DIAGNOSIS & MANAGMENT OF

Acute Respiratory Distress Syndrome

DR. VITRAG SHAH

FIRST YEAR FNB RESIDENT,

DEPARTMENT OF CCEM,

SGRH, DELHI

MODERATOR

DR.RAHUL

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SYMPTOMS…………

• Fever/chills

• Headache, myalgia

• Sore throat

• Cough

• Coryza

• Prostration

• Range of symptoms differs by age

– Vomiting & diarrhea in children/elderly

– Fever alone in infants

– May be atypical in elderly

• Serious complications can occur among high risk groups

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OUTLINE

What is ARDS

Berlin vs AECC definition & LIS

Risk Factors

Etiology

Clinical course & Pathophysiology

Differential diagnosis

Management General management & nursing care

Role of NIV

Ventilatory management

Management of Refractory hypoxemia

Non-Ventilatory management

Other drugs/therapies

Prognosis

Future/Research & Role of stem cells

References

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WHAT IS ARDS??

A type of inflammatory lung injury that is neither a primary disease or a single entity.

Rather, it is an expression of myriad other diseases that produce diffuse inflammation in the lungs, often accompanied by inflammatory injury in other organs & it is also the leading cause of acute respiratory failure.

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Physicians think they do a lot for a patient when they

give his disease a name --Immanuel Kant

First described as clinical syndrome in 1967 by

Ashbaugh & Petty .

Synonyms: Sponge Lung, Shock lung, Non-cardiogenic

pulmonary edema, Capillary leak syndrome, Traumatic

wet Lung, Adult hyaline membrane disease, ALI &

ARDS, and most recently, Only ARDS.

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THE BERLIN DEFINITION:-

The Berlin Definition of ARDS (published in 2012) replace the

American-European Consensus Conference’s definition of

ARDS (published in 1994).

The European society of intensive care medicine endorsed by

The American Thoracic Society and The Society of Critical Care

Medicine developed the Berlin definition in 2012.

The major changes to the Berlin Definition are that the term

“acute lung injury” has been eliminated, the pulmonary

capillary wedge pressure (ie, pulmonary artery occlusion

pressure) criteria has been removed, and minimal ventilator

settings have been added.

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SpO2 can be substituted for the PaO2 to calculate the SpO2/FIO2 ratio, which may be

more a feasible method of identifying severely ill patients in these resource-limited

environments.

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WHAT’S NOT INCLUDED…..

The draft definition of severe ARDS included the more

extensive involvement on the frontal chest radiograph

(3 or 4 quadrants) { from those with the minimal

criterion of “bilateral opacities” (2 quadrants) },

respiratory system compliance (40 mL/cm H2O),

positive end expiratory pressure (10 cm H2O), and

corrected expired volume per minute (10 L/min).

These variables were identified for further study

during the evaluation phase & not included in present

criteria.

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PCWP:

The problem is that the wedge pressure is not a measure of capillary hydrostatic pressure,

The PCWP is a measure of LAP and LAP cannot be the same as the pulmonary capillary pressure in presence of blood flow .

If the wedge (left-atrial) pressure were equivalent to the pressure in the pulmonary capillaries, there would be no pressure gradient for flow in the pulmonary veins. Thus, the capillary hydrostatic pressure must be higher than the wedge pressure.So PCWP will underestimate the actual capillary hydrostatic pressure.

This difference is small in the normal lung, but in severe ARDS, the capillary hydrostatic pressure can be double the wedge pressure.

Because of this discrepancy, the wedge pressure should be abandoned as a diagnostic criterion for ARDS.

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MURRAY LUNG INJURY SCORE (LIS)

Radiography

Oxygenation

Compliance

PEEP

But doesn’t exclude left heart failure

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Risk Factors

Older age

Chronic alcohol abuse

Metabolic acidosis

Critical illness.

Trauma patients

>80% of cases are caused by:

Sepsis

Bacterial pneumonia

Trauma

Multiple transfusions

Gastric acid aspiration

Drug overdose

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CLINICAL DISORDERS ASSOCIATED WITH THE

DEVELOPMENT OF ARDS

Indirect insult

Common Sepsis

Severe trauma

Shock

Less common Acute pancreatitis

Cardiopulmonary bypass

Transfusion-related TRALI

DIC

Burns

Head injury

Drug overdose

Direct insult

Common Aspiration pneumonia

Pneumonia

Less common Inhalation injury

Pulmonary contusions

Fat emboli

Near drowning

Reperfusion injury

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CLINICAL COURSE AND

PATHOPHYSIOLOGY

The natural history of ARDS is marked by three phases

1. Exudative (First 7 days)

2. Proliferative (After 7-21 days)

3. Fibrotic (After 3-4 weeks)

Each with characteristic clinical and pathologic features

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Alveolar

Damage

Capillary

Damage

Leakage

Oedema

Fluid

Inflammatory

Cellular

Infiltrates

V/Q

MismatchAtelectasis

↓Thoracic

Compliance

↑Dead Space

Hypoxic

Vasoconstriction

Hypoxia

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ARDS– PROBLEMS & CONCERNS

Strain (stretch) due to over distension of compliant

alveoli leading to volutrauma.

