Ards

ARDSPresented by: Dr. Jaya Prakash SPreceptors : Prof. G.C. Khilnani

Dr. Vinay Gulati

DEFINITION First defined -1971 Severe dyspnea, tachypnea, cyanosis Decreased pulmonary compliance Diffuse alveolar infiltrates on radiography

Disadvantage: lacks specific criteria

DEFINITION Murray et al – 1988 Pre existing direct or indirect lung injury Mild to moderate or severe lung injury Lung injury score: level of PEEP ratio of pao2/ Fio2 static lung compliance degree of infiltration on CXR Non pulmonary organ dysfunction Disadvantage:

Score not predictive of outcome No specific criteria to exclude cardiogenic pulmonary

edema

Am Rev Respir Dis 1988;138:720

DEFINITIONAECCC – 1994 Acute onset

Bilateral infiltrates on CXR

PCWP < 18mmHg or no clinical evidence of increased left atrial pressure

PaO2/FiO2 < 300 = ALI PaO2/FiO2 < 200 = ARDS

Am j Respir Crit Care Med 1994;149:818

DEFINITIONADVANTAGES

Recognizes that, severity of lung injury varies Simple, easy to use

DISADVANTAGES Does not specify cause Does not consider multi organ dysfunction Radiographic findings not specific

Am j Respir Crit Care Med 1994;149:818

EPIDEMIOLOGY Earlier numbers unclear (vague definition) Using 1994 criteria1

17.9/100,000 for acute lung injury 13.5/100,000 for ARDS

Incidence of ALI 2

Age- adjusted = 86.2/100,000 person-years 15-19 years = 16/100,000 person-years 75-84 years = 306/100,000 person-years

1. Luhr OR et al AJRCCM 19992. Gordon D et al NEJM 2005

EPIDEMIOLOGY No data on incidence from India

Incidence in PICU = 20.1/1000 admission

Most common cause = pneumonia (65%)

Mean period between triggering cause and ARDS = 2.2 days

Mortality = 75%

. Kabra S K et al Indian Paediatrics 2001

PRECIPITATING CAUSESDirect lung injury Pneumonia Aspiration

Pulmonary contusion Fat emboli Near drowning Toxic inhalation

Indirect lung injury Sepsis Severe trauma

Cardiopulmonary bypass Drug over dose Acute pancreatitis Transfusion related lung

injury

RISK FACTORS Chronic alcohol abuse1

Hypoproteinemia

Advanced age

APACHE score2

1 JAMA 1996;275:502 AJRCCM1992;151:293

RISK FACTORS… Hyper transfusion of blood products

Lack of diabetes1

Smoking

1 Crit Care Med 2000;28:2187

PATHOPHYSIOLOGY

Three phases:

Exudative phase – 0-7 days Proliferative phase – 7-21 days

Fibrotic phase - >3 weeks

EXUDATIVE PHASE Endothelial injury & vascular permeability

Alveolar epithelial injury

Alveolar & interstitial space – protein rich edema fluid

Increased con. Cytokines – IL-1,IL-8 & TNF-α

Increased leucocytic infiltration

EXUDATIVE PHASE Atelectasis & diminished aeration - dependent edema

Intra pulmonary shunting & hypoxemia

Micro vascular occlusion – Increase in dead space

Pulmonary hypertension

PROLIFERATIVE PHASE

Day 7 to day 21 Initiation of lung repair Proliferation of type-II pneumocytes

Synthesize surfactant Differentiate to type-I pneumocytes

Organization of alveolar exudates Pulmonary infiltrates – predominantly lymphocytes Procollagen peptide III – increased mortality

