Acute Lung Injuryand

ARDS

Andreas CredeEmergency Medicine Registrar

Overview

• Introduction

• Definition

• Pathophysiology

• Treatment

• New Stuff

• References

Introduction

• 1st described 1967 (Ashbaugh et al)

• Incidence 1.5 -7.5/ 100000 population

• 28 day mortality 25 – 30%1

• Diagnosis clinical

Definition

• Acute onset (<7days) respiratory failure/distress• Diffuse, bilateral infiltrates on CXR• Absent left atrial hypertension (PAOP

≤18mmHg)• Or absent clinical evidence of left atrial

hypertension

• PaO2/ FiO2 <300mmHg (ALI)

• PaO2/ FiO2 <200mmHg (ARDS)2

Risk Factors

• Alcoholism

• Genetic predisposition

Causes

• Direct Injury1

• Pneumonia• Aspiration• Drowning• Amniotic fluid and fat embolism• Alveolar haemorrhage• Smoke, toxic gas inhalation• Reperfusion (incl rapid drainage pleural effusion)• Unilateral lung re-implantation

Causes

• Indirect Injury1

• Severe Sepsis• Massive transfusion• Shock• Pancreatitis• Salicylate/ narcotic overdose• Anaphylaxis• Cardiopulmonary bypass

Differential

• LVF

• Fluid overload

• Mitral stenosis

• Lymphangitis carcinomatosis

• Interstitial lung disease1

Physical/ chemical injuryActivation Innate

Inflammatory Cascade

Leakage Protein Rich Oedema FluidInflammatory Cellular

Infiltrates

Diffusion AbnormalitiesV/Q Mismatch

Hypoxia

Respiratory Failure

Physical/ chemical injuryActivation Innate

Inflammatory Cascade

Cellular InfiltrateAtelectasis

Oedema Fluid

Reduced Thoracic Compliance + Vasoconstriction

Hypoxia

Respiratory Failure

Physical/ chemical injuryActivation Innate

Inflammatory Cascade

Small Vessel Thrombosis

Increased Dead Space

Hypoxia

Respiratory Failure

Alveolar Damage

Capillary Damage

Leakage Oedema

Fluid

InflammatoryCellular Infiltrates

V/Q Mismatch

Atelectasis

↓ThoracicCompliance

↑Dead Space

Hypoxic Vasoconstriction

Hypoxia

Respiratory Failure

Atelectasis/ Reduced Lung Compliance

Hypoxaemia↑ Dead Space

Histologically

• Exudative Phase3 • Neutrophilic Infiltrate• Alveolar Haemorrhage• Proteinaceous Pulmonary Oedema• Cytokines (TNF, IL1,8)

» ↑ Inflammation» ↑ Oxidative Stress and Protease Activity» ↓ Surfactant Activity» Atelectasis

Histologically

• Elastase- induced capillary and alveolar damage3

• ↑ Alveolar flooding

• ↓ Fluid clearance

• Capillary thrombosis• ↓ Anticoagulant proteins• ↑ Procoagulant proteins (Tissue Factor)• ↑ Anti- fibrinolytic Protein (Plasminogen Activator

Inhibitor)

Post Acute Phase

• Fibroproliferative Phase3

– Variable time period– Fibrosis– Chronic Inflammation– Neovascularisation

• Resolution3

– Improvement of hypoxaemia– Improved dead space and lung compliance– Resolution radiographic abnormalities– Can take up to 1 year– Residual restrictive or obstructive picture

Long Term

• Chronic Respiratory Disease

• Muscle Fatigue

• Muscle Wasting

• Weakness

Treatment

• Ventilation

• Fluid Management

• Steroids

• Other Stuff

Ventilation

• Tidal Volumes

• PEEP

• Positioning

• Weaning Protocols

Tidal Volume

• Recommended 4-6ml/kg4

• High tidal volumes4

• Overdistention of alveoli• Local inflammatory response resulting in systemic

inflammation• TNF, IL6, IL10,

Tidal Volume4

• Low tidal volume ventilation• Weight

• Predicted not actual

• Plateau Pressure • ≤30cm H2O

• Resp Rate • Titrated to pH 7.3-7.45

• PEEP and FiO2 • Adjusted to maintain saturation

• Low tidal volume may result in hypercarbia• ARMA (Respiratory Management in ALI/ARDS Trial)

• NaHCO3 infusions/ hyperventilation to maintain pH

Tidal Volumes

• Same sedation strategies• No ↑ duration of ventilation• High frequency oscillatory ventilation

shown no benefit over low tidal volume ventilation

• 30 day mortality not statistically significant (37% vs 52%, p=0.10)

• Earlier recovery from hypoxia

• Only ventilation strategy shown to reduce mortality (40% - 31%)4

PEEP

• Recommendation: lowest PEEP/ FiO2 to maintain saturation

• Recruits collapsed alveoli• In dependant regions• Over-distends in non-dependant regions

• ↓ Repetitive opening/ closing of alveoli: ↓ airway damage

• Endothelial/ epithelial stretch injury with subsequent capillary injury

• Similar cytokine response as ↑tidal volume

PEEP

PEEP

• ALVEOLI Trial4• Higher PEEP = improved oxygenation• In hospital mortality equal btw high and low PEEP• Time on ventilator similar• Duration non- pulmonary organ failure equal

PEEP

Adverse effects of PEEP Cardiac output• Volutrauma Lung water High VA/Q Dead space Endothelial permeability Epithelial permeability Bronchial blood flow

Fessler, ARRD 1993

PEEP + Lung Perfusion

Permutt, JAP 1961

PEEP

• Some Endpoints• Best PaO2

• Lowest Shunt

• Best O2 delivery

• Best lung perfusion

• Plateau Pressure ≤30cm H2O

• Optimise aeration on CT• Pressure/ volume curve becomes concave

Positioning

• Prone positioning1,4

• Redistribution of blood & ventilation to least affected areas of lung

• Secretion clearance• Shifts mediastinum anteriorly – assists recruitment

of atelectatic areas• ? reduce lung injury• Reduced lung compression by abdominal contents

Supine Ventilation

• ± 40% lung volume under lung, especially patients with large hearts

Prone Ventilation

Effect of Blood Flow in Prone Positioning7

Perc

en

t Flo

w

25

50

0

Supine

MidD ND

Dorsal VentralProne

Ventral Dorsal

D Mid

ND

Positioning

• Prone position4

• Transient improvement PaO2/FiO2

• No improvement: survival/ time on ventilator/ time in ICU

• Role:» High FiO2

» High plateau pressures

Weaning Protocols

• Reduce duration of mechanical ventilation vs patients managed by IMV protocol4

• Daily spontaneous breathing trial4• 30-120 mins unassisted ventilation• 4 Criteria before commencement

– Some reversal of underlying cause

– PEEP ≤8cm H2O/ FiO2 ≤50%

– Haemodynamic stability– Ability to initiate inspiratory effort

Fluid Management

Fluid Management

• Fluid movement regulated by:• Starling equation• Vessel wall

– Ability to filter fluid– Selective permeability to proteins

Fluid Management

Fluid Management

• Study of conservative vs liberal fluid management5

• 60 day mortality: 25.5 vs 28.4% p=0.30• 1st 28 days ventilator free: 14.6 vs 12.1 p<0.001• 1st 28 days ICU free: 13.4 vs 11.2 p<0.001• Difference in organ failure and need for dialysis not

statistically significant• No specific mention of CVP/ PAOP levels which to

aim for• Conservative = 4mmHg Liberal = 10-14mmHg CVP

Steroids

• Theoretical use to ↓inflammatory response associated with ARDS6

• 2006 study6

• No ↓60 day mortality (28.6% vs 29.2% p= 0.10)• Use of steroids 14+ days post onset: ↑ mortality• ↓ need for vasopressors• ↑ ventilator and shock free days• ↑ neuromuscular weakness• Short term improvement in oxygenation

Other stuff

• Extracorporeal membrane oxygenation• Improvement in oygenation• No ↑ long term survival

• Vasodilators• Improved oygenation• No ↑ long term survival

• Ketoconazole• Pentoxyfilline• Nutritional modification• Antioxidants• Surfactant• B2 stimulants1

Emergency Department Summary

• PREVENT!

• Low tidal volume ventilation

• Restrict PEEP

• Restrict Fluids (if possible)

• Initiate Weaning Protocol

• Supine Ventilation

Conclusion

• Many theoretical therapies

• Only proven strategy to improve survival is low tidal volume ventilation

• Therapies to reduce number of days needing scarce resources valuable in our setting

Thank You

References• 1. Wheeler, A.P. and Bernard, G.R. 2007,Acute Lung Injury and the Acute

Respiratory Distress Syndrome: A Clinical Review. Lancet; 369: 1553–65• 2. The Acute Respiratory Distress Syndrome Network. 2000, Ventilation

With Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome. N Engl J Med; 342:1301-08

• 3 Plantadosi, C.A and Schwartz, D.A. 2004, The Acute Respiratory Distress Syndrome. Ann Intern Med; 141:460-470.

• 4. Girard, T>D> and Bernard,G.R. 2007, Mechanical Ventilation in ARDS: A State-of-the-Art Review. Chest; 131;921-929

• 5. The National Heart, Lung and Blood Institue Acute Respiratory Distress Syndrome Clinical Trials Network. 2006, Comparison of Two Fluid-Management Strategies in Acute Lung Injury. N Engl J Med; 354:2564-75

• 6. The National Heart, Lung and Blood Institue Acute Respiratory Distress Syndrome Clinical Trials Network. 2006, Efficacy and Safety of Corticosteroids for Persistent Acute Respiratory Distress Syndrome. N Engl J Med; 354:1671-84

• 7. www.slideshare.net