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

Chapter 27 Chapter 27

Acute Lung Injury, Pulmonary Acute Lung Injury, Pulmonary Edema, and Multiple System Edema, and Multiple System

Organ FailureOrgan Failure

Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 2

ObjectivesObjectives Identify the approximate incident rate of acute Identify the approximate incident rate of acute

respiratory distress syndrome (ARDS) and how the respiratory distress syndrome (ARDS) and how the mortality rate has changed over the past several mortality rate has changed over the past several decades.decades.

State the risk factors associated with the onset of State the risk factors associated with the onset of ARDS.ARDS.

Describe how the normal lung prevents fluid from Describe how the normal lung prevents fluid from collecting in the parenchyma and how these collecting in the parenchyma and how these mechanisms can fail and cause pulmonary edema.mechanisms can fail and cause pulmonary edema.


Objectives (cont.)Objectives (cont.) Describe the effect pulmonary edema has on lung Describe the effect pulmonary edema has on lung

function including gas exchange and lung compliance.function including gas exchange and lung compliance.

Describe the relationship between multiple organ Describe the relationship between multiple organ dysfunction syndrome (MODS) and ARDS.dysfunction syndrome (MODS) and ARDS.

Identify the histopathology associated with the Identify the histopathology associated with the exudative phase and the fibroproliferative phase of exudative phase and the fibroproliferative phase of ARDS.ARDS.

State how hydrostatic and nonhydrostatic pulmonary State how hydrostatic and nonhydrostatic pulmonary edema are differentiated from one another in the edema are differentiated from one another in the clinical setting.clinical setting.


Objectives (cont.)Objectives (cont.)

Describe the principles of supportive care followed for Describe the principles of supportive care followed for patients with ARDS.patients with ARDS.

Describe how ventilator settings (e.g., tidal volume, Describe how ventilator settings (e.g., tidal volume, positive end-expiratory pressure, respiratory rate) are positive end-expiratory pressure, respiratory rate) are adjusted for patients with ARDS and MODS.adjusted for patients with ARDS and MODS.

Describe how mechanical ventilation can cause lung Describe how mechanical ventilation can cause lung injury and how ventilator-induced lung injury can be injury and how ventilator-induced lung injury can be avoided.avoided.

State the approaches to the management of ARDS State the approaches to the management of ARDS and MODS.and MODS.


Objectives (cont.)Objectives (cont.)

Describe the use of innovative mechanical ventilation Describe the use of innovative mechanical ventilation strategies in the support of patients with ARDS.strategies in the support of patients with ARDS.

State the effect of prone positioning on oxygenation State the effect of prone positioning on oxygenation and mortality in the ARDS patient.and mortality in the ARDS patient.

Describe the value of pharmacological therapies such Describe the value of pharmacological therapies such as nitric oxide and corticosteroids in the treatment of as nitric oxide and corticosteroids in the treatment of patients with ARDS.patients with ARDS.


IntroductionIntroduction

Pulmonary edemaPulmonary edema Abnormal fluid accumulation within lung Abnormal fluid accumulation within lung

parenchyma and alveoli resulting in hypoxemiaparenchyma and alveoli resulting in hypoxemia May be secondary to CHF or ALIMay be secondary to CHF or ALI Severe ALI is called ARDS or noncardiogenic Severe ALI is called ARDS or noncardiogenic

pulmonary edemapulmonary edema• Often occurs with MODSOften occurs with MODS

ARDS is a common cause of respiratory failure.ARDS is a common cause of respiratory failure. http://www.youtube.com/watch?v=kQ9eCywj_Hs

http://www.youtube.com/watch?v=kQ9eCywj_Hs


EpidemiologyEpidemiology

ARDS has many diverse causes.ARDS has many diverse causes.

Mortality rates have fallen from ~90% to Mortality rates have fallen from ~90% to ~40%~40% Due to better supportive careDue to better supportive care Early detectionEarly detection Effective management of cormorbiditiesEffective management of cormorbidities Application of new ventilatory strategiesApplication of new ventilatory strategies


ARDS Risk FactorsARDS Risk Factors


PathophysiologyPathophysiology

Pulmonary edemaPulmonary edema Fluid first accumulates in interstitial space.Fluid first accumulates in interstitial space. Followed by alveolar floodingFollowed by alveolar flooding

Impairs gas exchange and reduces lung complianceImpairs gas exchange and reduces lung compliance

Hydrostatic (cardiogenic) pulmonary edemaHydrostatic (cardiogenic) pulmonary edema Fluid accumulation in interstitium raises hydrostatic Fluid accumulation in interstitium raises hydrostatic

pressure rapidly and alveolar flooding follows.pressure rapidly and alveolar flooding follows. Flooding occur in “all or nothing” manner.Flooding occur in “all or nothing” manner. Fluid filling alveoli is identical to interstitial fluid.Fluid filling alveoli is identical to interstitial fluid.