High inspiratory pressures (Pplat) leading to barotrauma.

Release of inflammatory mediators from lung

(biotrauma)

Shear stress due to complete closure & re-opening of

non-compliant alveoli (atelectrauma).

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Earliest clinical signs of ARDS are tachypnea &

progressive hypoxemia usually refractory to oxygen ,

which usually leads to diffuse pulmonary infiltrates in

chest x-ray within 24 hours & leading to respiratory failure

requiring mechanical ventilation within 48 hours of illness.

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PROGRESSION OF ARDS:

If the injurious factor is not removed, the amount of inflammatory mediators released by the lungs in ARDS may results in

SIRS - Systemic inflammatory response syndrome

MODS - multi organ dysfunction syndrome

This adds up to impaired oxygenation which is the central problem of ARDS, which further impairs oxygen delivery.

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DIFFERENTIAL DIAGNOSIS

Most common

Cardiogenic pulmonary edema

Diffuse pneumonia

Alveolar hemorrhage

Less frequent

Acute interstitial lung diseases(e.g., acute interstitial

pneumonitis)

Acute immunologic injury (e.g., hypersensitivity

pneumonitis)

Toxin injury (e.g., radiation pneumonitis)

Neurogenic pulmonary edema

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1. CHEST X- RAY .

A homogeneous infiltrate and the absence of pleural effusions is more characteristic of ARDS.

Patchy infiltrates from the hilum, prominent pleural effusions, cardiomegaly & cephalization is more characteristic of cardiogenic pulmonary edema.

However, , pleural effusions can appear in ARDS, and the view is that CXR are not reliable for distinguishing ARDS from cardiogenic pulmonary edema

ARDS vs Cardiogenic Pulmonary Edemavitra

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2. Severity of Hypoxemia:

In the early stages of ARDS, the hypoxemia is often more

pronounced than the CXR abnormality

In the early stages of cardiogenic pulmonary edema, the CXR

abnormalities are often more pronounced than the

hypoxemia.

However, there are exceptions, and severe hypoxemia can

occur in cardiogenic pulmonary edema from a low cardiac

output

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3. BNP

In patients with hypoxic respiratory failure :

An BNP level of less than 100 pg/mL in a patient

with bilateral infiltrates and hypoxemia favors the

diagnosis of ARDS/acute lung injury (ALI) rather

than cardiogenic pulmonary edema.

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4. Bronchoalveolar Lavage:

The most reliable method for confirming or excluding the diagnosis of ARDS .

A.) Neutrophils

In normal subjects, neutrophils make up less than 5% of the cells recovered in lung lavage fluid, whereas in patients with ARDS, as many as 80% of the recovered cells are neutrophils.

A low neutrophil count in lung lavage fluid can be used to exclude the diagnosis of ARDS, while a high neutrophil count is considered evidence of ARDS .

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B.) Total Protein:

Because inflammatory exudates are rich in proteinaceousmaterial, lavage fluid similarly rich in protein→ evidence of

lung inflammation.

When the protein concentration in lung lavage fluid is

expressed as a fraction of the total protein concentration, the

following criteria can be applied

Protein (lavage/serum) <0.5 = Hydrostatic edema

Protein (lavage/serum) >0.7 = Lung inflammation

Lung inflammation is expected to produce a protein

concentration that is greater than 70% of the protein

concentration in serum.

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Although not specific, BAL can be used as evidence of ARDS if other causes of lung inflammation (e.g., pneumonia) can be excluded on clinical grounds.

BAL has not gained widespread acceptance as a diagnostic tool for ARDS, because most ICU physicians use the diagnostic criteria to evaluate possible ARDS.

