1) Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are defined by acute onset hypoxemia, bilateral pulmonary infiltrates on chest x-ray, and absence of heart failure with no clear single cause. 2) ARDS has an annual incidence of 60-80 per 100,000 people and carries a high mortality rate of 40-50%. Risk factors include sepsis, trauma, pneumonia, and aspiration. 3) Treatment involves identifying and treating the underlying cause, mechanical ventilation with low tidal volumes, maintaining adequate but not excessive fluid balance, and preventing ventilator-induced lung injury.

1. ACUTE LUNG INJURY (ALI)
ACUTE RESPIRATORY
DISTRESS SYNDROME(ARDS)

2. DEFINITION
The definition of ARDS includes the following four components:
• Acute onset (occurs within 24 hours of the inciting event in 50% of ARDS
patients)
• A ratio of Pao2 ∕ Fio2 ≤ 200 regardless of the level of positive end
respiratory pressure (PEEP)
• The detection of bilateral pulmonary infiltrates on frontal chest x-ray
• Absence of congestive heart failure (pulmonary artery wedge pressure
[PAWP] ≤18 mm Hg or no clinical evidence of elevated left atrial pressure
on the basis of chest radiograph or other clinical data)

3. DIAGNOSTIC CRITERIA FOR ALI AND
ARDS

4. PaO2/FIO2 between 200-300 identifies patients with ALI who are
likely to benefit from aggressive therapy.

5. EPIDEMIOLOGY
Annual incidences of
ALI : 80/100,000
ARDS : 60/100,000
Approximately
• 10% of all intensive care unit (ICU) admissions suffer from acute
respiratory failure
• 20% of these patients meeting criteria for ALI or ARDS.
Mortality is 40% to 50%.

6. ETIOLOGY
Indirect Lung Injury
• Sepsis
• Severe trauma
• Multiple bone fractures
• Flail chest
• Head trauma
• Burns
• Multiple transfusions
• Drug overdose
• Pancreatitis
• Post-cardiopulmonary bypass
• Pregnancy
• Eclampsia
• Amniotic fluid embolus
• Tumour lysis syndrome (p436)
• Malaria
Direct Lung Injury
• Pneumonia
• Aspiration of gastric contents
• Pulmonary contusion
• Near-drowning
• Toxic inhalation injury

7. DRUGS CAUSING ARDS
Narcotics
Cocaine
Salicylates
NSAIDS
Ethchlorvynol
Naloxone
Amiodarone (after general
anesthesia)
Thiazide diuretics
Tocolytic agents
Protamine
Cytarabine
Intrathecal methotrexate
Bleomycin
Dextran
Contrast media
Phenothiazines
Colchicine
Interleukin-2
Insulin
All-trans-retinoic acid59
Talc (intrapleural)

8. • Severe sepsis syndrome & Bacterial pneumonia …40-50 % of cases
• Aspiration of gastric contents & Near drowning …30 % of cases
• Trauma …20 % of cases
• Risk for ARDS increases from 25% in patients with severe trauma to 56%
in patients with trauma and sepsis.
• Higher the APACHE II score in trauma patients…more is the risk of
developing ARDS
• Associated medical/surgical conditions… ↑se risk of ARDS.

9. CLINICAL COURSE
The natural history of ARDS is marked by three phases:
1.Exudative(1-7 days)
2.Proliferative(7-21 days)
3.Fibrotic(starts after 3rd-4th week of initial injury)

10. PATHOLOGY

11. Contd.
Gram –ve bacteria → endotoxins → macrophages → pro-
inflammatory cytokines (IL-8, IL-1, and TNF) → neutrophils
→sequestration in the pulmonary microvasculature →margination
→egress into the alveolar space → undergo activation → leukotrienes,
oxidants, proteases & PAF → local tissue damage, accumulation of edema
fluid in the airspaces, surfactant inactivation, and hyaline membrane
formation. Macrophage-derived fibrogenic cytokines such as TGF-β and
PGDF stimulate fibroblast growth and collagen deposition associated with
the healing phase of injury.

