1. Presented by-
Dr.RAKESH KARNAWAT

2. Definition :
Alternative terminology:
 Da Nang Lung
 Transfusion Lung
 Post Perfusion Lung
 Shock Lung
 Traumatic Wet Lung
 Post traumatic Failure
 Post traumatic Pulmonary Insufficiency
 Wet lung
 White Lung
Taylor RW et al Res Medica 1983;1:17-21
Incidence: 10% of all ICU admissions
20% of these patients meet ALI criteria.
Historical Perspectives:
Year: 1967 by Ashbaugh and co – workers
Acute respiratory distress in adultss Ashbaugh DG et al .Lancet 1967
REVISION OF DEFINITIONS -1988: by Murray et al.

3. Onset Chest
Radiograp
h
Absence of Left
Atrial
Hypertension
Oxygenation
Acute Bilateral
alveolar or
interstitial
infiltrates
PCWP 18 mmHg
or no clinical
evidence of
increased left
atrial pressure
ALI: PaO2/FIO2
less then 300
mmHg
ARDS:
PaO2/FIO2 less
then 200
mmHg
AECCC 1994

4. The reliability of chest radiographic criteria has been
demonstrated to be moderate, with substantial inter-
observer variability
Hypoxemia criteria can be markedly affected by the
patient’s ventilator settings, especially the PEEP level
used
Wedge pressure can be difficult to interpret and if a
patient with ARDS develops a high wedge pressure that
should not preclude diagnosing that patient as having
ARDS

5. BERLIN CRITERIA
International expert panel met in 2011
The goal of developing the Berlin definition was to try and improve
feasibility, reliability, face and predictive validity for mortality compared
with the AECC definition JAMA2012;307:2526–2533
1. Lung injury of acute onset, within 1 week of an apparent clinical insult
and with progression of respiratory symptoms
2. Bilateral opacities on chest imaging not explained by
other pulmonary pathology (e.g. pleural effusion, pneumothorax or
nodules)
3. Respiratory failure not explained by heart failure or volume overload
4. Decreased arterial PaO2/FiO2 ratio:
Mild: 201 - 300 mmHg (≤ 39.9 kPa)
Moderate: 101 - 200 mmHg (≤ 26.6 kPa)
severe: ≤ 100 mmHg (≤ 13.3 kPa)
IntensiveCareMed 012;38:1573–1582.

6. CAUSESOFARDS/TYPES
Direct Lung Injury
(PULMONARY)
Indirect Lung Injury (EXTRA
PUL.)
Pneumonia Sepsis
Pulmonary contusion Severe trauma
Aspiration Multiple bone fractures
Near-drowning Flail chest
Toxic inhalation injury Head trauma
Burns
Multiple transfusions
Drug overdose
Pancreatitis

7. EDEMA
HYALINE
MEMBRANES
INTERSTITIALS
INFLAMMATION
INTERSTITIAL
FIBROSIS
FIBROSIS
EXUDATIVE PROLIFERATIVE FIBROTIC
DAY 0-7 14 21..
Clinical courseand
pathophysiology
Lancet 2007; 369:1553-65

8. Up to 1 week
Capillary and alveolar
cells are injured – protein
rich fluid to accumulates in
the interstitial and alveolar
spaces – Hyaline
membrane
Chemicals (cytokines TNF-a,
IL-1b, IL-6 and chemokines
Neutrophils, macrophages, prostacyclin,
leukotrienes, thromboxane, Free
radicals)
Interferes in gas exchange

9. PROLIFERATIVE
2 to 3rd week
organization of
alveolar
exudates,Type I
alveolar cells get
replaced by type
2 alveolar cells
Lymphocytes
Most patients
get recovered
FIBROTIC
Beyond 3rd week
Remodeling by
collagenous
tissue, arterial
thickening,
obliteration of
pre-capillary
vessels.
abnormal tissue
repair,
Type III collagen
Long term MV
support and O2
therapy
Increased
morbidity and

10. CHEST X-RAY
Progression from diffuse interstitial infiltrates to diffuse, fluffy, alveolar opacities

11. CT SCAN-ARDS
EXUDATIVE AND FIBROTIC PHASES
Reticular opacities - suggesting the development of interstitial
fibrosis.