Clark JG et al Ann Intern Med 1995

Fibrotic phase Many recover lung function - 3-4 weeks

Extensive ductal & interstitial fibrosis

Acinar architecture – emphysema with bullae

Progressive vascular occlusion & PHT

Pneumothorax, decreased compliance, increased dead space

HISTOPATHOLOGY

CLINICAL FEATURES Tachypnea & dyspnea

Fever ,cough & purulent sputum - infective etiology

Diffuse crackles

Focal findings of consolidation – pneumonia

ABG - PaO2 - 30 -55 mmHg

O2 sat.< 85% Failure to achieve > 95% sat. with supplemental O2

DIFFERENTIAL DIAGNOSIS Cardiogenic pulmonary edema

Diffuse alveolar hemorrhage

Acute eosinophilic pneumonia

Hypersensitivity pneumonitis

Drug induced pulmonary edema & pneumonitis

INVESTIGATIONS CHEST RADIOGRAPHY

CECT + HRCT – fluid, consolidation, atelectasis

PCWP < 18mmHg

ECHOCARDIOGRAPHY

BAL Precipitating cause unclear Hemodynamic instability - unsafe

RADIOLOGICAL FEATURES FEATURES ARDS CARDIOGENIC

PUL. EDEMACardiomegaly Unusual Present

Kerley B lines Unusual Present

Large pleural effusion Unusual Present

Opacities Patchy/Peripheral Diffuse

Hilar haziness Infrequent Present

Acute phase

FIBROSING ALVEOLITIS PHASE

MANAGEMENT OF ARDS

DIAGNOSISARDS should be suspected Sudden onset of respiratory distress Precipitating cause known Patients with known risk factors No clinical evidence of heart failure ABG - hypoxemia not responding to O2

PaO2/FiO2 < 300 = ALI PaO2/FiO2 < 200 = ARDS CXR – recent appearance of bilateral Pulm. infiltrates

APPROACH TO TREATMENT TREAT PRECIPITATING CAUSE

PROVIDE ICU SUPPORTIVE CARE

VENTILATORY MANAGEMENT

ADJUNCTS TO VENTILATOR MANAGEMENT

TREAT INFLAMATION & COAGULATION AS APPROPRIATE

REHABILITATION & RECOVERY

TREAT PRECIPITATING CAUSE Infections – Antibiotics, Drainage Aspiration – Prevent recurrence Drugs – Identify culprit and avoid Fractures – Operative fixation Pancreatitis – Supportive, NPO ± antibiotics Empirical antibiotic therapy in early phase of disease if sepsis

is cause

. Leeper et al New Horiz 1993

VENTILATORY MANAGEMENT Primary goal - adequate arterial oxygenation

Two approaches - TRADITIONAL APPROACH LUNG PROTECTIVE VENT. APPROACH

Both had same goal but different priority

TRADITIONAL VS PROTECTIVE APPROACH

Priority traditional app. Maintain pH & PaCO2

Improve comfort

Increase VT & plateau pressure

Priority protective app. Decrease VILI

Decrease VT & plateau pressure

VENTILATORY MANAGEMENT Basic research in animals & in vitro1 – High VT causes lung injury PEEP protective on VILI

Clinical research utilizing imaging2 – Lung is non- homogeneous Aerated alveoli subjected to over distention

ARDS Network – RCT lung protective ventilation

1 Am Rev Respir Dis 137:1159,19882 Am J Respir Crit Care Med 164:1701,2001

RCT- LUNG PROTECTIVE STRATEGYAuthors No. of

patientsMortality in low VT group

Mortality in higher VT group

p value

Amato et alNEJM 1998

53 38% 71% < 0.0001

Brochard et alAJRCCM 1998

116 46.5% 37.9% 0.39

Stewart et alNEJM 1998

120 50.0% 47% 0.72

ARDSNetNEJM2000

861 31.0% 39.8% 0.007

ARDS NETWORK Supported by National Institute of Health

Centers = 10

Hospitals = 24

ICUs = 75

Provides infrastructure for well designed, multi-center, randomized trials of potential new therapies

ARDSNet - LOW TIDAL VOLUME RCT RCT enrolled -861 patients

One study arm - VT 6mL/kg PBW if Pplat < 30 cm H2O Other study arm - VT 12mL/kg PBW if Pplat < 50cm H2O

