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ACUTE RESPIRATORYDISTRESS SYNDROME

Dr RAHUL ARORA

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ETIOLOGY &

PATHOGENESIS

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ARDS- Definition

Acute Respiratory Distress Syndrome is diffuse pulmonary parenchymal injury associated with :

Non Cardiogenic Pulmonary Edema resulting in severe respiratory distress and hypoxemic respiratory failure

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Distinguishing cardiogenic from non- cardiogenic pulmonary oedema.

CARDIOGENIC

Heart disease. Third heart sound Central distribution

of infiltrates Widening of

vascular pedicles.

NON- CARDIOGENIC

Absence of heart disease

No third heart sound Peripheral distribution Normal width of

vascular pedicle

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History of ARDS

Petty Ashbaugh Severe Dyspnea, Tachypnea

et. al ,1971 Cyanosis refractory to O2

Decreased Pulmonary

compliance

Atelectasis, vascular congestion,

hyaline membrane at autopsy.

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History contd….

Murray et al Preexisting Lung injury

1988 Mild to moderate or

severe lung injury

Non pulmonary organ

dysfunction

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History contd….

Bernard et Acute onset

al 1994 Bilateral infiltrates on

chest x-ray

PAWP <18 Mm Hg

Absence of clinical evidence

of left atrial hypertension

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Synonyms

Adult hyaline membrane disease Congestive atelectasis Progressive pulmonary consolidation Hemorrhagic atelactasis Pump lung Shock lung Wet lung White lung

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DAD(Diffuse Alveolar Damage ) DAD is a series of consistent although non

specific pathological change in the lung that result from any injurious factor that damage

ENDOTHELIUM or ALVEOLAR EPITHELIUM

1) BRONCHIOLITIS OBLITERANS ORGANISING

PNEUMONIA 2) ACUTE INTERSTITIAL PNEUMONIA

DAD follows known catastrophic event that result in ARDS

Sudden idiopathic Respiratory failure without history of catastrophic event seen in AIP

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Inflammatory reaction

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components of DAD

Initiating Agents activation of inflammatory cascade Lung sequestration of neutrophils Release of neutrophilic cytotoxic products

ALVELOAR WALL INJURY

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AETIOLOGY

PULMONARY EXTRA-PULMONARY

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Etiology (contd….)

Direct lung injury(pulmonary)

Pneumonia ( most common ) Aspiration Pulmonary contusion Fat emboli Near drowning Inhalation injury Oxygen Transthoracic radiation Reperfusion pulmonary oedema after Lung

Transplantation

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Etiology (contd….)

Indirect lung injury ( Extra-pulmonary)

Sepsis (most common) – bacterial/viral/parasitic Sever Trauma with Shock Cardio Pulmonary Bypass Drug overdose Acute Pancreatitis Transfusion of blood products Hypothermia Eclampsia Embolism

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TRALI :

Sudden onset of non-cardiogenic

pulmonary edema Often with systemic hypovolemia and

hypotension occuring during or within few

hours of transfusion Thought to be resulting from interaction of

specific leucocyte antibodies with leucocytes

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ARDS

A : ASPIRATION

R : ROAD TRAFFIC ACCIDENTS

D : DIFFUSE ALVEOLAR DISEASE

S : SEPSIS

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Pathogenesis of ARDS

Focus of infection Endotoxin

Complement direct cellular CellularActivation injury activation

Clotting cascade cytokine act. And proteolytic enzymes

MODS (lung, heart,GI, kidney, brain )

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Inflammatory mediators

Cytokines Complement proteins Coagulation proteins Prostaglandins Vaso-active peptides Platelet Activating Factor Neutrophil products

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PATHOPHYSIOLOGY & DIAGNOSIS

Dr Siva Krishna Kota

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Definition

Acute onset life threatening respiratory

failure with characteristic

ALI : PaO2/FiO2 < 300

ARDS : PaO2/FiO2 < 200

Physiological features

Pathological features

Radiologicalfeatures

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Pathophysiology

Profound inflammatory response secondary to a pulmonary or extrapulmonary insult.

Diffuse alveolar damage– acute exudative phase (1-7days)

– proliferative phase (3-10 days)

– chronic/fibrotic phase (> 1-2 weeks)

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(a) Exudative phase Basement membrane disruption

--Type I pneumocytes destroyed--Type II pneumocytes preserved

Surfactant deficiency

-- inhibited by fibrin--decreased type II cell production

-- impaired surfactant funtion

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Exudative phase

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Exudative phase

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Exudative phase (contd….)

