Acute Acute Respiratory Respiratory

Distress Distress SyndromeSyndromeHolly Starks, MS4Holly Starks, MS4

March 2007March 2007

OutlineOutline

Definitions and DiagnosisDefinitions and Diagnosis PathophysiologyPathophysiology Cardiogenic vs Non-cardiogenic Cardiogenic vs Non-cardiogenic

EdemaEdema Management of ARDSManagement of ARDS Pulmonary Artery CathetersPulmonary Artery Catheters

DefinitionDefinition A diffuse inflammatory injury of the A diffuse inflammatory injury of the

lungs which is an EXPRESSION of a host lungs which is an EXPRESSION of a host of various diseases and is not a specific of various diseases and is not a specific disease entity in and of itself. It is oftendisease entity in and of itself. It is often—but not always—accompanied by —but not always—accompanied by inflammatory injury of other organ inflammatory injury of other organ systems.systems.

Inflammatory cells and proteinaceous Inflammatory cells and proteinaceous fluid accumulate in the alveolar spaces fluid accumulate in the alveolar spaces leading to a decrease in diffusing leading to a decrease in diffusing capacity and hypoxemia. capacity and hypoxemia.

Acute Lung Injury (ALI) vs. Acute Lung Injury (ALI) vs. ARDSARDS

ALI is the term used for patients with ALI is the term used for patients with significant hypoxemia (PaO2/FiO2 significant hypoxemia (PaO2/FiO2 ratio of <300)ratio of <300)

ARDS is the term used for a subset of ARDS is the term used for a subset of ALI patients with severe hypoxemia ALI patients with severe hypoxemia (PaO2/FiO2 ratio of <200) (PaO2/FiO2 ratio of <200)

Fan, E. et al. Ventilatory Management of Acute Lung Injury and Acute Respiratory Distress Syndrome. 2005. JAMA. 294 (22). pp. 2889-96.

ARDS Diagnostic CriteriaARDS Diagnostic CriteriaFromFrom the American-European Consensus Conference on the American-European Consensus Conference on

ARDSARDS

1.1. Acute OnsetAcute Onset

2.2. Predisposing ConditionPredisposing Condition

3.3. Bilateral InfiltratesBilateral Infiltrates

4.4. PaO2/FiO2 < 200 mm HgPaO2/FiO2 < 200 mm Hg

5.5. Wedge Pressure ≤ 18 mm Hg or no Wedge Pressure ≤ 18 mm Hg or no clinical evidence of LA HTN.clinical evidence of LA HTN.

Note: According to The ICU Book, wedge pressure should be excluded from the diagnostic criteria because it underestimates capillary hydrostatic pressure (p 435).

Predisposing ConditionsPredisposing Conditions

Sepsis (#1 cause)Sepsis (#1 cause) Severe PNASevere PNA AspirationAspiration Near Drowning Near Drowning Smoke inhalation Smoke inhalation Multiple blood Multiple blood

product product transfusionstransfusions

Severe TraumaSevere Trauma DICDIC Drug overdose: Drug overdose:

Heroin, Heroin, methamphetamine, methamphetamine, cocaine cocaine

Acute pancreatitisAcute pancreatitis Severe BurnSevere Burn

Look for the + Tube Look for the + Tube Sign!!!!Sign!!!!

Positive Tube SignPositive Tube Sign

www.fhs.mcmaster.ca/.../photos.htm

The majority of patients with ARDS require intubation and mechanical ventilation

An Interesting NoteAn Interesting Note

All of the predisposing conditions All of the predisposing conditions share the ability to trigger a share the ability to trigger a systemic inflammatory response. systemic inflammatory response. Hum…. Hum….

The majority of ARDS deaths are The majority of ARDS deaths are NOT due to respiratory failure, but NOT due to respiratory failure, but multiple organ failure secondary to multiple organ failure secondary to systemic inflammatory processes. systemic inflammatory processes.