Pathophysiology (cont.)Pathophysiology (cont.)Nonhydrostatic (noncardiogenic) pulmonary edemaNonhydrostatic (noncardiogenic) pulmonary edema Fluid accumulates despite normal hydrostatic Fluid accumulates despite normal hydrostatic

pressure.pressure. Vascular endothelial injury alters permeability.Vascular endothelial injury alters permeability. Protein-rich fluid floods the interstitial space.Protein-rich fluid floods the interstitial space. Alveolar flooding occurs as osmotic pressures in capillaries Alveolar flooding occurs as osmotic pressures in capillaries

and interstitium equalize.and interstitium equalize. Alveolar epithelium is also injured.Alveolar epithelium is also injured.

There is also impaired pulmonary fluid clearance.There is also impaired pulmonary fluid clearance. The common mechanism for development of ARDS The common mechanism for development of ARDS

appears to be lung inflammation.appears to be lung inflammation.


Pathophysiology (cont.)Pathophysiology (cont.)Gas exchange and lung mechanics during ARDSGas exchange and lung mechanics during ARDS Restrictive changes with refractory hypoxemiaRestrictive changes with refractory hypoxemia

Altered permeability floods the lung, resulting in Altered permeability floods the lung, resulting in decreased lung compliance (Cdecreased lung compliance (CLL) and consolidation.) and consolidation.

Impaired surfactant synthesis and function worsens Impaired surfactant synthesis and function worsens gas exchange and Cgas exchange and CLL..

Loss of normal vascular response to alveolar Loss of normal vascular response to alveolar hypoxemiahypoxemia Unaerated alveoli receive blood flow in excess of ventilation Unaerated alveoli receive blood flow in excess of ventilation

so increased shunting occursso increased shunting occurs


Pathophysiology (cont.)Pathophysiology (cont.)


Pathophysiology (cont.)Pathophysiology (cont.)Role of organ–organ interactions in pathogenesis Role of organ–organ interactions in pathogenesis ALI resulting in MODS is probably related to PMN-ALI resulting in MODS is probably related to PMN-

mediated inflammation.mediated inflammation. Broad-spectrum antibiotic usage results in resistant Broad-spectrum antibiotic usage results in resistant

“bugs,” particularly in GI tract.“bugs,” particularly in GI tract. Escape GI tract and activate RE in liver/lymph/spleenEscape GI tract and activate RE in liver/lymph/spleen RE may activate and sustain systemic inflammatory response RE may activate and sustain systemic inflammatory response

that leads to ARDS and MODS.that leads to ARDS and MODS. Balance of antiinflammatory and proinflammatory Balance of antiinflammatory and proinflammatory

factors, severity of illness, comorbidities predisposes factors, severity of illness, comorbidities predisposes patients to ARDS and MODSpatients to ARDS and MODS



Histopathology and Clinical Histopathology and Clinical Correlates of ARDSCorrelates of ARDS

Exudative phase (1–3 days)Exudative phase (1–3 days) Characterized by diffuse damage to A/C membrane Characterized by diffuse damage to A/C membrane

and influx of inflammatory cells into interstitiumand influx of inflammatory cells into interstitium

Many alveoli fill with proteinaceous, eosinophilic Many alveoli fill with proteinaceous, eosinophilic

material called hyaline membranes.material called hyaline membranes. Composed of cellular debris and plasma proteinsComposed of cellular debris and plasma proteins

Type I pneumocytes are destroyed.Type I pneumocytes are destroyed.

Patients have profound dyspnea, tachypnea, and Patients have profound dyspnea, tachypnea, and refractory hypoxemia.refractory hypoxemia.


Histopathology and Clinical Histopathology and Clinical Correlates of ARDS (cont.)Correlates of ARDS (cont.)