Microatelectasis / alveolar collapse

-- interstitial edema

-- necrosed capillary endothelial

cell

-- alveolar cell + fibrin + plasma

protein together form hyaline

membrane

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Exudative phase (contd….)

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(b) Fibroproliferative phase

Type II pneumocyte proliferate -differentiate into Type I cells -reline alveolar walls -Regeneration of capillary endothelial cells

Fibroblast proliferation -interstitial/alveolar fibrosis -Lymphocytic infiltration -Collagen deposition

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Fibro-proliferative phase

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(c) Fibrotic phase

Characterized by:– local fibrosis– vascular obliteration

Repair process:– resolution or fibrosis depending on timing of intervention and management

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Clinico-pathological correlation

Stage I : unless direct lung injury is there clear on auscultation CXR unremarkableStage II : Hemodynamically stable no respiratory distress only mild tachypnea ( > 20/min ) ABG may show mild hypoxiaStage III:worsening hypoxemia dyspneic and cyanotic pt. ed work of breathing ed insp. pressure requirement in a patient on ventilator

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ARDS : Physiological features

A. Decreased lung compliance and volumes microatelectasis altered surfactant production & function FRC causes distal air trapping

B. Increased work of breathing in spontaneously breathing pts, increased ratio of Vd/Vt ratio.

respiratory failure unless assisted

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Physiological features (contd….)

C. Alteration in gas exchange (hypoxia) - perfusion of underventilated lung - perfusion of non ventilated lung - impaired diffusion - loss of HPV D. Pulmonary hypertension and RVF - pulmonary vasoconstriction - platelet aggregation and micro thrombosis - direct tissue damage & neurohormonal factors

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ARDS: Radiological feature

Vascular pedicle

< 55mm

No distention of UL zone vessels

Peripheral shadows

No pleural effusion

No septal lines

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Criteria for diagnosis

Clinical setting

Chest Xray findings

Physiological parameters

Pathological features

DIAGNOSIS

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Criteria for diagnosis

A. Clinical Settings : (i) pulm/extrapulm catastrophe (ii)exclusion of chronic pulmonary & left heart diseases (iii)clinical respiratory distress

B. CXRay : diffuse bilateral infiltrates sparing apex, cp- angle; with a narrow vascular pedicle

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Criteria for diagnosis ( cont..)

C. Physiologic parameters : (i) ABG :PaO2< 50 with FiO2 of > 0.6 (ii)Compliance < 50 ml/ cm of H2O (iii) shunt fraction (Qs/Qt>20%) (iv) dead space ventilation (Vd/Vt)

D. Pathologically -heavy lungs(>1kg), a post mortem finding -congestive atelectasis -hyaline membrane + fibrotic changes

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ALI (MURRAY) SCORE :

A. Chest Xray findings

(alveolar consolidation)

B. Oxygenation status

(PaO2 / FiO2 )

C. Pulmonary compliance

D. PEEP required

to maintain oxygenation

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ALI score (MURRAY-score) cont…..

1. Chest X film finding

Alveolar consolidation Score

One quadrant 1

Two quadrant 2

Three quadrant 3

Four quadrant 4

2. Oxygenation status

PaO2 / FiO2 Score

> 300 mmHg 0

225-299 mmHg 1

175-224 mmHg 2

100-174 mmHg 3

< 100 mmHg 4

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ALI score (MURRAY-score) cont…..

3. Pulmonary compliance

Compliance Score (ml/cmH2O)

> 80 0 60-79 1 40-59 2 20-39 3 < 19 4

4. PEEP settings

PEEP Score (cmH2O)

< 5 0 6-8 1 9-11 2 12-14 3 > 15 4

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ALI score (contd….)