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MANAGEMENT OF ARDS General principles & supportive care

Role of NIV

Lung-Protective Ventilation Protocol• LVV & VILI• Permissive hypercapnia• PEEP & Open lung ventilation• Lung Recruitment - Recruitment maneuvers• Mode of ventilator• Approach to patient-ventilator dyssynchrony• Role of Neuromuscular blockers

Management of Refractory Hypoxemia• Prone Position

• Other Modes of ventilation

• IRV

• Inhaled Nitric Oxide

• ECMO

Non Ventilatory Management Fluid management

Diuretics

Steroids

Blood Transfusion cut-off

Choice of Inotropic agent

Other drugs/Therapies

Prognosis

Future/Research & Role of stem cell

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Management of ARDS:-

General Principles:

(1) Early recognition and treatment of the underlying medical and surgical disorders (e.g., sepsis, aspiration, trauma);

(2) Minimizing procedures and their complications;

(3) Prophylaxis against venous thromboembolism, gastrointestinal bleeding, and central venous catheter infections;

(4) Prompt recognition of nosocomial infections; and provision of adequate nutrition, Glucose control.

(5) Use of sedatives and neuromuscular blockade

(6) Hemodynamic management

(7) Ventilatory strategies to decrease tidal volume (Vt) while maintaining adequate oxygenation

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MANAGEMENT OF HYPOXEMIA

Decrease oxygen consumption

Increase oxygen delivery

Ventilatory strategies (LPV)

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DECREASE OXYGEN CONSUMPTION

In diseases with severe pulmonary shunting, increasing the saturation of mixed venous blood (SvO2 ) may increase the SaO2 . Therapies that decrease oxygen consumption may improve SvO2

(and SaO2 subsequently) by decreasing the amount of oxygen extracted from the blood.

Common causes of increased oxygen consumption include fever, anxiety and pain, and use of respiratory muscles; therefore, arterial saturation may improve after treatment with anti-pyretics, sedatives, analgesics, or paralytics

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INCREASE OXYGEN DELIVERY

DO 2 = 10 x CO x (1.34 x Hgb x SaO 2 + 0.003 x

PaO 2 )

where DO 2 is oxygen delivered, CO is cardiac

output, Hgb is hemoglobin concentration, SaO 2 is

the arterial oxygen saturation, and PaO 2 is the

partial pressure of oxygen in arterial blood. As a

result, in addition to low SaO 2 , DO 2 may be

decreased by a low Hgb and a low CO. In turn, a

low DO 2 may decrease SvO 2 .

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ROLE OF NIV

No trials have compared NIV to invasive mechanical

ventilation, and the only evidence at present is studies such

as that by “Ferrer et al” in which NIPPV is compared with

supplemental oxygen by face mask alone. In this particular

trial, NIPPV was associated with decreased need for

intubation compared with oxygen by face mask in the

overall study population, but among patients with ARDS,

there were no differences in outcomes.

Their use should only be considered in patients with mild

disease (PaO2/FIO2 > 200 and no other organ dysfunction)

and immunocompromised patients who are

hemodynamically stable, able to tolerate wearing a face

mask, and able to maintain a patent airway.

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PaO2 55-80 mmhg

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The slope of this relationship represents the compliance of the respiratory system, and the goal

should be to ventilate patients on the steepest portion of the relationship where smaller pressure

changes are necessary to achieve the desired tidal volume. Lowering the tidal volume helps avoid

the upper, flat portion of this relationship (A), where large changes in pressure are necessary to

achieve small volume changes. Application of positive end-expiratory pressure helps avoid the

lower, flat portion of this relationship (B) by preventing repetitive opening and closing of the

alveoli.

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Lung-Protective Ventilation:

Since the introduction of positive-pressure mechanical ventilation, large inflation volumes(TV) were used to ↓tendency for atelectasis during MV.

The standard tidal volumes were 10 to 15 mL/kg, which are twice the size of tidal volumes used during quiet breathing (6 to 7 mL/kg).

In patients with ARDS, these large inflation volumes are delivered into lungs that have a marked ↓in functional volume. → VOLUTRAUMA.

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CXR in ARDS show homogeneous pattern of lung infiltration.

CT images reveal that the lung infiltration in ARDS is not spread evenly throughout the lungs, but rather is confined to dependent lung regions

The remaining area of uninvolved lung is the functional portion of the lungs in ARDS.(baby lungs)

The large inflation volumes delivered by mechanical ventilation cause overdistentionand rupture of BABY LUNG→ Ventilator-induced lung injury.

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Ventilator-Induced Lung Injury

MECHANISM

The following mechanisms of lung injury have been described:

1) Atelectrauma : collapse of alveoli and surfactant depletion. Ventilation with high FiO2

aggravates alveolar collapse due to absorption atelectasis

2) Oxygen toxicity : While this is well known, it is not clear what concentration of oxygen is

toxic over what period of time. It is generally assumed that FiO2 <0.6 is not toxic, however

an attempt must be made to maintain the FiO2 as low as possible.

