1. ARDS for the ED Physician
Rafi Israeli, MD
Assistant Professor of Medicine
Emergency services Institute
Cleveland Clinic Foundation
Cleveland, Oh

2. Conflicts of Interest
None

3. ARDS for the ED Physician
History
Clinical Course
Pathophysiology
Causes
Incidence
Therapy

4. History Drawback: No specific Criteria
1967: Ashbaugh, et al. described Adult Respiratory Distress Syndrome
Respiratory Distress
Cyanosis
Hypoxemia despite oxygen
Diffuse infiltrates on Chest Xray
Drawback: No specific Criteria

5. History Drawback: Does not predict Outcome
1988: Murray, et al. expanded the definition of ARDS using a 4- point scale, based on:
Extent of Chest Xray abnormalities
Severity of Hypoxia : PaO2/FiO2
Amount of PEEP
Search for cause of ARDS
Drawback: Does not predict Outcome
Does not exclude Cardiogenic Pulm Edema

6. History 1994:Ameican- European Consensus Conference Committee
Renamed Acute Resp Distress Syndrome
Described ARDS as “syndrome of inflammation and permeability”
Coined the term ALI as a precursor to ARDS

7. History
1994:Ameican- European Consensus Conference Committee Criteria:
Acute Onset
Bilateral infiltrates
PAWP≤ 18
ALI: PaO2/FiO2 ≤ 300
ARDS: PaO2/FiO2 ≤ 200
Drawback: Does not specify cause
ALI : Acute resp failure from pulmonary edema without an increase in pulmonary venous pressure.

9. Clinical Course Acute Phase
Rapid Onset
Exudates
Consolidations
Respiratory failure
Hypoxemia refractory to O2
Inflammation (even in non-edematous lung)
IL-1,6,8,10, Cytokines
Diminished Lung compliance

10. Clinical Course Acute Phase
Patchy infiltrates Coalesce
Air Bronchograms
Pulmonary Hypertension
Intrapulmonary Shunting
Endogenous Vasoconstrictors
Hyperadrenergic State

12. Clinical Course Fibrosing Alveolitis
Persistent Hypoxia
Pulmonary Fibrosis
Worsening Compliance
Neovascularization
Pulmonary Hypertension
Macrophages clear neutrophils
Chronic Inflammation

14. Clinical Course Recovery
Active transport of Na into interstitium
Endocytosis of Protein
Transcytosis of Protein
Alveolar Epithelial type II cells proliferate
Apoptosis of remaining neutrophils?

15. The Normal Alveolus (Left-Hand Side) and the Injured Alveolus in the Acute Phase of Acute Lung Injury and the Acute Respiratory Distress Syndrome (Right-Hand Side)
Figure 3. The Normal Alveolus (Left-Hand Side) and the Injured Alveolus in the Acute Phase of Acute Lung Injury and the Acute Respiratory Distress Syndrome (Right-Hand Side). In the acute phase of the syndrome (right-hand side), there is sloughing of both the bronchial and alveolar epithelial cells, with the formation of protein-rich hyaline membranes on the denuded basement membrane. Neutrophils are shown adhering to the injured capillary endothelium and marginating through the interstitium into the air space, which is filled with protein-rich edema fluid. In the air space, an alveloar macrophage is secreting cytokines, interleukin-1, 6, 8, and 10, (IL-1, 6, 8, and 10) and tumor necrosis factor {alpha} (TNF-{alpha}), which act locally to stimulate chemotaxis and activate neutrophils. Macrophages also secrete other cytokines, including interleukin-1, 6, and 10. Interleukin-1 can also stimulate the production of extracellular matrix by fibroblasts. Neutrophils can release oxidants, proteases, leukotrienes, and other proinflammatory molecules, such as platelet-activating factor (PAF). A number of antiinflammatory mediators are also present in the alveolar milieu, including interleukin-1-receptor antagonist, soluble tumor necrosis factor receptor, autoantibodies against interleukin-8, and cytokines such as interleukin-10 and 11 (not shown). The influx of protein-rich edema fluid into the alveolus has led to the inactivation of surfactant. MIF denotes macrophage inhibitory factor.
Ware L and Matthay M. N Engl J Med 2000;342:

