1. Chapter 27 Acute Lung Injury, Pulmonary Edema, and Multiple System Organ Failure

2. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 2 Objectives  Identify the approximate incident rate of acute respiratory distress syndrome (ARDS) and how the mortality rate has changed over the past several decades.  State the risk factors associated with the onset of ARDS.  Describe how the normal lung prevents fluid from collecting in the parenchyma and how these mechanisms can fail and cause pulmonary edema.

3. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 3 Objectives (cont.)  Describe the effect pulmonary edema has on lung function including gas exchange and lung compliance.  Describe the relationship between multiple organ dysfunction syndrome (MODS) and ARDS.  Identify the histopathology associated with the exudative phase and the fibroproliferative phase of ARDS.  State how hydrostatic and nonhydrostatic pulmonary edema are differentiated from one another in the clinical setting.

4. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 4 Objectives (cont.)  Describe the principles of supportive care followed for patients with ARDS.  Describe how ventilator settings (e.g., tidal volume, positive end-expiratory pressure, respiratory rate) are adjusted for patients with ARDS and MODS.  Describe how mechanical ventilation can cause lung injury and how ventilator-induced lung injury can be avoided.  State the approaches to the management of ARDS and MODS.

5. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 5 Objectives (cont.)  Describe the use of innovative mechanical ventilation strategies in the support of patients with ARDS.  State the effect of prone positioning on oxygenation and mortality in the ARDS patient.  Describe the value of pharmacological therapies such as nitric oxide and corticosteroids in the treatment of patients with ARDS.

6. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 6 Introduction  Pulmonary edema  Abnormal fluid accumulation within lung parenchyma and alveoli resulting in hypoxemia  May be secondary to CHF or ALI  Severe ALI is called ARDS or noncardiogenic pulmonary edema Often occurs with MODS Often occurs with MODS  ARDS is a common cause of respiratory failure.  http://www.youtube.com/watch?v=kQ9eCywj_Hs http://www.youtube.com/watch?v=kQ9eCywj_Hs

7. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 7 Epidemiology  ARDS has many diverse causes.  Mortality rates have fallen from ~90% to ~40%  Due to better supportive care  Early detection  Effective management of cormorbidities  Application of new ventilatory strategies

8. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 8 ARDS Risk Factors

9. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 9 Pathophysiology Pulmonary edema  Fluid first accumulates in interstitial space.  Followed by alveolar flooding  Impairs gas exchange and reduces lung compliance Hydrostatic (cardiogenic) pulmonary edema  Fluid accumulation in interstitium raises hydrostatic pressure rapidly and alveolar flooding follows.  Flooding occur in “all or nothing” manner.  Fluid filling alveoli is identical to interstitial fluid.

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13. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 13 Pathophysiology (cont.) Nonhydrostatic (noncardiogenic) pulmonary edema  Fluid accumulates despite normal hydrostatic pressure.  Vascular endothelial injury alters permeability.  Protein-rich fluid floods the interstitial space.  Alveolar flooding occurs as osmotic pressures in capillaries and interstitium equalize.  Alveolar epithelium is also injured.  There is also impaired pulmonary fluid clearance.  The common mechanism for development of ARDS appears to be lung inflammation.

14. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 14 Pathophysiology (cont.) Gas exchange and lung mechanics during ARDS  Restrictive changes with refractory hypoxemia  Altered permeability floods the lung, resulting in decreased lung compliance (C L ) and consolidation.  Impaired surfactant synthesis and function worsens gas exchange and C L.  Loss of normal vascular response to alveolar hypoxemia  Unaerated alveoli receive blood flow in excess of ventilation so increased shunting occurs

15. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 15 Pathophysiology (cont.)

16. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 16 Pathophysiology (cont.) Role of organ–organ interactions in pathogenesis  ALI resulting in MODS is probably related to PMN- mediated inflammation.  Broad-spectrum antibiotic usage results in resistant “bugs,” particularly in GI tract.  Escape GI tract and activate RE in liver/lymph/spleen  RE may activate and sustain systemic inflammatory response that leads to ARDS and MODS.  Balance of antiinflammatory and proinflammatory factors, severity of illness, comorbidities predisposes patients to ARDS and MODS

17. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 17

18. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 18 Histopathology and Clinical Correlates of ARDS Exudative phase (1–3 days)  Characterized by diffuse damage to A/C membrane and influx of inflammatory cells into interstitium  Many alveoli fill with proteinaceous, eosinophilic material called hyaline membranes.  Composed of cellular debris and plasma proteins  Type I pneumocytes are destroyed.  Patients have profound dyspnea, tachypnea, and refractory hypoxemia.

19. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 19 Histopathology and Clinical Correlates of ARDS (cont.) Fibroproliferative phase (3-7 days)  Inflammatory injury is followed by repair.  This involves hyperplasia of type II pneumocytes and proliferation of fibroblasts in lung parenchyma  Formation of intraalveolar and interstitial fibrosis  Lung remodeling following ARDS is variable.  Nearly complete recovery of C L and oxygenation in 6–12 months to  Severe disability due to extensive pulmonary fibrosis and obliteration of pulmonary vasculature

20. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 20 Histopathology and Clinical Correlates of ARDS (cont.) Differentiating CHF from ARDS in the clinical setting  First suspect CHF as it is much more common.  Any of these may be present in either group: Older patients Older patients Comorbidities Comorbidities Infection Infection Trauma Trauma Suspected aspiration Suspected aspiration

21. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 21 Histopathology and Clinical Correlates of ARDS (cont.)

22. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 22 Differentiating CHF From ARDS in the Clinical Setting  Radiographic findings  CHF: cardiomegaly, perihilar infiltrates, effusions  ARDS: peripheral alveolar infiltrates, air bronchograms with normal heart size  Hard to determine heart size and presence of effusions on supine A/P films  Complicated by possible coexistence of CHF and ARDS  PA catheter is a useful tool to differentiate.  PAWP > 18 necessary for hydrostatic pulmonary edema  PAWP < 18 suggests ARDS

23. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 23 Differentiating CHF From ARDS in the Clinical Setting (cont.)  PA catheter (cont.)  Carefully appraise results as a catheter placed in a non– zone 3 area may reflect high PEEP or P aw instead of PAWP.  Bronchoalveolar lavage fluid (BALF)  BALF from an ARDS patient will contain large amounts of inflammatory cells.  Identification of infectious agents if any  Evidence of aspiration if it occurred  Clinical characteristics as seen in Box 27-2

24. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 24 Therapeutic Approach to ARDS

25. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 25 Therapeutic Approach to ARDS (cont.) Hemodynamics and fluid management during ARDS  Optimized oxygen delivery (DO 2 ) is a primary goal of supportive therapy.  Care required as PEEP improves FRC, C L, and CaO 2, it may impair cardiac output (CO) and thus DO 2

26. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 26 Therapeutic Approach to ARDS (cont.) Hemodynamics and fluid management during ARDS (cont.)  Restriction of intravascular volume generally improves CaO 2 and DO 2.  Careful of overrestriction as may ⇓ CO and ⇓ DO 2  Prudent to avoid hypotension and keep SaO 2 >90%, ⇑ DO 2 with hyperlactatemia, ensure organ function (e.g., UO)

27. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 27 Therapeutic Approach to ARDS (cont.) Mechanical ventilation during ARDS  Three distinct lung zones in ARDS  Dependent regions are nonventilated due to dense alveolar infiltrate.  Region of dense infiltrates may be made available for gas exchange by proper ventilatory strategy.  Nondependent aerated region retains near-normal lung characteristics.  Lungs are effectively diminished to 20–30% of normal

28. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 28 Therapeutic Approach to ARDS (cont.) Setting V T  Conventional levels are not acceptable.  Distributed to the small aerated lung zones, leads to hyperinflation and overdistention  Excessive volume induces lung injury (volutrauma). Avoided by use of smaller V T Avoided by use of smaller V T  Optimal V T set by pressure-volume (P/V) relationships Should set between upper and lower P FLEX. Should set between upper and lower P FLEX.  Initiate V T of 5–7 ml/kg.

29. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 29 http://www.youtube.com/watch?v= 5bMwmmvdGI0

30. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 30 Therapeutic Approach to ARDS (cont.) Adjusting PEEP  Goal is to recruit additional alveoli and increase FRC and oxygenation.  Improving oxygenation enables a reduction in FIO 2 Reduces the risk of oxygen toxicity Reduces the risk of oxygen toxicity  Recruited alveoli avoid opening and closing injury.  Set PEEP at lowest level to ensure Arterial oxygenation: PaO 2 > 60 mm Hg, FIO 2 60 mm Hg, FIO 2 < 0.6 Adequate tissue oxygenation Adequate tissue oxygenation Alveoli patent throughout ventilatory cycle Alveoli patent throughout ventilatory cycle Avoid barotrauma with P aw < 35 cm H 2 O. Avoid barotrauma with P aw < 35 cm H 2 O.

31. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 31 Therapeutic Approach to ARDS (cont.) Adjusting the ventilatory rate  Compared to normal, ARDS patients require much higher V E to maintain PaCO 2  Small V T used to avoid volutrauma.  Permissive hypercapnia used to avoid high P aw  PaCO 2 60–80 mm Hg common, pH ~7.25  May require sedation and even paralysis to avoid air hunger and patient triggering at high rates  Routine use of IS recommended at this time..

32. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 32 Therapeutic Approach to ARDS (cont.)

33. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 33 Innovative Ventilation Strategies for ARDS Volume-controlled ventilation (VCV)  ARDS net protocol showed ~20% reduction in mortality with a lower tidal volume strategy  Initiate V T of 5–7 ml/kg  Adjust as required based on patient’s P/V curves High-frequency ventilation (HFV)  Designed to maintain adequate ventilation and reduce alveolar collapse through increased FRC  Uses rates up to 300 beats/min, V T 3–5 ml/kg  Evidence does not support routine use in adults.

34. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 34 Innovative Ventilation Strategies for ARDS (cont.) Inverse-ratio ventilation (IRV)  Designed to recruit alveoli through prolonged inspiration  I:E ratios may exceed 4:1.  Initial studies had significantly improved oxygenation but did not take into account PEEP levels.  Controlling for PEEP, there was no change in oxygenation associated with IRV.  Studies have not shown a survival benefit for IRV.  Routine use not recommended at this time, but may be used in face of refractory hypoxemia and high P aw

35. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 35 Innovative Ventilation Strategies for ARDS (cont.) Pressure-controlled ventilation (PCV)  Designed to prevent ventilator-associated lung injury  PIP of <30–35 cm H 2 O chosen  Likely to avoid overdistention and prevent volume- associated lung injury  V T varies with changes in C L and Raw.  Large swings in V T may be seen with PCV.  PCV has not proved superior to VCV.  If use must monitor V T carefully to avoid volutrauma.

36. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 36 Innovative Ventilation Strategies for ARDS (cont.) Airway pressure release ventilation (APRV)  Designed to recruit alveoli while minimizing ventilator-induced barotrauma through use of prolonged inspiration  V T is delivered during transient decreases in pressure, which may be patient triggered.  Patients may breathe anytime so appear to tolerate well  APRV is more effective than IRV for alveolar recruitment.  APRV is effective but not superior to VCV.

37. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 37 Innovative Ventilation Strategies for ARDS (cont.) Patient positioning (proning)  Prone positioning places the aerated lung regions in the dependent position better matching ventilation/perfusion.  Rationales for improved oxygenation of proning  Improved V/Q ratio, FRC, and CO  More effective bronchial drainage  Significant downsides include lack of tolerance, require specialized nursing care and equipment  No evidence of improved mortality..

38. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 38 Innovative Ventilation Strategies for ARDS (cont.) Extracorporeal membrane oxygenation (ECMO) and extracorporeal carbon dioxide removal (ECCO 2 R)  ECMO involves establishing an arteriovenous shunt that diverts a large percent of CO through an artificial lung that removes CO 2 and adds O 2  Shown to have no survival benefit over VCV

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40. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 40 Innovative Ventilation Strategies for ARDS (cont.) ECMO and ECCO 2 R (cont.)  ECCO 2 R has a venovenous circuit that diverts ~20% of CO to an artificial lung that primarily removes CO 2  Reduces need for high V E to remove CO 2 in lungs  No evidence of improved survival benefit  Routine use not recommended at this time

41. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 41 Pharmacological Therapies for ARDS Inhaled nitric oxide (INO)  Potent vasodilator thought to improve perfusion where ventilation is best  Studies to date have been mixed, but bottom line  Most effective on patients with high PVR  Some evidence of improved oxygenation  No reduction in ventilator days  No survival benefit  Highly toxic substances released on breakdown  Remains an experimental treatment for ARDS

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44. Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 44 Pharmacological Therapies for ARDS (cont.)  2 -Agonists   2 -Agonists shown to decrease alveolar permeability  Study used IV salbutamol (15 µ g/kg/hr)  Patients had significantly less lung water and P plat  No difference in P/F ratio or 28-day mortality  Further study required to determine if this will have a use or join the multitude of ineffective ARDS treatments.