3)Volutrauma : Ventilation at high volumes and pressures can lead to alveolar

overdistension, causing increased permeability pulmonary edema in the uninjured lung and

enhanced edema in the injured lung.

4)Cyclical shear stress injury : Cyclic opening and closing of atelectatic alveoli during

mechanical ventilation create tremendous shear stress at their junctions with open alveoli.

This results in damage to the capillary endothelium and the alveolar membrane.

5)Biotrauma : Alveolar over-distension along with the repeated collapse and reopening of

the alveoli can result in a whole cascade of proinflammatory cytokines which induce both a

pulmonary and systemic cytokine response, aggravating lung injury and causing systemic

multiorgan dysfunction.

6)Barotrauma : Pneumothorax, pneumomediastinum, interstitital emphysema.

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Lung-Protective Ventilation:

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Low-Volume Ventilation(LVV)

LVV protocol is designed to achieve three

goals :

Maintain a tidal volume of 6 mL/kg using

predicted body weight,

Keep the end-inspiratory plateau pressure

below 30 cm H2O, and

Avoid severe respiratory acidosis.

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MEDIAN ORGAN FAILURE

FREE DAYS

6ml/kg.

12ml/kg

.

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Permissive Hypercapnia

One of the consequences of low volume ventilation is a reduction in CO2 elimination via the lungs leading to hypercapnia and respiratory acidosis. Allowing hypercapniato persist in favor of maintaining lung-protective low-volume ventilation is known as permissive hypercapnia.

The degree of hypercapnia can be minimized by using the highest respiratory rate that does not induce auto-PEEP and shortening the ventilator tubing to decrease dead space. In addition, changing from a heat and moisture exchanger to a heated humidifier appears to decrease hypercapnia by decreasing dead space ventilation

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One of the more troublesome side effects of hypercapnia

is brainstem respiratory stimulation with subsequent

hyperventilation, which often requires neuromuscular

blockade to prevent ventilator asynchrony.

Data from clinical trials of permissive hypercapnia show

that arterial PCO2 levels of 60 to 70 mm Hg and

arterial pH levels of 7.2 to 7.25 are safe for most

patients .

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OPEN LUNG VENTILATION It is a stratergy that combines low tidal volume ventilation & enough

applied PEEP to maximize alveolar recruitment. The LTVV aims to

mitigate alveolar overdistention, while the applied PEEP seeks to

minimize cyclic atelectasis. Togather , these effects are expected to

decrese the risk of ventilator associated lung injury.

LTVV is applied as described and applied PEEP is set at least 2 cm

above the lower inflection point of the pressure volume curve are

used. Applied PEEP of 16 cm H 2 O is used if the lower inflection point

is uncertain.

Alternative approach : PEEP set at a high level following a recruitment

maneuver and then incrementally decreased until both the static lung

compliance decreased and the sPO2 decreased by 2% from the

previous measurement. The PEEP is then set 2 cm H 2 O above this

level.

PEEP adjustment based on the PEEP–FIO2 protocol used in ARMA is

likely the most feasible approach until more data are available.

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STRATEGY………..?

Aerated

Non aerated recruitable

Non aerated Non recruitable

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Titration of PEEP by oxygenation after assessment of lung recruitability. PEEP/FIO2

tables are from the ALVEOLI Trial. Adjust PEEP and FIO2 using the two tables as

guidelines to maintain PaO2 between 55 and 80 mmHg or SpO2 between 88% and

95%.

*Consider the using lower PEEP table as a guideline for PEEP titration for

patients who have active barotrauma or adverse PEEP-induced cardiovascular

changes.

(or decrease in PaCO2 at constant minute ventilation and tidal

volume)

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Positive End-Expiratory Pressure:

The high PEEP approach is a type of open lung ventilation that does not require pressure-volume curves. This is advantageous because pressure-volume curves are difficult to construct and generally require neuromuscular blockade.

Significance of PEEP:

Applied PEEP opens collapsed alveoli, which decreases alveolar overdistension because the volume of each subsequent tidal breath is shared by more open alveoli. If the alveoli remain open throughout the respiratory cycle, cyclic atelectasis is also reduced. Alveolar overdistensionand cyclic atelectasis are the principal causes of ventilator-associated lung injury.

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TITRATING PEEP BY ESOPHAGEAL PRESSURE

Esophageal pressure is an estimate of pleural pressure. It can be measured with an esophageal balloon catheter and then used to calculate the transpulmonary pressure.