17. Pathophysiology Alveolar Epithelial Basement Membrane Breakdown
Damage to Vascular Endothelium
Third Spacing of Protein-Rich fluid
Flooding of Alveoli
Shock
Type II cells damaged:
Less Surfactant
Diminished fluid removal

18. Pathophysiology Platelet Aggregation Microthrombi → Shunting
Fibrosis from disorganized repair of intersitium

19. Causes DIRECT LUNG INJURY Aspiration Pneumonia Pulmonary Contusion
INDIRECT LUNG INJURY
Aspiration
Pneumonia
Pulmonary Contusion
Toxic Inhalation
Near-Drowning
Sepsis
Shock
Extrathoracic Trauma
Multiple Fractures
Burns
Eclampsia
Pancreatitis
DIC

20. Incidence & Outcome 20-75 per 100,000 30% mortality
Recovery may take 6-12 months
Residual: Restriction
Obstruction
Gas- Exchange Abnormalities
Reduced Quality of Life

21. Therapy Treat Underlying Cause Enteral Feedings
Antibiotics
Surgery
Enteral Feedings
Peyer’s Patches
Less Catheter Sepsis
Supportive: ARDS Network (ARDSNet)

22. Therapy Mechanical Ventilation
The Problem: Ventilator- Induced Lung Injury
High volumes and pressures: Stress
Overdistension & Alveolar Cracking
Cyclic Opening and closing of atelectatic alveoli
Cause increased permeability and alveolar damage

23. Therapy Mechanical Ventilation
The Problem: Oxygen Toxicity
Free Radicals
Oxygen Washout and De-Recruitment
High FiO2 can lead to further alveolar damage

24. Intubation almost always necessary
In past, goal was to normalize pH, PaCO2, PaO2
High volumes and pressures were used
Worse outcomes

25. Therapy Lung-Protective Mechanical Ventilation
Amato et al. 1998, Effects of a protective- ventilation strategy on mortality in the acute respiratory distress syndrome. N. Engl. J. Med. 338:347-54
53 pts with early ARDS
Compared “conventional” ventilation of 12ml/kg to “protective” 6ml/kg
Low PEEP. PaCO
Improved survival at 28 days
Higher percentage of ventilator weaning
Less barotrauma
First trial to recommend low volume ventilation

26. Therapy Lung-Protective Mechanical Ventilation
The Acute Respiratory Distress Network 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. 342:1301-8
Larger Trial. 861 patients
Compared 12 ml/kg vs. 6ml/kg ventilation.
Plateau pressures 50 cm H2O vs. 30 cm H2O.
Trial ended early:
39.8% mortality vs. 31% mortality
THIS HAS CHANGED CLINICAL PRACTICE
Ideal body weight is used, not actual weight (the lungs don’t get any larger).

27. Therapy
PEEP

28. Therapy PEEP

29. Therapy Permissive Hypercapnea
Minute Ventilation=RR x Tidal Volume
High PEEP Levels (12-15cm H2O)
Low Tidal Volumes and Peak and Plateau Pressures result in Hypercapnea
Carvalho et al.(1997) found the following
Increased HR
Increased PA pressures
Increased Cardiac Output
Respiratory Acidosis
But no adverse Outcomes

30. Therapy Optimal PEEP What is optimal PEEP in individual Patient?
Gattinoni et al Lung Recruitment in Patients with ARDS. N. Engl. J. Med. 354:
What is optimal PEEP in individual Patient?
PEEP in non-recruitable lung causes overdistension: barotrauma and alveolar stress
Study measured %age of recruitable lung using CT

31. Therapy Optimal PEEP Inclusion Criteria PaO2:FiO2 < 300
Gattinoni et al Lung Recruitment in Patients with ARDS. N. Engl. J. Med. 354:
Inclusion Criteria
PaO2:FiO2 < 300
Bilateral pulmonary infiltrates
PACWP < 18
PEEP Trial Prior to CT, high airway pressures and PEEP were applied.
Lung weight measured by CT

