Presented by-

Dr.RAKESH KARNAWAT

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.

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

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

BERLIN CRITERIAInternational expert panel met in 2011

The goal of developing the Berlin definition was to try and improvefeasibility, reliability, face and predictive validity for mortality comparedwith the AECC definition JAMA2012;307:2526–2533

1. Lung injury of acute onset, within 1 week of an apparent clinical insultand with progression of respiratory symptoms

2. Bilateral opacities on chest imaging not explained byother pulmonary pathology (e.g. pleural effusion, pneumothorax ornodules)

3. Respiratory failure not explained by heart failure or volume overload4. 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.

CAUSES OF ARDS/TYPESDirect 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

EDEMA

HYALINE MEMBRANES

INTERSTITIALS INFLAMMATION

INTERSTITIAL FIBROSIS

FIBROSIS

EXUDATIVE PROLIFERATIVE FIBROTIC

DAY 0-7 14 21..

Clinical course and pathophysiology

Lancet 2007; 369:1553-65

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

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

mortality

CHEST X-RAYProgression from diffuse interstitial infiltrates to diffuse, fluffy, alveolar opacities

CT SCAN-ARDS

EXUDATIVE AND FIBROTIC PHASES

Reticular opacities - suggesting the development of interstitial fibrosis.

MANAGEMENT

Mechanical ventilation

Supportive measures

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

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

NIH ARDS NET MV PROTOCOL*PART I: Ventilator set up and adjustmentFIRST 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

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.

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.

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

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.

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.

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

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

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

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 secretionsImprovement 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

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

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 PATIENTS WITH ACUTE LUNG INJURY: JAMA 2004; 291:1603–1609.

KINETIC THERAPYBy 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.

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.

NONCONVENTIONAL VENTILATORY SUPPORT

1. HIGH FREQUENCY OSCILLATION

2. EXTRACORPOREAL SUPPORT

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 RESPIR CRIT CARE MED 2002;166:801–808.

OSCILLATOR HIGH FREQUENCY

VENTILATION

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.

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

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.

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

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]

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.

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.

Future non-ventilatory therapeutic optionsGene 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.

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

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

- Martin J. Tobin, MD

THANK YOU