12. MANAGEMENT
 Mechanical ventilation
 Supportive measures

13. 1. Recognition and treatment of the underlying
medical and surgical disorders (e.g., sepsis,
aspiration, trauma)
2. Minimise procedures and their complications
3. Prophylaxis against venous thromboembolism,
gastrointestinal bleeding, and central venous
catheter, arterial lines, urinary catheters
infection…etc.
4. Recognition of nosocomial infections
5. Provision of adequate nutrition

14. GOALS
 Oxygenation goal: paO2 of 55-80mmHg Or
SpO2 of 88-95%
 Plateau pressure goal:<30cm H2O
 pH goal:7.25-7.45
 I:E goal: 1:1 to 1:3

15. NIH ARDS NET MV PROTOCOL
*PART I: Ventilator set up and adjustment
FIRST STAGE:
1. Calculate IBW M=50+2.3(Ht in inches-6o), F=45.5+2.3(Ht in inches 50)
2. Select ACMV & Set initial TV to 8ml/kg
3.Add PEEP to 5-7 cm H2O
4. Reduce TV by 1 ml/kg at intervals of <2hours until TV=6ml/kg
5. Set RR < 35bpm
6. Set inspiratory flow rate above pt. demand(>80L/min)
JAMA 2010;303:865–
873
SECOND STAGE:
When TV=6ml/kg Measure Plateau Pressure:Target <30cm H2o
If Ppl;>30cm H2o Decrease TV in 1 ml/kg steps until Ppl drops <30cm H2o or TV down to
4ml/kg.
THIRD STAGE:
Monitor arterial blood gases for respiratory acidosis pH GOAL: 7.30-7.45
If pH 7.15-7.30: Increase RR until pH > 7.30 or PaCO2 < 25
If pH < 7.15: Increase RR to 35. If pH remains < 7.15, TV may be increased in 1 ml/kg steps until
pH > 7.15 . Can give NaHCO3
Alkalosis Management: (pH > 7.45) Decrease vent rate if possible.
ARDS Network,NEJM, 342:2000

16. PART II: WEANING
1. RR< 35(may be >35 for < 5 min)
2. Spo2 > 88% (may be <88% for< 15 min)
3. Respiratory distress is absent
pulse<120
absence of sweating
no dyspnea
no abdominal paradox
no marked use of accessory muscles of respiration.

17. CONDUCT A CPAP TRIAL DAILY WHEN
1.Fio2 < 0.40 and PEEP < 8
2.PEEP and Fio2 < values of previous day
3.Patient has acceptable spontaneous breathing efforts
4.Systolic BP > 90 mmHg without vasopressor support
CONDUCTING THE TRIAL
Set CPAP = 5cm H2O, FiO2=0.5
If RR<35 for 5min advance to PSV.
If CPAP trial is not tolerated then return to previous ACMV.

18. Pressure support weaning procedure
1. Set PEEP=5 and FiO2=0.5
2. Set PS ventilation based on RR during CPAP trial:
If RR<25: set PS=5cm H2O and if tolerated for more
than 2hrs,asses for unassisted breathing trial
If RR=25-35:set PS=20cm H2O then reduce by 5cm
H2O at <5min interval for 1-3hrs, then go to
unassisted trial
If initial PS not tolerated return to previous ACMV

19. 1. Place the pt.on a T-piece or CPAP<5 cm H2O
2. Asses for tolerance for 2 hours
1. RR<35/min
2. SpO2>90 and PaO2>60mmHg
3. Spontaneous TV>4ml/kg of IBW
4. Signs of respiratory distress are absent
3. If tolerated well - consider for extubation
4. If not tolerated, resume pre-weaning settings.

20. RECRUITMENT MANEUVERS
Traditionally RMs have been delivered as
sustained inflations, with peak inflation
pressures limited to between 30 and 40 cm
H2O, typically held for a period ranging from 15
to 40 seconds with the intention of reopening
collapsed regions of the lung
NEJM 2007; 354: 1775-1786
However, due to the unusually
high surface tension within
affected alveoli, the benefit is
often transient especially if not
followed by sufficiently high
levels of PEEP.

21. PEEP
 Increases the end expiratory or baseline airway
pressure to a value greater than atmospheric
pressor on ventilators.
 Improves oxygenation
prevents end exp collapse of alveoli
increase FRC
recruites nonventilated/poorly ventilated
alveoli
 Creates hydrostatic force,shift fluid from alveoli
to interstitium,relieves pulm.oedema

22. Pressure (cm H2O)
Volume (mL)
Upper Inflection Point
Lower Inflection Point
How to select appropriate
PEEP?
1. Volume-Pressure Curve
2. Incremental increase in
PEEP value
3. FiO2/PEEP ratio
Principle for FiO2 and PEEP Adjustment
FiO2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
PEEP 5 5-8 8-10 10 10-14 14 14-18 18-24

