Acute Lung Injury and ARDS Andreas Crede Emergency 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

Respiratory Failure

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 Resolution3 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 Plateau Pressure 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 50 Prone Ventral Dorsal D ND Mid Mid 25 Percent Flow ND D Dorsal Ventral Supine

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 Vasodilators Improvement in oygenation No ↑ long term survival Vasodilators Improved oygenation 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