Transpulmonary pressure = airway pressure -pleural pressure

The transpulmonary pressure can then be adjusted by titrating applied PEEP, since airway pressure is related to applied PEEP. Titrating applied PEEP to an end-expiratory transpulmonary pressure between 0 and 10 cm H 2 O may reduce cyclic alveolar collapse, while maintaining an end-inspiratory transpulmonary pressure ≤25 cm H 2 O may reduce alveolar overdistension.

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• PEEP by acting as a “stent” to keep small airways open at the end of expiration and ↓ shear forces.

• Advantages of PEEP:

• PEEP ↑arterial oxygenation by ↓ intra pulmonary shunting.

• Allows reduction in (FiO2) to safer levels hence ↓oxygen toxicity.

• PEEP can also open collapsed alveoli and reverse atelectasis - known as lung recruitment, and it increases the available surface area in the lungs for gas exchange

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Pitfalls of PEEP:

Increased applied PEEP has the potential to cause pulmonary barotrauma or ventilator-associated lung injury by increasing the plateau airway pressure and causing alveolar overdistension. It also has the potential to decrease blood pressure by reducing cardiac output.

“High applied peep should be administered to the

patients with refractory hypoxemia before implimenting

other rescue interventions because ARDS patients are a

heterogenous group , some of whom may have large

areas of recruitable lung that will respond to applied

PEEP.”

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LUNG RECRUITMENT

If there is recruitable lung, then PEEP will have a favorableeffect and will improve gas exchange in the lungs. However if there is no recruitable lung, PEEP can overdistend the lungs (because the lung volume is lower if areas of atelectasis cannot be aerated) and produce an injury similar to ventilator-induced lung injury.

Areas of atelectasis that contain pockets of aeration are most likely to represent recruitable lung, whereas areas of atelectasis that are airless are unlikely to be recruitable.

The impact of routine recruitment maneuvers on clinical outcomes is unclear, although one meta-analysis found that recruitment maneuvers did not affect mortality, length of hospital stay, or the incidence of barotrauma, despite improving the PaO 2 .

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RECRUITMENT MANEUVERS (RMS)

Current evidence suggests that that RMs should not be routinely used on all ARDS patients unless severe hypoxemia persists or as a rescue maneuver to overcome severe hypoxemia, to open the lung when setting PEEP, or following evidence of acute lung derecruitment such as a ventilator circuit disconnect

• Vital capacity maneuver (inflation of the lungs up to 40 cm H2O, maintained for 15 - 26 seconds)

• Intermittent sighs

• Intermittent increase of PEEP

• Continuous positive airway pressure (CPAP) of 35-40cm of H20 for 40 seconds.

• Increasing the ventilatory pressures to a plateau pressure of 50 cm H2O for 1-2 minutes .

• One study found that most of the alveolar recruitment occurred during the first ten seconds of the maneuver . This was followed by a decrease in the blood pressure, which recovered within 30 seconds after the recruitment maneuver. Significant airway overdistentiondoes not occur while single recruitment manuevre and recruited alveoli tend to remain open when lower pressure are instituted.

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RECRUITMENT MANEUVERS

Anesthesiology 2002, 96:795–802.

CPAP : 35-40 cm H20 for 30-40 seconds

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RECRUITMENT MANEUVERS

Anesthesiology 2002, 96:795–802.

Curr Opin Crit Care 2003; 9:22–27

Crit Care Med 2004; 32: 2371–77

Intermittent Sigh

Intermittent PEEP

Progressive PEEP

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MODE OF VENTILATOR

Randomized, controlled trials demonstrating superiority of volume

assist control over other modes in the management of ARDS are

lacking at this time, but it is the mode used in the majority of major

clinical trials in patients with ARDS and was the mode used in the

ARMA trial, which, as noted above, showed a clear mortality benefit.

PCV : Variable flow, so more comfortable if dyssynchrony, prolong i

time for oxygenation, control peak pressures

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NEUROMUSCULAR BLOCKERS

Administration of short-term (up to 48 hours)

neuromuscular blockade to patients with ARDS who

have severe gas exchange abnormalities (eg, PaO 2

/FiO 2 ≤120 mmHg) is probably safe and potentially

beneficial.

Improvements in patient–ventilator synchrony and

elimination of muscle activity and the associated oxygen

consumption,

Papazian L, Forel JM, Gacouin A, et al. Neuromuscular

blockers in early acute respiratory distress syndrome. N

Engl J Med 2010; 363:1107.