Score:

0 = none,

0.1-2.5 = mild - moderate

> 2.5 = severe

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VENTILATORY MANAGEMENT OF ARDS

Dr Pallavi Marghade

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Treatment Strategies

Rx underlying cause

Respiratory therapy for adequate oxygenation/ventilation

Adjunctive therapies

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Aims of Respiratory therapy

to attempt to avoid tracheal intubation to reduce maximum pulmonary pressures

generated avoid high Fio2 to prevent oxygen toxicity maximise alveolar recruitment finally at minimal cost to the

cardiovascular system

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Conventional ventilation

Consists of large tidal volume of 10-15ml/kg

Arterial oxygenation supported by raising Fio2

Applying PEEP

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Ventilator-Induced Lung Injury(VALI)

Conventional ventilation

In injured lungs

High peak inflation and plateau pressure

Overdistention of alveoli

Volutrauma, Barotrauma, Induction of cytokines

MODS

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VALI : Volutrauma

Direct physical damage to A-C membrane

stress failure

sudden & rapid increase in permeability

Gattinoni described three areas of lung on CT

Can’t be ventilated can be expanded in insp. Normal lung at all but collapses during exp. (baby lung)

overdistention of alveoli with normal Vt

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Flow - Time

Paw - Time

Volume - Time

0

60

60

Flo

w L

/min

Paw

cm

H2O

VT

ml

0

0

20

600

Time

VCV

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VALI (contd…..)

Barotrauma - Application of excessive pressure to the alveoli

Air passes from damaged A-C membrane into the interstitium,pleural space,mediastinum

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Flow - Time

Paw - Time

Volume - Time

0

60

60

Flo

w L

/min

Paw

cm

H2O

VT

ml

0

0

20

600

Time

PCV

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VALI (contd….)

Cyclical airway closure –

Repeated opening & closing of airways with each tidal volume

Atelectrauma

Surfactant loss high forces needed to open closed lung unit

Epithelial damage

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How does PEEP work?

0

20

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Mechanism of PEEP

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PEEP Vs Fio2 : A Dilemma

PEEP reduces intrapulmonary shunt and improves arterial oxygenation at lower Fio2

PEEP cardiac output

pulmonary edema dead space resistance to bronchial circulation lung volume and stretch during inspiration

LUNG INJURY( more in direct lung injury)

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“Open-Lung ” Approach to PEEP

“Open-lung” approach– Not practical

– Does not improve outcomes

Optimal PEEP– ???

– Most cases: PEEP

15 – 20 cmH2O

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Fio2

No detectable oxygen toxicity Fio2< 50%

Diseased lungs more prone to injury due to hyperoxia

Fio2 < 0.6 considered to be safe

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Optimal PEEP

Maximize O2 delivery

DO2 = 10 x CO x (1.34 x Hb x SaO2)

Maximize lung compliance Crs = Vt/(Pplateau – PEEP)

Lowest PEEP to oxygenate @ FIO2 < .60

Empiric approach: PEEP = 16 cmH2O and Vt = 6 ml/kg

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ARDS Network protocol

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 18-22

0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0

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Lung-Protective Ventilation

VT = 6 mL/kg

Limit plateau pressures < 30 cmH2O

– Volume controlled ventilation

Limit peak airway pressures < 40 cmH2O

– Pressure controlled ventilation

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Outcome

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Lung-Protective Ventilation

Complications: (derecruitement)

– Elevated PaCO2

• Limit: pH > 7.20 –7.25

– Worsening hypoxemia• Correction:

– Recruitement maneuver – increasing PEEP

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Alternate Modes of Mechanical Ventilation

Non invasive ventilation Inverse-ratio ventilation Airway pressure-release ventilation Bilevel airway pressure ventilation Proportional-assist ventilation High-frequency ventilation Tracheal gas insufflation ECMO

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Non InvasivePositive Pressure Ventilation

Tight fitting face mask as a interface

between the ventilator and patient.

Pressure controlled ventilation to prevent

leaks Pressure support ventilation patient’s effort triggers the

ventilator

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NIPPV (contd….)

ADVANTAGES Can maintain verbal communication Can eat during therapy Decreased incidence of nosocomial pneumonia Shorter requirement of ventilator assistance and ICU stay DISADVANTAGES Not feasible in obtunded and delirious patients Additional time commitments from nurses and respiratory therapist

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Proportional-Assist ventilation

Elevates airway pressure during inspiration Inspiratory airway pressure varies directly

with pt’s effort allowing breath to breath variation

Inspiratory assistance can be customised to the elastance and resistance properties

Best mode to use with NIPPV

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Inverse Ratio Ventilation

Atelectatic alveoli are recruited and stabilised by increasing the duration of inspiration

I/E should be > 1 During PCV---- inspiratory time VCV---- using deccelerating flow or adding inspiratory pauseDisdvantages : Auto PEEP Uncomfortable requiring sedation/paralysis

