1. Acute Respiratory Distress Syndrome
ACNP Boot Camp 2014
Stephanie Davidson, ACNP-BC

2. Objectives Review the causes and differentials for ARDS
Briefly discuss the pathophysiology
Discuss the clinical manifestations of ARDS
Understand evidence based treatment options

3. Statistics Epidemiology Annual incidence: 60/100,000
20% ICU patients meet criteria for ARDS
Morbidity / Mortality
26-44%, most (80%) deaths attributed to non-pulmonary organ failure or sepsis
Risk Factors
Advanced age, pre-existing organ dysfunction or chronic medical illness
Patient with ARDS from direct lung injury has higher incidence of death than those from non-pulmonary injury
Levy BD, & Choi AM, Harrison’s Principles of Internal Medicine, 2012

4. Non-cardiogenic pulmonary edema
Profound hypoxemia – difference between ali and ards.
Bernard et al. AJRCCM 1994; 149:818
Rice et al. Chest 2007: 132: 410

7. June 20, 2012, Vol 307, No. 23
-European Society of Intensive Care Medicine with endorsement from American Thoracic Society and Society of Critical Care Medicine
-Devised three mutually exclusive severity categories: Mild, Moderate and Severe
-Took into account: timing, chest imaging, origin of edema, oxygenation
et al. JAMA 2012; 307:2530

8. et al. JAMA 2012; 307:2530

9. Pneumonia
35%
ARDS network N Engl J Med 2000; 342:1301

10. Differentials Left ventricular failure/volume overload Mitral stenosis
Pulmonary veno-occlusive disease
Lymphangitic spread of malignancy
Interstitial and/or airway disease
Hypersensitivity pneumonia
Acute eosinophilic pneumonia
Acute interstitial pneumonitis

11. Pathophysiology
1. Direct or indirect injury to the alveolus causes alveolar macrophages to release pro-inflammatory cytokines
Ware et al. NEJM 2000; 342:1334

12. Pathophysiology
2. Cytokines attract neutrophils into the alveolus and interstitum, where they damage the alveolar-capillary membrane (ACM).
Ware et al. NEJM 2000; 342:1334

13. Pathophysiology
3. ACM integrity is lost, interstitial and alveolus fills with proteinaceous fluid, surfactant can no longer support alveolus
Ware et al. NEJM 2000; 342:1334

14. Pathophysiology Consequences of lung injury include:
Impaired gas exchange
Decreased compliance
Increased pulmonary arterial pressure

15. Impaired Gas Exchange V/Q mismatch Increased dead space
Related to filling of alveoli
Shunting causes hypoxemia
Increased dead space
Related to capillary dead space and V/Q mismatch
Impairs carbon dioxide elimination
Results in high minute ventilation

16. Decreased Compliance Hallmark of ARDS
Consequence of the stiffness of poorly or nonaerated lung
Fluid filled lung becomes stiff/boggy
Requires increased pressure to deliver Vt

17. Increased Pulmonary Arterial Pressure
Occurs in up to 25% of ARDS patients
Results from hypoxic vasoconstriction
Positive airway pressure causing vascular compression
Can result in right ventricular failure
Not a practice we routinely measure

18. Evidence based management of ARDS
Treat the underlying cause
Low tidal volume ventilation
Use PEEP
Monitor Airway pressures
Conservative fluid management
Reduce potential complications

19. Hypothesis:
In patients with ALI, ventilation with smaller tidal volumes (6 mL/kg) will result in better clinical outcomes than traditional tidal volumes (12 mL/kg) ventilation.
ARDS Network N Engl J Med 2000; 342:1301

20. Low Tidal Volume Ventilation
When compared to larger tidal volumes, Vt of 6ml/kg of ideal body weight:
Decreased mortality
Increased number of ventilator free days
Decreased extrapulmonary organ failure
Mortality is decreased in the low tidal volume group despite these patients having:
Worse oxygenation
Increased pCO2 (permissive hypercapnia)
Lower pH
ARDSnet. NEJM 2000; 342: 1301

21. Low Tidal Volume Ventilation
ARDS affects the lung in a heterogeneous fashion
Normal alveoli
Injured alveoli can potentially participate in gas exchange, susceptible to damage from opening and closing
Damaged alveoli filled with fluid, do not participate in gas exchange

22. Low Tidal Volume Ventilation
Protective measure to avoid over distention of normal alveoli
Uses low (normal) tidal volumes
Minimizes airway pressures
Uses Positive end-expiratory pressure (PEEP)

23. Hypothesis:
In patients with ALI ventilated with 6 mL/kg, higher levels of PEEP will result in better clinical outcomes than lower levels of PEEP.
N Engl J Med 2004; 351:327