32. Frequency Distribution of Patients According to the Percentage of Potentially Recruitable Lung (Panel A) and CT Images at Airway Pressures of 5 and 45 cm of Water from Patients with a Lower Percentage of Potentially Recruitable Lung (Panel B) and Those with a Higher Percentage of Potentially Recruitable Lung (Panel C)
Figure 2. Frequency Distribution of Patients According to the Percentage of Potentially Recruitable Lung (Panel A) and CT Images at Airway Pressures of 5 and 45 cm of Water from Patients with a Lower Percentage of Potentially Recruitable Lung (Panel B) and Those with a Higher Percentage of Potentially Recruitable Lung (Panel C). Panel A shows the frequency distribution of the 68 patients in the overall study group according to the percentage of potentially recruitable lung, expressed as the percentage of total lung weight. Acute lung injury without ARDS was defined by a PaO2:FIO2 of less than 300 but not less than 200, and ARDS was defined by a PaO2:FIO2 of less than 200. The percentage of potentially recruitable lung was defined as the proportion of lung tissue in which aeration is restored at airway pressures between 5 and 45 cm of water. Panel B shows representative CT slices of the lung obtained 2 cm above the diaphragm dome at airway pressures of 5 cm of water (left) and 45 cm of water (right) from a patient with a lower percentage of potentially recruitable lung (at or below the median value of 9 percent of total lung weight). Lung injury developed in the patient after an episode of severe acute pancreatitis (PaO2:FIO2, 296 at an airway pressure of 5 cm of water; PaCO2, 34 mm Hg; and respiratory-system compliance, 44 ml per centimeter of water). The percentage of potentially recruitable lung was 4 percent, and the proportion of consolidated lung tissue was 33 percent of the total lung weight. Panel C shows representative CT slices of the lung obtained 2 cm above the diaphragm dome at airway pressures of 5 cm of water (left) and 45 cm of water (right) from a patient in the group with a higher percentage of potentially recruitable lung. Lung injury developed in the patient after an episode of severe pneumonia (PaO2:FIO2, 106 at a PEEP of 5 cm of water; PaCO2,58 mm Hg; and respiratory-system compliance, 25 ml per cm of water). The percentage of potentially recruitable lung was 37 percent, and the proportion of consolidated lung tissue was 27 percent of the total lung weight.
Gattinoni L et al. N Engl J Med 2006;354:

33. Therapy Optimal PEEP Results
Gattinoni et al Lung Recruitment in Patients with ARDS. N. Engl. J. Med. 354:
Results
In patients where higher %age of recruitable lung, mortality higher, worse gas exchange.
Use of PEEP in patients with lower %age of recruitable lung was harmful.
Results were variable

34. Bedside Peep Adjustment
Increase the Peep and Plateau pressure constant= recruitment.
If increase in plateau pressure is proportional to PEEP increase= overdistension

35. Therapy Steroids Pros Cons Inflammatory nature of disease
Treatment of Fibrosing alveolitis
Cons
Historically, no benefit shown with high dose steroids
Increased infection

36. Therapy Steroids Systematic review of studies with low-dose steroids
Tang, et al Use of corticosteroids in acute lung injury and acute respiratory distress syndrome: A systematic review and meta-analysis. Crit Care Med 37;5:
Systematic review of studies with low-dose steroids
Primary outcome: Hospital mortality
Secondary outcomes: length of ventilation, ICU LOS, Lung injury score, PaO2:FiO2.

37. Therapy Steroids Results 9 studies reviewed (4 RCT, 5 cohort)
Tang, et al Use of corticosteroids in acute lung injury and acute respiratory distress syndrome: A systematic review and meta-analysis. Crit Care Med 37;5:
Results
9 studies reviewed (4 RCT, 5 cohort)
648 total subjects, mean age 51
40-250mg/d Methylprednisolone
7-32 days

38. Therapy Steroids Mortality: Trend toward reduction.
Tang, et al Use of corticosteroids in acute lung injury and acute respiratory distress syndrome: A systematic review and meta-analysis. Crit Care Med 37;5:
Mortality: Trend toward reduction.
RTC: P=0.08. Cohort: P=0.06.
Combined: P=0.01
Morbidity: Reduced ventilation: 4 days Reduced ICU stay: 4 days
Improved Disease Severity Scores
Improved PaO2:FiO2

39. Therapy Steroids
Tang, et al Use of corticosteroids in acute lung injury and acute respiratory distress syndrome: A systematic review and meta-analysis. Crit Care Med 37;5:
Adverse Effects: No difference in infection, musculoskeletal complications, GI bleeding, major organ failure.

40. Therapy Fluids
Can diuresis or fluid restriction minimize alveolar edema?
ARDSNet Comparison of Two-Fluid Management Strategies in Acute Lung Injury. N. Engl. J. Med. 354;
Prospective, RCT comparing liberal fluid use vs. conservative (more Lasix, less boluses).
More positive fluid balances in liberal vs. conservative .
Subjects were intubated, PaO2:FiO2< 300
Protocol initiated ~ 43 h post ICU admission.

41. Therapy Fluids
ARDSNet Comparison of Two-Fluid Management Strategies in Acute Lung Injury. N. Engl. J. Med. 354;
Hemodynamics: Lower intravascular pressures in conservative group
Lung Function: Lower PEEP, plateau pressures, shortened ventilation time in conservative group
Metabolic: Higher creatinine values in conservative.
Mortality: No difference in 60 day mortality

42. Therapy PA Catheter
1994 American- European criteria require the absence of LA hypertension
PAC information often ambiguous
Practitioners often misinterpret PAC info
Associated Risks

43. Therapy PA Catheter Included: intubated pts with PaO2:FiO2<300.
The Acute Respiratory Distress Network PAC versus CVC to Guide Treatment of Acute Lung Injury. N. Engl. J. Med. 354;
Included: intubated pts with PaO2:FiO2<300.
Bilateral infiltrates
Excluded: ALI > 48 Hours, dialysis, irreversible conditions
All pts were ventilated with low tidal volumes

44. Therapy PA Catheter Death within 60 days was similar
The Acute Respiratory Distress Network PAC versus CVC to Guide Treatment of Acute Lung Injury. N. Engl. J. Med. 354;
Death within 60 days was similar
Ventilator- Free days similar
No difference if patients were in shock
More Arrhythmias in PAC group

45. Diagnosis BNP
Bajwa et al Crit. Care. Med. Found that BNP Levels are elevated in ARDS.
Levitt et al Crit Care found that BNP levels do not distinguish CHF from ARDS.
Reasons
Myocardial Dysfunction in sepsis
Direct inflammation on myocytes
RA and RV stretch in ARDS

46. Diagnosis Procalcitonin
Marker that indicates likelihood of having a systemic response to a bacterial infection
One study found it to be a Marker for mortality in ARDS

47. Diagnosis Ultrasound
Copetti et al. Cardiovascular Ultrasound 2008, 6:16 
. Disrupted pleural line in ARDS vs. nl pleural line in APE.

48. Subpleural consolidations present in ARDS. Absent in CHF.

49. NIVPPV
Zhan, et al Early use of noninvasive positive pressure ventilation for acute lung injury: A multicenter randomized controlled trial. Crit Care Med
RTC
40 patients randomized to high flow oxygen vs. NIVPPV
Less intubations in NIVPPV (P <0.04)
Total organ system failure less in NIVPPV group (P<0.001)

50. NIVPPV
No good studies assesing NIVPPV as a means to prevent intubation in ARDS.

51. Prognosis
Prognosis primarily depends on underlying cause of lung injury
Sepsis has worst prognosis
Pneumonia has intermediate prognosis
Trauma has best prognosis

52. Surviving Sepsis Guidelines
6 cc/ kg Tidal Volume
End- inspiratory plateau pressures < 30
Hypercapnea is acceptable