ARDS

BY S F HASHMI
GUIDED BY DR D G MHAISEKAR SIR
22TH FEB 2011
Discovery of the disease
1954 model of the
Engstrom anesthesia / ventilator
had lead to discovery of the disease.

FIRST DESCRIBED
IN 1967 BY Ashbaugh et al

Synonyms:
1. Non-Cardiogenic pulmonary edema
2. Adult hyaline membrane disease
3. Capillary leak syndrome
4. Stiff lung syndrome
5. Shock lung
 DEFINITION
 The 1994North American - European
Consensus Conference (NAECC) criteria:
• Onset - Acute and persistent

• Radiographic criteria - Bilateral pulmonary

Infiltrates consistent with the presence of edema.

• Oxygenation criteria - Impaired oxygenation regardless

of the PEEP concentration, with a Pao2/Fio2 ratio ≤ 300
for ALI and ≤ 200 for ARDS.

• Exclusion criteria - Clinical evidence of left atrial

hypertension or a pulmonary-artery catheter occlusion
Pressure of ≥ 18 mm Hg.
 INCIDENCE & MORTALITY from ARDS
 Incidence : 80 per 100,000
 ARDS mortality rates - 31% to 74%

 The main causes of death are nonrespiratory

causes (i.e., die with, rather than of, ARDS).

 The cause of death in Respiratory failure

9% to 16% of patients with ARDS.

 Early deaths (within 72 hours) are caused by the

underlying illness or injury, whereas late deaths
are caused by sepsis or multiorgan dysfunction.
 CRITERIA FOR ALI & ARDS
PARAMETER
ALI ARDS
ONSET ACUTE ACUTE
HYPOXEMIA Pao2/ Fio2 < 300 Pao2/ Fio2 < 200
mm Hg mm Hg
CHEST XRAY B/L DIFFUSE B/L DIFFUSE
INFILTRATES INFILTRATES
NONCARDIAC PULMONARY ARTERY PULMONARY ARTERY WEDGE
CAUSE WEDGE PRESSURE < 18 mm PRESSURE < 18 mm of Hg.
of Hg. NO CLINICAL EVIDENCE OF
NO CLINICAL EVIDENCE OF LEFT ATRIAL HYPERTENSION
LEFT ATRIAL
HYPERTENSION
Cardiogenic vs. Non-Cardiogenic Edema

Non-Cardiogenic
Cardiogenic
 Protein,
Excess fluid
inflammatory
in alveoli cells, and fluid
 accumulation in the alveoli
Due to high pulmonary capillary pressure
 Due
(estimated
to highbypermeability
measuring pulmonary
oedema & artery
wedge pressure)
“other” systemic factors NOT elevated
pulmonary capillary pressure
Cardiogenic vs. Non-Cardiogenic Edema

Non-Cardiogenic
Cardiogenic
 Patchy
Infiltrates
infiltrates
are more appearing
homogeneous
in the lung bases first
 No
Effusions
pleuralmay
effusions
be present
 Clinical
No Kerleysigns
B’s and symptoms lag behind radiographic
 evidence (i.e. CXR
Radiographic is more
evidence impressive
lags than the
behind clinical degree
signs and of
hypoxemia)
symptoms (i.e. the CXR is unimpressive given the
degree of hypoxemia)
 Cardiogenic Non-Cardiogenic

Bilateral infiltrates predominately in Diffuse Bilateral patchy infiltrates

lung bases. Kerley B’s. homogenously distributed throughout the
Cardiomegaly. lungs. No Kerley B’s.
 Understanding ARDS…….
2 Types
 Pulmonary ARDS  Extrapulmonary
(Direct) ARDS (In-direct)
 CAUSES of ALI/ARDS
Direct insult Indirect insult
Common Common
Aspiration pneumonia Sepsis
Pneumonia Severe trauma
Shock
Less common Less common
Inhalation injury Acute pancreatitis
Pulmonary contusions Cardiopulmonary bypass
Fat emboli Transfusion-related
Disseminated
Near drowning
intravascular coagulation
Reperfusion injury Burns
Drug overdose
 Clinical disorders associated with ARDS

FREQUENT CAUSES

 SEPSIS
BACTEREMIA WITHOUT SEPSIS SYNDROME 4%

SEVERE SEPSIS/SEPSIS SYNDROME 35-45%

 MAJOR TRAUMA

MULTIPLE BONE FRACTURES 5-10%

PULMONARY CONTUSION 17-22%

 HYPERTRANSFUSION 5-36%
 ASPIRATION OF GASTRIC CONTENTS 22-36%
PATHOLOGICAL STAGES OF ARDS

Exudative (acute) phase (0- 4 days)

Proliferative phase (4- 8 days)

Fibrotic phase ( >8 days)

Recovery
 PATHOGENESIS

Insult (direct or indirect)

Activation of inflammatory cells

& mediators

Damage to alveolar capillary membrane

Increased permeability of alveolar capillary membrane

Influx of protein rich edema fluid and inflammatory cells into

air spaces
Dysfunction of surfactant
Exudative Phase
Proliferative Phase
PHYSIOLOGICAL ABNORMALITIES