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REFRACTORY HYPOXEMIA

Following modalities are used for Refractory

Hypoxemia apart from N-M Blockers, High PEEP

& other recruitment maneuvers

Prone Position

Other modes of ventilator

IRV

Inhaled Nitric Oxide

ECMO

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Prone position:

In several trials, MV in the prone position improves oxygenation. Other purported benefits include improvements in secretion clearance, increased end-expiratory volume, and decreased mechanical compression of the lungs by the heart.

Switching from the supine to prone position can improve pulmonary gas exchange by diverting blood away from poorly aerated lung regions in the posterior thorax and increasing blood flow in aerated lung regions in the anterior thorax.

The latest PROSEVA (Proning Severe ARDS Patients) trial confirmed these benefits in a formal randomized study. The bulk of data indicates that in severe acute respiratory distress syndrome, carefully performed prone positioning offers an absolute survival advantage of 10–17%, making this intervention highly recommended in this specific population subset.

Can be hazardous, leading to accidental endotracheal extubation, loss of central venous catheters, and orthopedic injury, pressure sores etc.

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POSSIBLE MECHANISMS

Recruitment of dependent lung zones,

Increased functional residual capacity (FRC)

Improved diaphragmatic excursion

Increased cardiac output

Improved ventilation-perfusion matching

Relief of compression of the lung by the heart and

Mediastinal structures

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OTHER MODES OF MV :

AIRWAY PRESSURE RELEASE VENTILATION (APRV):

Another “open lung” approach

It is a pressure control mode with spoteneous breaths; CPAP released periodicaly.

Two CPAP levels Higher CPAP is baseline pressure

Intermittent, brief release of Paw from higher CPAP level to lower CPAP level

Decrease in Paw augments TV

Spontaneous breathing at both upper & lower CPAP

Available on few ventilators

Like BiPAP/BiLevel but time at the lower pressure (“release time”) is usually short 0.6-1sec

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APRV

Airway Pressure Release Ventilation

From Mosby’s R. C. Equip. 6th ed. 1999.

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Inverse ratio ventilation (IRV)

Oxygenation can also be improved by increasing mean airway pressure with "inverse ratio ventilation."

The inspiratory (I) time is lengthened so that it is longer than the expiratory (E) time (I:E ratio as high as 7:1 have been used).

When the inspiratory time is increased, there is an obligatory decrease in the expiratory time. This can lead to air trapping, auto-PEEP, barotrauma, hemodynamic instability, and decreased oxygen delivery.

↓ FIO2 to 0.60 to avoid possible oxygen toxicity,

But no mortality benefit in ARDS has been demonstrated.

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o There are potential side effects associated with

prolonging the inspiratory time that should be

considered.

o In addition, a prolonged inspiratory time may require

significant sedation or neuromuscular blockage,

particulary if the inspiratory time surpasses the

expiratory time.

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High-frequency ventilation (HFV) –

High frequency oscillatory ventilation (HFOV) delivers

small tidal volumes (1–2 mL/kg) using rapid pressure

oscillations (300 cycles/min). The small tidal volumes

limit the risk of volutrauma, and the rapid pressure

oscillations create a mean airway pressure that

prevents small airway collapse and limits the risk of

atelectrauma.

HFOV requires a specialized ventilator

Partial liquid ventilation (PLV) with perfluorocarbon,

an inert, high-density liquid that easily solubilizes

oxygen and carbon dioxide, has revealed promising

preliminary data on pulmonary function in patients with

ARDS, but no survival benefit.

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INHALED NITRIC OXIDE

Inhaled nitric oxide (5–10 ppm) is a selective

pulmonary vasodilator that can improve arterial

oxygenation in ARDS by increasing flow to areas of

high dead space ventilation. iNO flows only into well

ventilated areas, so improves shunt.

However, the increase in arterial oxygenation is

temporary (1–4 days), and there is no associated

survival benefit

Adverse effects of inhaled nitric oxide include

methemoglobinemia (usually mild) and renal

dysfunction.

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EXTRA CORPOREAL MEMBRANE OXYGENATION:-

Extracorporeal membrane oxygenation (ECMO) is the use of a modified heart–lung machine to provide respiratory, circulatory, or both support at the bedside, usually for at least a number of days or even weeks.

Extracorporeal membrane oxygenation (ECMO) uses technology derived from cardiopulmonary bypass (CPB) that allows gas exchange outside the body. In addition, circulatory support can also be provided.

ECMO is a valuable option for the management of severe but reversible causes of respiratory failure or cardiogenic shock refractory to conventional treatment.