12. PATHOPHYSIOLOGY
• Initially severe hypoxemia with shunting → increased alveolar ventilation
→low or normal PaCO2
• As the disease progresses, especially in patients who require continued
ventilatory support, fibroproliferation develops →decreased lung
compliance →decreased functional residual capacity
• As the lungs remodel and scar →loss of microvasculature →pulmonary
hypertension and increased dead space →marked elevations in minute
ventilation required to achieve a normal PaCO2 even as oxygenation
abnormalities are improving →increased work of breathing
• The cardinal feature is refractory hypoxemia secondary to damage to
alveolar-capillary barrier.

14. HISTOLOGY
Diffuse alveolar damage in acute lung injury and ARDS. Some alveoli are
collapsed; others are distended. Many are lined by bright pink hyaline
membranes (arrow).
In the healing stage there is resorption of hyaline membranes with thickened
alveolar septa containing inflammatory cells, fibroblasts, and collagen

15. INFERENCE:
• There is an imbalance of pro- and anti-inflammatory mediators causing
acute inflammatory injury to the alveolar epithelium and capillary
endothelium.
• Neutrophils and their products have a crucial role in the pathogenesis of
ARDS.
• The characteristic histologic picture is that of alveolar edema, epithelial
necrosis, accumulation of neutrophils, and presence of hyaline membranes
lining the alveolar ducts

16. PHYSICAL FINDINGS & CLINICAL PRESENTATION
Signs and symptoms
• Dyspnea
• Chest discomfort
• Cough
• Anxiety
Physical examination
• Tachypnea
• Tachycardia
• Hypertension
• Coarse crepitations of both lungs
• Fever may be present if infection is
the underlying etiology

17. INVESTIGATIONS
• All routine investigations (haemogram, cell counts, RFTs, LFTs, urine exam,
ECG, blood cultures & sensitivity, etc).
• ABGs:
1. Initially: varying degrees of hypoxemia, generally resistant to supplemental
oxygen
2. Respiratory alkalosis, decreased Pco2
3. Widened alveolar-arterial gradient
4. Hypercapnia as the disease progresses
• Bronchoalveolar lavage
1. The most prominent finding is an increased number of
polymorphonucleocytes.
2. The presence of eosinophilia has therapeutic implications, because these
patients respond to corticosteroids.
• Blood and urine cultures

18. IMAGING STUDIES
• The chest radiogram might be normal in the initial hours after the
precipitating event.
• Bilateral interstitial infiltrates are usually seen within 24 hr; they often are
more prominent in the bases and periphery.
• “White out” of both lung fields can be seen in advanced stages.
• CT scan of chest: diffuse consolidation with air bronchograms, bullae,
pleural effusions. Pneumomediastinum and pneumathoraces may also be
present.

19. A representative anteroposterior (AP) chest x-ray in the exudative phase of ARDS that
shows diffuse interstitial and alveolar infiltrates, which can be difficult to distinguish
from left ventricular failure.

20. A representative computed tomographic scan of the chest during the exudative
phase of ARDS in which dependent alveolar edema and atelectasis
predominate

21. DIFFERENTIAL DIAGNOSIS
1. Cardiogenic pulmonary edema
2. Diffuse pneumonia
3. Alveolar hemorrhage
4. Acute interstitial lung diseases e.g. acute interstitial
pneumonitis
5. Acute immunologic injury e.g. hypersensitivity pneumonitis
6. Toxin injury (e.g., radiation pneumonitis)
7. Viral pneumonitis
8. Lymphangitic carcinomatosis

22. FEATURES ASSOCIATED WITH NONCARDIOGENIC AND
CARDIOGENIC PULMONARY EDEMA

23. TREATMENT
General Principles
(1) the recognition and treatment of the underlying medical and surgical disorders
(e.g., sepsis, aspiration, trauma)
(2) respiratory support
(3) minimizing procedures and their complications
(4) prophylaxis against venous thromboembolism, gastrointestinal bleeding, and
central venous catheter infections
(5) the prompt recognition of nosocomial infections
(6) provision of adequate nutrition.