Pathology of ARDSPathology of ARDS

A diffuse inflammatory processA diffuse inflammatory process Circulating neutrophils are activated and become Circulating neutrophils are activated and become

“sticky.” They adhere to the vascular endothelium “sticky.” They adhere to the vascular endothelium and spill their cytoplasmic granules which then and spill their cytoplasmic granules which then damage the endothelium leading to leaky damage the endothelium leading to leaky capillaries. The result: An exudative fluid capillaries. The result: An exudative fluid accumulates in the lung parenchyma, which leads accumulates in the lung parenchyma, which leads to further damage locally (i.e. alveolar cell to further damage locally (i.e. alveolar cell damage) decreasing oxygenation and lung damage) decreasing oxygenation and lung compliance. compliance.

Fibrin Deposition. Fibrin release is triggered by Fibrin Deposition. Fibrin release is triggered by tissue factor. Over time the fibrin can later tissue factor. Over time the fibrin can later remodel to form fibrosis. remodel to form fibrosis.

Marino, P.L. The ICU Book. 3rd Ed. Lippincott Williams & Wilkins. Philadelphia. 2007.

www.cesil.com/.../numero6_05/rossi/articolo1.htm

Again…Again…

ARDS is a diffuse ARDS is a diffuse inflammatory inflammatory process process involving both lungs, in which involving both lungs, in which the overall lung volume increases the overall lung volume increases secondary to inflammatory and secondary to inflammatory and proteinaceous materials accumulating proteinaceous materials accumulating in the lung parenchyma. This results in in the lung parenchyma. This results in a loss of compliance and severe loss of a loss of compliance and severe loss of gas exchange. gas exchange.

The overall lung volume increases, The overall lung volume increases, but the there is a decreased volume but the there is a decreased volume of lung available for gas exchange.of lung available for gas exchange.

Histologic FindingsHistologic Findings

Typical Typical histological histological findings in ARDSfindings in ARDS alveolar alveolar

inflammation, inflammation, thickened septal from thickened septal from protein leak (pink), protein leak (pink), congestion and congestion and decreased alveolar decreased alveolar volumevolume

www.burnsurgery.com/.../pulmonary/part3/sec4.htm

←←Normal Lung Histology—large Normal Lung Histology—large alveolar volumes, septal spaces very alveolar volumes, septal spaces very thin, no cellular congestion. thin, no cellular congestion.

Hyaline Protein in air spaces

Cellular Congestion

Determining ARDS Determining ARDS RadiographicallyRadiographically

Can be difficult to do. Should always Can be difficult to do. Should always try to make the diagnosis in light of try to make the diagnosis in light of the clinical picture.the clinical picture.

Need to determine Cardiogenic vs. Need to determine Cardiogenic vs. Non-cardiogenic edema. Non-cardiogenic edema.

Cardiogenic vs. Non-Cardiogenic vs. Non-Cardiogenic EdemaCardiogenic Edema

CardiogenicCardiogenic Patchy infiltrates Patchy infiltrates

appearing in the lung appearing in the lung bases firstbases first

Effusions may be Effusions may be presentpresent

Clinical signs and Clinical signs and symptoms lag behind symptoms lag behind radiographic evidence radiographic evidence (i.e. CXR is more (i.e. CXR is more impressive than the impressive than the degree of hypoxemia)degree of hypoxemia)

Non-CardiogenicNon-Cardiogenic Infiltrates are more Infiltrates are more

homogeneoushomogeneous No pleural effusionsNo pleural effusions No Kerley B’sNo Kerley B’s Radiographic Radiographic

evidence lags behind evidence lags behind clinical signs and clinical signs and symptoms (i.e. the symptoms (i.e. the CXR is unimpressive CXR is unimpressive given the degree of given the degree of hypoxemia)hypoxemia)

Cardiogenic vs. Non-Cardiogenic vs. Non-Cardiogenic EdemaCardiogenic Edema

CardiogenicCardiogenic Excess fluid in Excess fluid in

alveoli alveoli Due to high Due to high

pulmonary pulmonary capillary pressure capillary pressure (estimated by (estimated by measuring measuring pulmonary artery pulmonary artery wedge pressure)wedge pressure)

