Acute Respiratory Distress Syndrome David Sweet. CASE GF, is a 57 yo male who presents to SPH with a one week history of feeling unwell. His wife states

Acute Acute Respiratory Respiratory

Distress Distress SyndromeSyndromeDavid SweetDavid Sweet

CASECASE

GF, is a 57 yo male who presents to SPH with GF, is a 57 yo male who presents to SPH with a one week history of feeling unwell. His wife a one week history of feeling unwell. His wife states that he was having intermittent fevers, states that he was having intermittent fevers, general feelings of malaise and dry cough. general feelings of malaise and dry cough. Over the last 24 hours he has become Over the last 24 hours he has become progressively unwell with more severe cough progressively unwell with more severe cough and mild confusion. At 8 AM when he refused and mild confusion. At 8 AM when he refused to get off the couch and his lips looked blue; to get off the couch and his lips looked blue; GFs wife called the ambulance. When probed GFs wife called the ambulance. When probed wife states has had decrease oral intake and wife states has had decrease oral intake and occasional diarrhea over the last 48hrs. occasional diarrhea over the last 48hrs.

CaseCase PMHx: PMHx: EtOH EtOH Prev pancreatitis in 2004 Prev pancreatitis in 2004 HTNHTN BPHBPH Raynauds syndrome Raynauds syndrome Prev episode of stable VT with negative Prev episode of stable VT with negative

angio and EP studies for inducible VT 4 angio and EP studies for inducible VT 4 months previous. months previous.

He had a UTI 1 months ago. He had a UTI 1 months ago.

CaseCase

Social: Lives in apt complex with his wife Social: Lives in apt complex with his wife and his pet parrot. Has two children not and his pet parrot. Has two children not living at home. Currently doing home living at home. Currently doing home renovations. renovations.

Meds: norvasc, amiodarone, thiazide. Meds: norvasc, amiodarone, thiazide. avodart avodart

Allergies: nil Allergies: nil

CaseCase Upon arrival to the Emergency room he was in Upon arrival to the Emergency room he was in

obvious respiratory distress with RR=40 and obvious respiratory distress with RR=40 and Sats 85% on double flow non-rebreather. He Sats 85% on double flow non-rebreather. He was intubated by the emergency physician was intubated by the emergency physician using etomidate and succinylcholine. His using etomidate and succinylcholine. His blood pressure dropped post intubation blood pressure dropped post intubation requiring phenylephrine and has now received requiring phenylephrine and has now received 2 L of NS. As you are standing in the 2 L of NS. As you are standing in the Emergency Dept, you are consulted Emergency Dept, you are consulted immediately as there is a septic patient immediately as there is a septic patient coming though the doors (88 yo DNR that is coming though the doors (88 yo DNR that is hypotensive and you hear the EP ask for hypotensive and you hear the EP ask for dopamine…….sigh). dopamine…….sigh).

CaseCase The EP tells you that he has ordered blood work The EP tells you that he has ordered blood work

and a ABG. You go to the patients bedside. He is and a ABG. You go to the patients bedside. He is just being placed on the ventilator by the RT. He just being placed on the ventilator by the RT. He is stated as “stable” by the bedside nurse, Sats is stated as “stable” by the bedside nurse, Sats 96 on Fio2=1.00, 110/54, 130, temp 36.2, and is 96 on Fio2=1.00, 110/54, 130, temp 36.2, and is dyssynchronous with the Vent. You have a dyssynchronous with the Vent. You have a excellent resident who immediately takes over excellent resident who immediately takes over bedside management. Orders another L of NS, bedside management. Orders another L of NS, ensures BC have been drawn and asks for ensures BC have been drawn and asks for moxifloxacin to be given. Orders a CXR, sedates moxifloxacin to be given. Orders a CXR, sedates the patient. Places an arterial line, IJ central line the patient. Places an arterial line, IJ central line and continues resuscitating him. and continues resuscitating him.

CaseCase

His physical exam reveals crackles His physical exam reveals crackles in his bases bilaterally. His skin is in his bases bilaterally. His skin is mottled and cold with no rash. mottled and cold with no rash. Neuro (no meningeal signs prev to Neuro (no meningeal signs prev to intubation), CV, abd, genital, ext intubation), CV, abd, genital, ext exam in non-contributory. exam in non-contributory.

Initial CXR shows bilateral basilar Initial CXR shows bilateral basilar infiltrate.infiltrate.

ECG= NS tachy.ECG= NS tachy.

CaseCase

Hb 150, Hct 0.55 WCC 18.2, Neut 12.3 Hb 150, Hct 0.55 WCC 18.2, Neut 12.3 Plat 79Plat 79

Film – few schistocyes, toxic Film – few schistocyes, toxic granulation. granulation.

INR 1.4, PTT 42, Fib 2.78INR 1.4, PTT 42, Fib 2.78 Na 134, K 4.4, Cl 107, HCO3 13, Urea Na 134, K 4.4, Cl 107, HCO3 13, Urea

18.8, creat 17818.8, creat 178 CK 508, Trop <0.1 LDH 540CK 508, Trop <0.1 LDH 540 Albumin 20, Lactate 8.1Albumin 20, Lactate 8.1

CaseCase

ABG pre intubation sent by RT:ABG pre intubation sent by RT: pH=7.22, CO2=27, PaO2=98, pH=7.22, CO2=27, PaO2=98,

HCO3=13, Base excess= neg 16. HCO3=13, Base excess= neg 16. New ABG returns as you are looking New ABG returns as you are looking

at the computer (post intubation):at the computer (post intubation): ABG= pH=7.11, PaCO2=38, ABG= pH=7.11, PaCO2=38,

PaO2=105, HCO3=12, Base PaO2=105, HCO3=12, Base excess=neg 17. FiO2=1.00excess=neg 17. FiO2=1.00

CaseCase Questions:Questions:1) What is the differential diagnosis? Are there any 1) What is the differential diagnosis? Are there any

clues in the story to the etiology? What is the clues in the story to the etiology? What is the most likely diagnosis?most likely diagnosis?

2) Based on the laboratory/ABG results what 2) Based on the laboratory/ABG results what concurrent issues are present in this disorder? concurrent issues are present in this disorder? What is the likely precipitants in this case?What is the likely precipitants in this case?

3) Any further investigations?3) Any further investigations?4) What treatments would you recommend now? 4) What treatments would you recommend now?

Do you agree with the abx choice?Do you agree with the abx choice?5) What initial ventilator settings would you have 5) What initial ventilator settings would you have

this patient on?this patient on?

CaseCase

The resident feels this is a pneumonia The resident feels this is a pneumonia and comments that it likely meets criteria and comments that it likely meets criteria for ARDS. A medical student then speaks for ARDS. A medical student then speaks up and asks “what is ARDS”? up and asks “what is ARDS”?

6.6.What is the Definition of ARDS?What is the Definition of ARDS?

7.7.What is the Epidemiology of ARDS?.What is the Epidemiology of ARDS?.

8.8.What is the Pathophysiology/Clinical What is the Pathophysiology/Clinical Stages and likely causes of ARDS.? Stages and likely causes of ARDS.?

ARDS ARDS

During 1960s, with widespread use of During 1960s, with widespread use of PPV a distinct form of bilateral lung PPV a distinct form of bilateral lung disease noted.disease noted.

Coined “Shock Lung” in trauma Coined “Shock Lung” in trauma patients in Viet Nam surgical hospitals.patients in Viet Nam surgical hospitals.

Then referred as Adult Respiratory Then referred as Adult Respiratory Distress Syndrome. Distress Syndrome.

Currently described as Acute Currently described as Acute Respiratory Distress Syndrome.Respiratory Distress Syndrome.

Bernard, GR. Acute Respiratory Distress Syndrome: A Historical Perspective. Am J Respir Bernard, GR. Acute Respiratory Distress Syndrome: A Historical Perspective. Am J Respir Crit Care Med 2005; 172:798Crit Care Med 2005; 172:798

What defines What defines ARDS?ARDS?

DefinitionsDefinitions

For more than 20 yrs there was lack of For more than 20 yrs there was lack of a uniformed description of ARDS.a uniformed description of ARDS.

1994 American-European Consensus 1994 American-European Consensus Conference on ARDS issued the Conference on ARDS issued the following definitions for:following definitions for:

1)ALI= Acute lung injury1)ALI= Acute lung injury

2)ARDS= Acute Respiratory Distress 2)ARDS= Acute Respiratory Distress SyndromeSyndrome

Bernard, G, Artigas, A, Carlet, J, et al. The American-European consensus conference on Bernard, G, Artigas, A, Carlet, J, et al. The American-European consensus conference on ARDS: Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J ARDS: Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994; 149:818. Respir Crit Care Med 1994; 149:818.


ALI:ALI: Bilateral radiographic inflitratesBilateral radiographic inflitrates PaO2/FiO2 PaO2/FiO2 between 201 and 300between 201 and 300

regardless of level of PEEPregardless of level of PEEP No clinical evidence for elevated left No clinical evidence for elevated left

atrial pressure. If measured, the atrial pressure. If measured, the pulmonary capillary wedge pressure pulmonary capillary wedge pressure is 18 mmHg or lessis 18 mmHg or less


ARDS:ARDS: Bilateral radiographic inflitratesBilateral radiographic inflitrates PaO2/FiO2 PaO2/FiO2 less than 200less than 200

regardless of level of PEEPregardless of level of PEEP No clinical evidence for elevated left No clinical evidence for elevated left

atrial pressure. If measured, the atrial pressure. If measured, the pulmonary capillary wedge pressure pulmonary capillary wedge pressure is 18 mmHg or lessis 18 mmHg or less


By definition is ACUTE. By definition is ACUTE. Typically will develop over 4-48 hrs Typically will develop over 4-48 hrs

and will persist for days to weeks. and will persist for days to weeks. Some equate with the Some equate with the

pathophysiologic entity of increased pathophysiologic entity of increased capillary permeability. This is capillary permeability. This is discouraged as there are other discouraged as there are other pathophysiologic mechanisms in pathophysiologic mechanisms in ARDS. ARDS.

DefinitionsDefinitions Early pathologic features of ARDS are generally Early pathologic features of ARDS are generally

described as diffuse alveolar damage (DAD). described as diffuse alveolar damage (DAD). There is minimal alveolar septal thickening, There is minimal alveolar septal thickening, hyperplasia of pneumocytes, and eosinophilic hyperplasia of pneumocytes, and eosinophilic hyaline membranes present.hyaline membranes present.

Beskow, CO, Drachenberg, CB, Bourquin, PM, et al. Diffuse alveolar damage. Morphologic features Beskow, CO, Drachenberg, CB, Bourquin, PM, et al. Diffuse alveolar damage. Morphologic features in bronchoalveolar lavage fluid. Acta Cytol 2000; 44:640.in bronchoalveolar lavage fluid. Acta Cytol 2000; 44:640.

EpidemiologyEpidemiology

EpidemiologyEpidemiology ALI= ALI= - Age-adjusted incidence of 86 per 100,000 - Age-adjusted incidence of 86 per 100,000

person-yearsperson-years Mortality of 39%Mortality of 39%

ARDS= ARDS= - Age-adjusted incidence of 64 per 100,00 - Age-adjusted incidence of 64 per 100,00

person-years person-years Mortality of 41%Mortality of 41%**190,600 cases of ALI in US each year, **190,600 cases of ALI in US each year,

which associated with 74,500 deaths.which associated with 74,500 deaths.Rubenfeld, GD, Caldwell, E, Peabody, E, et al. Incidence and outcomes of acute lung injury. Rubenfeld, GD, Caldwell, E, Peabody, E, et al. Incidence and outcomes of acute lung injury.

N Engl J Med 2005; 353:1685.N Engl J Med 2005; 353:1685.

Epidemiology Epidemiology Intensive Care Units:Intensive Care Units: 10-15% of admitted patients meet criteria for 10-15% of admitted patients meet criteria for

ARDSARDS 20% of mechanically ventilated patients meet 20% of mechanically ventilated patients meet

criteria for ARDScriteria for ARDS Mortality rate varies on the basis of Mortality rate varies on the basis of

underlying cause, most dying of MOF rather underlying cause, most dying of MOF rather than resp. insufficiency.than resp. insufficiency.

Large trials suggest overall mortality of ARDS Large trials suggest overall mortality of ARDS ranges from 25-58%.ranges from 25-58%.

Frutos-Vivar, F, Nin, N, Esteban, A. Epidemiology of acute lung injury and acute respiratory Frutos-Vivar, F, Nin, N, Esteban, A. Epidemiology of acute lung injury and acute respiratory distress syndrome. Curr Opin Crit Care 2004; 10:1 distress syndrome. Curr Opin Crit Care 2004; 10:1

Maccallum, NS, Evans, TW. Epidemiology of acute lung injury. Curr Opin Crit Care 2005; 11:43. Maccallum, NS, Evans, TW. Epidemiology of acute lung injury. Curr Opin Crit Care 2005; 11:43.

PathophysiologyPathophysiology


In healthy lung, a tight regulation on In healthy lung, a tight regulation on movement of fluid to maintain dry alveoli movement of fluid to maintain dry alveoli and a small amount of interstitial fluid. and a small amount of interstitial fluid.

In lung injury this regulation is lost. In lung injury this regulation is lost. There is excess fluid in both interstitium There is excess fluid in both interstitium and alveoli.and alveoli.

Results in impaired gas exchange, dec Results in impaired gas exchange, dec compliance, and increased pulmonary compliance, and increased pulmonary arterial pressures. arterial pressures.


Normal pulmonary capillary Normal pulmonary capillary endothelium is selectively permeable; endothelium is selectively permeable; serum protein remains intravascular, serum protein remains intravascular, fluid crosses the membranes under fluid crosses the membranes under control of:control of:

1)1) Hydrostatic forcesHydrostatic forces2)2) Osmotic forcesOsmotic forces

George, RB, Chesson, AL, Rennard, SI. Functional anatomy of the respiratory system. In: George, RB, Light, RW, George, RB, Chesson, AL, Rennard, SI. Functional anatomy of the respiratory system. In: George, RB, Light, RW, Matthay, MA, et al (Eds), 3rd ed, Chest Medicine. Essentials of Pulmonary and Critical Care Medicine, Matthay, MA, et al (Eds), 3rd ed, Chest Medicine. Essentials of Pulmonary and Critical Care Medicine, Williams & Wilkins, Baltimore, 1995, p. 3Williams & Wilkins, Baltimore, 1995, p. 3


The Starling equation describes the The Starling equation describes the forces that direct fluid movement. forces that direct fluid movement. Simplified version of the equation is:Simplified version of the equation is:

Q=K * [(Pmv – Ppmv) – rc (mv – Q=K * [(Pmv – Ppmv) – rc (mv – pmv)]pmv)]

Q= net transvascular flowQ= net transvascular flow

K= permeabilityK= permeability

Pmv= hydrostatic pressure in lumenPmv= hydrostatic pressure in lumen

Ppmv= hydrostatic pressure in perimicrovascular spacePpmv= hydrostatic pressure in perimicrovascular space

Rc= reflection coefficient of capillary barrierRc= reflection coefficient of capillary barrier

Mv= oncotic pressure of circMv= oncotic pressure of circ

Pmv= oncotic pressure of perimicrovasc compPmv= oncotic pressure of perimicrovasc comp


The balance of equation usually allows The balance of equation usually allows small amounts of fluid into interstitium small amounts of fluid into interstitium but 3 mech prevent alveolar edema.but 3 mech prevent alveolar edema.