9% absolute & 22% relative, mortality reduction in low VT

N Eng J Med 2000;342:1301-8

MAIN OUTCOME VARIABLESVARIABLE LOW VT

GROUPS TRADITIONAL VT GROUPS

P value

Death before discharge home (%)

31.0 39.8 0.007

Breathing without assistance by day 28 (%)

65.7 55.0 <0.001

No. of ventilator-free days days1 to 28

12 ± 11 10 ± 11 0.007

Barotrauma , days 1 to 28 (%)

10 11 0.43

No. of days without organ failure , days 1 to 28

15 ± 11 12 ± 11 0.006

RECOMMENDED CORE VENTILATOR MANAGEMENT

VENT. SETUP AND ADJUSTMENT

Calculate PBW - Male = 50 + 2.3 [height (inches) - 60] Female = 45.5 + 2.3 [height (inches) -60]

Select - Assist Control Mode

Set initial VT to 8 ml/kg PBW

VENT. SETUP AND ADJUSTMENT

Reduce VT by 1 ml/kg - At intervals of 2 hours until VT = 6ml/kg PBW

Set initial rate -To approximate baseline minute ventilation (not > 35 bpm) Adjust VT and RR -To achieve pH and plateau pressure goals listed below

Set insp. flow rate -Above patient demand (usually > 80L/min)

OXYGENATION GOAL

Fio2 0.3 0.4 0.4 0.5 0.5 0.6 0.7 0.7

PEEP 5 5 8 8 10 10 10 12

Fio2 0.7 0.8 0.9 0.9 0.9 1.0 1.0 1.0

PEEP 14 14 14 16 18 20 22 24

• PaO2 = 55-80mmHg or SPo2 = 88-95%

• Use incremental Fio2-PEEP combination

PLATEAU PRESSURE GOAL PLATEAU PRESSURE < 30 cm H2O

If Pplat > 30 cm H2O - decrease VT by 1 ml/kg steps (minimum = 4ml/kg)

If Pplat < 25 cm H2O - VT < 6 ml/kg, increase VT by 1 ml/kg until Pplat>25 or VT=6 ml/kg

If Pplat < 30 & breath stacking occurs - increase VT in 1 ml/kg (maximum = 8 ml/kg)

pH GOAL (7.30 - 7.45)

Acidosis Management

pH 7.15 - 7.30 – Increase RR until pH > 7.30 or PaCO2 < 25 (Max. RR = 35)

pH < 7.15 – Increase RR to 35 pH remains < 7.15, NaHCO3 infused Alkalosis Management

pH > 7.45 – Decrease RR if possible

PROTECTIVE VS CONVENTIONAL VENTILATION

ROLE OF PEEP

PEEP- BENEFITS/ LIMITATION BENEFITS LIMITATIONS

1. Recruitment 1.↓Cardiac output

2. Compliance 2. Airway pressure

3.↓ FiO2 requirements 3. Venous pressure

4. Displaces alveolar edema fluid into interstitium

4. Over distension of units

ALVEOLI - TRIAL HIGHER VS LOWER PEEP N= 549 (lower PEEP = 273 , higher PEEP = 276)

PEEP = lower ( 8.3 ± 3.2 ) , higher (13.2 ± 3.5)

Oxygenation and respiratory system compliance improved in patients with higher PEEP

No difference in mortality, duration of mechanical ventilation

N Eng J Med 2004;351:327

VILI

ADJUNCTS TO VENTILATOR MANAGEMENT

FACTT TRIAL FLUID MANAGEMENT STRATEGIES Study involved 1001 patients 503 in conservative group (CVP<4 / PAOP<8mmHg) 498 in liberal group (CVP=10-14 / PAOP=14-18mmHg) Fluid management strategy applied for 7days Primary end point – death at 60 days Secondary end point – no. of ventilator free days organ failure free days measures of lung physiology

N Engl J Med 2006;354:2564-75

CONCLUSION Conservative strategy

Improved lung function Shortened mechanical.vent.duration & ICU care No increase in non pulmonary organ failure No significant improvement in mortality