Non-CardiogenicNon-Cardiogenic Protein, Protein,

inflammatory cells, inflammatory cells, and fluid and fluid accumulation in accumulation in the alveolithe alveoli

Due to “other” Due to “other” systemic factors systemic factors NOT elevated NOT elevated pulmonary pulmonary capillary pressurecapillary pressure

Cardiogenic vs. Non-Cardiogenic vs. Non-Cardiogenic Edema via CXRCardiogenic Edema via CXR

Cardiogenic Non-Cardiogenic

Bilateral infiltrates predominately in lung bases. Kerley B’s. Cardiomegaly.

Diffuse Bilateral patchy infiltrates homogenously distributed throughout the lungs. Positive tube sign. No Kerley B’s.

Cardiogenic vs. Non-Cardiogenic vs. Non-Cardiogenic Edema via CTCardiogenic Edema via CT

CardiogenicNon-Cardiogenic

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No septal thickening. Diffuse alveolar infiltrates. Atelectasis of dependent lobes usually seen (not well shown here)

Septal thickening. More severe in lung bases.

Cardiogenic Edema:Cardiogenic Edema:Weenie Man ENDOtheliumWeenie Man ENDOthelium

Vascular Endothelium Vascular Endothelium breaks under stress breaks under stress easily, however it also easily, however it also repairs itself quickly repairs itself quickly

Cardiogenic edema Cardiogenic edema often develops often develops quickly and can quickly and can resolve quickly resolve quickly because vascular because vascular endothelium is able endothelium is able to repair itself quickly to repair itself quickly

Non-Cardiogenic Edema: Non-Cardiogenic Edema: Muscle Man EPItheliumMuscle Man EPIthelium

Alveolar epithelium is quite Alveolar epithelium is quite resistant to damage. It resistant to damage. It withstands greater force withstands greater force before becoming damaged. before becoming damaged. However, once “broken” it However, once “broken” it takes much longer to heal takes much longer to heal than weenie man than weenie man endothelium. endothelium.

Cellular damage in Non-Cellular damage in Non-Cardiogenic edema runs Cardiogenic edema runs along a spectrum from along a spectrum from predominately vascular predominately vascular endothelial damage to endothelial damage to predominately alveolar predominately alveolar epithelial damageepithelial damage

Management for ARDSManagement for ARDS

There is no definitive treatment for ARDSThere is no definitive treatment for ARDS

Management: Reducing Management: Reducing Ventilator-Induced Lung Ventilator-Induced Lung

InjuryInjury Low tidal volume mechanical Low tidal volume mechanical

ventilationventilation In ARDS there is a large amount of poorly In ARDS there is a large amount of poorly

compliant (i.e. non-ventilating) lung and a small compliant (i.e. non-ventilating) lung and a small amount of healthy, compliant lung tissue. Large amount of healthy, compliant lung tissue. Large tidal volume ventilation can lead to over-inflation tidal volume ventilation can lead to over-inflation of the healthy lung tissue resulting in ventilator-of the healthy lung tissue resulting in ventilator-induced lung injury of that healthy tissue. induced lung injury of that healthy tissue.

PEEPPEEP Setting a PEEP prevents further lung injury due Setting a PEEP prevents further lung injury due

to shear forces by keeping airways patent during to shear forces by keeping airways patent during expirationexpiration

The Flip SideThe Flip Side Is there such thing as too low a TV?Is there such thing as too low a TV?

Tidal Volume must be sufficient for gas exchange to take Tidal Volume must be sufficient for gas exchange to take place. Permissive hypercapnia is the term used to state place. Permissive hypercapnia is the term used to state that a certain degree of hypercapnia and its resulting that a certain degree of hypercapnia and its resulting acidemia can be allowed in order to maintain lung-acidemia can be allowed in order to maintain lung-protective TVs. protective TVs.

Absolute limits is unclear, but a pH of 7.2-7.25 and a PCO2 of Absolute limits is unclear, but a pH of 7.2-7.25 and a PCO2 of 60-70 mm Hg is a good cut off range.60-70 mm Hg is a good cut off range.