Fibroproliferative phase (3-7 days)Fibroproliferative phase (3-7 days) Inflammatory injury is followed by repair.Inflammatory injury is followed by repair. This involves hyperplasia of type II pneumocytes and This involves hyperplasia of type II pneumocytes and

proliferation of fibroblasts in lung parenchymaproliferation of fibroblasts in lung parenchyma Formation of intraalveolar and interstitial fibrosisFormation of intraalveolar and interstitial fibrosis

Lung remodeling following ARDS is variable.Lung remodeling following ARDS is variable. Nearly complete recovery of CNearly complete recovery of CLL and oxygenation in and oxygenation in

6–12 months to 6–12 months to Severe disability due to extensive pulmonary Severe disability due to extensive pulmonary

fibrosis and obliteration of pulmonary vasculaturefibrosis and obliteration of pulmonary vasculature



Differentiating CHF from ARDS in the clinical Differentiating CHF from ARDS in the clinical settingsetting

First suspect CHF as it is much more First suspect CHF as it is much more common.common. Any of these may be present in either group:Any of these may be present in either group:

• Older patientsOlder patients

• ComorbiditiesComorbidities

• InfectionInfection

• TraumaTrauma

• Suspected aspirationSuspected aspiration




Differentiating CHF From ARDS Differentiating CHF From ARDS in the Clinical Settingin the Clinical Setting

Radiographic findingsRadiographic findings CHF: cardiomegaly, perihilar infiltrates, effusionsCHF: cardiomegaly, perihilar infiltrates, effusions ARDS: peripheral alveolar infiltrates, air bronchograms with normal ARDS: peripheral alveolar infiltrates, air bronchograms with normal

heart sizeheart size Hard to determine heart size and presence of effusions on supine Hard to determine heart size and presence of effusions on supine

A/P filmsA/P films Complicated by possible coexistence of CHF and ARDSComplicated by possible coexistence of CHF and ARDS

PA catheter is a useful tool to differentiate.PA catheter is a useful tool to differentiate. PAWP > 18 necessary for hydrostatic pulmonary edemaPAWP > 18 necessary for hydrostatic pulmonary edema PAWP < 18 suggests ARDSPAWP < 18 suggests ARDS


Differentiating CHF From ARDS Differentiating CHF From ARDS in the Clinical Setting (cont.)in the Clinical Setting (cont.)

PA catheter (cont.)PA catheter (cont.) Carefully appraise results as a catheter placed in a non–Carefully appraise results as a catheter placed in a non–

zone 3 area may reflect high PEEP or Pzone 3 area may reflect high PEEP or Pawaw instead of PAWP. instead of PAWP.

Bronchoalveolar lavage fluid (BALF)Bronchoalveolar lavage fluid (BALF) BALF from an ARDS patient will contain large amounts of BALF from an ARDS patient will contain large amounts of

inflammatory cells. inflammatory cells. Identification of infectious agents if anyIdentification of infectious agents if any Evidence of aspiration if it occurredEvidence of aspiration if it occurred

Clinical characteristics as seen in Box 27-2Clinical characteristics as seen in Box 27-2


Therapeutic Approach to ARDSTherapeutic Approach to ARDS


Therapeutic Approach to Therapeutic Approach to ARDS (cont.)ARDS (cont.)

Hemodynamics and fluid management during Hemodynamics and fluid management during ARDSARDS

Optimized oxygen delivery (DOOptimized oxygen delivery (DO22) is a primary ) is a primary

goal of supportive therapy.goal of supportive therapy.

Care required as PEEP improves FRC, CCare required as PEEP improves FRC, CLL, ,

and CaOand CaO22, it may impair cardiac output (CO) , it may impair cardiac output (CO)

and thus DOand thus DO22



Hemodynamics and fluid management during ARDS Hemodynamics and fluid management during ARDS (cont.)(cont.)

Restriction of intravascular volume generally Restriction of intravascular volume generally improves CaOimproves CaO22 and DO and DO22.. Careful of overrestriction as may Careful of overrestriction as may ⇓⇓CO and CO and ⇓⇓DODO22

Prudent to avoid hypotension and keep SaOPrudent to avoid hypotension and keep SaO22 >90%, >90%,

⇑⇑DODO22 with hyperlactatemia, ensure organ function with hyperlactatemia, ensure organ function

(e.g., UO)(e.g., UO)



Mechanical ventilation during ARDSMechanical ventilation during ARDS Three distinct lung zones in ARDSThree distinct lung zones in ARDS

Dependent regions are nonventilated due to dense Dependent regions are nonventilated due to dense alveolar infiltrate.alveolar infiltrate.

Region of dense infiltrates may be made available Region of dense infiltrates may be made available for gas exchange by proper ventilatory strategy.for gas exchange by proper ventilatory strategy.

Nondependent aerated region retains near-normal Nondependent aerated region retains near-normal lung characteristics.lung characteristics.