Decreased ventilation

Impaired diffusion

Reduced perfusion
 CLINICAL FEATURES – SYMPTOMS

 Precipitating insult is usually evident

 Early (24 – 48hrs)

- Cough, breathlessness, fatigue

 Late (after 48hrs)

- due to worsening hypoxemia
- agitation, anxiety, confusion
CLINICAL FEATURES – SIGNS

 Dyspnoea
 Tachypnoea
 Tachycardia
 Restlessness
 Cyanosis even with supplemental oxygen
( refractory hypoxemia)
 DIFFERENTIAL DIAGNOSIS
 Cardiogenic pulmonary edema
 Diffuse alveolar hemorrhage
 Acute pulmonary embolism
 Acute eosinophilic pneumonia
 Hypersensitivity pneumonitis
 Pulmonary alveolar protienosis
 Sarcoidosis
 Leukemic infiltration
 Drug induced pulmonary edema
 INVESTIGATIONS
 Chest x-ray & CT thorax:
bilateral diffuse alveolar infiltrates more on
the peripheral lung fields.
R/O Cardiogenic edema if there is
* cardiomegaly
* pulmonary artery dilatation
* bat’s wing perihilar distribution
* responding to diuretics
NEONATAL RESPIRATORY DISTRESS SYNDROME
 INVESTIGATIONS
 Arterial blood gas analysis:
PaO2 range 55 – 60 mm of Hg
Initially respiratory alkalosis later
mixed acidosis
 Routine CBC, urea, creatinine, Na, K
 Echocardiogram to R/O Cardiogenic
cause.
 PAWP < 18mm of Hg  ALI / ARDS
 INVESTIGATIONS
Bronchoscopy
LUNG BIOPSY
SERUM MARKERS
Von willebrand’s factor or
complement in serum may be
high.

Acute phase reactants like

ceruloplasmin or cytokine (TNF,IL-
SWANZE GAZE CATHETER
 B R O N C H O A L V E O L A R LAVAGE
Inflammatory mediators like cytokines, reactive
oxygen species , leukotrienes & activated
complement fragments are found in the fluid.

Cellular analysis shows more than 60% of

Neutrophils.

As ARDS resolves neutrophils are replaced with

alveolar macrophages.

 Marker of pulmonary fibrosis called Procollagen

peptide III (P C P III) and this correlates with mortality.

Presence of more eosinophils suggest eosinophilic

pneumonia, high lymphocyte counts may be seen in
hypersensitivity pneumonitis, sarcoidosis, BOOP etc
Histologic Findings
Hyaline Protein in air
spaces
Cellular Congestion

 Typical histological
findings in ARDS
 alveolar inflammation,
thickened septal from
protein leak (pink),
congestion and decreased
alveolar volume

←Normal Lung Histology—large

alveolar volumes, septal spaces
very thin, no cellular congestion.
ASSESSMENT OF SEVERITY
 Murray lung injury score:
- Chest x-ray
- Hypoxemia
- PEEP
- Compliance
Score
0  no lung injury
1 – 2.5  mild to moderate lung injury
> 2.5  severe lung injury
POOR PROGNOSIS FACTORS

 Advanced age
 Extra pulmonary organ dysfunction
 Sepsis
 HIV
 Alcoholism
 Active malignancy
 Organ transplantation
• PHARMACOLOGICAL TREATMENT 3
• Steroids, vasodilators, surfactant, anti inflammatory
• SUPPORTIVE THERAPY (5P’s)
• Perfusion, Position, Protective lung ventilation,
2
Protocol weaning, Preventing complications
• TREATMENT OF CAUSE 1
• e.g. antibiotics for pneumonia
TREATMENT OF ALI/ARDS
 TREATMENT - Ventilation
Goals of ventilation in ARDS are to:
 Maintain oxygenation by keeping O2
saturation at 85-90%
 Avoiding oxygen toxicity and complication of
mechanical ventilation – decreasing FiO2 to
less than 65% within the 1st 24-48 hours .
Tidal Volume Strategies in ARDS

Traditional Low Stretch

Approach Approach
High priority to High priority to lung
traditional goals of
protection.
acid-base balance
and patient comfort.
Lower priority to traditiona
Lower priority to goals of acid-base balance
lung protection. and comfort.
ARDS Network Low VT Trial
Ventilator procedures
1) Volume-assist-control mode
 Tidal Volume 6 vs. 12 ml/kg of BW.
 Plateau pressure  30 vs.  50 cmH2O
2) Ventilator rate setting
6-35 (breaths/min) to achieve pH goal of
7.3 to 7.45
3) I/E ratio : 1.1 to 1.3
4) Oxygenation goal :
PaO2 55 - 80 mmHg / SpO2 88 - 95%
5) Allowable combination of FiO2 and PEEP
Ventilator-Induced Lung Injury
Two primary mechanistic factors:
 Overdistension of the alveoli by high
transpulmonary pressures
 Shear-stress forces produced by repetitive
alveolar recruitment and derecruitment
(collapse) - Atelectrauma

The extent of this injury has been reduced in

animals through the use of PEEP levels that
prevent derecruitment at end-expiration.
Recognized Mechanisms
of Airspace Injury