Is there such thing as too much PEEP?Is there such thing as too much PEEP? PEEP serves to help open less compliant alveoli and keep PEEP serves to help open less compliant alveoli and keep

alveolar open during expiration, but it too can lead to alveolar open during expiration, but it too can lead to overinflation of alveoli that are already maintaining overinflation of alveoli that are already maintaining aeration. aeration.

Setting PEEP too high also increases intrathoracic Setting PEEP too high also increases intrathoracic pressure leading to decreased venous return. pressure leading to decreased venous return.

Start patients at a PEEP trial of 5 – 12 cm H2O and increase if Start patients at a PEEP trial of 5 – 12 cm H2O and increase if needed.needed.

Diuretics—A Good or Bad Diuretics—A Good or Bad Therapy in ARDS?Therapy in ARDS?

YesYes Diuretics have been Diuretics have been

shown to decrease shown to decrease any pulmonary edema any pulmonary edema that is present, that is present, increase lung increase lung compliance, and compliance, and improve gas improve gas exchange. However exchange. However they have shown no they have shown no survival benefit. survival benefit.

NoNo Diuretics are not anti-Diuretics are not anti-

inflammatory agents: inflammatory agents: lung infiltrates in ARDS lung infiltrates in ARDS are neutrophils and are neutrophils and proteins, NOT edemaproteins, NOT edema

Hemodynamic Hemodynamic compromise: tissue compromise: tissue oxygenation = #1 oxygenation = #1 concern. Aggressive concern. Aggressive diuretics decrease diuretics decrease venous pressures venous pressures leading to decrease CO leading to decrease CO and increased tissue and increased tissue ischemiaischemia

FACTT Study: New FACTT Study: New Evidence for the Benefits of Evidence for the Benefits of

Diuretic Use in ARDSDiuretic Use in ARDS Large prospective trial addressed the use of Large prospective trial addressed the use of

conservative (higher, more frequent lasix conservative (higher, more frequent lasix doses) verse liberal fluid management (more doses) verse liberal fluid management (more frequent fluid boluses). frequent fluid boluses).

Outcomes: NO significant difference in 60-Outcomes: NO significant difference in 60-day mortality between the two groups, day mortality between the two groups, however the conservative fluid group had however the conservative fluid group had improved lung function, shorter durations of improved lung function, shorter durations of mechanical ventilation, and shorter ICU mechanical ventilation, and shorter ICU stays, SUPPORTING THE USE OF stays, SUPPORTING THE USE OF DIURETICS. DIURETICS.

ARDS Clinical Trial Network. 2006. Comparison of Two Fluid-Management Strategies in Acute Lung Injury. N Engl J Med. 354 (24). pp 2564-75.

Management: Fluid Management: Fluid StatusStatus

Remember, the #1 goal in therapy is Remember, the #1 goal in therapy is to decrease tissue ischemia. We must to decrease tissue ischemia. We must maintain ARDS patient’s CO to insure maintain ARDS patient’s CO to insure tissue profusion.tissue profusion. In the FACTT study, conservative fluid In the FACTT study, conservative fluid

therapy was not followed if a patient therapy was not followed if a patient

was deemed to be in shock, in the was deemed to be in shock, in the

presence of oliguria, or if a patient’s presence of oliguria, or if a patient’s

circulation was deemed inadequate.circulation was deemed inadequate.

Use of Pulmonary Arterial Use of Pulmonary Arterial Catheters in ARDSCatheters in ARDS

Swan-Ganz Catheter

History of Pulmonary History of Pulmonary Arterial CathetersArterial Catheters

1945: Dexter used PAC 1945: Dexter used PAC under fluoro to diagnose under fluoro to diagnose congenital heart disease, congenital heart disease, mitral valve disease, and mitral valve disease, and left ventricular failure. left ventricular failure.