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Flow - Time

0

60

60

Flo

w L

/min

I E I E

Normal ventilation

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0

60

60

Flo

w L

/min

I E I E I E

Reduce auto-PEEP by reducing I-time - Decrease respiratory rate - Decrease tidal volume - Increase Inspiratory flow rate

Inverse ratio ventilation

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Airway Pressure Release Ventilation

Similar to IRV but Pt. can breath spontaneously during prolonged period of increased airway pressure

Potential lung protective effects of IRV Air trapping occurs

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TRACHEAL GAS INSUFFLATION (TGI)

In ARDS/ALI1. Increase physiological dead space2. permissive hypercapnia

DURING CONVENTIONAL VENTILATION :Bronchi and trachea are filled with alveolar gas at end exhalation which is forced back into the alveoli during next inspiration.

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TGI (contd…..)

IN TGI Stream of fresh air (4 to 8 L/min) insufflated through a small catheter or through small channel in wall of ET into lower trachea flushing Co2 laden gas.

COMPLICATION1) Dessication of secretions 2) Airway mucosal injury 3) Nidus for accumulation of secretions4) Auto – PEEP

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HIGH FREQUENCY VENTILATION

Utilizes small volume (<VD) and high RR (100 b/min) Avoids over distention (VALI). Alveolar recruitment. Enhances gas mixing, improves V/Q.

APPLICATION : 1. Neonatal RDS.2. ARDS.3. BPF.

COMPLICATION :1. Necrotizing trachebronchitis. 2. Shear at interface of lung. 3. Air trapping.Two controlled studies (113 and 309) no benefit.

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Prone Ventilation

Proposed mechanism – how it improves oxygenation 1) Increase in FRC2) Improved ventilation of previously dependent regions.

(a) Difference in diaphragmatic supine: dorsal and ventral portion move

symmetrically prone :dorsal > ventral

PPL at dorsal Higher LessTP pressure Lower MoreResult Atelactasis opening

PPL

-3.0

+2.8

PPL

-1.0

+1.0Supine prone

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Prone ventilation (contd….)

c) Decrease chest wall compliance in p.p Redistribution of tidal volume to atelactatic dorsal region.

d) Weight of heart may affect ventilation.3. Improvement in Cardiac output 4. Better clearance of secretions 5. Improved lymphatic damage

Effect on gas exchange

Improves oxygenation – allows decrease Fio2; PEEP - Variable - not predictable

response rate – 50-70%

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Prone Ventilation (contd…)

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PRONE VENTILATION (contd….)CONTRAINDICATION

- Unresponsive cerebral hypertension - Unstable bone fractures - Left heart failure- Hemodynamic instability - Active intra abdominal pathology

TIMING ARDS > 24 hrs./ 2nd day FREQUENCY Usually one time per dayDURATION 2 to 20 hrs/day. OUTCOME Improvement in oxygenation No improvement in survival

POSITIONING ACHIEVED BY Circ electric, bed (Late 1970s).Manual 2 stepLight weight portable support frame (Vollman prone positioner)

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PRONE VENTILATION (contd….)NO. OF PERSONS 3-5POSITION OF ABDOMEN

allowed to protrude ; partial/complete restrictionPOSITION OF HEAD

Head down/ Head up position. ADEQUATE SEDATION +/- NMBACOMPLICATIONS

- pressure sore- Accident removal of ET; Catheters - Arrhythmia - Reversible dependent odema (Face, anterior chest wall)

Gattinoni et al, in a MRCT evaluated the effect of 7 hr / day prone positioning x 10 day improvement in oxygenation, no survival benefit

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EXTRACORPOREAL MEMBRANE OXYGENATION

Adaptation of conventional cardiopulmonary bypass technique.

Oxygenate blood and remove CO2 extracorporally.

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ECMO (contd….)TYPES

1. High-flow venoarterial bypass system.

2. Low-flow venovenous bypass system.

Criteria for treatment with extracorporeal gas exchange

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

Qs /Qt > 30%; Cstat <30 ml/cmH2O

Gattinoni showed decreased mortality to 50% by using ECMO as compared to 90% mortality in historical control group, therefore the results are encouraging

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ARDS study : KEM Hospital

Statistics:

study done over 2 years, mortality – 46.2% commonest etiology – pneumonia &

tropical diseases 50% of pts with renal and hematologic complication

didn’t survive MODS, LIS, APACHE-II were the mortality predictors

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ARDS study : KEM Hospital (contd….)