Airway Trauma

“Stretch”

“Shear”
 Ventilator-Induced
Lung Injury
Positive pressure ventilation may injure the lung
via several different mechanisms

Alveolar distension Repeated closing and opening Oxygen toxicity

“VOLUTRAUMA” of collapsed alveolar units
“ATELECTRAUMA”

Lung inflammation
“BIOTRAUMA”

VILI

Multiple organ dysfunction syndrome

Gas
Extravasation
Barotrauma
APPLICATION OF PEEP
Alternatives to ARDSNET

 Pressure control- inverse ratio

ventilation
(PC-IRV)
 Airway pressure release ventilation (APRV)
 High frequency oscillatory ventilation

All modes may improve oxygenation because

of sustained recruitment, but to date none is
known to offer a survival advantage.
NON-VENTILATORY-BASED
STRATEGIES IN THE
MANAGEMENT OF ARDS/ALI
Fluid and hemodynamic management

Inhaled nitric oxide

Prone position ventilation

Steroids

Other drug therapy

FACTT STUDY : IN ARDS
CONSERVATIVE
(higher, more frequent Lasix doses)
verse
LIBERAL FLUID MANAGEMENT
(more frequent fluid boluses).

 Outcomes : NO significant difference in 60-day

mortality between the two groups, however the
conservative fluid group had improved lung function ,
shorter durations of mechanical ventilation, and
shorter ICU stays, SUPPORTING THE USE OF
DIURETICS.
 PRONE VENTILATION
 Effect on gas exchange
Improves oxygenation – allows decrease Fio2;
PEEP
response rate – 50-70%
 Proposed mechanism –
1) Increase in FRC
2) Improved ventilation of previously dependent
regions.
(a) Difference in diaphragmatic movement
supine : dorsal and ventral portion move
symmetrically
prone :dorsal > ventral
 b) Decrease chest wall compliance in
prone position.
c) Redistribution of tidal volume to
atelactatic dorsal region.
3) Improvement in Cardiac output
4) Better clearance of secretions
5) Improved lymphatic damage
TRACHEAL GAS INSUFFLATION (TGI)
In ARDS /ALI
1. Increase physiological dead space
2. permissive hypercapnia

IN TGI
Stream of fresh air (4 to 8 L/min) insufflated
through – small catheter or through small channel
in wall of ET into lower trachea flushing Co2 laden
gas.
 EXTRACORPOREAL MEMBRANE
OXYGENATION
OXYGENATE BLOOD and REMOVE CO2 EXTRACORPORALLY.

 TYPES
1) High-flow VENOARTERIAL bypass system.
2) Low-flow VENOVENOUS bypass system.
 CRITERIA
Fast entry criteria
PaO2 <50 mmHg for >2 h at FiO2 1.0; PEEP > 5 cmH2O

Slow entry criteria

PaO2 <50 mmHg for >12 h at FiO2 0.6; PEEP > 5 cmH2O
maximal medical therapy >48 h
 SURFACTANT REPLACEMENT THERAPY
 IN ARDS THERE IS DEFICIENCY AND ABNORMAL
FUNCTION OF SURFACTANT

A) Decrease production .
B) Abnormal composition .
C) Inhibitors of surfactant function .
D) Conversion of large to small surfactant aggregates
E) Alteration/Destruction caused by substances in alveolar
space (plasma, fibrinogen, fibrin, )

 IMPAIRED SURFACTANT FN 
1) ATELACTASIS / COLLAPSE
2) INCREASE EDEMA FORMATION
 SURFACTANT REPLACEMENT.
 Improved lungs function , compliance ,
oxygenation.
 Surfactant of possible therapeutic use :
Class Origin Example
1. Natural Amniotic Human amniotic fluid
surfactant
2. Modified - Bovine Infasurf, alveofact
Natural BLESS, Survanta
- Procine Curosurf
3. Synthetic Exosurf, ALEC, KL4
Surfactant, Venticute
 DOSE
Sufficient dose should reach alveolar environment
 TIMING
• As early as possible [<48 hr]
• Little benefit at 3 to 5 days [Fibrosis already set]
 ENHANCED RESOLUTION OF ALVEOLAR
EDEMA
Alveolar clearance of edema depends on active
SODIUM TRANSPORT across the alveolar
epithelium
b2 adrenergic stimulation :
1. Salmetrol
2. Dopamine
3. Dobutamine

 ENHANCED REPAIR :
Mitogen for type-II pneumatocyte :
1. HEPATOCYTE GROWTH FACTOR
2. KERATINOCYTE GROWTH FACTOR.
 COMPLICATIONS ( ACUTE )
 ACUTE RESPIRATORY FAILURE

 VENTILATOR ASSO PNEUMONIA

 VENTILATOR ASSO LUNG INJURY

(VALI)
 DVT AND PULMONARY
EMBOLISM
 PRESSURE SORES
 COMPLICATIONS (CHRONIC)
 REDUCED EXERCISE CAPACITY

 DECREASED QUALITY OF LIFE

 POST TRAUMATIC STRESS DISORDER

(depression, anxiety, decreased memory &
concentration.
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