Lungs are effectively diminished to 20–30% of normalLungs are effectively diminished to 20–30% of normal



Setting VSetting VTT Conventional levels are not acceptable.Conventional levels are not acceptable.

Distributed to the small aerated lung zones, leads to Distributed to the small aerated lung zones, leads to hyperinflation and overdistentionhyperinflation and overdistention

Excessive volume induces lung injury (volutrauma).Excessive volume induces lung injury (volutrauma).• Avoided by use of smaller VAvoided by use of smaller VTT

Optimal VOptimal VTT set by pressure-volume (P/V) set by pressure-volume (P/V)

relationshipsrelationships• Should set between upper and lower PShould set between upper and lower PFLEXFLEX. .

Initiate VInitiate VTT of 5–7 ml/kg. of 5–7 ml/kg.


http://www.youtube.com/watch?v=5bMwmmvdGI0





Adjusting PEEPAdjusting PEEP Goal is to recruit additional alveoli and increase FRC and Goal is to recruit additional alveoli and increase FRC and

oxygenation.oxygenation. Improving oxygenation enables a reduction in FIOImproving oxygenation enables a reduction in FIO22

• Reduces the risk of oxygen toxicityReduces the risk of oxygen toxicity Recruited alveoli avoid opening and closing injury.Recruited alveoli avoid opening and closing injury. Set PEEP at lowest level to ensureSet PEEP at lowest level to ensure

• Arterial oxygenation: PaOArterial oxygenation: PaO22 > 60 mm Hg, FIO > 60 mm Hg, FIO22 < 0.6 < 0.6

• Adequate tissue oxygenationAdequate tissue oxygenation

• Alveoli patent throughout ventilatory cycleAlveoli patent throughout ventilatory cycle

• Avoid barotrauma with PAvoid barotrauma with Pawaw < 35 cm H < 35 cm H22O.O.



Adjusting the ventilatory rateAdjusting the ventilatory rate Compared to normal, ARDS patients require much higher Compared to normal, ARDS patients require much higher

VVEE to maintain PaCO to maintain PaCO22

Small VSmall VTT used to avoid volutrauma. used to avoid volutrauma.

Permissive hypercapnia used to avoid high PPermissive hypercapnia used to avoid high Pawaw

PaCOPaCO22 60–80 mm Hg common, pH ~7.25 60–80 mm Hg common, pH ~7.25 May require sedation and even paralysis to avoid air hunger and May require sedation and even paralysis to avoid air hunger and

patient triggering at high ratespatient triggering at high rates

Routine use of IS recommended at this time.Routine use of IS recommended at this time.

. .




Innovative Ventilation Strategies Innovative Ventilation Strategies for ARDSfor ARDS

Volume-controlled ventilation (VCV)Volume-controlled ventilation (VCV) ARDS net protocol showed ~20% reduction in ARDS net protocol showed ~20% reduction in

mortality with a lower tidal volume strategymortality with a lower tidal volume strategy Initiate VInitiate VTT of 5–7 ml/kg of 5–7 ml/kg Adjust as required based on patient’s P/V curvesAdjust as required based on patient’s P/V curves

High-frequency ventilation (HFV)High-frequency ventilation (HFV) Designed to maintain adequate ventilation and Designed to maintain adequate ventilation and

reduce alveolar collapse through increased FRCreduce alveolar collapse through increased FRC Uses rates up to 300 beats/min, VUses rates up to 300 beats/min, VTT 3–5 ml/kg 3–5 ml/kg

Evidence does not support routine use in adults.Evidence does not support routine use in adults.


Innovative Ventilation Strategies Innovative Ventilation Strategies for ARDS (cont.)for ARDS (cont.)

Inverse-ratio ventilation (IRV)Inverse-ratio ventilation (IRV) Designed to recruit alveoli through prolonged Designed to recruit alveoli through prolonged

inspirationinspiration I:E ratios may exceed 4:1.I:E ratios may exceed 4:1.

Initial studies had significantly improved oxygenation but did Initial studies had significantly improved oxygenation but did not take into account PEEP levels.not take into account PEEP levels.

Controlling for PEEP, there was no change in oxygenation Controlling for PEEP, there was no change in oxygenation associated with IRV.associated with IRV.

Studies have not shown a survival benefit for IRV.Studies have not shown a survival benefit for IRV.