23. This is again a vent.manuveor used in case of refractory
hypoxemia *Oxygenation can be improved by increasing
mean airway pressure with "inverse ratio ventilation." In
this technique, the inspiratory (I) time is lengthened so
that it is longer than the expiratory (E) time (I:E 1:1 to I.E.
I:3).
With diminished time to exhale, dynamic hyperinflation
leads to increased end-expiratory pressure, just like PEEP.
*This mode of ventilation has the advantage of improving
oxygenation with lower peak pressures than conventional
ventilation. Although inverse ratio ventilation can improve
oxygenation and help in reducing FIO2 to 0.60 to avoid
possible oxygen toxicity.
No mortality benefit or survival benefit in ARDS has been
demonstrated.
INVERSE RATIO VENTILATION

24. Prone PositionMechanisms to improve oxygenation:
Prone position reverses
gravitationally distributed
perfusion to the better-
ventilated ventral lung regions
and improved ventilation of
previously dependent dorsal
lung, both of which would
improve ventilation/perfusion
matching. More efficient
drainage of secretions
Improvement in oxygenation
is immediate but there is no
difference in mortality.
Optimum timing or duration ?
Because of the lack of clear benefit
in survival and the potential
complications of prone
positioning,we believe that there
is not enough evidence to support
its routine use in all patients with
acute lung injury and ARDS
Gattinoni et al., NEJM, 2001;45:568–573

25. Fekri Abroug et al; An updated study-level meta-analysis of
randomised controlled trials on proning in ARDS and acute
lung injury.Critical Care 2011, 15; 6
Analysis showed that prone ventilation significantly reduces
ICU mortality in ARDS patients and suggested that long
prone durations should be applied
Two large RCT’s compared the effect of prone vs supine
positioning on mortality
Conclusion: Both studies showed that prone positioning does
not improve survival and that it may be associated with
harmful effects such as decubitus ulcers and self-
extubation

26. Improves ventilation-perfusion matching and
improves oxygenation by dilating the local pulmonary
capillaries
No improvement on survival
Nitric Oxide Routine use is not recommended
Nitric Oxide
Taylor R W E et.al.LOW-DOSE INHALED NITRIC OXIDE IN
PATIENTSWITHACUTE LUNG INJURY: JAMA 2004; 291:1603–1609.

27. KINETIC THERAPY
By continuously rotating critically ill patients from side-to-side to at least
40°, gravitational pressor can help in improving ventilation perfusion
mismatch , increased FRC & thus helpful to improve oxygenation and
benefit patients with ALI/ARDS.

28. These are fluoro carbons with a high oxygen-
carrying capacity & having intrinsic anti
inflammatory properties which are injected in
the lung to improve the oxygenation but
none of these shown any benefit in the pt.

29. NONCONVENTIONAL VENTILATORY
SUPPORT
1. HIGH FREQUENCY OSCILLATION
2. EXTRACORPOREAL SUPPORT

30. HFOV is used again in case of refractory hypoxemia where u
put the pt on high frequency vent.mode techniques using
ventilation frequencies of greater than 60 breath per minute
and tidal volumes between 1 to 5ml/kg
Highfrequency oscillatory ventilation improves gas exchange,
inflates the lungs uniformly,reduces ventilator-induced lung
injury, and reduces levels of systemic inflammatory
mediators.
Patients in the high-frequency oscillatory ventilation group
showed an earlier improvement in the PaO2/FiO2 ratio
compared with in the PaO2/FiO2 ratio compared with those
on conventional ventilation, although the difference did not
persist for more than 24 hours.
AMJ RESPIRCRIT CARE MED 2002;166:801–808.

31. VENTILATION

32. ROLE OF ECMO
ECMO was proposed to maintain the lung “at rest” while
providing adequate gas exchange & this is found to be
efficient in removing 20% of CO2
• Substantial risk of infection and bleeding
• Not routinely recommended
• No improvement on survival
• Recent trial ; A modified technique (low-frequency positive-
pressure ventilation with extracorporeal CO2 removal
[LFPPV-ECCO2R]) is proposed to inflate the lungs to
moderate pressures to maintain FRC while CO2 removal is
ensured by a low flow partial venovenous bypass.

