1. Acute Lung Injury and ARDS
Andreas Crede
Emergency Medicine Registrar

2. Overview Introduction Definition Pathophysiology Treatment New Stuff
References

3. Introduction 1st described 1967 (Ashbaugh et al)
Incidence / 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 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

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 Plateau Pressure
Predicted not actual
Plateau Pressure
≤30cm H2O
Resp Rate
Titrated to pH
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. Effect of Blood Flow in Prone Positioning750
Prone
Ventral
Dorsal D ND
Mid
Mid 25
Percent Flow ND D
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
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 Vasodilators
Improvement in oygenation
No ↑ long term survival
Vasodilators
Improved oygenation
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:
3 Plantadosi, C.A and Schwartz, D.A. 2004, The Acute Respiratory Distress Syndrome. Ann Intern Med; 141:
4. Girard, T>D> and Bernard,G.R. 2007, Mechanical Ventilation in ARDS: A State-of-the-Art Review. Chest; 131;
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:
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: 7.