60% of pts required mechanical ventilation survivors spent less no. of days than the non

survivors on ventilator due to innate complication of mechanical ventilation

Use of steroids didn’t reduce mortalityPFT done in 7 survivors showed abnormality due

to both ARDS & VALI long term assessment was not possible because of

non-compliance of patients to follow up.

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ADJUNCTIVE THERAPYIN ARDS

Dr Prashant Pawar

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Adjunctive therapies

1. Treatment of infective complications/inciting cause2. Hemodynamic Management – Fluids, Vasopressors.3. Nutritional support4. Selective Pulmonary vasodilators.5. Surfactant replacement therapy. 6. Anti-inflammatory Strategies. a) Corticosteroids. b) Cycloxygenase & lipoxygenase inhibitors. c) Lisofylline and pentoxifylline.7. Antioxidants – NAC : Procysteine8. Anticoagulants.9. Partial liquid ventilation.

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Treatment of infective complications

Most common complication is nosocomial infection due to gram negative organisms and it is the major cause of death

Antibiotics to be chosen as per :• Initial insult of ARDS• Sputum culture best taken shortly after intubation• Bronchoalveolar lavage• Blood culture & sensitivity

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HEMODYNAMIC MANAGEMENT

Controversial Restrictive Fluid management Benefits shown by studies

pulmonary edema formation compliance and lung function • Negative fluid balance is associated with improved survival • Net positive balance <1 litre in first 36 hrs. associated with improved survival • decrease length of ventilation, ICU stay and hospitalization.

.

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Fluid management (contd..)

Detrimental effects Ineffective Circulatory Volume (Sepsis).

Reduced cardiac output and decreased tissue perfusion.

Goal Guidelines for management of tissue hypoxia International consensus conference (AJRCCM- 1996)

1. Promote oxygen delivery Adequate volume CVP – 8-12 mmHgPAOP-14-16 mmHg (Optimal CO; less risk of Edema)

2. Crystalloids vs Colloids:No clear evidence 3. Blood Transfusion : Hb < 10 gm/dl 4. Reduce oxygen demand :

a) Sedation : Analgesia, NMBAb) Treat Hyperpyrexia c) Early institution of mech. vent. (shock).

5. No role of supraphysiological. oxygen delivery.

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Vasopressors

Vasopressors Following restoration of intravascular volume to

euvolemic levels

(CVP:4-8cm of H2O, PCWP:6-14 mmHg) GOAL to achieve MAP 55 to 65 mmHg No clear evidence that any vasopressor or

combination of them is superior.

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Nutritional support

Goals of nutritional support nutrients as per pt’s metabolic demand Treatment & prevention of macro/micro nutrients deficiency. Enteral mode is to be preferred ( less infection and low cost) High fat, low carbohydrate diet es RQ, CO2 production and duration of ventilation Immunomodulatory nutrition like amino acids, omega-3 fatty acids. ( no survival benefit)

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Selective pulmonary vasodilators

1. Inhaled Nitric oxide (iNo)

2. iv almitrine with/without iNo.

3. Aerosolized prostacyclins.

4. Inhibition of cyclic nucleotide phosphodiesterase.

5. Inhalation of Endothelin receptor antagonists

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Inhaled nitric oxide

Mechanism : Endothelial derived relaxing factor Smooth muscle vasodilation through

activation of cyclic GMPBenefits in ARDs1. Improves Oxygenation 2. Improves V/Q mismatch.3. Reduction in pulmonary artery pressure4. Inhibits platelet aggregation and neutrophil adhesion.

Selectivity of iNORapid inactivation on contact with hemoglobin.

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Inhaled nitric oxide

DOSAGE:Effect Dose

Increase PaO2 1-2 ppm to <10 ppmdecrease PAP 10-40 ppm

Time of Response : <10 min to several hours. Response to iNo is not static phenomenon.

Mortality Benefits : None Possible role in severe refractory hypoxemia a/w PAH

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Inhaled nitric oxide

Side effects :

Usually Minimal

1. Rebound pulmonary hypertension & hypoxemia

2. Methemoglobinemia

3. Toxic NO2 ; Nitrous & Nitric Acid

Prevented by decreasing contact time & conc. of gas.

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Almitrine

Given iv : in low doses Potentates hypoxic pulmonary vasoconstriction Decreases shunt and thus improved oxygenation

Has additive effect with :

iNo

iNo + prone position

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Pulmonary vasodilators(contd…)

Prostacyclins: iv prostacyclin decreases pulmonary arterial pressure non selectively, can increase shunt; worsen

oxygenation. Inhaled prostacyclin selectively vasodilates the well ventilated areas Selectivity in dose of 17-50 ng/kg/min.

PGI2- Not metabolized in lung so lost at higher doses.

PGE1- 70-80% is metabolized in lung.

PDE –5 Inhibitors: Dipyridamole ; Sildenafil

Endothelin receptor antagonist Nonselective ET antagonist-bosentan Selective ETA 2 antagonist –LU-B1352

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Surfactant replacement therapy

Deficiency and functional abnormality of surfactant 1. Decreases production 2. Abnormal composition 3. Inhibitors of surfactant function4. Conversion of large to small surfactant aggregates 5. Alteration/Destruction caused by substances in alveolar space

(plasma, fibrinogen, fibrin, alb; Hb) Impaired surfactant function: 1) Atelactasis / collapse 2) Increase edema formation Benefits : Improved lungs function., compliance, oxygenation. Mortality benefits: none

Surfactant Delivery Techniques

Instillation Lavage Aerosolization

• Rapid

•Can deliver large volume

•Homogenous distribution

• May remove toxic substances.

•Can deliver large volume.

•Homogenous distribution.

Continuous smaller volume.

Non uniform distribution.

• Techn. Not

standardized • Short term

impairment in ventilation

• Vol. recover can be poor

• Short term impairment in ventilation.

Slow, no optimal device, Filters may plug.

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Anti inflammatory therapy

Glucocorticoids:No evidence of benefit in early sepsis/ARDSMethyl prednisolone in late stages associated

with improved LIS score & decreased mortalitySteroids

-Inhibit transcriptional activation of various cytokines -Inhibit synthesis of phospholipase A2 -Reduced production of prostanoids, PAF -Decreases Fibrinogenesis Increased Risk of Nosocomial Infection

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Anti infl. Therapy(contd….)

Lisophylline & Pentoxifyline

Phosphodiesterase inhibitor

-Inhibit neutrophil chemotaxis & activation

Lisophylline inhibits release of FreeFattyAcids from cell membrane under oxidative stress

NIH ARDS trial shows no benefits.

Ketoconazole

Potent inhibitor of thromboxane and LT synthesis

Reported to prevent ALI/ARDS in high risk surgical patients

NIH ARDS trial shows no benefits.

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Cycloxygenase inhibitors

TxA2 and Prostaglandin produced from AA by Cyclooxygenase pathway.

Cause

1. Neutrophil chemotaxis and adhesion

2. Broncho-constriction

3. vascular permeability

4. platelet aggregation Animal studies shown that Cycloxygenase inhibitors

attenuate lung injury ;and improve pulmonary hypertension and hypoxemia

Clinical trials of ibuprofen : No proven benefits

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Antioxidants therapy

Reactive oxygen metabolites derived from neutrophils, macrophages and endothelial cells

OXIDANTS INCLUDE

Super oxide ion (02-), hydrogen peroxide (H2O2)

hypochlorous acid (Hocl), hydroxyl radical (OH..) Interact with proteins, lipid and DNA ENDOGENOUS ANTIOXIDANTS Superoxide dismutase, Glutathione, Catalase Vit E & Vit C ; Sulfhydryls Antioxidant therapy

replenishing glutathione-cysteine derivatives : N-Acetyl Cysteine & procysteine Beneficial effects not proven

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ANTICOAGULANT THERAPY IN ARDS

In ARDS – Fibrin deposition intra-alveolar and interstitial.

Local procoagulant activity and reduced fibrinolysis.

Procoagulant Fibrinolysis

TF (VIIa) Fibrinolytic inhibitors

PAI–1 ; PAI-2, 2 antiplasmin

urokinase and tPA

Fibrin causes__

Inhibit surfactant atelactasis

with Fibrinonectin Matrix on which fibroblast aggregation

and fibroblast proliferation

Potent chemotactic (Neutrophil recruitment)

Lung vasculature PAH

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Activated Protein- C

Protein-c :Naturally occuring anticoagulant 1.Inactivates Va & VIIa – limit thrombin generation.2.Inhibit PAI-1 activity - fibrinolysis.3.Anti-inflam. - cytokines, inhibit apoptosis.