Veno-venous ECMO is designed to provide gas exchange, while veno-arterial ECMO provides both gas exchange and haemodynamic support.

Acute respiratory distress syndrome associated with pneumonia (viral or bacterial) is the most common cause of refractory hypoxemia that requires ECMO support.

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NON-VENTILATORY MANAGEMENT

Fluid management

Diuretics

Steroids

Blood Transfusion cut-off

Choice of Inotropic agent

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Fluids management:

Patients with ARDS should receive intravenous fluids only sufficient to achieve an adequate cardiac output, tissue oxygen delivery, and organ function, as assessed by urine output, acid-base status, and arterial pressure.

Once the patient is beyond the early, resuscitative phase of their illness, efforts should be made to decrease the amount of volume administered and maintain an even balance between the volume of fluid administered to and eliminated from the patient, referred to as “euvolemia”. The benefits of this approach were demonstrated in the Fluid and Catheter Treatment Trial (FACTT) .There were no differences in 60-day mortality between the two groups, but the conservative approach was associated with improved gas exchange and shorter duration of mechanical ventilation without increasing the incidence of acute kidney injury or other non-pulmonary organ failures.

Goal: MAP ≥ 65mmHg, avoid hypoperfusion

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Fluid management in ARDS is usually aimed at reducing

extravascular lung water with diuretics. While this approach

has shown modest benefits in clinical measures like lung

compliance, gas exchange, and length of time on the

ventilator, but little survival benefit.

The first problem with the use of diuretic therapy in ARDS

is the nature of the lung infiltration. While diuretics can

remove the watery edema fluid that forms as a

consequence of heart failure, the lung infiltration in ARDS

is an inflammatory process, and diuretics don't reduce

inflammation.

Diuretic therapy can be tailored to achieve the lowest

cardiac filling pressures that do not compromise cardiac

output and systemic oxygen transport.

ROLE OF DIURETICSvitra

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The golden rule is that hydrostatic pressures should be

kept as low as possible, provided that oxygen delivery to

the tissues is not compromised .

As techniques to monitor the regional circulation become

available, titration of fluid requirements will become more

precise.

There is no place for systematic fluid restriction and

diuretics to eliminate edema, as the function of other

tissues may deteriorate with inadequate perfusion.

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ROLE OF STEROIDS

IN UNRESOLVING ARDS

Because of apparent benefit in small trials, it was thought that there might be a role for high-dose corticosteroid therapy in patients with late (fibroproliferative phase) ARDS. However, an ARDS Study Network trial of methylprednisolone for patients with ARDS persisting for at least 7 days demonstrated no benefit in terms of 60-day mortality.Patients treated later in the course of ARDS, 14 days after onset, had worsened mortality with corticosteroid therapy.

The benefit of steroids in ARDS may be explained by the ability of steroids to promote collagen breakdown and inhibit fibrosis

One of the successful regimens involved methylprednisolone in a dose of 1-2 mg/kg/day.

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1.Steinberg KP, Hudson LD, Goodman RB, et al found that in the subgroup of patients randomized 7 to 13 days after the onset of ARDS, methylprednisolone caused a non-statistically significant reduction in 60-day mortality (27 versus 36 percent) and 180-day mortality (27 versus 39 percent). In contrast, among patients randomized more than 14 days after the onset of ARDS, methylprednisolone increased 60-day mortality (35 versus 8 percent) and 180-day mortality (44 versus 12 percent). Methylprednisolone increased ventilator-free days, shock-free days, oxygenation, lung compliance, and blood pressure, but also increased neuromuscular weakness.

2. In a double-blind trial, patients with early ARDS (defined as ≤72 hours), Meduri GU, Golden E, Freire AX, et al found that glucocorticoid therapy reduced the duration of mechanical ventilation, length of ICU stay, and ICU mortality (21 versus 43 percent).

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HEMOGLOBIN

Transfusion is often recommended to keep the Hb

above 10 g/dL, but this practice has no scientific

basis or documented benefit, even in ventilator-

dependent patients.

Considering that blood transfusions can cause

ARDS, it is wise to avoid transfusing blood products

in patients with ARDS AND threshold should be 7

g/dL.

If there is no evidence of tissue dysoxia or

impending dysoxia (e.g., an oxygen extraction ratio

>50%), there is no need to correct anemia with

blood transfusions.

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INOTROPIC AGENT

Cardiac output may be augmented by raising filling pressures if they are low (if pulmonary edema is not exacerbated) or by using inotropic agents. However, raising oxygen delivery to supernormal levels is not clinically useful and may be harmful in some circumstances.

