Acute Respiratory Distress Syndrome

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. 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 • 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. -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. 2008; 299(6):637-645

27. -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):646-655.

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 • 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) = 50 + 2.3(height in inches – 60) • Females (kg) = 45.5 + 2.3(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: 795-805.

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; 368:806-813

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: 1107-1116.

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. 2006; 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: 1302-1308. ARDSNet: Higher versus lower Positive End-Expiratory Pressures in patients with the acute respiratory distress syndrome. New Engl J Med. 2004; 351: 327-336. ARDSNet: Efficacy and Safety of Corticosteroids for persistent acute respiratory distress syndrome. New Engl J Med. 2006; 354: 1671-1684. ARDSNet: Comparison of Two fluid management strategies in acute lung injury. New Engl J Med. 2006; 354: 2564-75. ARDSNet: Pumonary Artery versus Central Venous catheter to guide treatment of acute lung injury. New Eng J Med. 2006; 354: 2213-2224. Et al: Acute respiratory distress syndrome: The Berlin Definition. JAMA. 2012; 307(23): 2526-2533. Ferguson N, et al: High frequency oscillation in early acute respiratory distress syndrome. New Engl J Med. 2013; 368: 795-805. Guerin C et al: Prone positioning in severe acute respiratory distress syndrome. New Engl J Med. 2013; 368: 2159-2168.