APC administ. Improved survival. absolute risk reduction in mortality Faster resolution of respiratory dysfuntion. Adverse effects Risk of bleeding Efficacy proved in severe sepsis

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ARDS and -agonists

ENHANCED RESOLUTION ALVEOLAR EDEMA Alveolar clearance of edema depends on active sodium transport across the alveolar epithelium

2 adrenergic stimulation :

1. Salmeterol 2. Dopamine3. Dobutamine

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Partial Liquid Ventilation

In ARDS there is increased surface tension which can be eliminated by filling the lungs with liquid (PFC).

Perflurocarbon: Colourless, clear, odourless, inert, high vapour pressure Insoluble in water or lipids Most common used – perflubron ( Perfluoro octy

bromide)Characteristics of PLV 1.Improved Compliance/ Gas exchange

2. Anti-inflam. properties 3.Decreased risk of nosocomial pneumonia.

4.Reduces pulmonary vascular resistance. 5.Little effect on hemodynamics

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Partial Liquid Ventilation (contd....)

Mechanism of action Reduces surface tension Alveolar recruitment – liquid PEEP. Selective distribution

to dependent regions. surfactant phospholipid synthesis and secretion. Anti Inflammatory properties A. Indirect : mitigation of VALIB. Direct

a) endotoxin stimulated release of TNF; IL-1; IL-8.

b) decreases production of reactive oxygen species.c) Inhibit neutrophil activation and chemostaxis. d) Lavage of cellular debris.

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Total Liquid

Ventilation

Partial Liquid

Ventilation

1. Ventilator Liquid Conventional

2. Tidal volume delivered of Oxygenated PFC Gas

3. Lungs are filled Completely by PFC

Filled till FRC by PFC

4. Feasibility Experimental Yes

5. Disadvantage Loss of gas by evap., cost.

Partial Liquid Ventilation (contd..)

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Partial Liquid Ventilation (contd..)

Recommended dose of PFC 20ml/kg

-Beyond this dose – decrease cardiac output

-More clinical trials are required to demonstrate efficacy. Additive effect of PLV has been

shown in combination with:-NO -Surfactant -HFOV -prone ventilation

Trials of PLV in ARDS confirmed safety but not efficacy.

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Mystery Unsolved

THRIVE FOR THE BEST

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What have we learnt?ALI- Syndrome of

pulmonary inflammation, vasoconstriction, greater permeability of both alveolar capillary endothelium & epithelium, non-cardiogenic pulmonary oedema

arterial hypoxemia resistant to O2

therapy, appearance of diffuse infiltrates on

X-ray chest

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ARDS

Not a single disease but rather a pathophysiologic syndrome

Catastrophic acute respiratory failure of diverse etiology & high mortality

No single test or marker to accurately diagnose or predict the outcome of ARDS

Represents the pulmonary expression of systemic inflammatory process

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ARDS

Associated with triggering events.Lungs bear the brunt of the injury as it

receives entire C O with exposure to circulating agents and

exposure to environmental insults during ventilation

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ARDSDysregulated inflammatory-reparative processes lung injury & repair

Important to understand the initiators & mediators of immunochemical response of ARDS & its effects O2 debt & tissue hypoxia , improper tissue O2 utilization

O2 debt from ↓ ed tissue perfusion organ failure ; monitoring O2 debt & optimizing peripheral tissue oxygenation imp; transcutaneous surface electrode for high risk surgical patients

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ARDS- notions about fluid therapy

Hypovolemia – major pathophysiologic factor of ARDS

Pulmonary edema – an effect, not the cause of ARDS

Fluid restriction may ↓ CO & tissue perfusion & worsen non pulmonary organ function

ARDS – an end organ failure of an antecedent hypovolemic-hypoxemic event except for ARDS caused by direct lung injury

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ARDS: Lung Protection Evidence supports a volume and pressure

limited approach In majority of patients with ARDS lung

recruitment and overinflation occur simultaneously in different lung regions as seen on CT imaging

• High PAP opens collapsed ARDS lung and partially opens oedematous ARDS lung.

• High PEEP and Low Vt decrease lung cytokines and survival.

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ARDS: Lung Protection

Use of high PEEP and Recruitment maneuvers may not help when low potential for recruitment.(consolidation)

Improving oxygenation by itself does not equate with improved outcome

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The Future

Quantify the degree of primary v secondary ARDS, to optimise ventilation strategy.

Monitor Real Time changes in ventilation

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The End

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