1. Assistant Professor of Anesthesiology
ARDS
Ruben J Azocar, M.D.
Assistant Professor of Anesthesiology
Boston University School of Medicine
ITACCS
Key West 2006

2. ARDS: Definitions
First described in 1967 as Adult Respiratory Distress Syndrome
American-European Consensus Conference Committee (1994) criteria
Acute onset
Bilateral infiltrates in chest radiography
Pulmonary-artery wedge pressure<18 mmHg
Acute lung injury PaO2/FiO2<300
Acute respiratory distress syndrome PaO2/FiO2<200

3. ARDS: Causes

4. ARDS:Epidemiology Incidence: 80 per 100,000 Outcomes:
Traditionally 40-60% mortality
Majority of deaths due to MSOF
Low tidal volume ventilation decreases mortality
Other critical care improvements may be involved
Predictive factors for death: CLD, non pulmonary organ dysfunction, sepsis and advance age
Survivors: Most of them will have normal pulmonary function within a year

5. ARDS:Pathogenesis ARDS is the manifestation of SIRS in the lungs
Influx of protein rich edema into the air spaces due to increased permeability of the alveolar-capillary barrier
Endothelial damage pathophysiology is similar to that of SIRS/SEPSIS

6. ARDS:Pathogenesis Epithelial damage
Loss of epithelial integrity which in normal conditions less permeable than endothelium
Type II cells injury
disrupts normal epithelial fluid transport
reduces production of surfactant
May lead to septic shock in patients with pneumonia
Severely injured epithelium lead to disorganized repair and fibrosis

7. ARDS:Pathogenesis Neutrophils Cytokines Ventilator induced injury
Unbalanced production of pro-inflammatory and anti-inflammatory cytokines
Ventilator induced injury
High FiO2
Overdistention
Recruitment/De-recruitment
May exacerbate and perpetuate ARDS/ALI as well as SIRS/Sepsis/MSOF

8. ARDS: Exudative Phase
The definition applies for the acute “exudative” phase
Rapid onset
Hypoxemia refractory to supplemental oxygen
CXR similar to pulmonary edema
CT Scan: Alveolar filling, consolidation and atelectasis in the dependent lung zones
Pathologic findings:
diffuse alveolar damage with capillary injury and disruption of the alveolar epithelium
hyaline membranes
protein rich fluid edema with neutrophils and macrophages

9. ARDS:Pathogenesis

10. ARDS: Exudative Phase
CT Scan During Acute Phase

11. ARDS: Fibroproliferative phase
Some patients progress to fibrosing alveolitis with persistent hypoxemia, increase alveolar dead space and further decrease in pulmonary compliance
The process may start as early as 5-7 days
The alveolar space becomes filled with mesenchymal cells and their products as well as new blood vessels

12. ARDS: Fibroproliferative phase
Pulmonary HTN due to obliteration of pulmonary bed may lead or worsen RV dysfunction
CXR shows linear opacities.
PTX and bullae are common
Histologically, there is fibrosis and partial resolution of the pulmonary edema
Mortality is 80% if this phase persists

13. ARDS: Fibroproliferative phase
CT Scan during fibroproliferative phase.
Diffuse interstitial opacities and bullae

14. ARDS:Pathogenesis

15. ARDS:Treatment Recent decrease of mortality
Treatment of underlying cause
Better supportive ICU Care
Prevention of infections
Appropriate nutrition
GI prophylaxis
Thromboembolism prophylaxis

16. ARDS Treatment Mechanical ventilation
Buys time for the lungs to heal and solve the inciting cause
“New” ventilator strategies
Recognition of ventilator induced injury (VILI)
Overdistention
Recruitment/de-recruitment
Mechanical ventilation induces cytokine response which is worse with alveoli overdistention and recruitment/ de-recruitment of the lung (Ranieri et al JAMA 1999;282: 54-61)

17. ARDS: Treatment

18. ARDS: Treatment Protective ventilation Smaller tidal volumes
Avoid overdistention
Tolerate “permissive hypercarbia”
“Open lung” ventilation
Avoid alveolar collapse and reopening

19. Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome The Acute Respiratory Distress Syndrome Network N Engl J Med 2000;342:1301-8
Study stopped after 2nd interim analysis
Reduction of mortality by 22%

20. NIH/ARDS Network VARIABLES PROTOCOL Ventilator mode Tidal Volume
Plateau Pressure
Ventilation rate/pH goal
Inspiration flow, I:E
Oxygenation goal
FIO2/PEEP
Weaning
PROTOCOL
Volume assist control
< 6mL/Kg body weight
<30 cm H2O
6-35/min adjusted for pH of 7.30 if possible
Adjust to 1:1-1:3
PaO2>55 and or SpO2>88%
Combinations
PS wean when FiO2/PEEP<.40/8

21. Ventilation with Lower Tidal Volumes
The goal of providing small tidal volumes is to maintain the patient on the steep, more compliant portion of the curve without exceeding the upper inflection point

22. ARDS:Permissive Hypercapnia
Hypercarbic acidosis
Hypoxemia
Respiratory failure and arrest
Decrease myocardial contractility
Cerebral vasodilatation
Decrease seizure threshold
Hyperkalemia
Permissive hypercapnia
Supplemental oxygen overcomes CO2 induced hypoxia
No evolution to respiratory arrest
Lack of significant deleterious effects
Is hypercarbia beneficial?

23. Kregenov et al: Hypercapnic acidosis and mortality in ALI CCM 2006;34:1-7
Patients from the low tidal volume trial
Hypercapnic acidosis was associated with reduced 28-day mortality in the 12 mL/kg VT group after controlling for comorbidities and severity of lung injury.
These results are consistent with a protective effect of hypercapnic acidosis against ventilator-associated lung injury that was not found when the further ongoing injury was reduced by 6 mL/kg predicted body weight tidal volumes.

24. Effect of a protective ventilation strategy on mortality in ARDS Amato M et al NEJM 1998;338:347-354
End-expiratory pressure above the lower inflection point
VT less 6ml/kg
Driving pressures less than 20 cm H2O above PEEP
Permissive hypercarbia
38% Mortality in protective group vs. 71% in control group
66% of patient in “protective” group wean off ventilation vs. 29% control group
No difference in survival at 28 days

25. Optimal “PEEP”
Positive end-expiratory pressure should be high enough to shift the end-expiratory pressure above the lower inflection point by 2-3 cm H2O (usually cm H2O)
Allows maximal alveolar recruitment
Decreases injury by repeated opening and closing of small airways

26. Ventilation of an ex Vivo Rat Lung
Slutsky, A. S. et al. N Engl J Med 2006;354:

27. Higher Vs. Lower PEEP in Patients With ARDS, NEJM 2004
NIH/ARDS Trail Network
549 patients
Lower PEEP 8.3+/- 3.2
Higher PEEP 13.2+/-3.5
All on low tidal volume ventilation
No differences on clinical outcome
Trial stop due to rule of futility

28. BUT…..
In the first 171 patients: “the difference in mean PEEP levels between study groups on days 1 to 7 was less that the difference in the previous study that tested the effects of higher PEEP levels and smaller tidal volumes”
Should have these patients not been included, would have the trial been stopped early?

29. ARDS: Treatment Recruiting maneuvers Prone positioning Steroids APRV
Volume cycle vs. pressure cycle
Inverse-Ratio Ventilation
Non invasive Positive Pressure Ventilation
High-Frequency Ventilation
Tracheal Gas Insufflation
Extracorporeal gas exchange
Fluorocarbon Liquid Gas Exchange

30. Recruitment maneuvers
Lung recruitment in patients with ARDS Gattinoni NEJM 2006;354:
Sixty eigt patients with ALI/ARDS underwent whole lung CT Scan during breath holding session at airway pressures of 5, 15 and 45 cm of water
The percentage of potentially recruitable lung was defined as the proportion of lung tissue in which aeration was restored (Recruited)

31. Recruitment
The potentially recruitable lung was significantly variable but highly correlated with the percentage of lung tissue in which aeration was maintained with PEEP
Patients with more recruitable lung were sicker
Greater lung weight
Poorer oxygenation
Poorer compliance
Higher levels of death space
Higher mortality

32. Recruitment
Knowing the % of recruitable lung might be the key to the effects of PEEP
PEEP in patients with limited recruitable areas might be of little benefit or harmful
Overdistention
Worsening of Shunt
Authors suggest PEEP of 15 for those recruitables and 10 for those who are not

33. ARDS Treatment Prone positioning
In about 70% of ARDS patients, prone positioning improves the PaO2 by > 20%
Consider a lung recruitment strategy, since allows a decrease in FiO2 and PEEP
A more uniform distribution of pleural pressure gradients, result in greater ventilation of dependent lung than in supine positioning

34. ARDS Treatment Gattinoni et al, NEJM 2001;345:568-573
304 patients with ARDS
Prone group: at least six hours/day for ten days
Better oxygenation in the prone patients
Similar incidence of complications
No improvement in survival
However patient only prone for 7 hours a day and up to 10 days

35. ARDS Treatment Fluid and hemodynamic management
Optimal fluid management is controversial
There is data supporting fluid restriction as a mean to minimize lung edema
However maintenance and preservation of oxygen delivery may require fluid administration
Euvolemia, judicious use of vasopressors
Effects of ventilation in circulation
To Swan or not to Swan

36. Swan and ARDS
PAC versus CVP to guide treatment of ALI NEJM 2006; 354:
1000 patients
Mortality at 60 days was similar between groups, as well as the ventilator free days and days not spent in the ICU
Fluid balances were similar among the groups
PAC had double complications mainly arrhythmias

37. APRV
It uses a release of airway pressure from an elevated baseline to simulate expiration.
The elevated baseline facilitates oxygenation avoids collapsing of alveoli and the timed releases aid in carbon dioxide removal.
Potential advantages of APRV include lower airway pressures, lower minute ventilation, minimal adverse effects on cardio-circulatory function.
Airway pressure release ventilation is consistent with lung protection strategies that strive to limit lung injury associated with mechanical ventilation, particularly recruitment/derecruitment
More (larger) studies are needed to define its role in ALI/ARDS

38. ARDS:Treatment Inhaled nitric oxide and other vasodilators Surfactant
Most ARDS/ALI patient may have mild to moderate pulmonary HTN
Improvement in oxygenation was small and not sustained
No change on mortality or duration of mechanical ventilation
May be used as “rescue” therapy
Surfactant
Successful in neonatal respiratory distress syndrome

39. ARDS: Treatment Glucocorticoids No benefits in acute phase
Some evidence of improvement during proliferative phase (Meduri et al JAMA 1998;280: )
Methylprednisolone 2mg/kg initially for 32 days
Improvement in Lung injury scores, MOSD scores and mortality
Benefits may be noticed by day 3
High risk of infection
? May consider a short course of high dose as rescue therapy

40. ARDS: Steroids
Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome NEJM :
180 patients
Mortality at 60 days
28.9% mortality in the placebo group and 29.2% in the methylprednisolone group
Methylprednisolone increased the number of ventilator free and shock free days during the first 28 days in association with an improvement in oxygenation, respiratory system compliance and blood pressure with fewer vasopressor days
But methylprednisolone was associated with a significant increase days mortality in patients enrolled at least 14 days after the onset of ARDS

41. ARDS: Treatment Anti-inflammatory Strategies Antioxidant therapy
Prostaglandin agonist/inhibitors
Lisofylline and pentoxifylline
Anti IL-8
Antioxidant therapy
Enhanced resolution of pulmonary edema
Enhanced repair of alveolar epithelial barrier

42. ARDS: Questions