Routine use not recommended at this time, but may Routine use not recommended at this time, but may be used in face of refractory hypoxemia and high Pbe used in face of refractory hypoxemia and high Pawaw



Pressure-controlled ventilation (PCV)Pressure-controlled ventilation (PCV) Designed to prevent ventilator-associated lung injury Designed to prevent ventilator-associated lung injury

PIP of <30–35 cm HPIP of <30–35 cm H22O chosenO chosen Likely to avoid overdistention and prevent volume-Likely to avoid overdistention and prevent volume-

associated lung injuryassociated lung injury VVTT varies with changes in C varies with changes in CLL and Raw. and Raw.

Large swings in VLarge swings in VTT may be seen with PCV. may be seen with PCV.

PCV has not proved superior to VCV.PCV has not proved superior to VCV.

If use must monitor VIf use must monitor VTT carefully to avoid volutrauma. carefully to avoid volutrauma.



Airway pressure release ventilation (APRV)Airway pressure release ventilation (APRV) Designed to recruit alveoli while minimizing ventilator-induced Designed to recruit alveoli while minimizing ventilator-induced

barotrauma through use of prolonged inspirationbarotrauma through use of prolonged inspiration

VVTT is delivered during transient decreases in pressure, which is delivered during transient decreases in pressure, which may be patient triggered.may be patient triggered.

Patients may breathe anytime so appear to tolerate well Patients may breathe anytime so appear to tolerate well

APRV is more effective than IRV for alveolar recruitment.APRV is more effective than IRV for alveolar recruitment.

APRV is effective but not superior to VCV.APRV is effective but not superior to VCV.



Patient positioning (proning)Patient positioning (proning) Prone positioning places the aerated lung regions in Prone positioning places the aerated lung regions in

the dependent position better matching the dependent position better matching ventilation/perfusion.ventilation/perfusion.

Rationales for improved oxygenation of proningRationales for improved oxygenation of proning Improved V/Q ratio, FRC, and COImproved V/Q ratio, FRC, and CO More effective bronchial drainageMore effective bronchial drainage

Significant downsides include lack of tolerance, Significant downsides include lack of tolerance, require specialized nursing care and equipmentrequire specialized nursing care and equipment

No evidence of improved mortalityNo evidence of improved mortality

. . . .



Extracorporeal membrane oxygenation (ECMO) Extracorporeal membrane oxygenation (ECMO) and extracorporeal carbon dioxide removal and extracorporeal carbon dioxide removal (ECCO(ECCO22R)R)

ECMO involves establishing an arteriovenous ECMO involves establishing an arteriovenous shunt that diverts a large percent of CO shunt that diverts a large percent of CO through an artificial lung that removes COthrough an artificial lung that removes CO22

and adds Oand adds O22

Shown to have no survival benefit over VCVShown to have no survival benefit over VCV




ECMO and ECCOECMO and ECCO22R (cont.)R (cont.) ECCOECCO22R has a venovenous circuit that R has a venovenous circuit that

diverts ~20% of CO to an artificial lung that diverts ~20% of CO to an artificial lung that primarily removes COprimarily removes CO22

Reduces need for high VReduces need for high VEE to remove CO to remove CO22 in lungs in lungs No evidence of improved survival benefitNo evidence of improved survival benefit

Routine use not recommended at this timeRoutine use not recommended at this time


Pharmacological Therapies Pharmacological Therapies for ARDSfor ARDS

Inhaled nitric oxide (INO)Inhaled nitric oxide (INO) Potent vasodilator thought to improve perfusion Potent vasodilator thought to improve perfusion

where ventilation is bestwhere ventilation is best

Studies to date have been mixed, but bottom lineStudies to date have been mixed, but bottom line Most effective on patients with high PVRMost effective on patients with high PVR Some evidence of improved oxygenation Some evidence of improved oxygenation No reduction in ventilator daysNo reduction in ventilator days No survival benefitNo survival benefit Highly toxic substances released on breakdownHighly toxic substances released on breakdown

Remains an experimental treatment for ARDSRemains an experimental treatment for ARDS




Pharmacological Therapies Pharmacological Therapies for ARDS (cont.)for ARDS (cont.)

22-Agonists-Agonists 22-Agonists shown to decrease alveolar permeability-Agonists shown to decrease alveolar permeability

Study used IV salbutamol (15 Study used IV salbutamol (15 µµg/kg/hr) g/kg/hr) Patients had significantly less lung water and PPatients had significantly less lung water and Pplatplat

No difference in P/F ratio or 28-day mortalityNo difference in P/F ratio or 28-day mortality

Further study required to determine if this will have a Further study required to determine if this will have a use or join the multitude of ineffective ARDS use or join the multitude of ineffective ARDS treatments. treatments.

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