If volume infusion is not indicated, dobutamine is preferred over vasodilators for augmenting the cardiac output because vasodilators will increase intrapulmonary shunt and will add to the gas exchange abnormality in ARDS. Dopamine should be avoided in ARDS because it constricts pulmonary veins, and this will cause an exaggerated rise in the pulmonary capillary hydrostatic pressure.

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OTHER DRUG THERAPY – UNPROVEN BENIFIT

INHALED VASODILATORS : PGE1 (pulmonary vasodilatation and anti-inflammatory effects on neutrophils/macrophages) , Aerosolized PGI2 (selective pulmonary vasodilatation of ventilated lung areas), NO

GM-CSF

Almitrine (selective pulmonary vasoconstrictor of nonventilated lung areas)

Surfactant (prevents alveolar collapse and protects against intrapulmonary injury and infection)

Antioxidants - dietary oil supplementation – Omega-3 fatty acid, N-acetylcysteine (protect the lung from free oxygen radical production)

Anti-inflammatory drugs (Lisofylline, Ibuprofen, ketoconazole, Statin)

No recommendation can be made for their use - Rescue modality in the patient with refractory hypoxia?

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Mortality:

Recent mortality estimates for ARDS range from

26 to 58% with substantial variability.

The underlying cause of the ARDS is the most

common cause of death among patients who die

early. In contrast, nosocomial pneumonia and

sepsis are the most common causes of death

among patients who die later in their clinical

course . Patients uncommonly die from

respiratory failure.

Thus, improvement in survival is likely secondary

to advances in the care of septic/infected

patients and those with multiple organ failure.

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Functional Recovery in ARDS Survivors

o ARDS pts experience prolonged respiratory failure and remain dependent on mechanical ventilation for survival.

o Patients usually recover their max lung function within 6 mnths.

o One year after endotracheal extubation, over a 1/3 of ARDS survivors have normal spirometry values and diffusion capacity.

o Most of the remaining patients have only mild abnormalities in their pulmonary function.

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Recovery of lung function is strongly associated with the

extent of lung injury in early ARDS

When caring for ARDS survivors it is important to be

aware of the burden of emotional and respiratory

symptoms.

There are significant rates of depression and

posttraumatic stress disorder in ARDS survivors

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FUTURE DIRECTIONS:

With the high mortality rates associated with ARDS and sepsis, the search continues to identify targets.

Effective anti-sepsis interventions may reduce the incidence of ARDS and improve outcomes from it.

1) Antibodies against macrophage migration inhibitory factor (MIF),

2) Antibodies against high-mobility group B-1 protein (HMGB1),

3.) Stem cell therapy (MSC)

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ROLE OF STEM CELLS – PHASE-I CLINICAL

TRAIL GOING ON

Stem cells constitute a promising therapeutic strategy for patients suffering from ALI/ARDS.

MSCs appear closest to clinical translation, given the evidence that they may favourably modulate the immune response to reduce lung injury, while maintaining host immune-competence and also facilitating lung regeneration and repair.

However, gaps remain in our knowledge regarding the mechanisms of action of MSCs, the optimal MSC administration and dosage regimens, and the safety of MSCs in critically ill patients. It is anticipated that these remaining knowledge deficits will be addressed in ongoing and future studies.

Other stem cells, such as ESCs and iPCs, are at an earlier stage in the translational process, but offer the hope of directly replacing injured lung tissue.

Ultimately, lung-derived stem cells may offer the greatest hope for lung diseases, given their role in replacing and repairing the native damaged lung tissues.

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JAMA, June 20, 2012—Vol 307, No. 23 : Berlin Definition

Harrison‘s Principles Of Internal Medicine 19th Edition

The ICU Book, 3rd Edition - Paul L. Marino

UpToDate : www.uptodate.com

eMedicine : www.medscape.com

Mechanical ventilation 3rd Edition - David W Chang

Susen Pilbeam Text Book Of Mechanical Ventiltor

Human Mesenchymal Stem Cells For Acute Respiratory Distress Syndrome (START)Clinicaltrial : http://clinicaltrials.gov/show/NCT01775774

M, Luks Andrew. 2013. "Ventilatory strategies and supportive care in acute respiratory distress syndrome." Influenza and other respiratory viruses 7 Suppl 3: 8-17. doi:10.1111/irv.12178.

Carl F. Haas, MLS, RRT “Mechanical Ventilation with Lung Protective Strategies: What Works?” Crit Care Clin 27 (2011) 469–486

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QUESTIONS…….?

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THANK YOU

THANK YOU

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