1975: Swan developed a 1975: Swan developed a technique that enabled technique that enabled the use of PAC at the the use of PAC at the bedside. Initially used bedside. Initially used to guide therapy to guide therapy following acute MI.following acute MI. By inflating a small balloon at the By inflating a small balloon at the

end of the catheter he was able end of the catheter he was able to float the tip of the catheter to float the tip of the catheter through the right heart into the through the right heart into the pulmonary arteries. pulmonary arteries.

Uses of the PACUses of the PAC Guide therapy, aid in determining Guide therapy, aid in determining

diagnoses, help determine prognosisdiagnoses, help determine prognosis Measures Measures

Central venous and pulmonary artery Central venous and pulmonary artery pressurespressures

Pulmonary capillary wedge pressure (PCWP) Pulmonary capillary wedge pressure (PCWP) → left-arterial pressure→ left-arterial pressure

Mixed venous blood gasesMixed venous blood gases Cardiac outputCardiac output

Can also determine systemic and pulmonary Can also determine systemic and pulmonary vascular resistances from the above vascular resistances from the above measurementsmeasurements

Uses of the PAC in ARDSUses of the PAC in ARDS

Used to aid in diagnosisUsed to aid in diagnosis Traditionally placed to confirm non-Traditionally placed to confirm non-

cardiogenic edema verses cardiogenic cardiogenic edema verses cardiogenic edema in cases of uncertaintyedema in cases of uncertainty If PCWP is elevated > 18 mm Hg then by If PCWP is elevated > 18 mm Hg then by

diagnostic criteria—as set by the American-diagnostic criteria—as set by the American-European Consensus—the edema is NOT European Consensus—the edema is NOT noncardiogenic.noncardiogenic.

Used to guide treatmentUsed to guide treatment

Should PCWP Be Used to Should PCWP Be Used to Confirm the Diagnosis of Confirm the Diagnosis of

ARDS?ARDS? PCWP is an estimate of left atrium pressurePCWP is an estimate of left atrium pressure When the PAC balloon is inflated it occludes blood When the PAC balloon is inflated it occludes blood

flow through the lungs. The pressure measured in flow through the lungs. The pressure measured in this closed circuit is equal to the pressure in the this closed circuit is equal to the pressure in the left-atrium. left-atrium.

In ARDS, PCWP is used to estimate pulmonary In ARDS, PCWP is used to estimate pulmonary capillary pressure. PCWP CANNOT be equal capillary pressure. PCWP CANNOT be equal to pulmonary capillary pressure and left atrial to pulmonary capillary pressure and left atrial pressure. If this were true there would be no pressure. If this were true there would be no pressure gradient making forward blood flow pressure gradient making forward blood flow through the pulmonary arteries possible. through the pulmonary arteries possible. Therefore Therefore PCWP underestimates PCWP underestimates pulmonary capillary pressurepulmonary capillary pressure..

Suggests wedge pressure should not be part Suggests wedge pressure should not be part of the of the diagnosticdiagnostic criterion for ARDS. criterion for ARDS.

Further Reason Why PCWP Further Reason Why PCWP Should Not Be Used to Should Not Be Used to

Diagnose ARDSDiagnose ARDS In ARDS, arterial and venous thrombosis in the In ARDS, arterial and venous thrombosis in the

pulmonary vasculature is very common (i.e. pulmonary vasculature is very common (i.e. destruction of the weenie man endothelium). destruction of the weenie man endothelium). This means there is a disruption in the arterial-This means there is a disruption in the arterial-venous circuit within the lung. But wait; don’t venous circuit within the lung. But wait; don’t we need a complete circuit to measure the left we need a complete circuit to measure the left atrium pressure from a catheter sitting in the atrium pressure from a catheter sitting in the pulmonary artery? pulmonary artery?

It is conceivable that a PAC may in fact be It is conceivable that a PAC may in fact be measuring measuring VENTILATORY PRESSURESVENTILATORY PRESSURES notnot left atrial pressure. left atrial pressure.

