1. Chapter 27 Acute Lung Injury, Pulmonary Edema, and Multiple System Organ Failure1

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.
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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.
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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.
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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.
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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
ARDS is a common cause of respiratory failure.
CHF – congestive heart failure, ALI – acute lung injury, ARDS - acute respiratory distress syndrome, MODS - multiple organ dysfunction syndrome
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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
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8. ARDS Risk Factors
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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. 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.
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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 (CL) and consolidation.
Impaired surfactant synthesis and function worsens gas exchange and CL.
Loss of normal vascular response to alveolar hypoxemia
Unaerated alveoli receive blood flow in excess of ventilation so increased shunting occurs
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15. Pathophysiology (cont.)
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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
RE – reticuloendothelial
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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.
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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 CL and oxygenation in 6–12 months to
Severe disability due to extensive pulmonary fibrosis and obliteration of pulmonary vasculature
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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
Comorbidities
Infection
Trauma
Suspected aspiration
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21. Histopathology and Clinical Correlates of ARDS (cont.)
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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
PA – pulmonary artery, PAWP – pulmonary artery wedge pressure
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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 Paw 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
PEEP – Positive end expiratory pressure, Paw – airway pressure, PAWP – pulmonary artery wedge pressure
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24. Therapeutic Approach to ARDS
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25. Therapeutic Approach to ARDS (cont.)
Hemodynamics and fluid management during ARDS
Optimized oxygen delivery (DO2) is a primary goal of supportive therapy.
Care required as PEEP improves FRC, CL, and CaO2, it may impair cardiac output (CO) and thus DO2
PEEP – Positive end expiratory pressure, FRC – functional residual capacity, CL – lung compliance, CaO2 – arterial oxygen content, UO – urine output
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26. Therapeutic Approach to ARDS (cont.)
Hemodynamics and fluid management during ARDS (cont.)
Restriction of intravascular volume generally improves CaO2 and DO2.
Careful of overrestriction as may ⇓CO and ⇓DO2
Prudent to avoid hypotension and keep SaO2 >90%, ⇑DO2 with hyperlactatemia, ensure organ function (e.g., UO)
UO – urine output
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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
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28. Therapeutic Approach to ARDS (cont.)
Setting VT
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 VT
Optimal VT set by pressure-volume (P/V) relationships
Should set between upper and lower PFLEX.
Initiate VT of 5–7 ml/kg.
Initiate VT of 5-7 ml/kg (page 27-15) {comp: please insert proper page number}
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29.
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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 FIO2
Reduces the risk of oxygen toxicity
Recruited alveoli avoid opening and closing injury.
Set PEEP at lowest level to ensure
Arterial oxygenation: PaO2 > 60 mm Hg, FIO2 < 0.6
Adequate tissue oxygenation
Alveoli patent throughout ventilatory cycle
Avoid barotrauma with Paw < 35 cm H2O.
Paw – mean airway pressure
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31. Therapeutic Approach to ARDS (cont.)
Adjusting the ventilatory rate
Compared to normal, ARDS patients require much higher VE to maintain PaCO2
Small VT used to avoid volutrauma.
Permissive hypercapnia used to avoid high Paw
PaCO2 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. .
Paw – mean airway pressure
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32. Therapeutic Approach to ARDS (cont.)
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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 VT 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, VT 3–5 ml/kg
Evidence does not support routine use in adults.
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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 Paw
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35. Innovative Ventilation Strategies for ARDS (cont.)
Pressure-controlled ventilation (PCV)
Designed to prevent ventilator-associated lung injury
PIP of <30–35 cm H2O chosen
Likely to avoid overdistention and prevent volume- associated lung injury
VT varies with changes in CL and Raw.
Large swings in VT may be seen with PCV.
PCV has not proved superior to VCV.
If use must monitor VT carefully to avoid volutrauma.
PIP – peak inspiratory pressure, VCV - Volume Controlled Ventilation
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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
VT 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.
PIP – peak inspiratory pressure, VCV - Volume Controlled Ventilation
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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 . .
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38. Innovative Ventilation Strategies for ARDS (cont.)
Extracorporeal membrane oxygenation (ECMO) and extracorporeal carbon dioxide removal (ECCO2R)
ECMO involves establishing an arteriovenous shunt that diverts a large percent of CO through an artificial lung that removes CO2 and adds O2
Shown to have no survival benefit over VCV
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39. Innovative Ventilation Strategies for ARDS (cont.)
ECMO and ECCO2R (cont.)
ECCO2R has a venovenous circuit that diverts ~20% of CO to an artificial lung that primarily removes CO2
Reduces need for high VE to remove CO2 in lungs
No evidence of improved survival benefit
Routine use not recommended at this time
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40. 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
PVR – pulmonary vascular resistance,
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41. Pharmacological Therapies for ARDS (cont.)
2-Agonists
2-Agonists shown to decrease alveolar permeability
Study used IV salbutamol (15 µg/kg/hr)
Patients had significantly less lung water and Pplat
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.
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