24. PEEP Higher levels of PEEP/FiO2 does not improve outcomes
may negatively impact outcomes:
Causing increased airway pressure
Increase dead space
Decreased venous return
Barotrauma

25. PEEP Positive End Expiratory Pressure Every ARDS patient needs it
Goal is to maximize alveolar recruitment and prevent cycles of recruitment/derecruitment

26. -No statistically significant difference in mortality outcomes
-983 patients, randomized into control group with ALI protocol, low Vt and PEEP vs. Open lung group with low Vt, higher PEEP and recruitment maneuvers
-No statistically significant difference in mortality outcomes
Meade, M et al, JAMA ; 299(6):

27. -Multicenter randomized trial, 767 patients
-Multicenter randomized trial, 767 patients. Set a PEEP aimed to increase alveolar recruitment while limiting hyperinflation
-Randomly assigned two groups: moderate PEEP (5-9cm H2O) vs. level of PEEP to reach a plateau pressure of 28-30cm H2O
-Found that it didn’t significantly reduce mortality; however, it did improve lung function and decreased days on vent and organ failure duration
Mercatt, M, et al. JAMA. 2008; 299(6):

28. PEEP As FiO2 increases, PEEP should also increase
ARDSnet. NEJM 2004; 351, 327

29. Auto Peep

30. Airway Pressures in ARDS
Plateau pressure is most predictive of lung injury
Goal plateau pressure < 30, the lower the better
Decreases alveolar over-distention and reduces risk of lung strain
Adjust tidal volume to ensure plateau pressure at goal
It may be permissible to have plateau pressure > 30 in some cases
Obesity
Pregnancy
Ascites
Terragni et al. Am J Resp Crit Care Med. 2007; 175(2):160

31. Permissible Plateau Pressures
Assess cause of high Plateau Pressures
Always represents some pathology:
Stiff, non-compliant lung: ARDS, heart failure
Pneumothorax
Auto-peeping
Mucus Plug
Right main stem intubation
Compartment syndrome
Chest wall fat / Obesity

32. Airway Pressures Peak Inspiratory Pressure Airway Pressures
Plateau Pressure
PEEP
Time

33. Fluid and Catheter Treatment Trial
--No need for routine PAC use is ALI patients
--Support use of conservative strategy fluid management in patients with ALI
N Engl J Med 2006; 354: 2213

34. Results
Using the data from a PAC compared to that from a CVC in an explicit protocol:
Did not alter survival.
Did not improve organ function.
Did not change outcomes for patients entering in shock compared to those without shock.
PAC use resulted in more non-fatal complications, mostly arrhythmias.
N Engl J Med 2006; 354: 2213

35. ~Hypothesis: Diuresis or fluid restriction may improve lung function but could jeopardize extrapulmonary organ perfusion
~Conclusion: Conservative fluid management improved lung function and shortened mechanical ventilation times and ICU days without increasing nonpulmonary organ failures
N Engl J Med. 2006;354:2564

36. Fluid Management
Increased lung water is the underlying cause of many of the clinical abnormalities in ARDS (decreased compliance, poor gas exchange, atelectasis)
After resolution of shock, effort should be made to attempt diuresis
CVP used as guide, goal <4
Shortens time on vent and ICU length of stay (13 days vs 11 days)
ARDSnet. NEJM 2006; 354: 2564

37. Hypothesis: Early application of prone positioning would improve survival in patients with severe ARDS.
Conclusion: Early application of prolonged prone positioning significantly decreased 28 day and 90 mortality in patients with severe ARDS.
Guerin et al. NEJM. 2013; 368:2159

38. Weaning Daily CPAP breathing trial Pressure support weaning
FiO2 <.40 and PEEP <8
Patient has acceptable spontaneous breathing efforts
No vasopressor requirements, use judgement
Pressure support weaning
PEEP 5, PS at 5cm H2O if RR <25
If not tolerated, ↑RR, ↓Vt – return to A/C
Unassisted breathing
T-piece, trach collar
Assess for 30minutes-2 hours

39. Weaning Tolerating Breathing Trial? SpO2 ≥90
Spontaneous Vt ≥4ml/kg PBW
RR ≤35
pH ≥7.3
Pass Spontaneous Awakening Trial (SAT)
No Respiratory Distress ( 2 or more)
HR > 120% baseline
Accessory muscle use
Abdominal Paradox
Diaphoresis
Marked Dyspnea
If tolerated, consider extubation

40. Putting it all together
1) Calculate patient’s predicted body weight:
Men (kg) = (height in inches – 60)
Females (kg) = (height in inches – 60)
Set Vt = predicted body weight x 6cc
Set initial rate to approximate baseline minute ventilation (RR x Vt)
Set FiO2 and PEEP to obtain SaO2 goal of >=88%
Diurese after resolution of shock
Refer to ARDSnet guidelines