PAC is not useful for routine hemodynamic management Associated with more complication than CVC

PRONE POSITION VENTILATION ADVANTAGE

Improved gas exchange More uniform alveolar ventilation Recruitment of atelectic dorsal regions Improved postural drainage Redistribution of perfusion from edematous & dependant

region DISADVANTAGE

Accidental extubation Pressure sores Increase requirement for sedation

PRONE POSITION VENTILATION

PRONE POSITION VENTILATIONType of study No. of

PatientsFindings Study

Observational 39 Inconclusive Nakos et al AJRCCM 2000

Phase 3 Trial 304 Improved oxygenation, not

survival

Gattinoni et alNEJM 2001

Phase 3 Trial 791 No Benefit Claude G et al JAMA 2004

RECRUITMENT MANEUVERS Recruitment maneuver – evolved from traditional “sighs” Sighs – 2 or 3 normal sized VT breath increase surfactant’s surface tension lowering properties Purpose – open totally partially collapsed alveoli Recruitment were first used - clinical trial by Amato et al Application of CPAP – 35-40 cm H2O for 30 sec Lack of evidence – for using in clinical practice Complication –

Slight drop in PaO2 during maneuver Transient hypotension

N Engl J Med 338:347,1998

SALVAGE INTERVENTIONS TRACHEAL GAS INSUFFLATION

Uses 100% humidified O2 delivered near carina

Reduces anat. dead space ,washes CO2 from trachea

Disadvantage – Tracheal erosion Oxygen toxicity Hemodynamic compromise & barotrauma Increased risk of VILI

HIGH FREQUENCY VENTILATIONHIGH FREQUENCY OSCILLATORY VENT.

Low tidal volume – 1-3ml/kg

High frequency – 300-3000 b/min

Airway pressure oscillation – piston/microprocessor flow controller at selected rate &displacement

Caution - VILI due to high distending pressure

Needs further study comparing HFOV to ARDSNet protocol

High frequency oscillatory ventilationNO. OF

PATIENTMORTALITY

HFOVMORTALITY

CONVEN.MORTALITY

DIFF. ( p value)

STUDY

148 37% 52% 0.10 Derdak et al

AJRCCM 2002

61 32% 38% 0.79 Bollen et al

Critical Care 2005

HFOV

HIGH FREQUENCY VENTILATORHIGH FREQUENCY JET VENTILATOR

Tidal volume of 1-5 ml/kg

RR- 60 -300 breaths per minute

Multiple trials failed to show benefit over conventional Vent.

Better avoided as a salvage intervention

INVERSE RATIO VENTILATION Normally I:E = 1: 2 or 3 In IRV I:E > 1: 1 Used in patients - difficult hypoxemic respiratory failure Either pressure or volume cycled mode Observational study has shown improved oxygenation1

LIMITATIONS

Auto PEEP is a problem with this mode Increased mean air way pressure reduced cardiac filling Require heavy sedation Needs further study

1 Wang SH et al Am J Surg 2002

PARTIAL LIQUID VENTILATION Perflurocarbons are instilled in to trachea

High solubility of respiratory gases in PFCs

Helps in alveolar recruitment

Increases alveolar stability – artificial surfactant

Preliminary results – safe & efficacious

Radio dense – hinders CXR interpretation Am J Respir Crit Care Med 2002;165:1781

SALVAGE INTERVENTIONSVentilatory Strategies Type of

studyNo. of

PatientsFindings Study

Extra corporeal memb. oxygenation

Phase 3 90 No Benefit Zapol et al JAMA 1979

Extra corporeal removal of CO2

Phase 3 40 No Benefit Morris et al AJRCCM 2000

High frequency jet ventilation

Phase 3 309 No Benefit Carlon et al Chest 1983

Partial Liquid Ventilation

Pilot study

90 Decrease duration of MV

in < 55yrs.

Hirschl et alAJRCCM 2002

ECMO

PHARMACOLOGICAL APPROACHES

ROLE OF STEROIDSTreatment Type of

studyNo. of

PatientsFindings Study

Glucocorticoids ( acute phase)

Phase 3 87 No Benefit Bernard et al NEJM 1987

Glucocorticoids ( acute phase)

Phase 3 59 No Benefit Luce et al

Am Rev Res Dis 1988

Glucocorticoids ( late phase)

Phase 3 24 Decrease mortality

small study

Meduri et al JAMA 1998

ARDSNet- LaSRS

Double blind RCT – 180 patients ARDS at least 7days – assigned methylprednisolone/ placebo

RESULTS No decrease in mortality at 60 days rather, increased

mortality in patients enrolled 14 days after ARDS onset Increased no. of ventilator & shock free days No increased rate of infectious complication Higher rate of neuromuscular weakness

CONCLUSION - No support for routine use of steroids for persistent ARDS

N Engl J Med 2006;354:1671

INHALED NITRIC OXIDE Pulmonary vasodilator

Selectively improves perfusion of ventilated areas

Reduces intrapulmonary shunting

Improves arterial oxygenation

No systemic side effects

Expensive

INHALED NITRIC OXIDE

Treatment Type of study

No. of Patients

Findings Study

Inhaled NO Phase 3 203 No Benefit Payen et al Inten Care Med

1999Inhaled NO Meta

Analysis513 Transient imp.

oxygenation, no mortality benefit

Sokol et al Anesth Analg

2003

Inhaled NO Phase 3 385 Transient imp. oxygenation, no mortality benefit

Taylor RW JAMA 2004

SURFACTANT AND PROSTAGLANDIN

Treatment Type of study

No. of Patients

Findings Study

Surfactant Phase 3 448 Improved gas exchange but not survival

Roger G et al NEJM 2004

Surfactant Phase 3 725 No benefit Anzueto et al NEJM 1996

Alprostadil Phase 3 350 Stopped for lack of efficacy

Abraham et al CCM 1999

Alprostadil Phase 3 100 No benefit Bone et al Chest 1989

MISCELLANEOUSTreatment Type of

studyNo. of

PatientsFindings Study

Ketoconazole Phase 2 234 No Benefit ARDS Network JAMA 2000

Procysteine Phase 3 215 Stopped for lack of efficacy

Unpublished data

Lisofylline Phase 2-3

235 Stopped for lack of efficacy

Unpublished data

RECENT ONGOING TRIALS

SURFAXIN lucinactant PHASE II

SIVELESTAT Neutrophil elastase inhib. PHASE I-II

XIGRIS Activated protein C PHASE II

CO carbon monoxide PHASE I -II

RECOVERY PHASE Most patients who die, do so within first two weeks

Recovery takes several weeks

Resolution of alveolar edema by 7 – 10 days

Decision for tracheostomy after 7- 10 days of illness

Beta –agonist enhance alveolar fluid clearance1

Use of keratinocyte growth factor ( KGF ) will enhance epithelialization2

1. Saladis F et al J Appl Physio 19992. Yano T et al J Respir Cell Mol Bio 1996

PREDICTORS OF MORTALITY Age > 65 years Organ transplantation HIV infection Cirrhosis Active malignancy Sepsis PaO2/FiO2 ratio –Does not predict the outcome

Epstein SK AJRCCM 1998

Long term sequelae Pulmonary functions-mildly impaired Decreased quality of life Neurocognitive impairment Depression Post traumatic stress disorder Physical debilitation Long term sequeale – active area of ongoing research

TAKE HOME MESSAGE Definition of syndrome is key to understand ARDS

Complex response of lung to direct and indirect insults

Mortality has improved

lower tidal volume Ventilation – only therapeutic approach shown to improve survival

TAKE HOME MESSAGE conservative fluid management improves lung mechanics

No role for steroids in persistent ards

Critical care is no longer just physiologic support – the type of care influences outcome, including potential for harm

Long term sequelae in Survivors