Should PCWP Be Used to Should PCWP Be Used to Dictate the Treatment of Dictate the Treatment of

ARDS?ARDS? The Fluid and Catheter Treatment The Fluid and Catheter Treatment

Trial (FACTT)Trial (FACTT) A randomized, multi-center trial A randomized, multi-center trial

comparing outcomes of ARDS patients comparing outcomes of ARDS patients with use of PACs vs. CVCs (central with use of PACs vs. CVCs (central venous catheters).venous catheters).

FACTTFACTT

Result: Result: No differenceNo difference in mortality, in mortality, number of days on the ventilator or number of days on the ventilator or in the ICU, lung or kidney function, in the ICU, lung or kidney function, rates of hypotension, ventilator rates of hypotension, ventilator settings or use of dialysis between settings or use of dialysis between two groups. The PAC group had ≈ two groups. The PAC group had ≈ twice as many catheter-related twice as many catheter-related complications (mainly arrhythmias).complications (mainly arrhythmias).

ARDS Clinical Trial Network. 2006. Pulmonary-Artery versus Central Venous Catheter to Guide Treatment of Acute Lung Injury. N Engl J Med. 354 (21). pp 2213-24.

FACTT Conclusions in FACTT Conclusions in Regards to PACsRegards to PACs

PAC-guided therapy for ARDS does PAC-guided therapy for ARDS does not improve survival or organ-not improve survival or organ-function, reduce ventilator time or function, reduce ventilator time or decrease ICU-stays. Although decrease ICU-stays. Although associated with more complications, associated with more complications, major harm did not occur from PAC major harm did not occur from PAC use. use. The evidence does not favor The evidence does not favor the routine use of the PAC.the routine use of the PAC.

Other Evidence For or Other Evidence For or Against PACAgainst PAC

There have been multiple studies designed There have been multiple studies designed to determine the effect of mortality and to determine the effect of mortality and morbidity of PAC use in ICU patients. morbidity of PAC use in ICU patients. No randomized trials that I could find No randomized trials that I could find

suggested that PAC use either increased or suggested that PAC use either increased or decreased mortality. decreased mortality.

Their use may provide useful information in Their use may provide useful information in limited settings, but their use should be limited settings, but their use should be pursued with though towards how the pursued with though towards how the information gathered will aid patient information gathered will aid patient management. management.

ReferencesReferences• ARDS Clinical Trial Network. 2006. Comparison of Two Fluid-Management

Strategies in Acute Lung Injury. N Engl J Med. 354 (24). pp 2564-75.• ARDS Clinical Trial Network. 2006. Pulmonary-Artery versus Central Venous

Catheter to Guide Treatment of Acute Lung Injury. N Engl J Med. 354 (21). pp 2213-24.

• Fan, E., Needham, D.M., Stewart, T.E. Ventilatory Management of Acute Lung Injury and Acute Respiratory Distress Syndrome. 2005. JAMA. 294 (22). pp. 2889-96.

• Hansen-Flaschen, J., Siegel, M.D. Acute Respiratory Distress Syndrome: Definition; Epidemiology; Diagnosis; and Etiology. 2006. www.utdol.com.

• Heresi, G.A., Arroligo, A.C., Weidemann, H.P., Matthay, M.A. 2006. Pulmonary Artery Catheter and Fluid Management in Acute Lung Injury and the Acute Respiratory Distress Syndrome. Clin Chest Med. 27. pp 627-628.

• Marino, P.L. The ICU Book. 3rd Ed. Lippincott Williams & Wilkins. Philadelphia. pp. 419-35.

• Petty, T.L. Acute Respiratory Distress Syndrome: Consensus, Definitions, and Future Directions. 1996. Crit Care Med. 24(4). pp 555-556.

• Rouby, J-J., Puybasset, L., Nieszkowska, A., Lu, Q. Acute Respiratory Distress Syndrome: Lessons form Computed Tomography of the Whole Lung. 2003. Crit Care Med. 31(4S). pp. S285-95.

• Weinhouse, G.L., Manaker, S. Swan-Ganz Catheterization: Indications and Complications. 2006. www.utdol.com.