory, reduced attention, and
concentration and processing speed
• Depression and Anxiety
• PTSD

54.
DIFFERENTIAL DIAGNOSIS
• Pulmonary edema due to left heart failure
• DAH
• Acute eosinophilic pneumonia
• Lupus pneumonitis
• AIP
• Pulmonary alveolar proteinosis
• BOOP/COP
• Hypersensitivity pneumonitis
• Leukemic infiltration
• Drug induced pulmonary edema and pneumonitis
• Acute major pulmonary embolus
• Sarcoidosis
• Interstitial pulmonary fibrosis

55.
To conclude
• ARDS is a manifestation of an
underlying pathology with 50%
mortality
• Early recognition and proper
ventilatory management is the
only solution now

56.
THANK YOU