Acute Lung Injury and ARDS

1. Acute Lung InjuryandARDS Andreas Crede Emergency Medicine Registrar

2. Overview • Introduction • Definition • Pathophysiology • Treatment • New Stuff • References

3. Introduction • 1st described 1967 (Ashbaugh et al) • Incidence 1.5 -7.5/ 100000 population • 28 day mortality 25 – 30%1 • Diagnosis clinical

4. 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

6. Risk Factors • Alcoholism • Genetic predisposition

7. 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

8. Causes • Indirect Injury1 • Severe Sepsis • Massive transfusion • Shock • Pancreatitis • Salicylate/ narcotic overdose • Anaphylaxis • Cardiopulmonary bypass

9. Differential • LVF • Fluid overload • Mitral stenosis • Lymphangitis carcinomatosis • Interstitial lung disease1

14. Respiratory Failure

16. Histologically • Exudative Phase3 • Neutrophilic Infiltrate • Alveolar Haemorrhage • Proteinaceous Pulmonary Oedema • Cytokines (TNF, IL1,8) • ↑ Inflammation • ↑ Oxidative Stress and Protease Activity • ↓ Surfactant Activity • Atelectasis

17. 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)

18. 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

19. Long Term • Chronic Respiratory Disease • Muscle Fatigue • Muscle Wasting • Weakness

20. Treatment • Ventilation • Fluid Management • Steroids • Other Stuff

21. Ventilation • Tidal Volumes • PEEP • Positioning • Weaning Protocols

22. Tidal Volume • Recommended 4-6ml/kg4 • High tidal volumes4 • Overdistention of alveoli • Local inflammatory response resulting in systemic inflammation • TNF, IL6, IL10,

23. 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

24. 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

25. 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

26. PEEP

27. 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

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

29. Fessler, ARRD 1993

30. PEEP + Lung Perfusion Permutt, JAP 1961

31. 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

32. 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

33. Supine Ventilation • ± 40% lung volume under lung, especially patients with large hearts

34. Prone Ventilation

35. D Mid ND D Mid ND Ventral Dorsal Prone Effect of Blood Flow in Prone Positioning7 50 25 Percent Flow 0 Dorsal Ventral Supine

36. Positioning • Prone position4 • Transient improvement PaO2/FiO2 • No improvement: survival/ time on ventilator/ time in ICU • Role: • High FiO2 • High plateau pressures

37. 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

38. Fluid Management

39. Fluid Management • Fluid movement regulated by: • Starling equation • Vessel wall • Ability to filter fluid • Selective permeability to proteins

40. Fluid Management

41. 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

42. 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

43. 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

44. Emergency Department Summary • PREVENT! • Low tidal volume ventilation • Restrict PEEP • Restrict Fluids (if possible) • Initiate Weaning Protocol • Supine Ventilation

45. 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

46. Thank You

47. 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