34. FLUID MANAGEMENT
Maintaining a normal or low left atrial filling pressure minimizes
pulmonary edema and prevents further decrements in arterial
oxygenation and lung compliance, improves pulmonary mechanics,
shortens ICU stay and the duration of mechanical ventilation, and
is associated with a lower mortality.
ARDSNet05: Fluid and Catheter Treatment Trial (FACTT)
These results support the use of a conservative strategy of fluid
management in patients with acute lung injury untill unless pt is
having hypotension or hypoperfusion of critical organs.
Am J Respir Crit Care Med 2012;186:1256–1263.
Hypoalbuminemic patients should receive coloids whereas all other patients
should receive crystalloid fluids to decrease the pulmonary congestion

35. ROLE OF GLUCOCORTICOIDS
The main aim of giving glucocorticoids is to reduce
inflamation process in the lung.
Many attempts have been made to treat both early and late
ARDS pt.with glucocorticoids to reduce this potentially
deleterious pulmonary inflammation but only few studies
have shown the benefitial effect.
*Current evidence does not support the use of
glucocorticoids in the care of early ARDS patients.
*Glucocorticoids can be used in the late phase of ARDS to
decrease fibrotic tissue formation.

36. A BRIEF SUMMARY OF THE AVAILABLE STUDIES-
STEROIDS
*High-dose methylprednisolone (30 mg/ kg) I.V every 6 hours for 4
doses) given to patients within 24 hours of the diagnosis of ARDS
has not improved outcome or reduced mortality
*In fact, one study showed a higher mortality associated with early
steroid therapy in ARDS (Bone 1987)
*Secondary infection are increased in patients receiving high dose
methyl-prednisolone for ARDS (Bone 1987)
*High-dose methylprednisolone (2-3 mg/kg/day) given to 25
patients with late ARDS (2 weeks duration) resulted in a beneficial
response in 21 patients and an 86% survival in the responders
(Meduri 1994)
*Medurri: The surviving patients treated with corticosteroids had
significant reductions in plasma levels of chemical mediators like
TNF-a , IL-1b, IL-6, and IL-8

37. Nowaday, the new points are based on clinical
evidences, we should give corticosteroid in the
fibroproliferative phase of ARDS, 7-14 days, without
evidence of infection
Treated patients had:
- earlier reduction in lung injury score
- reduced time on vent [p=.002]
- reduced ICU stay [p =.007]
- reduced ICU mortality [21% vs 43%] p=.03
- lower rate of ICU infections [p = .0002]

38. ROLE OF SURFACTANT
These are all experimental studies & none of them shown
any clinical benefit in the pts.
Though there are many evidences in support of surfactant
replacement therapy for neonatal respiratory distress
syndrome but the results from its use in adult ARDS
patients have not shown any clinical benefits.

39. ROLE OF ACTIVATED PROTEIN-C
It was used previously as it inactivates Va & VIIa –
limit thrombin generation & fibrinolysis. It also
has anti-inflam.activity but because of its more
adverse effects ex. Increase risk of bleeding
(3.5% vs 2.0%) it is no longer used now a days.

40. Future non-ventilatory therapeutic options
Gene and mesenchymal stem cells therapies- these approaches hold
promise in the treatment of ARDS.
 Gene therapy for ALI/ARDS
Lung injury in ARDS is characterized by a pro-inflammatory increase in
vascular permeability and neutrophil infiltration, which sustain alveolar
edema and damage to alveolar barrier. Lung gene transfer encoding for
IL10 has been shown to reduce the release of inflammatory cytokines with
improvement in oxygenation & pulmonary vascular resistance. Similar anti-
inflammatory effects have been found with the delivery of genes encoding
anti-inflammatory cytokines such as interferon protein 10 (IP-10), IL 12,
Heme oxygenases (HO) and transforming growth factor beta-1 (TGF-β1)
 Mesenchymal stem cells
Mesenchymal stem cells (MSC) are multipotent stromal cells that can
differentiate into a variety of cells types, having regenerative properties
and may repair damaged tissues & this properties make them promising
as a therapeutic approach in ARDS. In addition, they can release many
molecules, which contribute to immunomodulatory and anti-inflammatory
effects.
Although all these strategies have demonstrated to improve oxygenation,
their impact on mortality is controversial.

41. Evidence-Based Recommendations for
ARDS Therapies
Treatment Recommendationa
Mechanical ventilation
Low tidal volume A
High-PEEP or "open-lung" C
Prone position C
Recruitment maneuvers C
High-frequency ventilation and ECMO D
Surfactant replacement, inhaled nitric oxide, and other
antiinflammatory therapy e.g., ketoconazole, PGE1, NSAIDs
D
Glucocorticoids
Fluid Therapy
C
B

43. FUTURE PROSPECTIVES
 Numerous pharmacological Rx are
underinvestigation to stop the cascade of events
leading to ARDS
 Neutrrophil inhibitors
 Interleukin-1 receptor antagonist
 Pulmonary specific vasodilator
 Surfactant replacement therapy
 Antisepsis agent
 Gene Therapy

44. - Martin J. Tobin, MD

45. THANK YOU