1)1) Retained intravascular proteinRetained intravascular protein

2)2) Interstitial lymphatics can return large Interstitial lymphatics can return large quantities of fluid to circulationquantities of fluid to circulation

3)3) Tight junctions between alveolar Tight junctions between alveolar epithelial cellsepithelial cells


Clinical ARDS is result of inflammatory injury Clinical ARDS is result of inflammatory injury to alveoli producing DAD.to alveoli producing DAD.

Lungs are very vulnerable to injury b/c they Lungs are very vulnerable to injury b/c they receive the entire CO and as pro-receive the entire CO and as pro-inflammatory mediators (TNF, IL-1, IL-6, IL-inflammatory mediators (TNF, IL-1, IL-6, IL-8) released into blood stream the lungs feel 8) released into blood stream the lungs feel their full effect.their full effect.

Additionally, neutrophils are recruited to the Additionally, neutrophils are recruited to the lungs, become activated and release reactive lungs, become activated and release reactive oxygen species and proteases which damage oxygen species and proteases which damage endothelium and alveoli. endothelium and alveoli.

PathophysiologyPathophysiology As a result, the normal barriers to alveolar As a result, the normal barriers to alveolar

edema are lost.edema are lost.1)1) Protein escapes vascular space, oncotic Protein escapes vascular space, oncotic

gradient lost.gradient lost.2)2) Fluid pours into interstitium and Fluid pours into interstitium and

overwhelms the lymphatics.overwhelms the lymphatics.3)3) Air spaces fill with bloody, proteinaceous Air spaces fill with bloody, proteinaceous

edema fluid and debris from degenerating edema fluid and debris from degenerating cells.cells.

4)4) Functional surfactant is lost, resulting in Functional surfactant is lost, resulting in alveolar collapse.alveolar collapse.

Ware, LB, Matthay, MA. Alveolar fluid clearance is impaired in the majority of patients with acute lung injury Ware, LB, Matthay, MA. Alveolar fluid clearance is impaired in the majority of patients with acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med 2001; 163:1376. and the acute respiratory distress syndrome. Am J Respir Crit Care Med 2001; 163:1376.

PathophysiologyPathophysiology Consequences:Consequences:1)1) Impaired gas exchange= V/Q Impaired gas exchange= V/Q

mismatching and shunting.mismatching and shunting.2)2) Dec lung compliance= Low compliance is Dec lung compliance= Low compliance is

due to stiffness of poorly or nonaerated due to stiffness of poorly or nonaerated lung more so than changes in PV lung more so than changes in PV characteristics of residual fxning lung characteristics of residual fxning lung units. (Baby lung)units. (Baby lung)

3)3) Pulmonary HTN= present in up to 25% of Pulmonary HTN= present in up to 25% of Px with ARDs. Multifactorial. RV Px with ARDs. Multifactorial. RV dysfunction associated with inc risk of dysfunction associated with inc risk of death!death!

Monchi, M, Bellenfant, F, Cariou, A, et al. Early predictive factors of survival in the acute respiratory Monchi, M, Bellenfant, F, Cariou, A, et al. Early predictive factors of survival in the acute respiratory distress syndrome. A multivariate analysis. Am J Respir Crit Care Med 1998; 158:1076distress syndrome. A multivariate analysis. Am J Respir Crit Care Med 1998; 158:1076

Clinical StagesClinical Stages

Clinical StagesClinical Stages ARDs progresses through three relatively ARDs progresses through three relatively

discrete pathologic stages.discrete pathologic stages.

1) 1) Exudative stageExudative stage: DAD, in 1: DAD, in 1stst week progresses week progresses to to

2) 2) Proliferative stageProliferative stage: characterized by : characterized by resolution of pulmonary edema and proliferation resolution of pulmonary edema and proliferation of type II alveolar cells, squamous metaplasia, of type II alveolar cells, squamous metaplasia, interstitial infiltration by myofibroblasts, and interstitial infiltration by myofibroblasts, and early deposition of collagen. early deposition of collagen.

3) 3) Fibrotic stageFibrotic stage: obliteration of normal lung : obliteration of normal lung architecture, diffuse fibrosis, and cyst formation. architecture, diffuse fibrosis, and cyst formation.

Tomashefski, JFJ. Pulmonary pathology of the adult respiratory distress syndrome. Clin Chest Med 1990; 11:593 Tomashefski, JFJ. Pulmonary pathology of the adult respiratory distress syndrome. Clin Chest Med 1990; 11:593


Initial Course (exudative phase):Initial Course (exudative phase): Usually symptoms predominated by Usually symptoms predominated by

cause of ARDs (eg abd pain from cause of ARDs (eg abd pain from pancreatitis, fever and shock from pancreatitis, fever and shock from sepsis)sepsis)

Pulmonary dysfunction develops within Pulmonary dysfunction develops within 24-48 hrs of inciting event.24-48 hrs of inciting event.

Worsening tachypnea, dyspnea, Worsening tachypnea, dyspnea, hypoxemia and diffuse crackles on exam. hypoxemia and diffuse crackles on exam.


Labs non-specific. May show inc WBC, Labs non-specific. May show inc WBC, DIC and lactic acidosis.DIC and lactic acidosis.

ABG= acute resp alkalosis, inc DAaO2, ABG= acute resp alkalosis, inc DAaO2, severe hypoxemiasevere hypoxemia

CXR= Bilateral patchy infiltrates, does CXR= Bilateral patchy infiltrates, does not need to be widespread or severe not need to be widespread or severe opacification.opacification.

CT= generally demonstrates patchy abn CT= generally demonstrates patchy abn with inc density in dependent lung zones.with inc density in dependent lung zones.

Clinical StagesClinical Stages Proliferative stage:Proliferative stage: Oxygenation tends to improve somewhat Oxygenation tends to improve somewhat

over first few days as edema resolves, most over first few days as edema resolves, most patients remain ventilator-dependent due to:patients remain ventilator-dependent due to:

1)1) Continued hypoxemiaContinued hypoxemia2)2) High minute vent requirements (Classically High minute vent requirements (Classically

the Dead Space may begin to increase at the Dead Space may begin to increase at this stage and ventilation may become more this stage and ventilation may become more of an issue)of an issue)

3)3) Poor compliancePoor complianceGattinoni, L, Bombino, M, Pelosi, P, et al. Lung structure and function in different stages of severe adult Gattinoni, L, Bombino, M, Pelosi, P, et al. Lung structure and function in different stages of severe adult

respiratory distress syndrome. JAMA 1994; 271:1772respiratory distress syndrome. JAMA 1994; 271:1772


CXR= Densities become less dense CXR= Densities become less dense as edema resolves, interstitial as edema resolves, interstitial infiltrates remain. infiltrates remain.

May start to develop interstitial May start to develop interstitial emphysema and lung cysts.emphysema and lung cysts.

At this point may become dominated At this point may become dominated by complications such as by complications such as barotrauma, nosocomial infection or barotrauma, nosocomial infection or dev of MODS. (discussed later)dev of MODS. (discussed later)


Fibrotic Stage:Fibrotic Stage: Will see progressive increasing Will see progressive increasing

airway pressures, progressive airway pressures, progressive pulmonary HTN and a honeycomb pulmonary HTN and a honeycomb appearance on CXRappearance on CXR

EtiologyEtiology

Causes and predisposing Causes and predisposing conditionsconditions

Traditionally conceptualized as a pattern of injury Traditionally conceptualized as a pattern of injury that does not differ significantly depending upon that does not differ significantly depending upon cause.cause.

Now called in question with revolution of CT scan.Now called in question with revolution of CT scan. Additionally studies have found more severe Additionally studies have found more severe

reductions in lung compliance and less reductions in lung compliance and less responsiveness to PEEP in ARDS from a responsiveness to PEEP in ARDS from a pulmonary process than those with pulmonary process than those with extrapulmonary precipitant. extrapulmonary precipitant.

Gattinoni, L, Pelosi, P, Suter, P, et al. Acute respiratory distress syndrome caused by pulmonary and extrapulmonary Gattinoni, L, Pelosi, P, Suter, P, et al. Acute respiratory distress syndrome caused by pulmonary and extrapulmonary disease: Different syndromes. Am J Respir Crit Care Med 1998; 158:3. disease: Different syndromes. Am J Respir Crit Care Med 1998; 158:3.

Tugrul, S, Akinci, O, Ozcan, PE, et al. Effects of sustained inflation and postinflation positive end-expiratory pressure in Tugrul, S, Akinci, O, Ozcan, PE, et al. Effects of sustained inflation and postinflation positive end-expiratory pressure in acute respiratory distress syndrome: focusing on pulmonary and extrapulmonary forms. Crit Care Med 2003; 31:738. acute respiratory distress syndrome: focusing on pulmonary and extrapulmonary forms. Crit Care Med 2003; 31:738.

Abbreviated list of Abbreviated list of conditions associated with conditions associated with

ARDS ARDS SepsisSepsis AspirationAspiration Infectious pneumoniaInfectious pneumonia Severe traumaSevere trauma Surface burnsSurface burns Multiple blood Multiple blood

transfusionstransfusions Leukoagglutin Leukoagglutin

reactionsreactions PancreatitisPancreatitis Drug overdoseDrug overdose Near drowningNear drowning Smoke inhalationSmoke inhalation

Following bone marrow Following bone marrow transplantationtransplantation

Drug reactionDrug reaction Venous air embolismVenous air embolism Amniotic fluid embolismAmniotic fluid embolism Neurogenic pulmonary edemaNeurogenic pulmonary edema Acute eosinophilic Acute eosinophilic

pneumonia*pneumonia* Bronchiolitis obliterans Bronchiolitis obliterans

organizing pneumonia organizing pneumonia (BOOP)*(BOOP)*

Miliary tuberculosis*Miliary tuberculosis* Cardiopulmonary bypassCardiopulmonary bypass Pulmonary contusionPulmonary contusion Multiple fracturesMultiple fractures Following upper airway Following upper airway

obstructionobstruction


Sepsis: most common causeSepsis: most common cause Risk of developing ARDS with sepsis may be Risk of developing ARDS with sepsis may be

especially high in patients with alcoholism.especially high in patients with alcoholism. One prospective study analyzed the incidence One prospective study analyzed the incidence

of ARDS in 220 Px with septic shock.of ARDS in 220 Px with septic shock. 70% in chronic alcohol abusers 70% in chronic alcohol abusers 31% in non-alchohol abusers 31% in non-alchohol abusers ? Proposed mechanism= dec levels of ? Proposed mechanism= dec levels of

glutathione in epithelial lining, predispose to glutathione in epithelial lining, predispose to oxidative injury.oxidative injury.

Doyle, RL, Szaflarski, N, Modin, GW, et al. Identification of patients with acute lung injury. Predictors of mortality. Am J Respir Crit Care Med 1995; Doyle, RL, Szaflarski, N, Modin, GW, et al. Identification of patients with acute lung injury. Predictors of mortality. Am J Respir Crit Care Med 1995; 152:1818. 152:1818.

Moss, M, Bucher, B, Moore, FA, et al. The role of chronic alcohol abuse in the development of acute respiratory distress syndrome in adults. JAMA Moss, M, Bucher, B, Moore, FA, et al. The role of chronic alcohol abuse in the development of acute respiratory distress syndrome in adults. JAMA

1996; 21996; 2


Trauma:Trauma: Several mechanism can lead to ARDS Several mechanism can lead to ARDS1)1) Bilateral lung contusionsBilateral lung contusions2)2) Fat embolism: 12-24 hrs after injury, less Fat embolism: 12-24 hrs after injury, less

common now as fractures are immobilized common now as fractures are immobilized prior to transfer. prior to transfer.

3)3) SepsisSepsis4)4) Massive tissue injuryMassive tissue injury ALI and ARDS contribute to length of critical ALI and ARDS contribute to length of critical

illness, these disorders don not appear to inc illness, these disorders don not appear to inc risk of death. In comparison to other causes of risk of death. In comparison to other causes of ARDS, trauma-related is associated with better ARDS, trauma-related is associated with better prognosis. prognosis.

Rubenfeld, GD, Caldwell, E, Peabody, E, et al. Incidence and outcomes of acute lung injury. N Engl J Med 2005; Rubenfeld, GD, Caldwell, E, Peabody, E, et al. Incidence and outcomes of acute lung injury. N Engl J Med 2005;

353:1685.353:1685.


Transfusion relatedTransfusion related More than 15 pRBCs is an important risk More than 15 pRBCs is an important risk

factor even without trauma.factor even without trauma. Transfusion of smaller volumes of pRBCs Transfusion of smaller volumes of pRBCs

may also increase risk of developing ARDS may also increase risk of developing ARDS and inc mortality in Px with established and inc mortality in Px with established ARDS.ARDS.

TRALI: even one unit of plasma-containing TRALI: even one unit of plasma-containing blood can result in TRALI. FFP, plts, blood can result in TRALI. FFP, plts, pRBCs all implicated. Symptoms become pRBCs all implicated. Symptoms become apparent within 6 hours.apparent within 6 hours.

Gong, MN, Thompson, BT, Williams, P, et al. Clinical predictors of and mortality in acute respiratory Gong, MN, Thompson, BT, Williams, P, et al. Clinical predictors of and mortality in acute respiratory distress syndrome: potential role of red cell transfusion. Crit Care Med 2005; 33:1191. distress syndrome: potential role of red cell transfusion. Crit Care Med 2005; 33:1191.

Khan, H, Belsher, J, Yilmaz, M, et al. Fresh-frozen plasma and platelet transfusions are associated with Khan, H, Belsher, J, Yilmaz, M, et al. Fresh-frozen plasma and platelet transfusions are associated with development of acute lung injury in critically ill medical patients. Chest 2007; 131:1308. development of acute lung injury in critically ill medical patients. Chest 2007; 131:1308.


Toxicological causes?:Toxicological causes?:

1)1) ASAASA

2)2) OpioidsOpioids

3)3) PhenothiazinesPhenothiazines

4)4) TCAsTCAs

5)5) Also idosyncratic rxn to Also idosyncratic rxn to protamineprotamine, , nitrofuantoinnitrofuantoin, , chemotherapeuticschemotherapeutics, , contrast materialcontrast material

CaseCase

The resident also states that the chest X-The resident also states that the chest X-ray looks very similar to previous cases of ray looks very similar to previous cases of pulmonary edema that she has seen. She pulmonary edema that she has seen. She asks you if there are any diagnostic tests asks you if there are any diagnostic tests and evidence that can help you determine and evidence that can help you determine if this is ARDS vs cardiogenic pulmonary if this is ARDS vs cardiogenic pulmonary edema? (Aside from clinical exam) edema? (Aside from clinical exam)

Cardiogenic Cardiogenic pulmonary edema pulmonary edema

vs ARDSvs ARDS

DiagnosisDiagnosis During first several days ARDS will During first several days ARDS will

resemble acute cardiogenic pulmonary resemble acute cardiogenic pulmonary edema in both a clinical and radiographic edema in both a clinical and radiographic sense. sense.

Distinction usually made from clinical Distinction usually made from clinical circumstances associated with onset but circumstances associated with onset but occasionally additional diagnostic tests occasionally additional diagnostic tests may help.may help.

1) BNP1) BNP2) Echo2) Echo3) PAC3) PAC

DiagnosisDiagnosis

BNP:BNP: May be helpful in distinguishing ARDS from May be helpful in distinguishing ARDS from

hemodynamic pulmonary edema.hemodynamic pulmonary edema. A level below 100 pg/ml indicates heart A level below 100 pg/ml indicates heart

failure unlikely.failure unlikely. A higher level is not helpful. On study A higher level is not helpful. On study

looking at 24 px with Severe Sepsis or Septic looking at 24 px with Severe Sepsis or Septic Shock and 51 px with acute heart failure Shock and 51 px with acute heart failure found that values not significantly different. found that values not significantly different.

Rubenfeld, GD, Caldwell, E, Granton, J, et al. Interobserver variability in applying a radiographic definition for ARDS. Chest 1999; Rubenfeld, GD, Caldwell, E, Granton, J, et al. Interobserver variability in applying a radiographic definition for ARDS. Chest 1999; 116:1347. 116:1347.

Rudiger, A, Gasser, S, Fischler, M, et al. Comparable increase of B-type natriuretic peptide and amino-terminal pro-B-type natriuretic Rudiger, A, Gasser, S, Fischler, M, et al. Comparable increase of B-type natriuretic peptide and amino-terminal pro-B-type natriuretic peptide levels in patients with severe sepsis, septic shock, and acute heart failure. Crit Care Med 2006; 34:2140. peptide levels in patients with severe sepsis, septic shock, and acute heart failure. Crit Care Med 2006; 34:2140.

DiagnosisDiagnosis Echocardiography:Echocardiography: Most commonly used test to distinguish Most commonly used test to distinguish

questionable cardiogenic component of questionable cardiogenic component of ARDS.ARDS.

Can detect LV dysfunction, severe aortic or Can detect LV dysfunction, severe aortic or mitral valve abnormalities, estimation of mitral valve abnormalities, estimation of diastolic dysfuction and volume overload. diastolic dysfuction and volume overload.

Interpretation may be difficult in the Interpretation may be difficult in the presence of over/under resuscitation, renal presence of over/under resuscitation, renal failure, sepsis induced myocardial failure, sepsis induced myocardial dysfunction, PPV. dysfunction, PPV.

DiagnosisDiagnosis

Pulmonary artery catheterization Pulmonary artery catheterization (PAC):(PAC):

Classically clinicians would look for a Classically clinicians would look for a wedge > 18 mmHg. Need to be wedge > 18 mmHg. Need to be interpreted with caution in the face of interpreted with caution in the face of patients on high levels of PPV and PEEP. patients on high levels of PPV and PEEP.

Also, it is estimated that as many as 20% of Also, it is estimated that as many as 20% of px with ARDS have concomitant LV dysfxn.px with ARDS have concomitant LV dysfxn.

Ware, LB, Matthay, MA. Clinical practice. Acute pulmonary edema. N Engl J Med 2005; 353:2788. Ware, LB, Matthay, MA. Clinical practice. Acute pulmonary edema. N Engl J Med 2005; 353:2788.

Montgomery, A, Stager, M, Carico, C, et al. Causes of mortality in patients with the adult respiratory Montgomery, A, Stager, M, Carico, C, et al. Causes of mortality in patients with the adult respiratory distress syndrome. Am Rev Respir Dis 1985; 132:485. distress syndrome. Am Rev Respir Dis 1985; 132:485.

DiagnosisDiagnosis Therefore, the dx cannot be made easily Therefore, the dx cannot be made easily

when the wedge pressure is elevated.when the wedge pressure is elevated. More useful to follow the wedge pressure More useful to follow the wedge pressure

with treatment and how infiltrates and with treatment and how infiltrates and hypoxemia change with treatment. hypoxemia change with treatment.

If the infiltrates and hypoxemia do not If the infiltrates and hypoxemia do not improve appreciable within 24-48 hrs improve appreciable within 24-48 hrs after normalization of wedge pressure after normalization of wedge pressure more likely ARDS has occurred as well.more likely ARDS has occurred as well.

DiagnosisDiagnosis

Additionally, PAC has never been Additionally, PAC has never been shown to confer benefit in ARDS.shown to confer benefit in ARDS.

Recent multi-center trail (FACTT) Recent multi-center trail (FACTT) found no improvement in survival or found no improvement in survival or organ function, but more complications organ function, but more complications in PAC group vs CVC monitoring.in PAC group vs CVC monitoring.

Wheeler, AP, Bernard, GR, Thompson, BT, et al. Pulmonary-artery versus central venous Wheeler, AP, Bernard, GR, Thompson, BT, et al. Pulmonary-artery versus central venous catheter to guide treatment of acute lung injury. N Engl J Med 2006; 354:2213.catheter to guide treatment of acute lung injury. N Engl J Med 2006; 354:2213.

CaseCase The patient is moved to the ICU. The patient The patient is moved to the ICU. The patient

receives EGDT and you modify the antibiotic receives EGDT and you modify the antibiotic choices. Over the next 24 hrs the patient receives choices. Over the next 24 hrs the patient receives 9L of crystalloid and colloid. Currently on 20 9L of crystalloid and colloid. Currently on 20 ug/min of Levophed, ScvO2 has always been greater ug/min of Levophed, ScvO2 has always been greater than 70% and dobutamine was never used nor was than 70% and dobutamine was never used nor was transfusion. A Stat ECHO on arrival reveals a transfusion. A Stat ECHO on arrival reveals a mildly reduced EF (40%) but no wall motion abn mildly reduced EF (40%) but no wall motion abn and RV is mildly dilated and PA systolic is 45. and RV is mildly dilated and PA systolic is 45. Arrival CXR to the ICU shows worsening bilateral Arrival CXR to the ICU shows worsening bilateral infiltrates and you make the decision to do early infiltrates and you make the decision to do early bronchoscopy/BAL.bronchoscopy/BAL.

10.10. Your resident asks how bronchoscopy is going Your resident asks how bronchoscopy is going to help you management?to help you management?

Bronchoscopy in ARDsBronchoscopy in ARDs

Useful tool if cannot determine etiology from Useful tool if cannot determine etiology from history.history.

Able to visualize airways and perform Able to visualize airways and perform bronchoalveolar lavage.bronchoalveolar lavage.

Occult aspiration= see acute inflammation Occult aspiration= see acute inflammation localized to dependent regions and see food localized to dependent regions and see food material.material.

DAH= finding of frothy blood in airways and DAH= finding of frothy blood in airways and increasing bloody returns with recurrent increasing bloody returns with recurrent lavage. Find hemosiderin-laden macrophages lavage. Find hemosiderin-laden macrophages on microscopy.on microscopy.

Bronchoscopy in ARDsBronchoscopy in ARDs

Gram stain= Can identify organisms Gram stain= Can identify organisms and cellular components.and cellular components.

Culture and staining= look for aerobic Culture and staining= look for aerobic bacteria, mycobacteria, legionella bacteria, mycobacteria, legionella pneumophila, pneumocystis, viruses.pneumophila, pneumocystis, viruses.

Cytologic preps examined for Cytologic preps examined for eosinophils, viral inclusion bodies and eosinophils, viral inclusion bodies and cancer. cancer.

Others= eg) foamy macrophages seen Others= eg) foamy macrophages seen with BOOP and amiodarone toxicity. with BOOP and amiodarone toxicity.

CaseCase

During bronchoscopy you find moderate During bronchoscopy you find moderate amounts of secretions and no bloody amounts of secretions and no bloody returns. Initial gram stain only shows returns. Initial gram stain only shows neutrophils, negative for foamy neutrophils, negative for foamy macrophages. hemosiderin-laden macrophages. hemosiderin-laden macrophages and few esinophils. macrophages and few esinophils.

CaseCase 11.11. Your fantastic Your fantastic

senior fellow then senior fellow then states there are several states there are several clinical syndromes that clinical syndromes that present with present with inflammatory prodrome inflammatory prodrome and acute respiratory and acute respiratory failure. They have failure. They have specific treatments and specific treatments and prognosis, therefore prognosis, therefore should be considered. should be considered.

CaseCase

1) Diffuse alveolar hemorrage syndromes 1) Diffuse alveolar hemorrage syndromes (DAH)(DAH)

2) Acute interstitial pneumonia (Hammer-2) Acute interstitial pneumonia (Hammer-Rich)Rich)

3) Idiopathic acute eosinophilic pneumonia3) Idiopathic acute eosinophilic pneumonia

4) Cryptogenic organizing pneumonia4) Cryptogenic organizing pneumonia

Briefly describe each of these entities with Briefly describe each of these entities with respect to symptoms, diagnosis and respect to symptoms, diagnosis and treatment!treatment!

DAHDAH

DAHDAH

Is included in the differential of Is included in the differential of hypoxia with bilateral infiltrates.hypoxia with bilateral infiltrates.

Hemopysis will be absent in 33% of Hemopysis will be absent in 33% of cases.cases.

Is defined by injury to alveolar-Is defined by injury to alveolar-capillary basement membrane and capillary basement membrane and bleeding into alveolar spaces.bleeding into alveolar spaces.

Collard, HR, Schwarz, MI. Diffuse alveolar hemorrhage. Clin Chest Med 2004; 25:583Collard, HR, Schwarz, MI. Diffuse alveolar hemorrhage. Clin Chest Med 2004; 25:583

DAHDAH

A variety of diseases are associated A variety of diseases are associated with the development of diffuse with the development of diffuse alveolar hemorrhage syndrome.alveolar hemorrhage syndrome.

All fit within one of three All fit within one of three histological patternshistological patterns

1)1) Pulmonary capillaritisPulmonary capillaritis

2)2) Bland pulmonary hemorrhageBland pulmonary hemorrhage

3)3) Diffuse alveolar damageDiffuse alveolar damage

DAHDAHPulmonary CapillaritisPulmonary Capillaritis Systemic vasculitidesSystemic vasculitides::- Wegener's Wegener's

granulomatosisgranulomatosis- Microscopic polyangiitisMicroscopic polyangiitis- Henoch-Schoenlein Henoch-Schoenlein

purpurapurpura Collagen vascular Collagen vascular

diseases:diseases: - Systemic lupus Systemic lupus

erythematosus erythematosus - PolymyositisPolymyositis- Rheumatoid arthritisRheumatoid arthritis- SclerodermaScleroderma

DAHDAH

Bland pulmonary Bland pulmonary hemorrhagehemorrhage

- Goodpasture's - Goodpasture's syndromesyndrome

- Systemic lupus - Systemic lupus erythematosuserythematosus

- Post bone marrow - Post bone marrow transplanttransplant

- Severe coagulopathies- Severe coagulopathies- Mitral stenosis- Mitral stenosis- Penicillamine, - Penicillamine,

nitrofurantoin, nitrofurantoin, amiodaroneamiodarone

DAHDAH

Diffuse alveolar Diffuse alveolar damagedamage

ARDS and its ARDS and its causescauses

DAHDAH

Clinical presentation:Clinical presentation: Onset is often abrupt or of short Onset is often abrupt or of short

duration (<7 days)duration (<7 days) Cough, fever and dyspnea and may Cough, fever and dyspnea and may

present in extremis requiring PPV.present in extremis requiring PPV. May have constellation of new May have constellation of new

alveolar infiltrates, falling hgb and alveolar infiltrates, falling hgb and hemorragic fluid on sequential hemorragic fluid on sequential bronchoalveolar lavagebronchoalveolar lavage

DAHDAH

DAHDAH

CXR:CXR:- Diffuse, bilateral, patchy, basal Diffuse, bilateral, patchy, basal

consolidation on chest radiograph consolidation on chest radiograph (sparing the apex)(sparing the apex)

- Resembles pulmonary edema but Resembles pulmonary edema but normal heart size can be clue. normal heart size can be clue.

CT:CT:- alveolar densities with sparing of alveolar densities with sparing of

peripheral lung fields peripheral lung fields

DAHDAH

A number of diseases that cause A number of diseases that cause DAH are also associated with DAH are also associated with pulmonary-renal syndrome.pulmonary-renal syndrome.

Usually cause a focal segmental Usually cause a focal segmental necrotizing glomerulonephritis.necrotizing glomerulonephritis.

Will see elevated creatinine and abn Will see elevated creatinine and abn urinalysis (red blood cells, white urinalysis (red blood cells, white blood cells, red and white cell casts.)blood cells, red and white cell casts.)

DAHDAH

As previously mentioned in DAH will see As previously mentioned in DAH will see progressive hemorrhagic return with progressive hemorrhagic return with BAL.BAL.

Will also see hemosiderin-laden Will also see hemosiderin-laden macrophages, which may be macrophages, which may be demonstrated by prussian blud staining.demonstrated by prussian blud staining.

Additionally, specific diagnosis/etiology Additionally, specific diagnosis/etiology can be made from specific auto-can be made from specific auto-antibodies or lung/kidney/skin biopsy.antibodies or lung/kidney/skin biopsy.

DAHDAH

Many of the possible diagnosis are Many of the possible diagnosis are treated with either corticosteroids, treated with either corticosteroids, immunosuppressive therapy or immunosuppressive therapy or plasmapheresis.plasmapheresis.

Therefore must think of these Therefore must think of these diagnosis in the setting of ARDS.diagnosis in the setting of ARDS.

Failure to treat in the settting of Failure to treat in the settting of acute hypoxic respiratory failure acute hypoxic respiratory failure may significantly worsen prognosis. may significantly worsen prognosis.

Schwarz, MI, Mortenson, RL, Colby, TV, et al. Pulmonary capillaritis. The association with progressive Schwarz, MI, Mortenson, RL, Colby, TV, et al. Pulmonary capillaritis. The association with progressive irreversible airflow limitation and hyperinflation. Am Rev Respir Dis 1993; 148:507irreversible airflow limitation and hyperinflation. Am Rev Respir Dis 1993; 148:507

Acute Interstitial Acute Interstitial Pneumonia Pneumonia Hamman-Rich SyndromeHamman-Rich Syndrome

Acute Interstitial Acute Interstitial PneumoniaPneumonia

Rare and fulminate form of lung injury Rare and fulminate form of lung injury described by Hamman and Rich in 1935.described by Hamman and Rich in 1935.

Occurs in previously healthy individuals Occurs in previously healthy individuals without a history of lung disease who without a history of lung disease who present within days to weeks following present within days to weeks following onset of symptoms.onset of symptoms.

Similar in presentation to ARDS, and Similar in presentation to ARDS, and likely is a subset of idiopathic ARDS.likely is a subset of idiopathic ARDS.

Hamman, L, Rich, AR. Fulminating diffuse interstitial fibrosis of the lungs. Trans Am Clin Climatol Assoc 1935; Hamman, L, Rich, AR. Fulminating diffuse interstitial fibrosis of the lungs. Trans Am Clin Climatol Assoc 1935; 51:15451:154

Hamman, L, Rich, AR. Acute diffuse interstitial fibrosis of the lungs. Bull Johns Hopkins Hosp 1944; 74:177 Hamman, L, Rich, AR. Acute diffuse interstitial fibrosis of the lungs. Bull Johns Hopkins Hosp 1944; 74:177


Exact mechanism of damage to Exact mechanism of damage to pulmonary endothelium unknow.pulmonary endothelium unknow.

Likely neutrophil-mediated.Likely neutrophil-mediated. Results in damage of alveolar walls, Results in damage of alveolar walls,

inc alveolar capillary permeability, inc alveolar capillary permeability, interstitial edema, intralveolar haline interstitial edema, intralveolar haline membranes.membranes.

As with ARDS after initial insult also As with ARDS after initial insult also have a fibroblast proliferation phasehave a fibroblast proliferation phase


Most patients over age of 40. Most patients over age of 40. Usually begins with a prodromal illness Usually begins with a prodromal illness

lasting 7-14 days prior to presentation.lasting 7-14 days prior to presentation. Fever, cough and shortness of breath.Fever, cough and shortness of breath.

Labs nonspecificLabs nonspecific. .

Primack, SL, Hartman, TE, Ikezoe, J, et al. Acute interstitial Primack, SL, Hartman, TE, Ikezoe, J, et al. Acute interstitial pneumonia: Radiographic and CT findings in nine patients. pneumonia: Radiographic and CT findings in nine patients. Radiology 1993; 188:817 Radiology 1993; 188:817


CXR= diffuse, bilateral air-space CXR= diffuse, bilateral air-space opacification.opacification.

CT= A combination of ground-glass CT= A combination of ground-glass attenuation, airspace consolidation, attenuation, airspace consolidation, traction bronchiectasis, and architectural traction bronchiectasis, and architectural distortion distortion

The extent of ground-glass attenuation The extent of ground-glass attenuation and traction bronchiectasis increases with and traction bronchiectasis increases with disease duration.disease duration.


Diagnosis is based upon two Diagnosis is based upon two findings:findings:

1)1) Presence of a clinical syndrome of Presence of a clinical syndrome of idiopathic ARDS.idiopathic ARDS.

2)2) Pathologic confirmation.Pathologic confirmation. Thus a open or thoracoscopic lung Thus a open or thoracoscopic lung

biopsy is required to confirm the biopsy is required to confirm the diagnosis.diagnosis.


AIP should be distiguished from two other AIP should be distiguished from two other forms of idiopathic interstitial pneumonia:forms of idiopathic interstitial pneumonia:

1)1) Usual interstitial pneumonia (UIP)Usual interstitial pneumonia (UIP)

2)2) Desquamative interstitial pneumonia Desquamative interstitial pneumonia (DIP)(DIP)

These both have a more subacute/chronic These both have a more subacute/chronic presentations and therefore are not presentations and therefore are not included in differential of a acute ARDS included in differential of a acute ARDS picture.picture.

Vourlekis, JS, Brown, KK, Cool, CD, et al. Acute interstitial pneumonitis. Case series and review of the literature. Vourlekis, JS, Brown, KK, Cool, CD, et al. Acute interstitial pneumonitis. Case series and review of the literature. Medicine (Baltimore) 2000Medicine (Baltimore) 2000

UIPUIP

DIPDIP


Treatment:Treatment: Mainly supportive care.Mainly supportive care. Mech vent is often required.Mech vent is often required. Currently unclear if steroid therapy is Currently unclear if steroid therapy is

effective.effective. Mortality is high (>60%), and majority die Mortality is high (>60%), and majority die

within 6 months of presentation. within 6 months of presentation. If survive usual do so with complete recovery If survive usual do so with complete recovery

of lung function.of lung function.Vourlekis, JS, Brown, KK, Cool, CD, et al. Acute interstitial pneumonitis. Case series and review of the literature. Medicine (Baltimore) Vourlekis, JS, Brown, KK, Cool, CD, et al. Acute interstitial pneumonitis. Case series and review of the literature. Medicine (Baltimore)

2000; 79:3692000; 79:369

Idiopathic Acute Idiopathic Acute Eosinophilic Eosinophilic PneumoniaPneumonia

(AEP)(AEP)

Idiopathic Acute Idiopathic Acute Eosinophilic PneumoniaEosinophilic Pneumonia

First described as a cause of respiratory First described as a cause of respiratory failure in 1989.failure in 1989.

Etiology: Unknown, some feel is an acute Etiology: Unknown, some feel is an acute hypersensitivity reaction to unidentified hypersensitivity reaction to unidentified inhaled antigen in otherwise healthy people. inhaled antigen in otherwise healthy people.

Several reports people have been involved in Several reports people have been involved in unusual outdoor activities just prior to illness.unusual outdoor activities just prior to illness.

Temporal relationship noticed to recent onset Temporal relationship noticed to recent onset of cigarette smoking. of cigarette smoking.

Philit, F, Etienne-Mastroianni, B, Parrot, A, et al. Idiopathic acute eosinophilic pneumonia: a study of 22 patients. Am J Respir Crit Philit, F, Etienne-Mastroianni, B, Parrot, A, et al. Idiopathic acute eosinophilic pneumonia: a study of 22 patients. Am J Respir Crit

Care Med 2002; 166:1235Care Med 2002; 166:1235 Miki, K, Miki, M, Nakamura, Y, et al. Early-phase neutrophilia in cigarette smoke-induced acute eosinophilic Miki, K, Miki, M, Nakamura, Y, et al. Early-phase neutrophilia in cigarette smoke-induced acute eosinophilic

pneumonia. Intern Med 2003; 42:839pneumonia. Intern Med 2003; 42:839


Ages of 20 and 40.Ages of 20 and 40. Begins with acute febrile illness of less Begins with acute febrile illness of less

than 3 weeks duration; most less than than 3 weeks duration; most less than 7 days.7 days.

Malaise, myalgias, night sweats, Malaise, myalgias, night sweats, nonproductive cough and dyspnea are nonproductive cough and dyspnea are present in almost every patient. present in almost every patient.

O/E= fever (often high) and tachypnea, O/E= fever (often high) and tachypnea, bilateral basilar crackles. bilateral basilar crackles.


Labs: generally elevated WBCs with neutrophilic Labs: generally elevated WBCs with neutrophilic leukocytosis. leukocytosis.

With progression of disease the eosinophil fraction With progression of disease the eosinophil fraction becomes markedly elevated.becomes markedly elevated.

CXR= bilateral diffuse mixed alveolar and reticular CXR= bilateral diffuse mixed alveolar and reticular opacities are seen. Bilateral effusions are often opacities are seen. Bilateral effusions are often present (if tap will have marked eosinophilia with present (if tap will have marked eosinophilia with high pH.)high pH.)

CT= bilateral, random, and patchy group-glass or CT= bilateral, random, and patchy group-glass or reticular opacities. In height of disease will have reticular opacities. In height of disease will have peripheral ground-glass opacities along the peripheral ground-glass opacities along the bronchovascular bundles. bronchovascular bundles.

Hayakawa, H, Sato, A, Toyoshima, M, et al. A clinical study of idiopathic eosinophilic pneumonia. Chest 1994; Hayakawa, H, Sato, A, Toyoshima, M, et al. A clinical study of idiopathic eosinophilic pneumonia. Chest 1994; 105:1462 105:1462

Ogawa, H, Fujimura, M, Matsuda, T, et al. Transient wheeze. Eosinophilic bronchobronchiolitis in acute Ogawa, H, Fujimura, M, Matsuda, T, et al. Transient wheeze. Eosinophilic bronchobronchiolitis in acute

eosinophilic pneumonia. Chest 1993; 104:493eosinophilic pneumonia. Chest 1993; 104:493



BAL is useful in making the diagnosis.BAL is useful in making the diagnosis. Often show a very high (>25%) and Often show a very high (>25%) and

total number of eosinophils.total number of eosinophils. The proportions of BAL lymphocytes The proportions of BAL lymphocytes

and neutrophils are also frequently and neutrophils are also frequently increased.increased.

Rarely will need to do open lung biopsy. Rarely will need to do open lung biopsy. Philit, F, Etienne-Mastroianni, B, Parrot, A, et al. Idiopathic acute eosinophilic pneumonia: a study of 22 patients. Am J Respir Crit Philit, F, Etienne-Mastroianni, B, Parrot, A, et al. Idiopathic acute eosinophilic pneumonia: a study of 22 patients. Am J Respir Crit

Care Med 2002; 166:1235Care Med 2002; 166:1235


Treatment:Treatment: Spontaneous improvement has been Spontaneous improvement has been

reported.reported. Uniformly respond to IV and oral Uniformly respond to IV and oral

corticosteroid therapy.corticosteroid therapy. Response is often dramatic, occurring Response is often dramatic, occurring

within 12 to 48 hours, and there is no within 12 to 48 hours, and there is no relapse following withdrawl of the relapse following withdrawl of the steroids. steroids.

Cryptogenic Cryptogenic Organizing Organizing PneumoniaPneumonia

Idiopathic BOOPIdiopathic BOOP

Cryptogenic Organizing Cryptogenic Organizing PneumoniaPneumonia

Distinct clinical entity with features of Distinct clinical entity with features of pneumonia.pneumonia.

Due to proliferation of granulation tissue Due to proliferation of granulation tissue within small airways (proliferative within small airways (proliferative bronchiolitis) and alveolar ducts, chronic bronchiolitis) and alveolar ducts, chronic inflammation in surrounding alveoli.inflammation in surrounding alveoli.

Pathogenesis remains unknown. Pathogenesis remains unknown. Abnormal vascuar endothelial growth factor Abnormal vascuar endothelial growth factor

and matrix metalloproeinase regulation.and matrix metalloproeinase regulation.

Choi, KH, Lee, HB, Jeong, MY, et al. The role of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in cryptogenic Choi, KH, Lee, HB, Jeong, MY, et al. The role of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in cryptogenic organizing pneumonia. Chest 2002; organizing pneumonia. Chest 2002; 121:1478121:1478



Presents in the 40s and 50sPresents in the 40s and 50s May have had symptoms for up to May have had symptoms for up to

month or more before presentation.month or more before presentation. Mimics CAP. Mimics CAP. Heralded by flu-like illness (fever, Heralded by flu-like illness (fever,

malaise, fatigue, and cough). Also malaise, fatigue, and cough). Also may have weight loss. may have weight loss.

Labs= Inc WBC, Inc ESR, Inc CRP.Labs= Inc WBC, Inc ESR, Inc CRP.


CXR= bilateral, diffuse alveolar opacities with CXR= bilateral, diffuse alveolar opacities with normal lung volumes. May be peripherally located. normal lung volumes. May be peripherally located.

The infiltrates may also be migratory and recurrent.The infiltrates may also be migratory and recurrent. CT= patchy air-space consolidation, ground-glass CT= patchy air-space consolidation, ground-glass

opacities, small nodular opacities, and bronchial opacities, small nodular opacities, and bronchial wall thickening and dilation. wall thickening and dilation.

More often in the More often in the periphery and lower lung periphery and lower lung zones.zones.

Davison, AG, Heard, BE, McAllister, WAC, Turner-Warwick, MEH. Cryptogenic organizing pneumonitis. Q J Med 1983; 52:382 Davison, AG, Heard, BE, McAllister, WAC, Turner-Warwick, MEH. Cryptogenic organizing pneumonitis. Q J Med 1983; 52:382

Ujita, M, Renzoni, EA, Veeraraghavan, S, et al. Organizing pneumonia: perilobular pattern at thin-section CT. Radiology 2004; Ujita, M, Renzoni, EA, Veeraraghavan, S, et al. Organizing pneumonia: perilobular pattern at thin-section CT. Radiology 2004;

232:757232:757


Diagnosis:Diagnosis: BAL is very helpful: Classically a “mixed BAL is very helpful: Classically a “mixed

cellular pattern”cellular pattern” Similar to hypersensitivity pneumonitis. Similar to hypersensitivity pneumonitis.

Proportion of macrophages is lower, Proportion of macrophages is lower, lymphocytes, neutrophils and eosinophils lymphocytes, neutrophils and eosinophils are higher. are higher.

Foamy macrophagesFoamy macrophages Occasionally, mast cells and plasma cellsOccasionally, mast cells and plasma cells

King, TE Jr, Mortenson, RL. Cryptogenic organizing pneumonia. The North American experience. Chest 1992; 102:8SKing, TE Jr, Mortenson, RL. Cryptogenic organizing pneumonia. The North American experience. Chest 1992; 102:8S


An open biopsy or thoracoscopic lung An open biopsy or thoracoscopic lung biopsy is suggested to confirm diagnosis.biopsy is suggested to confirm diagnosis.

Need generous amount of lung tissue.Need generous amount of lung tissue. Important to provide pathologist with Important to provide pathologist with

adequate clinical information to guide adequate clinical information to guide search for specific lesions and to rule search for specific lesions and to rule out other possible causes that have out other possible causes that have similar pathologic picture. similar pathologic picture.

Miyagawa, Y, Nagata, N, Shigematsu, N. Clinicopathological study of migratory lung infiltrates. Thorax 1991; Miyagawa, Y, Nagata, N, Shigematsu, N. Clinicopathological study of migratory lung infiltrates. Thorax 1991;

46:23346:233


Treatment:Treatment: SupportiveSupportive Corticosteroid pulse then taper.Corticosteroid pulse then taper. Some who cant tolerate steroids or Some who cant tolerate steroids or

deteriorate are treated with deteriorate are treated with cyclophophamide.cyclophophamide.

Prognosis= 2/3 recover in weeks to Prognosis= 2/3 recover in weeks to months. 1/3 will have persistant months. 1/3 will have persistant disease. May relapse. disease. May relapse.

CaseCase

The patient then slowly deteriorates The patient then slowly deteriorates from an oxygenation point of view and from an oxygenation point of view and after a brief period of a FiO2 of 0.60 is after a brief period of a FiO2 of 0.60 is now requiring 0.80. The CXR has now now requiring 0.80. The CXR has now blossomed into severe bilateral blossomed into severe bilateral infiltrates. A CT scan was performed infiltrates. A CT scan was performed and shows a diffuse bilateral and shows a diffuse bilateral groundglass appearance with groundglass appearance with consolidation in the dorsal aspects of consolidation in the dorsal aspects of the lung. the lung.

CaseCase The urin output has picked up and the The urin output has picked up and the

creatinine is dropping. You are currently on creatinine is dropping. You are currently on a volume control ventilation (6cc/kg, a volume control ventilation (6cc/kg, rate=28, plat are 28, PEEP=7 nil autoPEEP). rate=28, plat are 28, PEEP=7 nil autoPEEP). ABG: pH=7.35, PaCo2=35, PaO2=75 ABG: pH=7.35, PaCo2=35, PaO2=75 HCO3=20. HCO3=20.

12) She questions if the amount of fluid she has 12) She questions if the amount of fluid she has given the patient and if this is detrimental? Is given the patient and if this is detrimental? Is there any evidence to how we should manage there any evidence to how we should manage the fluid balance in Px with ARDS? the fluid balance in Px with ARDS?

Fluid Fluid management in management in

ARDSARDS

Fluid management in Fluid management in ARDSARDS

Pulmonary edema in ARDS is directly Pulmonary edema in ARDS is directly related to increased vascular permeability related to increased vascular permeability but the quantity depends on hydrostatic but the quantity depends on hydrostatic pressure. pressure.

Mitchell, JP, Schuller, D, Calandrino, FS, et al. Improved outcome based on fluid management in critically ill patients Mitchell, JP, Schuller, D, Calandrino, FS, et al. Improved outcome based on fluid management in critically ill patients requiring pulmonary artery catheterization. Am Rev Respir Dis 1992; 145:990requiring pulmonary artery catheterization. Am Rev Respir Dis 1992; 145:990


Thus, even in px who are not overloaded Thus, even in px who are not overloaded a conservative strategy approach may be a conservative strategy approach may be beneficial. beneficial.


RCT, n=1000RCT, n=1000 Conservative group=CVP <4 mmHg, Conservative group=CVP <4 mmHg,

PAOP< 8 mmHg. (Unable to obtain in PAOP< 8 mmHg. (Unable to obtain in study)study)

Liberal group= CVP 10-14, PAOP 14-18.Liberal group= CVP 10-14, PAOP 14-18. Fluid balance= -136 cc vs 6992 ccFluid balance= -136 cc vs 6992 cc


Vent free days= 15 vs 12 (p=0.001) Vent free days= 15 vs 12 (p=0.001) ICU free days= 13 vs 11 (p=0.001)ICU free days= 13 vs 11 (p=0.001) 60 day mortality 25.5% vs 28.4% (p=0.30)60 day mortality 25.5% vs 28.4% (p=0.30)


Important to knowImportant to know1)1) Needed to be out of shock for 12 hrs Needed to be out of shock for 12 hrs

before diuretics given. before diuretics given. 2)2) Requiring dialysis was Requiring dialysis was

contraindication to the study contraindication to the study 3)3) Average time to study entry was 43 Average time to study entry was 43

hours.hours. Study found no difference between Study found no difference between

prevalence of shock or need for renal prevalence of shock or need for renal replacement therapy once randomized.replacement therapy once randomized.


Can we incorporate this into our practice? Can we incorporate this into our practice? Likely we should attempt a conservative Likely we should attempt a conservative

strategy of fluid management in select px strategy of fluid management in select px with ARDS or ALI.with ARDS or ALI.

Attempt goals of CVP <4 and PAOP < 8 Attempt goals of CVP <4 and PAOP < 8 (may be difficult to obtain.) (may be difficult to obtain.)

Must be balanced with EGDT and early Must be balanced with EGDT and early phases of sepsis when fluid replacement phases of sepsis when fluid replacement is crucial. is crucial.


Simplified algorithm for conservative fluid Simplified algorithm for conservative fluid management.management.

CaseCase 13. The fellow asks the resident if there is 13. The fellow asks the resident if there is

anything else we can do with conventional anything else we can do with conventional ventilation or the PEEP. ventilation or the PEEP.

14. What are the primary mechanisms of 14. What are the primary mechanisms of Ventilator induced lung injury (VILI)?Ventilator induced lung injury (VILI)?

15. What is the concept of “Baby Lung”?15. What is the concept of “Baby Lung”? 16. Do you have a strategy to determining 16. Do you have a strategy to determining

the “Best PEEP”? the “Best PEEP”? 17. Is there any evidence for higher 17. Is there any evidence for higher PEEP and Open Lung ventilationPEEP and Open Lung ventilation(not including oscillators)(not including oscillators)

Mechanical VentilationMechanical Ventilation Mechanical Ventilation is the corner stone Mechanical Ventilation is the corner stone

of supportive therapy ARDS management.of supportive therapy ARDS management. Primary issue in ARDS is that it is a Primary issue in ARDS is that it is a

heterogeneous disease process within the heterogeneous disease process within the lungs. lungs.

Much of the lungs is so consolidated it Much of the lungs is so consolidated it cannot be recruited to participate in gas cannot be recruited to participate in gas exchange.exchange.

Therefore, the effective lung being Therefore, the effective lung being ventilated is much smaller than usual. This ventilated is much smaller than usual. This is the concept of “baby lung”. is the concept of “baby lung”.

Fan, E, Needham, DM, Stewart, TE. Ventilatory management of acute lung injury and acute respiratory distress syndrome. JAMA 2005; 294:2889Fan, E, Needham, DM, Stewart, TE. Ventilatory management of acute lung injury and acute respiratory distress syndrome. JAMA 2005; 294:2889

Mechanical VentilationMechanical Ventilation Additionally, different areas of lung have Additionally, different areas of lung have

different “time constants”different “time constants” What are time constants?What are time constants? Different physiologic properties Different physiologic properties

pertaining to their compliance, inflation pertaining to their compliance, inflation and deflation times relative to each other. and deflation times relative to each other.

Therefore, at a set driving pressure and Therefore, at a set driving pressure and PEEP, some areas will never inflate while PEEP, some areas will never inflate while others will open and close cyclically and others will open and close cyclically and still others will be continuously distended still others will be continuously distended and damaged. and damaged.

Mechanical VentilationMechanical Ventilation

Last 15 years there has been a Last 15 years there has been a growing appreciation of ventilator-growing appreciation of ventilator-related morbidity and Ventilator related morbidity and Ventilator Induced Lung Injury (VILI).Induced Lung Injury (VILI).

Clinicians strive to determine the Clinicians strive to determine the optimal modes of ventilation to optimal modes of ventilation to reduce VILI and improve survival. reduce VILI and improve survival.


Primary mechanisms of VILI are felt Primary mechanisms of VILI are felt to be barotrauma and biotrauma.to be barotrauma and biotrauma.

Barotrauma= High airway/alveolar Barotrauma= High airway/alveolar pressure results in air migrating into pressure results in air migrating into extrapulmonary compartments extrapulmonary compartments (discuss later).(discuss later).

Biotrauma= Both tidal hyperinflation Biotrauma= Both tidal hyperinflation and cyclic atelectasis. and cyclic atelectasis.

Terragni, PP, Rosboch, G, Tealdi, A, et al. Tidal Hyperinflation during Low Tidal Volume Terragni, PP, Rosboch, G, Tealdi, A, et al. Tidal Hyperinflation during Low Tidal Volume Ventilation in Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med 2007; Ventilation in Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med 2007; 175175


What is tidal hyperinflation and What is tidal hyperinflation and cyclic atelectasis? cyclic atelectasis?

Tidal hyperinflation= over-inflation Tidal hyperinflation= over-inflation of aerated lung units.of aerated lung units.

Cyclic atelectasis= areas of diseased Cyclic atelectasis= areas of diseased lung appear to collapse and open lung appear to collapse and open cyclically with each breath. This cyclically with each breath. This places stress and damages adjacent places stress and damages adjacent lung that remains open. lung that remains open.

Mechanical VentilationMechanical Ventilation Key protective modalities/ideologies areKey protective modalities/ideologies are

1)1) Low tidal volume ventilation (ARDSnet Low tidal volume ventilation (ARDSnet ARMA study) and the idea of the “baby ARMA study) and the idea of the “baby lung”. lung”.

2)2) Use of PEEP and open lung ventilation to Use of PEEP and open lung ventilation to improve hypoxemia and limit cyclic improve hypoxemia and limit cyclic atelectasis.atelectasis.

Fan, E, Needham, DM, Stewart, TE. Ventilatory management of acute lung injury and acute respiratory distress syndrome. JAMA 2005; 294:2889Fan, E, Needham, DM, Stewart, TE. Ventilatory management of acute lung injury and acute respiratory distress syndrome. JAMA 2005; 294:2889


Clinical value of low tidal volume ventilation Clinical value of low tidal volume ventilation “clearly” demonstrated in ARDSnet study.“clearly” demonstrated in ARDSnet study.

ARMA (originally called KARMA….know ARMA (originally called KARMA….know why?)why?)


RCT of 861 patients.RCT of 861 patients. 6 cc/kg IBW and Plat 6 cc/kg IBW and Plat

<30cm H2O<30cm H2O 12 cc/kg IBC and 12 cc/kg IBC and

Plat <50cm H2OPlat <50cm H2O Stopped early at Stopped early at

interim analysis b/c interim analysis b/c of significant lower of significant lower mortality (31 mortality (31 vs 40 % p=0.007).vs 40 % p=0.007).


Issues:Issues:

1) Was study control group tidal 1) Was study control group tidal volume inappropriate high? (studies volume inappropriate high? (studies showed no true standard of care!)showed no true standard of care!)

2) Practice Misalignment? 2) Practice Misalignment?

Mechanical VentilationMechanical Ventilation Issues:Issues:3) People fear that low tidal volume will result 3) People fear that low tidal volume will result

in more discomfort, therefore inc sedation? in more discomfort, therefore inc sedation? - Secondary analysis of one ARDSnet center Secondary analysis of one ARDSnet center

showed neither inc dose nor duration of showed neither inc dose nor duration of sedation.sedation.

4) Hypercapnia does occur when attempting to 4) Hypercapnia does occur when attempting to use low tidal volume ventilation! Is this safe?use low tidal volume ventilation! Is this safe?

- Multiple studies have shown that modest, Multiple studies have shown that modest, permissive hypercapnia is safe!permissive hypercapnia is safe!

Kahn JM et al. Low tidal volume ventilation does not increase sedation use ni patients with acute lung injury. Crit Care Med 2005; Kahn JM et al. Low tidal volume ventilation does not increase sedation use ni patients with acute lung injury. Crit Care Med 2005; 33:766-77133:766-771

Laffey JG et al. Permissive hypercapnia role in protective lung ventilation strategies. Intensive Care Med 2004; 30247-356.Laffey JG et al. Permissive hypercapnia role in protective lung ventilation strategies. Intensive Care Med 2004; 30247-356.

PEEP and Open PEEP and Open Lung VentilationLung Ventilation

PEEP and Open Lung PEEP and Open Lung VentilationVentilation

Rational behind PEEP= Preventing subsequent Rational behind PEEP= Preventing subsequent recollapse of difficult to recruit lung units.recollapse of difficult to recruit lung units.

Several benefits:Several benefits:1)1) Improve V/Q matching.Improve V/Q matching.2)2) Alveoli will not have to repeatedly construct Alveoli will not have to repeatedly construct

surfactant monolayer, and this improves surfactant monolayer, and this improves compliance.compliance.

3)3) Prevent cyclic atalectasis. Prevent cyclic atalectasis. Overall goal is to improve oxygenation and Overall goal is to improve oxygenation and

reduce the levels of required FiO2 to less toxic reduce the levels of required FiO2 to less toxic levels. levels.

Plotz FB, Slutsky AS, van Vught AJ, Heijnen CJ. Ventilator-induced lung injury and multiple system organ failure: a critical review of facts and Plotz FB, Slutsky AS, van Vught AJ, Heijnen CJ. Ventilator-induced lung injury and multiple system organ failure: a critical review of facts and

hypotheses. Intensive Care Med. 2004;30:1865-1872hypotheses. Intensive Care Med. 2004;30:1865-1872



3 basic approaches to setting 3 basic approaches to setting appropriate level of PEEP.appropriate level of PEEP.

1)1) Visual-Visual- variety of radiologic, nuc variety of radiologic, nuc med, CT tech to determine amount of med, CT tech to determine amount of recruitable and over distended recruitable and over distended lung…..currently not readily available.lung…..currently not readily available.

2)2) Mechanical-Mechanical- using pressure-volume using pressure-volume relationships….not easy to capture relationships….not easy to capture regional variations within lung. Tech regional variations within lung. Tech challenging. challenging.


3) 3) Gas-exchange approaches-Gas-exchange approaches- use use FiO2, PaO2 or calculated shunt FiO2, PaO2 or calculated shunt fraction to target and adjust PEEP. fraction to target and adjust PEEP.

Many of the PEEP studies (such as Many of the PEEP studies (such as ALVEOLI by ARDSnet) use ALVEOLI by ARDSnet) use predetermined algorithms based on predetermined algorithms based on this idea. this idea.



ALVEOLI (ARDSnet group) N=549ALVEOLI (ARDSnet group) N=549 RCT of aggressive PEEP (12-24 cm H2O) vs RCT of aggressive PEEP (12-24 cm H2O) vs

conservative PEEP (5-24 cm H2O) conservative PEEP (5-24 cm H2O) approach guided by gas exchange.approach guided by gas exchange.

All low tidal volumeAll low tidal volume


Successfully achieved different Successfully achieved different levels of PEEPlevels of PEEP

High PEEP Low High PEEP Low PEEP PEEP

Day 1Day 1 14.7 8.9 14.7 8.9

Day 3 12.9 8.5Day 3 12.9 8.5

Day 7 12.9 8.4Day 7 12.9 8.4


Aggressive Aggressive strategy improved strategy improved gas exchange, gas exchange, atalectasis and atalectasis and compliance, the compliance, the plateau pressue plateau pressue was higher but the was higher but the mortality was mortality was unchanged. unchanged.

P = 0.48P = 0.48

If hi PEEP reduced If hi PEEP reduced atelectasis more, why didn’t atelectasis more, why didn’t

outcomes improve?outcomes improve? Maybe it really didMaybe it really did- Sig imbalances in age and P/F favored low Sig imbalances in age and P/F favored low

PEEP, adjustments showed “trends” for hi PEEP, adjustments showed “trends” for hi PEEPPEEP

- Might “recruitable” subgroups benefit?Might “recruitable” subgroups benefit? But maybe it didn’tBut maybe it didn’t- Benefits of more recruitment countered by Benefits of more recruitment countered by

overdistention elsewhereoverdistention elsewhere- In setting of low VT and recruitment of “easy” In setting of low VT and recruitment of “easy”

alveoli, further recruitment of “tough” alveoli alveoli, further recruitment of “tough” alveoli adds little benefit (prevent cyclic injury, allow adds little benefit (prevent cyclic injury, allow fixed)fixed)


In 2007, two additional, large RCTs In 2007, two additional, large RCTs studying aggressive vs conservative studying aggressive vs conservative PEEP were completed and preliminary PEEP were completed and preliminary analysis reported.analysis reported.

Canadian/Australian/Saudi Arabian Canadian/Australian/Saudi Arabian Lung Open Ventilation Study (LOVS)Lung Open Ventilation Study (LOVS)

French ExPress study.French ExPress study.Meade MO, Cook DJ, Arabi Y, et al. A multinational randomized controlled trial of a lung open ventilation strategy in ALI/ARDS -- Meade MO, Cook DJ, Arabi Y, et al. A multinational randomized controlled trial of a lung open ventilation strategy in ALI/ARDS --

preliminary results. Am J Respir Crit Care Med. 2007;A507preliminary results. Am J Respir Crit Care Med. 2007;A507

Mercat A, Richard JC, Brochard L, et al. Comparison of two strategies for setting PEEP in ALI/ARDS (ExPress study). Am J Respir Crit Mercat A, Richard JC, Brochard L, et al. Comparison of two strategies for setting PEEP in ALI/ARDS (ExPress study). Am J Respir Crit

Care Med. 2007;A507Care Med. 2007;A507


In both the new trials:In both the new trials:

1)1) Higher vent-free days Higher vent-free days and better compliance and better compliance in the aggressive in the aggressive PEEP group.PEEP group.

2)2) No mortality benefit.No mortality benefit.

3)3) Non significant Non significant subgroup benefit in subgroup benefit in sickest patients. sickest patients.

??? What will meta-??? What will meta-analysis show? analysis show?

ALVEOLIALVEOLI LOVSLOVS ExPressExPress

NN 583583 983983 767767

Aggressive Aggressive PEEPPEEP

15 cm H15 cm H22O*O* 13 cm H13 cm H22O*O* 15 cm H15 cm H22O*O*

PaOPaO22/FiO/FiO22 222 mm Hg*222 mm Hg* 187 mm Hg*187 mm Hg* 218 mm Hg*218 mm Hg*

PplatPplat 27 cm H27 cm H22O*O* 30 cm H30 cm H22O*O* 27 cm H27 cm H22O*O*

MortalityMortality 27%27% 36%36% 28%28%

Conservative Conservative PEEPPEEP

8 cm H8 cm H22O*O* 9 cm H9 cm H22O*O* 7 cm H7 cm H22O*O*

PaOPaO22/FiO/FiO22 168 mm Hg*168 mm Hg* 149 mm Hg*149 mm Hg* 150 mm Hg*150 mm Hg*

PplatPplat 24 cm H24 cm H22O*O* 25 cm H25 cm H22O*O* 21 cm H21 cm H22O*O*

MortalityMortality 25%25% 40%40% 31%31%


So……how should we manage our So……how should we manage our PEEP?PEEP?

Thoughts?Thoughts? Use enough PEEP to reduce FiO2 to 0.6 Use enough PEEP to reduce FiO2 to 0.6

or less while still keeping your plat <30 or less while still keeping your plat <30 (after maximizing your MAP). If unable (after maximizing your MAP). If unable to do this…..think about tech (ie HFOV.)to do this…..think about tech (ie HFOV.)

There is association between higher There is association between higher PEEP and barotrauma.PEEP and barotrauma.


What about recruitment maneuvers What about recruitment maneuvers in the ALVEOLI study?in the ALVEOLI study?

First 80 patients in the High PEEP First 80 patients in the High PEEP group were randomized to group were randomized to recruitment maneuvers vs sham recruitment maneuvers vs sham maneuvers.maneuvers.

Resulted in only small and transient Resulted in only small and transient increases in PaO2….therefore was increases in PaO2….therefore was discontinued.discontinued.

CaseCase

The patient continues to deteriorate and is The patient continues to deteriorate and is now on inverse ratio PC ventilation (2:1) with now on inverse ratio PC ventilation (2:1) with a PEEP of 18. The PaO2 is 68 on FiO2 of a PEEP of 18. The PaO2 is 68 on FiO2 of 0.80. Hemodynamically they have actually 0.80. Hemodynamically they have actually improved and are requiring only 10 of improved and are requiring only 10 of levophed. They are currently deeply sedated levophed. They are currently deeply sedated on propofol and fentenyl and you gain no on propofol and fentenyl and you gain no benefit from paralysis. There is adequate urin benefit from paralysis. There is adequate urin output and the creatine and lactate have output and the creatine and lactate have returned to normal. Your BAL cultures comes returned to normal. Your BAL cultures comes back negative viral, bacterial and fungal. back negative viral, bacterial and fungal.

CaseCase

18.Your resident asks if there is anything 18.Your resident asks if there is anything else we can do in this situation and if there else we can do in this situation and if there are any other treatments? (Your fellow are any other treatments? (Your fellow comments on the fact we don’t have a comments on the fact we don’t have a diagnosis!) diagnosis!)

19. What is the role of lung biopsy in 19. What is the role of lung biopsy in ARDS ARDS I Love

Meduri!!!!!!!!

Lung biopsy in Lung biopsy in ARDSARDS

Lung BiopsyLung Biopsy

In general, reserved for carefully In general, reserved for carefully selected patients with ARDs of unclear selected patients with ARDs of unclear etiology.etiology.

Suspected Dx of CA, DAH, cryptogenic Suspected Dx of CA, DAH, cryptogenic organizing pneumonitis, undiagnosis organizing pneumonitis, undiagnosis underlying lung disease such as underlying lung disease such as sarcoidosis, acute interstitial pneumonia sarcoidosis, acute interstitial pneumonia (Hamman-Rich Syndrome).(Hamman-Rich Syndrome).

Patel, SR, Karmpaliotis, D, Ayas, NT, et al. The role of open-lung biopsy in ARDS. Chest 2004; 125:197Patel, SR, Karmpaliotis, D, Ayas, NT, et al. The role of open-lung biopsy in ARDS. Chest 2004; 125:197

Papazian, L, Thomas, P, Bregeon, F, et al. Open-lung biopsy in patients with acute respiratory distress syndrome. Papazian, L, Thomas, P, Bregeon, F, et al. Open-lung biopsy in patients with acute respiratory distress syndrome. Anesthesiology 1998; 88:935 Anesthesiology 1998; 88:935

Lung BiopsyLung Biopsy Considered reasonably safe Considered reasonably safe Retrospective review of 57 px with ARDS mean Retrospective review of 57 px with ARDS mean

PaO2/FiO2 ratio of 145 mmHg that received PaO2/FiO2 ratio of 145 mmHg that received open lung biopsy.open lung biopsy.

Major complication rate=7% (death, Major complication rate=7% (death, hemothorax, new dialysis), no deaths from hemothorax, new dialysis), no deaths from procedure.procedure.

Overall complication rate=39% (most air leaks)Overall complication rate=39% (most air leaks) Results of biopsy resulted in additional tx in Results of biopsy resulted in additional tx in

60% and withdrawl of unnecessary tx in 37%. 60% and withdrawl of unnecessary tx in 37%. Patel, SR, Karmpaliotis, D, Ayas, NT, et al. The role of open-lung biopsy in ARDS. Chest 2004; 125:197Patel, SR, Karmpaliotis, D, Ayas, NT, et al. The role of open-lung biopsy in ARDS. Chest 2004; 125:197. .

CaseCase 20. Your Fellow is also a believer of Meduri 20. Your Fellow is also a believer of Meduri

and asks if we should start steroids? How do and asks if we should start steroids? How do you interpret the literature? what is the best you interpret the literature? what is the best evidence currently?evidence currently?

21. Your fellow then sheepishly brings up 21. Your fellow then sheepishly brings up nitric and pronation. What is the current nitric and pronation. What is the current evidence for these therapeutic maneuvers?evidence for these therapeutic maneuvers?

22. What are the potential harms with 22. What are the potential harms with proning and NO. proning and NO.

23. Is there currently any role for the use 23. Is there currently any role for the use oscillation? What is the current evidence for oscillation? What is the current evidence for oscillation?oscillation?

Corticosteroids Corticosteroids in ARDSin ARDS

Corticosteroids in ARDSCorticosteroids in ARDS

Studied extensively in ARDS.Studied extensively in ARDS. There are clear roles in situations There are clear roles in situations

when ARDS has been precipitated by when ARDS has been precipitated by a steroid-responsive process (AEP).a steroid-responsive process (AEP).

Uncertain how they should be used Uncertain how they should be used in other cases of ARDS. in other cases of ARDS.

Davis, WB, Wilson, HE,Wall, RL. Eosinophilic alveolitis in acute respiratory failure. A clinical marker Davis, WB, Wilson, HE,Wall, RL. Eosinophilic alveolitis in acute respiratory failure. A clinical marker for a non-infectious etiology. Chest 1986; 90:7for a non-infectious etiology. Chest 1986; 90:7


Empirically used for ARDS in 70s and Empirically used for ARDS in 70s and early 80s.early 80s.

Used less after several studies found that Used less after several studies found that they had no benefit and may cause harm.they had no benefit and may cause harm.

In the last several years we have seen In the last several years we have seen many new studies re-looking at steroids in many new studies re-looking at steroids in ARDS.ARDS.

Weigelt, JA, Norcross, JF, Borman, KR, et al. Early steroid therapy for respiratory failure. Arch Surg 1985; 120:536Weigelt, JA, Norcross, JF, Borman, KR, et al. Early steroid therapy for respiratory failure. Arch Surg 1985; 120:536 Luce, JM, Montgomery, AB, Marks, JD, et al. Ineffectiveness of high-dose methylprednisolone in preventing Luce, JM, Montgomery, AB, Marks, JD, et al. Ineffectiveness of high-dose methylprednisolone in preventing

parenchymal lung injury and improving mortality in patients with septic shock. Am Rev Respir Dis 1988; 138:62parenchymal lung injury and improving mortality in patients with septic shock. Am Rev Respir Dis 1988; 138:62

Bernard, GR, Luce, JM, Sprung, CL, et al. High-dose corticosteroids in patients with the adult respiratory distress Bernard, GR, Luce, JM, Sprung, CL, et al. High-dose corticosteroids in patients with the adult respiratory distress syndrome. N Engl J Med 1987; 317:1565syndrome. N Engl J Med 1987; 317:1565


Corticosteroids in ARDSCorticosteroids in ARDS Recent studies have looked more at the use Recent studies have looked more at the use

of steroids in late ARDS.of steroids in late ARDS. Best and largest study to date is the Best and largest study to date is the

ARDSnet groups study. ARDSnet groups study.

Steinberg, KP, Hudson, LD, Goodman, RB, et al. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Steinberg, KP, Hudson, LD, Goodman, RB, et al. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med 2006; 354:1671Engl J Med 2006; 354:1671

Corticosteroids in ARDSCorticosteroids in ARDS Double Blind RCTDouble Blind RCT 180 px with persistent ARDS to receive either 180 px with persistent ARDS to receive either

methylprednisolone or placebo for 21 days.methylprednisolone or placebo for 21 days. Persistent ARDS= ongoing disease 7 to 28 days Persistent ARDS= ongoing disease 7 to 28 days

after onset.after onset. No diff in 60 day mortality (29.2% vs 28.6%) or 180 No diff in 60 day mortality (29.2% vs 28.6%) or 180

day mortality (31.5% vs 31.9%)day mortality (31.5% vs 31.9%)

Corticosteroids in ARDSCorticosteroids in ARDS Px randomized 7-13 days, steroid caused a Px randomized 7-13 days, steroid caused a

nonstatistically significant reduction in 60 day nonstatistically significant reduction in 60 day mortality (27% vs 36%) and 180 day mortality (27% mortality (27% vs 36%) and 180 day mortality (27% vs 39%).vs 39%).

Px randomized more than 14 days after onset; inc 60 Px randomized more than 14 days after onset; inc 60 day mortality (35% vs 8%) and 180 day mortality day mortality (35% vs 8%) and 180 day mortality (44% vs 12%)(44% vs 12%)

Steroids inc ventilator free days, shock free days, Steroids inc ventilator free days, shock free days, oxygenation, lung compliance, and blood pressure oxygenation, lung compliance, and blood pressure but also inc neuromuscular weakness. but also inc neuromuscular weakness.

Px in steroid group had a significant inc in Px in steroid group had a significant inc in reintubation (9% vs 28% p=0.006) as the steroids reintubation (9% vs 28% p=0.006) as the steroids were stopped post extubation….did they not find were stopped post extubation….did they not find mortality benefit because of this?mortality benefit because of this?

Based on this trial corticosteroids cannot be Based on this trial corticosteroids cannot be recommended in early or late ARDS.recommended in early or late ARDS.


Recently Meduri revisited steroid use in Recently Meduri revisited steroid use in Early ARDS. Early ARDS.

Double blind RCT. N= 91 in 2:1 ratio.Double blind RCT. N= 91 in 2:1 ratio. Early ARDS (<72 hrs).Early ARDS (<72 hrs). Compared to previous studies, this study Compared to previous studies, this study

gave steroids in lower doses and for longer gave steroids in lower doses and for longer duration.duration.


Reduced mech Reduced mech vent, length of ICU vent, length of ICU stay, ICU mortality stay, ICU mortality (21% vs 43%)….too (21% vs 43%)….too good to be true?good to be true?

Needs repetition Needs repetition and confirmation and confirmation before can be before can be advised!advised!

NONO

NONO

Conceptually NO is a local vasodilator. Conceptually NO is a local vasodilator. Several well done studies have looked at NO.Several well done studies have looked at NO. One Multicenter RCT assigned 385 px with One Multicenter RCT assigned 385 px with

moderate/severe ARDS to placebo vs NO at 5 moderate/severe ARDS to placebo vs NO at 5 ppm.ppm.

Induced short-term improvement and Induced short-term improvement and oxygenation; however, no improvement in oxygenation; however, no improvement in duration of mech vent, 28 day mortality, or one duration of mech vent, 28 day mortality, or one year survival.year survival.

Taylor, RW, Zimmerman, JL, Dellinger, RP, et al. Low-dose inhaled nitric oxide in patients with acute lung injury. A randomized controlled Taylor, RW, Zimmerman, JL, Dellinger, RP, et al. Low-dose inhaled nitric oxide in patients with acute lung injury. A randomized controlled trial. JAMA 2004; 291:1603trial. JAMA 2004; 291:1603

NONO

Another multicenter double blind RCT Another multicenter double blind RCT N=177N=177

Used increasing concentrations of Used increasing concentrations of inhaled NO or placebo.inhaled NO or placebo.

Improved oxygenation modestly but Improved oxygenation modestly but was not sustained.was not sustained.

No difference in 28 day mortality (not No difference in 28 day mortality (not powered for this).powered for this).

Dellinger, RP, Zimmerman, JL, Taylor, RW, et al. Effects of inhaled nitric oxide in patients with acute Dellinger, RP, Zimmerman, JL, Taylor, RW, et al. Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: Results of a randomized phase II trial. Inhaled Nitric Oxide in ARDS respiratory distress syndrome: Results of a randomized phase II trial. Inhaled Nitric Oxide in ARDS Study Group. Crit Care Med 1998; 26:15Study Group. Crit Care Med 1998; 26:15

NONO

In addition, meta-analysis of 10 RCTs In addition, meta-analysis of 10 RCTs (1237 px)(1237 px)

Comparing inhaled NO vs placebo or Comparing inhaled NO vs placebo or conventional Tx.conventional Tx.

NO did not improve mortality, duration NO did not improve mortality, duration of MV, or ventilator free days. of MV, or ventilator free days.

It did increase P/F ratio on first day of It did increase P/F ratio on first day of tx, but there was no effect on mean tx, but there was no effect on mean pulmonary arterial pressure.pulmonary arterial pressure.

Adhikari, NK, Burns, KE, Friedrich, JO, et al. Effect of nitric oxide on oxygenation and mortality in acute lung Adhikari, NK, Burns, KE, Friedrich, JO, et al. Effect of nitric oxide on oxygenation and mortality in acute lung injury: systematic review and meta-analysis. BMJ 2007; 334:779injury: systematic review and meta-analysis. BMJ 2007; 334:779

NONO Need to keep in mind that there are some potential Need to keep in mind that there are some potential

harms.harms.1)1) May produce toxic radicals (unknown if worse than May produce toxic radicals (unknown if worse than

high FiO2).high FiO2).2)2) Methemoglobin and NO2 may inc when high does of Methemoglobin and NO2 may inc when high does of

NO are given, and these should both be watched.NO are given, and these should both be watched.3)3) Inhaled NO have immunosuppressant properties Inhaled NO have immunosuppressant properties

then could in theory in risk of infection.then could in theory in risk of infection.4)4) NO can cuase DNA strand breaks and base NO can cuase DNA strand breaks and base

alteration.alteration.Eichacker, PQ. Inhaled nitric oxide in adult respiratory distress syndrome: Do we know the risks versus benefits? [editorial]. Crit Care Eichacker, PQ. Inhaled nitric oxide in adult respiratory distress syndrome: Do we know the risks versus benefits? [editorial]. Crit Care

Med 1997; 25:563Med 1997; 25:563Adhikari, NK, Burns, KE, Friedrich, JO, et al. Effect of nitric oxide on oxygenation and mortality in acute lung injury: systematic review Adhikari, NK, Burns, KE, Friedrich, JO, et al. Effect of nitric oxide on oxygenation and mortality in acute lung injury: systematic review

and meta-analysis. BMJ 2007; 334:779and meta-analysis. BMJ 2007; 334:779Greene, JH, Klinger, JR. The efficacy of inhaled nitric oxide in the treatment of acute respiratory distress syndrome. An evidence-based Greene, JH, Klinger, JR. The efficacy of inhaled nitric oxide in the treatment of acute respiratory distress syndrome. An evidence-based

medicine approach. Crit Care Clin 1998; 14:387medicine approach. Crit Care Clin 1998; 14:387Weinberger, B, Laskin, DL, Heck, DE, Laskin, JD. The toxicology of inhaled nitric oxide. Toxicol Sci 2001; 59:5Weinberger, B, Laskin, DL, Heck, DE, Laskin, JD. The toxicology of inhaled nitric oxide. Toxicol Sci 2001; 59:5

NONO

Current recommendation?Current recommendation? What do you think?What do you think? Can be used as a temporizing Can be used as a temporizing

measure in the face of profound measure in the face of profound hypoxia?hypoxia?

Can be used as a bridge while Can be used as a bridge while attempting recruitment? attempting recruitment?

Prone VentilationProne Ventilation

Prone VentilationProne Ventilation Mechanisms of action:Mechanisms of action: More homogeneous Ppl More homogeneous Ppl

gradient in ventrodorsal gradient in ventrodorsal and cephalocaudal planes.and cephalocaudal planes.

Increased FRC and V/Q Increased FRC and V/Q matching. matching.

Improved bronchial Improved bronchial drainage. drainage.

Improved aerosol delivery. Improved aerosol delivery. Abdomen is unsupported.Abdomen is unsupported.Pelosi, P, Brazzi, L, Gattinoni, L. Prone position in acute respiratory distress Pelosi, P, Brazzi, L, Gattinoni, L. Prone position in acute respiratory distress

syndrome. Eur Respir J 2002; 20:1017syndrome. Eur Respir J 2002; 20:1017

Prone VentilationProne Ventilation Efficacy: Two primary outcomes that have Efficacy: Two primary outcomes that have

been studied are oxygenation and mortality.been studied are oxygenation and mortality. Oxygenation:Oxygenation: Originally reported to improve in case series Originally reported to improve in case series

in the 70s.in the 70s. Prospective studies have now shown that Prospective studies have now shown that

prone position will increase oxygenation in prone position will increase oxygenation in 60-80% of Px.60-80% of Px.

Some will maintain improved oxygenation Some will maintain improved oxygenation even after return to supine.even after return to supine.

Piehl, MA, Brown, RS. Use of extreme position changes in acute respiratory failure. Crit Care Med 1976; 4:13Piehl, MA, Brown, RS. Use of extreme position changes in acute respiratory failure. Crit Care Med 1976; 4:13Papazian, L, Gainnier, M, Marin, V, et al. Comparison of prone positioning and high-frequency oscillatory Papazian, L, Gainnier, M, Marin, V, et al. Comparison of prone positioning and high-frequency oscillatory

ventilation in patients with acute respiratory distress syndrome. Crit Care Med 2005; 33:2162ventilation in patients with acute respiratory distress syndrome. Crit Care Med 2005; 33:2162Chatte, G, Sab, JM, Dubois, JM, et al. Prone position in mechanically ventilated patients with severe acute Chatte, G, Sab, JM, Dubois, JM, et al. Prone position in mechanically ventilated patients with severe acute

respiratory failure. Am J Respir Crit Care Med 1997; 155:473respiratory failure. Am J Respir Crit Care Med 1997; 155:473

Fridrich, P, Krafft, P, Hochleuthner, H, Mauritz, W. The effects of long-term prone positioning Fridrich, P, Krafft, P, Hochleuthner, H, Mauritz, W. The effects of long-term prone positioning in patients with trauma-induced adult respiratory distress syndrome. Anesth Analg 1996; in patients with trauma-induced adult respiratory distress syndrome. Anesth Analg 1996; 83:120683:1206

Prone VentilationProne Ventilation Additionally, patients whose oxygenation improves Additionally, patients whose oxygenation improves

during trial of prone positioning tend to improve during trial of prone positioning tend to improve each time prone positioning repeated.each time prone positioning repeated.

Chatte, G, Sab, JM, Dubois, JM, et al. Prone position in mechanically ventilated patients with severe acute respiratory failure. Chatte, G, Sab, JM, Dubois, JM, et al. Prone position in mechanically ventilated patients with severe acute respiratory failure. Am J Respir Crit Care Med 1997; 155:473Am J Respir Crit Care Med 1997; 155:473

Fridrich, P, Krafft, P, Hochleuthner, H, Mauritz, W. The effects of long-term prone positioning in patients Fridrich, P, Krafft, P, Hochleuthner, H, Mauritz, W. The effects of long-term prone positioning in patients with trauma-induced adult respiratory distress syndrome. Anesth Analg 1996; 83:1206with trauma-induced adult respiratory distress syndrome. Anesth Analg 1996; 83:1206

Prone VentilationProne Ventilation Mortality: Published studies have not shown Mortality: Published studies have not shown

a survival advantage!!a survival advantage!! RCT, N=304 with ALI/ARDS randomized to RCT, N=304 with ALI/ARDS randomized to

supine vent or six hours prone daily for 10 supine vent or six hours prone daily for 10 days. Improved PaO2/FiO2 but not 10-day, days. Improved PaO2/FiO2 but not 10-day, ICU, 6 months mortality.ICU, 6 months mortality.

Risk of complications similar.Risk of complications similar. Post-hoc suggest dec 10 day mort in sickest Post-hoc suggest dec 10 day mort in sickest

Px with PaO2/FiO2 < 88 (23.1% vs 47.2%)Px with PaO2/FiO2 < 88 (23.1% vs 47.2%) ?? Relatively short duration of proning, used ?? Relatively short duration of proning, used

low levels of PEEP and Vt of >10cc/kglow levels of PEEP and Vt of >10cc/kgGattinoni, L, Tognoni, G, Pesenti, A, et al. Effect of prone positioning on the survival of patients with acute Gattinoni, L, Tognoni, G, Pesenti, A, et al. Effect of prone positioning on the survival of patients with acute

respiratory failure. N Engl J Med 2001; 345:568respiratory failure. N Engl J Med 2001; 345:568

Prone VentilationProne Ventilation Another RCT, N=791 with ALI randomized to Another RCT, N=791 with ALI randomized to

supine vs prone for 8 hr/day (most got only 4 supine vs prone for 8 hr/day (most got only 4 days worth)days worth)

Inc PaO2/FiO2 for first 28 days (p<0.001), but Inc PaO2/FiO2 for first 28 days (p<0.001), but no change 28 day (32.4% vs 31.5%), 90 day no change 28 day (32.4% vs 31.5%), 90 day mortality (43.4% vs 42.2%) or duration of mortality (43.4% vs 42.2%) or duration of Mech Vent. Mech Vent.

Statistically significant inc in complications.Statistically significant inc in complications.- Selective intubation (p=0.01)Selective intubation (p=0.01)- ETT obstruction (p=0.002)ETT obstruction (p=0.002)- Pressure sores (p=0.005)Pressure sores (p=0.005)

Guerin, C, Gaillard, S, Lemasson, S, et al. Effects of systematic prone positioning in hypoxemic acute respiratory failure: a randomized Guerin, C, Gaillard, S, Lemasson, S, et al. Effects of systematic prone positioning in hypoxemic acute respiratory failure: a randomized controlled trial. JAMA 2004; 292:2379controlled trial. JAMA 2004; 292:2379

Prone VentilationProne Ventilation More recent well designed trial by Mancebo.More recent well designed trial by Mancebo. Multicenter RCT, N=136 with ARDS. Multicenter RCT, N=136 with ARDS.

Randomized to supine vs “high dose” prone Randomized to supine vs “high dose” prone vent. Both groups had standardized ventilation vent. Both groups had standardized ventilation and weaning strategy.and weaning strategy.

Px proned were that way for average of 17 hrs Px proned were that way for average of 17 hrs a day for mean of 10 days.a day for mean of 10 days.

Improved mortality (43% vs 58% p=0.12)Improved mortality (43% vs 58% p=0.12) Multivariate analysis found that supine position Multivariate analysis found that supine position

was independent predictor of mortality!was independent predictor of mortality!Mancebo, J, Fernandez, R, Blanch, L, et al. A multicenter trial of prolonged prone ventilation in severe acute respiratory distress syndrome. Am J Respir Mancebo, J, Fernandez, R, Blanch, L, et al. A multicenter trial of prolonged prone ventilation in severe acute respiratory distress syndrome. Am J Respir

Crit Care Med 2006; 173:1233Crit Care Med 2006; 173:1233

Prone VentilationProne Ventilation Predicting Benefit based on physiology:Predicting Benefit based on physiology: Px with early diffuse lung injury with edematous Px with early diffuse lung injury with edematous

lungs and dependent collapse respond best to lungs and dependent collapse respond best to prone position.prone position.

Px with anterior predominance of infiltrates or Px with anterior predominance of infiltrates or injury with marked consolidation or fibrosis do not!injury with marked consolidation or fibrosis do not!

Therefore, Px with an extrapulmonary cause of Therefore, Px with an extrapulmonary cause of ARDS and diffuse disease are more likely to ARDS and diffuse disease are more likely to benefit!benefit!

Additionally, Px with inc IAP and poor chest wall Additionally, Px with inc IAP and poor chest wall compliance may benefit.compliance may benefit.

Lim, CM, Kim, EK, Lee, JS, et al. Comparison of the response to the prone position between pulmonary and extrapulmonary acute respiratory distress syndrome. Lim, CM, Kim, EK, Lee, JS, et al. Comparison of the response to the prone position between pulmonary and extrapulmonary acute respiratory distress syndrome. Intensive Care Med 2001; 27:477Intensive Care Med 2001; 27:477

Mure, M, Glenny, RW, Domino, KB, Hlastala, MP. Pulmonary gas exchange improves in the prone position with abdominal Mure, M, Glenny, RW, Domino, KB, Hlastala, MP. Pulmonary gas exchange improves in the prone position with abdominal distension. Am J Respir Crit Care Med 1998; 157:1785distension. Am J Respir Crit Care Med 1998; 157:1785


Contraindications:Contraindications: Spinal instabilitySpinal instability Hemodynamic and cardiac rhythm Hemodynamic and cardiac rhythm

disturbancesdisturbances Multiple trauma Multiple trauma PregnancyPregnancy Raised intracranial pressureRaised intracranial pressure Abdominal surgeryAbdominal surgeryCurley, MA. Prone positioning of patients with acute respiratory distress syndrome: a systematic review. Am J Curley, MA. Prone positioning of patients with acute respiratory distress syndrome: a systematic review. Am J

Crit Care 1999; 8:397Crit Care 1999; 8:397


Complications:Complications: Nerve compressionNerve compression Crush injury Crush injury Venous stasisVenous stasis Airway securityAirway security Pressure soresPressure sores Dislodging vascular catheters Dislodging vascular catheters Retinal damageRetinal damage

Prone VentilationProne Ventilation Conclusions:Conclusions: Improve oxygenation but not mortality.Improve oxygenation but not mortality. May benefit the sickest ARDS Px if used early May benefit the sickest ARDS Px if used early

and for prolonged periods (? Px with diffuse, and for prolonged periods (? Px with diffuse, non-pulmonary ARDS).non-pulmonary ARDS).

Think about in people with high abd Think about in people with high abd pressures and non-compliant chest walls.pressures and non-compliant chest walls.

May attempt if goals of lung-protective vent May attempt if goals of lung-protective vent are not being met, if there is persistent are not being met, if there is persistent acidosis or tissue hypoxia despite standard acidosis or tissue hypoxia despite standard ventilation.ventilation.

Another study showed improved oxygenation Another study showed improved oxygenation with HFOV post proning!!with HFOV post proning!!

High-frequency High-frequency VentilationVentilation


Proposed as alternate form of lung Proposed as alternate form of lung protective ventilation.protective ventilation.

Theoretically could prevent overdistention Theoretically could prevent overdistention and cyclic atelectasis.and cyclic atelectasis.

Combines very high respiratory rates with Combines very high respiratory rates with tidal volumes that are smaller than the tidal volumes that are smaller than the anatomic dead space.anatomic dead space.

Multiple mechanisms of gas transport.Multiple mechanisms of gas transport.

Wunsch, H, Mapstone, J. High-frequency ventilation versus conventional ventilation for treatment of acute lung injury and acute Wunsch, H, Mapstone, J. High-frequency ventilation versus conventional ventilation for treatment of acute lung injury and acute respiratory distress syndrome. Cochrane Database Syst Rev 2004; :CD004085respiratory distress syndrome. Cochrane Database Syst Rev 2004; :CD004085



4 basic types:4 basic types:

1)1) High-frequency positive High-frequency positive pressure ventilation.pressure ventilation.

2)2) High-frequency jet High-frequency jet ventilation (HFJV)ventilation (HFJV)

3)3) High-frequency High-frequency oscillatory ventilation oscillatory ventilation (HFOV)(HFOV)

4)4) High-frequency High-frequency percussive ventilation percussive ventilation (FFPV)(FFPV)

** We only use HFOV and is ** We only use HFOV and is what will be discussed!what will be discussed!


Vt is employed using a oscillatory Vt is employed using a oscillatory pump. pump.

Set the MAP (which is higher than Set the MAP (which is higher than conventional ventillarion) by adjusting conventional ventillarion) by adjusting flow rate and expiratory back pressure.flow rate and expiratory back pressure.

The ventilator then oscillates around The ventilator then oscillates around this MAP and avoids low end-expiratory this MAP and avoids low end-expiratory pressures and high peak pressures. pressures and high peak pressures.


Optimize oxygenation by manipulating Optimize oxygenation by manipulating MAP and FiO2.MAP and FiO2.

Optimize ventilation by adjusting Optimize ventilation by adjusting amplitude (Vt), frequency, or introduction amplitude (Vt), frequency, or introduction of a cuff leak.of a cuff leak.

Primarily studied in children and neonates.Primarily studied in children and neonates. Several non-randomized trials showed Several non-randomized trials showed

improvements in oxygenation but not improvements in oxygenation but not mortality.mortality.

Derdak, S, Mehta, S, Stewart, TE, et al. High-frequency oscillatory ventilation for acute respiratory distress syndrome Derdak, S, Mehta, S, Stewart, TE, et al. High-frequency oscillatory ventilation for acute respiratory distress syndrome in adults: a randomized, controlled trial. Am J Respir Crit Care Med 2002; 166:801in adults: a randomized, controlled trial. Am J Respir Crit Care Med 2002; 166:801


Multicenter RCT, N=148, HFOV vs PCV Multicenter RCT, N=148, HFOV vs PCV (6-10cc/kg)(6-10cc/kg)

MAP was higher in HFOV group compared MAP was higher in HFOV group compared to PCV (expected)to PCV (expected)

HFOV group showed earlier improvements HFOV group showed earlier improvements in PaO2/FiO2 (<16 hours, p=0.0008). This in PaO2/FiO2 (<16 hours, p=0.0008). This did not last longer than 24 hours.did not last longer than 24 hours.

30 day mortality rate was lower in HFOV 30 day mortality rate was lower in HFOV but no stat. sig. (37% vs 52%, p=0.10)but no stat. sig. (37% vs 52%, p=0.10)

Control group had higher tidal volumes Control group had higher tidal volumes than recommended (8 +/- 2 ml/kg)than recommended (8 +/- 2 ml/kg)

Derdak, S, Mehta, S, Stewart, TE, et al. High-frequency oscillatory ventilation for acute respiratory distress syndrome in Derdak, S, Mehta, S, Stewart, TE, et al. High-frequency oscillatory ventilation for acute respiratory distress syndrome in adults: a randomized, controlled trial. Am J Respir Crit Care Med 2002; 166:801adults: a randomized, controlled trial. Am J Respir Crit Care Med 2002; 166:801


Another RCT, N=61 with ARDS, HFOV vs Another RCT, N=61 with ARDS, HFOV vs conventional.conventional.

Improvement in oxygenation but not in Improvement in oxygenation but not in mortality.mortality.

But trial was small and had poor recruitment, But trial was small and had poor recruitment, early termination, and unequal oxygenation early termination, and unequal oxygenation index in groups after randomization.index in groups after randomization.

Both of these trials enrolled Px before the Both of these trials enrolled Px before the benefits of low tidal volume ventilation were benefits of low tidal volume ventilation were know!know!

Bollen, CW, van Well, TJ, Sherry, T, et al. High frequency oscillatory ventilation compared with conventional mechanical ventilation in Bollen, CW, van Well, TJ, Sherry, T, et al. High frequency oscillatory ventilation compared with conventional mechanical ventilation in adult respiratory distress syndrome: a randomized controlled trial (ISRCTN24242669). Crit Care, 2005, 9:430adult respiratory distress syndrome: a randomized controlled trial (ISRCTN24242669). Crit Care, 2005, 9:430


Risks of barotrauma and Risks of barotrauma and hemodynamic compromise with hemodynamic compromise with high frequency are comparable to high frequency are comparable to conventional ventilation.conventional ventilation.

We are currently waiting for the We are currently waiting for the results of the OSCILLATE trial!results of the OSCILLATE trial!

Demory, D, Michelet, P, Arnal, JM, et al. High-frequency oscillatory ventilation following Demory, D, Michelet, P, Arnal, JM, et al. High-frequency oscillatory ventilation following prone positioning prevents a further impairment in oxygenation. Crit Care Med 2007; prone positioning prevents a further impairment in oxygenation. Crit Care Med 2007; 35:10635:106

Gluck, E, Heard, S, Patel, C, et al. Use of ultrahigh frequency ventilation in Gluck, E, Heard, S, Patel, C, et al. Use of ultrahigh frequency ventilation in patients with ARDS: A preliminary report. Chest 1993; 103:1413patients with ARDS: A preliminary report. Chest 1993; 103:1413

Other contraversial Other contraversial treatmentstreatments

ECMO= CAESAR study (?positive) to be ECMO= CAESAR study (?positive) to be presented at SCCM presented at SCCM

Partial liquid ventilation= Negative, not Partial liquid ventilation= Negative, not recommendedrecommended

Current multicenter phase II trial looking Current multicenter phase II trial looking at APC in ALI (expected to finish 2008)at APC in ALI (expected to finish 2008)

GM-CSFGM-CSF Aerosolized B-agonist therapy in Aerosolized B-agonist therapy in

ALI/ARDS.ALI/ARDS. ECCO2R (Novalung)ECCO2R (Novalung)

Other contraversial Other contraversial treatmentstreatments

Also know about:Also know about: IRVIRV APRVAPRV Currently found to have short-term Currently found to have short-term

physiologic benefits but b/c lack of physiologic benefits but b/c lack of RCT not recommended for routine RCT not recommended for routine use at this time.use at this time.

Complications of Complications of ARDSARDS

ComplicationsComplications

Primary complications:Primary complications:

1)1) BarotraumaBarotrauma

2)2) Nosocomial infectionNosocomial infection

3)3) MOFMOF

4)4) DVTDVT

5)5) Untoward effects from sedation Untoward effects from sedation and paralysisand paralysis

BarotraumaBarotrauma When air escapes the alvolar space and When air escapes the alvolar space and

migrates into the extrapulmonary migrates into the extrapulmonary compartments.compartments.

Includes pneumothorax, interstitial Includes pneumothorax, interstitial emphysema, SC emphysema, emphysema, SC emphysema, pneumomediastinum, pneumoperitoneum and pneumomediastinum, pneumoperitoneum and air embolism.air embolism.

In one study specifically looking at In one study specifically looking at barotrauma in 100 ARDS Px:barotrauma in 100 ARDS Px:

13% of ARDS Px.13% of ARDS Px. Directly contributed to death in less than 2%. Directly contributed to death in less than 2%. Schnapp, LM, Chin, DP, Szaflarski, N, et al. Frequency and importance of barotrauma in 100 patients with acute Schnapp, LM, Chin, DP, Szaflarski, N, et al. Frequency and importance of barotrauma in 100 patients with acute

lung injury. Crit Care Med 1995; 23:272lung injury. Crit Care Med 1995; 23:272

BarotraumaBarotrauma

In another study of 84 Px with ARDS In another study of 84 Px with ARDS mortality rates were:mortality rates were:

66% in Px with pneumothorax.66% in Px with pneumothorax. 46% in Px without pneumothorax.46% in Px without pneumothorax. In different study looking at 725 Px In different study looking at 725 Px

with ARDS there was no significant with ARDS there was no significant difference in mortality among Px difference in mortality among Px with and without barotrauma. with and without barotrauma.

Gattinoni, L, Bombino, M, Pelosi, P, et al. Lung structure and function in different stages of severe Gattinoni, L, Bombino, M, Pelosi, P, et al. Lung structure and function in different stages of severe adult respiratory distress syndrome. JAMA 1994; 271:1772adult respiratory distress syndrome. JAMA 1994; 271:1772

Weg, JG, Anzueto, A, Balk, RA, et al. The relation of pneumothorax and other air leaks to mortality in Weg, JG, Anzueto, A, Balk, RA, et al. The relation of pneumothorax and other air leaks to mortality in the acute respiratory distress syndrome. N Engl J Med 1998; 338:341the acute respiratory distress syndrome. N Engl J Med 1998; 338:341

BarotraumaBarotrauma

Currently unclear if results from high airway Currently unclear if results from high airway pressures or is simply a marker of severe lung pressures or is simply a marker of severe lung injury.injury.

Retrospective analysis of ARDSnet trial found Retrospective analysis of ARDSnet trial found that peak, mean, plateau and driving that peak, mean, plateau and driving pressures do not seem to correlate with risk of pressures do not seem to correlate with risk of pneumothorax.pneumothorax.

They did find that higher levels of PEEP They did find that higher levels of PEEP associated with increased risk of barotrauma. associated with increased risk of barotrauma.

Eisner, MD, Thompson, BT, Schoenfeld, D, et al. Airway pressures and early barotrauma in patients with acute lung injury and acute Eisner, MD, Thompson, BT, Schoenfeld, D, et al. Airway pressures and early barotrauma in patients with acute lung injury and acute respiratory distress syndrome. Am J Respir Crit Care Med 2002; 165:978respiratory distress syndrome. Am J Respir Crit Care Med 2002; 165:978

OutcomeOutcome

OutcomeOutcome Survival has improved for Px with ARDS, Survival has improved for Px with ARDS,

with mortality decreasing from 67% in with mortality decreasing from 67% in 1990 to 30% in 2006.1990 to 30% in 2006.

Likely related to improved supportive care Likely related to improved supportive care and ventilatory strategies.and ventilatory strategies.

One study suggests that the improved One study suggests that the improved mortality is limited to Px with ARDS and mortality is limited to Px with ARDS and no sepsis (eg Trauma related ARDS)no sepsis (eg Trauma related ARDS)

Wheeler, AP, Bernard, GR, Thompson, BT, et al. Pulmonary-artery versus central venous Wheeler, AP, Bernard, GR, Thompson, BT, et al. Pulmonary-artery versus central venous catheter to guide treatment of acute lung injury. N Engl J Med 2006; 354:2213 catheter to guide treatment of acute lung injury. N Engl J Med 2006; 354:2213

Wiedemann, HP, Wheeler, AP, Bernard, GR, et al. Comparison of two fluid-management Wiedemann, HP, Wheeler, AP, Bernard, GR, et al. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med 2006; 354:2564 strategies in acute lung injury. N Engl J Med 2006; 354:2564

Stapleton, RD, Wang, BM, Hudson, LD, et al. Causes and timing of death in patients Stapleton, RD, Wang, BM, Hudson, LD, et al. Causes and timing of death in patients with ARDS. Chest 2005; 128:525 with ARDS. Chest 2005; 128:525

OutcomesOutcomes

Survivors may have abnormalities in Survivors may have abnormalities in pulmonary function and exercise pulmonary function and exercise endurance, which can persist for years (no endurance, which can persist for years (no changes with low tidal volume vent).changes with low tidal volume vent).

In addition, impaired neurocognitive In addition, impaired neurocognitive function and quality of life have been function and quality of life have been reported two years after acute illness.reported two years after acute illness.

Neff, TA, Stocker, R, Frey, HR, et al. Long-term assessment of lung function in survivors of severe ARDS. Neff, TA, Stocker, R, Frey, HR, et al. Long-term assessment of lung function in survivors of severe ARDS. Chest 2003; 123:845 Chest 2003; 123:845

Orme, J Jr, Romney, JS, Hopkins, RO, et al. Pulmonary function and health-related quality of life in Orme, J Jr, Romney, JS, Hopkins, RO, et al. Pulmonary function and health-related quality of life in survivors of acute respiratory distress syndrome. Am J Respir Crit Care Med 2003; 167:690 survivors of acute respiratory distress syndrome. Am J Respir Crit Care Med 2003; 167:690

Hopkins, RO, Weaver, LK, Collingridge, D, et al. Two-Year Cognitive, Emotional, and Quality-of-Life Hopkins, RO, Weaver, LK, Collingridge, D, et al. Two-Year Cognitive, Emotional, and Quality-of-Life Outcomes in Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med 2005; 171:340Outcomes in Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med 2005; 171:340

OutcomesOutcomes

Factors that are correlated with Factors that are correlated with abnormal lung fxn one year after abnormal lung fxn one year after recovery:recovery:

1)1) Duration of PPV Duration of PPV

2)2) Lowest static thoracic complianceLowest static thoracic compliance

3)3) Mean PA pressureMean PA pressure

4)4) Requiring FiO2 >0.6 for more than Requiring FiO2 >0.6 for more than 24 hrs.24 hrs.

OutcomesOutcomes

Factors correlating with better Factors correlating with better functional outcome at one year:functional outcome at one year:

1)1) Absence of steroid treatmentAbsence of steroid treatment

2)2) Absence of illness acquired during Absence of illness acquired during ICU stayICU stay

3)3) Rapid resolution of lung injuryRapid resolution of lung injury

Herridge, MS, Cheung, AM, Tansey, CM, et al. One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Herridge, MS, Cheung, AM, Tansey, CM, et al. One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med 2003; 348:683Med 2003; 348:683

Elliott, CG, Rasmusson, BY, Crapo, RO, et al. Prediction of pulmonary function abnormalities after adult Elliott, CG, Rasmusson, BY, Crapo, RO, et al. Prediction of pulmonary function abnormalities after adult respiratory distress syndrome (ARDS). Am Rev Respir Dis 1987; 135:634respiratory distress syndrome (ARDS). Am Rev Respir Dis 1987; 135:634

Ghio, AJ, Elliott, CG, Crapo, RO, et al. Impairment after adult respiratory distress syndrome. An evaluation Ghio, AJ, Elliott, CG, Crapo, RO, et al. Impairment after adult respiratory distress syndrome. An evaluation based on American Thoracic Society recommendations. Am Rev Respir Dis 1989; 139:1158based on American Thoracic Society recommendations. Am Rev Respir Dis 1989; 139:1158

ConclusionsConclusions

ConclusionsConclusions

ARDS common entity in the ICU.ARDS common entity in the ICU. Think about other diagnosis that Think about other diagnosis that

can present like ARDS.can present like ARDS.

1)1) DADDAD

2)2) AIPAIP

3)3) IAEPIAEP

4)4) ICPICP

ConclusionConclusion

Use bronchoscopy/BAL early.Use bronchoscopy/BAL early. Think about lung biopsy if diagnosis Think about lung biopsy if diagnosis

uncertain.uncertain. Low tidal volume, optimize PEEP for Low tidal volume, optimize PEEP for

now.now. NO as a bridge?NO as a bridge? Proning in specific cases.Proning in specific cases. Say no to drugs! (steroids)Say no to drugs! (steroids) Watch for OSCILLATE/ CEASAR Watch for OSCILLATE/ CEASAR

Documents

Acute Respiratory Distress Syndrome David Sweet. CASE GF, is a 57 yo male who presents to SPH with a one week history of feeling unwell. His wife states