25. MANAGEMENT OF MECHANICAL VENTILATION
ARDSNet VENTILATORY MANAGEMENT PROTOCOL FOR TIDAL
VOLUME AND PLATEAU PRESSURE:
1.Calculate PBW.
Male PBW: 50 + 2.3 (height in inches - 60)
Female PBW: 45.5 + 2.3 (height in inches - 60)
2.Select assist-control mode.
3.Set initial VT at 8 mL/kg PBW.
4.Reduce VT by 1 mL/kg at intervals <2 hr until VT = 6 mL/kg PBW.
5.Set initial RR to approximate baseline minute ventilation (maximum RR = 35/min).
6.Set inspiratory flow rate higher than patient's demand (usually > 80 L/min)
7.Adjust VT and RR further to achieve Pplat and pH goals.
• If Pplat > 30 cm H2O: decrease VT by 1 mL/kg PBW (minimum = 4 mL/kg
PBW).
• If pH ≤7.30, increase RR (maximum = 35).
• If pH <7.15, increase RR to 35; consider sodium bicarbonate administration or
increase VT.

26. VENTILATOR-INDUCED LUNG INJURY
Mechanism of injury:
• repeated alveolar overdistension
• recurrent alveolar collapse
ARDS is a heterogenous disorder:
• principally involves dependent portions of the lung
• relative sparing of other regions
• Because of their differing compliance, attempts to fully inflate the
consolidated lung may lead to overdistension and injury to the more
"normal" areas of lung.

27. ARDS NETWORK RCT:
• sponsored by the National Institutes of Health
• compared low tidal volume (6 mL/kg PBW) ventilation to conventional
tidal volume (12 mL/kg PBW) ventilation
• Mortality was significantly lower in the low tidal volume patients (31%)
compared to the conventional tidal volume patients (40%).
• represents the most substantial benefit in ARDS mortality demonstrated for
any therapeutic intervention in ARDS to date.

28. PREVENTION OF ALVEOLAR COLLAPSE
• Without an increase in end-expiratory pressure, significant alveolar collapse
can occur at end-expiration, impairing oxygenation.
• Static pressure–volume curve for the respiratory system can be constructed in
most modern ventilators
• The lower inflection point on the curve represents alveolaer opening
• The pressure at this point , usually 12–15 mmHg in ARDS, is a theoretical
"optimal PEEP" for alveolar recruitment
• PEEP should be applied in small increments of 3 to 5 cm H2O (up to a
maximum of 15 cm H2O) to achieve acceptable arterial saturation (>0.9) with
nontoxic FiO2 values (<0.6) and acceptable airway plateau pressures (>30 to 35
cm H2O)
• Mortality benefit could not be demonstrated in RCTs

29. INVERSE RATIO VENTILATION
• Improves oxygenation by increasing mean airway pressure
• inspiratory (I) time is lengthened so that it is longer than the expiratory (E) time
(I:E > 1:1)
• With diminished time to exhale, dynamic hyperinflation leads to increased end-
expiratory pressure, similar to ventilator-prescribed PEEP.
• advantage of improving oxygenation with lower peak pressures than
conventional ventilation.
• helps reduce FIO2 to 0.60 to avoid possible oxygen toxicity, no mortality benefit
in ARDS has been demonstrated.

30. FLUID BALANCE
• aggressive attempts to reduce left atrial filling pressures with fluid
restriction and diuretics should be an important aspect of ARDS
management
• If hypotension , administer sufficient fluid to maintain a PAWP of 6-8 cm
H2O so as to avoid pre-renal ARF
• if further circulatory support is required, administer an inotropic agent

31. GLUCOCORTICOIDS
▪ARDS Network trial does not support the use of steroids
▪Trial on use of steroids in late phase of ARDS is underway
• Surfactant replacement → not recommended
• Inhaled nitric oxide → not recommended
• Anti-inflammatory therapy → not recommended