41. Troubleshooting Common Problems

42. Refractory Hypoxia
Mechanical Trouble (tubing, ventilator, ptx, plugging)
Neuromuscular blockade
Recruitment maneuvers – positioning, “good lung down” optimizes V/Q mismatch
Increase PEEP
Inhaled epoprostenol sodium (Flolan)
When inhaled, the vasodilator reaches the normal lung, is concentrated in normal lung segments and recruits blood flow to functional alveoli where it is oxygenated.  This decreases shunting and hypoxemia
High frequency ventilation

43. -Randomized control trial, stopped with 548 of 1200 patients
-Found early initiation of HFOV does not reduce and may increase hospital mortality
Ferguson, N, et al, NEJM 2013; 368:

44. -Multicenter randomized trial with 795 patients enrolled
-found there is no significant effect of 30 day survival between patients who received HFOV and conventional mechanical ventilation
Young, D, et al,NEJM. 2013; 368:

45. -Neuromuscular blocking agents may increase oxygenation and decrease ventilator associated lung injury in severe ARDS patients
-Multicenter double blind trial with 340 patients; received 48hrs of cisatracurium (Nimbex) or placebo
-Found that early administration of NBA improved 90 day survival and increased time off vent without increase in muscle weakness
Papazian, L, et al. NEJM 2010; 363:

46. Supportive Therapies Treat underlying infection
DVT prophylaxis / stress ulcer prevention
HOB 30°
Hand washing
Use full barriers with chlorhexadine
Sedation / analgesia
Feeding protocol
Avoid contrast nephropathy
Pressure ulcer prevention, turning Q2h
Avoid steroid use

47. ~No benefit of corticosteroids on survival
~When initiated 2 weeks after onset of ARDS, associated with significant increase in mortality rate compared to placebo group
N Engl J Med ; 354:1671

48. Conclusion Recovery dependent on health prior to onset
Within 6 months, will have reached max recovery
At 1 year post-extubation, >1/3 have normal spirometry
Significant burden of emotional and depressive symptoms with increased depression and PTSD in ARDS survivors
Survivor clinic catches symptoms early by screening patients
New treatment modalities, lung protective ventilation
Levy BD, & Choi AM, Harrison’s Principles of Internal Medicine, 2012

49. Questions ?

50. References
Acute Respiratory Distress Syndrome Network: Ventilation with Tidal Volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. New Engl J Med. 2000; 342: ARDSNet: Higher versus lower Positive End-Expiratory Pressures in patients with the acute respiratory distress syndrome. New Engl J Med. 2004; 351: ARDSNet: Efficacy and Safety of Corticosteroids for persistent acute respiratory distress syndrome. New Engl J Med. 2006; 354: ARDSNet: Comparison of Two fluid management strategies in acute lung injury. New Engl J Med. 2006; 354: ARDSNet: Pumonary Artery versus Central Venous catheter to guide treatment of acute lung injury. New Eng J Med. 2006; 354: Et al: Acute respiratory distress syndrome: The Berlin Definition. JAMA. 2012; 307(23): Ferguson N, et al: High frequency oscillation in early acute respiratory distress syndrome. New Engl J Med. 2013; 368: Guerin C et al: Prone positioning in severe acute respiratory distress syndrome. New Engl J Med. 2013; 368:

51. References
Levy B.D., Choi A.M. (2012). Chapter 268. Acute Respiratory Distress Syndrome. In A.S. Fauci, D.L. Kasper, J.L. Jameson, D.L. Longo, S.L. Hauser (Eds), Harrison's Principles of Internal Medicine, 18e. Retrieved August 17, 2013 from Meade M, et al: Ventilation Strategy Using low tidal volumes, recruitment maneuvers and high post end expiratory pressure for acute lung injury and acute respiratory distress syndrome. JAMA. 2008; 299(6): Mercatt M, et al: Post end-expiratory pressure settings in adults with acute lung injury and acute respiratory distress syndrome. JAMA. 2008; 299(6): Papazian L, et al: Neuromuscular blockers in early acute respiratory distress syndrome. New Engl J Med. 2010; 363: RiceTW et al: Comparison of the SpO2/FiO2 Ration and the PaO2/FiO2 Ratio in patients with acute lung injury or acute respiratory distress syndrome. Chest. 2007; 132:

52. References
Terragan PP et al: Tidal hyperinflation during low tidal volume ventilation in Acute respiratory distress syndrome. J Resp Crit Care Med. 2007; 175:
Ware LB, Matthay MA: The Acute Respiratory Distress Syndrome. New Engl J Med ; 342:
Young D, et al: High frequency oscillation for acute respiratory distress syndrome. New Engl J Med. 2013; 368: