The Management of The Management of Acute Respiratory Acute Respiratory Distress SyndromeDistress Syndrome

署立桃園醫院 胸腔內科署立桃園醫院 胸腔內科林倬睿醫師林倬睿醫師

Outlines Outlines

IntroductionIntroduction

Ventilator strategyVentilator strategy

Adjunctive therapyAdjunctive therapy

Case demonstrationCase demonstration

定義 定義 DefinitionDefinition

急性 急性 Acute onsetAcute onset

缺氧 缺氧 PaO2/FiO2 < 200 mmHgPaO2/FiO2 < 200 mmHg

CXR: bilateral infiltratesCXR: bilateral infiltrates 雙側浸潤雙側浸潤 排除心因性呼吸衰竭 排除心因性呼吸衰竭 PAWP < 18 mmHg, PAWP < 18 mmHg,

no clinical evidence of LA HTNno clinical evidence of LA HTN

致病原因致病原因 Direct injuryDirect injury

PneumoniaPneumonia Gastric aspirationGastric aspiration DrowningDrowning Fat and amniotic Fat and amniotic

fluid embolismfluid embolism Pulmonary contusionPulmonary contusion Alveolar hemorrhageAlveolar hemorrhage Toxic inhalationToxic inhalation Reperfusion Reperfusion

Indirect injuryIndirect injury Severe sepsisSevere sepsis TransfusionsTransfusions ShockShock Salicylate or narcotic Salicylate or narcotic

overdoseoverdose Pancreatitis Pancreatitis

Differential DiagnosisDifferential Diagnosis

Left ventricular failureLeft ventricular failure Intravascular volume overloadIntravascular volume overload Mitral stenosisMitral stenosis Veno-occlusive diseaseVeno-occlusive disease Lymphangitic carcinomaLymphangitic carcinoma Interstitial and airway diseasesInterstitial and airway diseases

Hypersensitivity pneumonitisHypersensitivity pneumonitis Acute eosinophilic pneumoniaAcute eosinophilic pneumonia Bronchiolitis obliterans with organising pneumoniaBronchiolitis obliterans with organising pneumonia

Lancet 2007; 369:1553-65

Prognosis & OutcomePrognosis & Outcome

Predictive of death: advanced age, shock, Predictive of death: advanced age, shock, hepatic failurehepatic failure

Overall 28-day mortality: 20-40%Overall 28-day mortality: 20-40% Lung function: returns to normal over 6-12 Lung function: returns to normal over 6-12

monthsmonths Common complications: neuropsychiatric Common complications: neuropsychiatric

problems, neuromuscular weaknessproblems, neuromuscular weakness

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Pathophysiology Pathophysiology

Exudative phaseExudative phase Cytokines Cytokines inflammation inflammation surfactant dysfunc surfactant dysfunc

tion tion atelectasis atelectasis Elastase Elastase epithelial barrier damage epithelial barrier damage edema edema Procoagulant tendency Procoagulant tendency capillary thrombosis capillary thrombosis

Fibroproliferative phaseFibroproliferative phase Chronic inflammationChronic inflammation Fibrosis Fibrosis neovascularisationneovascularisation

Lancet 2007; 369:1553-65

NEJM 2000;342:1334-1349

NEJM 2000;342:1334-1349

NEJM 2000;342:1334-1349

Treatment Treatment

No specific treatmentNo specific treatment Mainstay of treatment: Mainstay of treatment: supportive caresupportive care

Avoid iatrogenic complicationsAvoid iatrogenic complications Treat the underlying causeTreat the underlying cause Maintain adequate oxygenationMaintain adequate oxygenation

Supportive CareSupportive Care

Prevention of deep vein thrombosis, gastrPrevention of deep vein thrombosis, gastrointestinal bleeding, and pressure ulcersointestinal bleeding, and pressure ulcers

Semi-recumbent positionSemi-recumbent position Enteral nutritionEnteral nutrition Infection controlInfection control Goal-directed sedation practiceGoal-directed sedation practice Glucose control Glucose control

Ventilator StrategyVentilator Strategy

Ventilator-induced Lung Injury Ventilator-induced Lung Injury (VILI)(VILI)

BarotraumaBarotrauma VolutraumaVolutrauma AtelectraumaAtelectrauma Biotrauma Biotrauma

OverOverDistensionDistension

CollapseCollapse

Volutrauma Volutrauma

Increased alveolar waIncreased alveolar wall stress (stretch) by hill stress (stretch) by high tidal volumegh tidal volume

Parenchymal injuryParenchymal injury Gross physical disruptiGross physical disrupti

onon Stretch-responsive inflStretch-responsive infl

ammatory pathwaysammatory pathways

AJRCCM 1998; 157: 294-323

Atelectrauma Atelectrauma

Cyclic closing and reopening of alveoliCyclic closing and reopening of alveoli Alveolar shear stress-related injuryAlveolar shear stress-related injury Heterogeneous nature of lung aeration in Heterogeneous nature of lung aeration in

ALI/ARDSALI/ARDS

PEEPPEEP PEEPPEEPPEEPPEEP

Lu

ng

ed

ema

Lu

ng

ed

ema

The PEEP EffectThe PEEP Effect

NEJM 2006;354:1839-1841

Ventilator-induced Lung Injury Ventilator-induced Lung Injury (VILI)(VILI)

UpperDeflection point

LowerInflection point

ARDS Network, 2000: ARDS Network, 2000: Multicenter, randomized 861 patientsMulticenter, randomized 861 patients

Lung-protective Lung-protective ventilationventilation

Conventional Conventional ventilationventilation

Tidal VolumeTidal Volume (ml/kg) (ml/kg) 6 6 1212

PPplateauplateau <30<30 <50<50

PEEPPEEP ProtocolProtocol ProtocolProtocolActual PEEPActual PEEP 8.18.1 9.19.1Result (p<0.001)Result (p<0.001) 31.0%31.0% 39.8%39.8%

Principle for FiO2 and PEEP AdjustmentPrinciple for FiO2 and PEEP AdjustmentFiO2FiO2 0.30.3 0.40.4 0.50.5 0.60.6 0.70.7 0.80.8 0.90.9 1.01.0

PEEPPEEP 55 5-85-8 8-108-10 1010 10-1410-14 1414 14-1814-18 18-2418-24

NEJM 2000; 342: 1301-1308

Lung-Protective VentilationLung-Protective Ventilation

Result:Result: Lower 22% mortality (31% vs 39.8%)Lower 22% mortality (31% vs 39.8%) Increase ventilator-free daysIncrease ventilator-free days

Lung-Protective VentilationLung-Protective Ventilation

NEJM 2000; 342: 1301-1308

Concerns when using lung-Concerns when using lung-protective strategy…protective strategy…

Heterogeneous distributionHeterogeneous distribution Hypercapnia Hypercapnia Auto-PEEPAuto-PEEP Sedation and paralysisSedation and paralysis Patient-ventilator dyssynchronyPatient-ventilator dyssynchrony Increased intrathoracic pressureIncreased intrathoracic pressure Maintenance of PEEPMaintenance of PEEP

Other Ventilator StrategiesOther Ventilator Strategies

Lung recruitment maneuversLung recruitment maneuvers Prone positioningProne positioning High-frequency oscillatory ventilation High-frequency oscillatory ventilation

(HFOV)(HFOV)

Lung RecruitmentLung Recruitment

To open the collapsed To open the collapsed alveolialveoli

A sustained inflation A sustained inflation of the lungs to higher of the lungs to higher airway pressure and airway pressure and volumes volumes Ex.: PCV, Pi = 45 Ex.: PCV, Pi = 45

cmH2O, PEEP = 5 cmH2O, PEEP = 5 cmH2O, RR = 10 /min, cmH2O, RR = 10 /min, I : E = 1:1, for 2 I : E = 1:1, for 2 minutesminutes

NEJM 2007; 354: 1775-1786

Lung RecruitmentLung Recruitment

NEJM 2007; 354: 1775-1786

Lung RecruitmentLung Recruitment

NEJM 2007; 354: 1775-1786

Potentially recruitable (PEEP 5 Potentially recruitable (PEEP 5 15 cmH2O) 15 cmH2O) Increase in PaO2:FiO2Increase in PaO2:FiO2 Decrease in PaCO2Decrease in PaCO2 Increase in complianceIncrease in compliance

The effect of PEEP correlates with the percenThe effect of PEEP correlates with the percentage of potentially recruitalbe lungtage of potentially recruitalbe lung

The percentage of recruitable lung correlates The percentage of recruitable lung correlates with the overall severity of lung injurywith the overall severity of lung injury

Lung RecruitmentLung Recruitment

Sensitivity : 71%

Specificity : 59%

NEJM 2007; 354: 1775-1786

The percentage of potentially recruitable luThe percentage of potentially recruitable lung:ng: Extremely variable,Extremely variable, Strongly associated with the response to PEEStrongly associated with the response to PEE

PP Not routinely recommendedNot routinely recommended

Lung RecruitmentLung Recruitment

Prone PositionProne Position

Prone PositionProne Position

Mechanisms to Mechanisms to improve oxygenation:improve oxygenation: Increase in end-Increase in end-

expiratory lung volumeexpiratory lung volume Better ventilation-Better ventilation-

perfusion matchingperfusion matching More efficient drainage More efficient drainage

of secretionsof secretions

Prone PositionProne Position

NEJM 2001;345:568-573

Prone PositionProne Position

NEJM 2001;345:568-573

Improve oxygenation in about 2/3 of all Improve oxygenation in about 2/3 of all treated patientstreated patients

No improvement on survival, time on No improvement on survival, time on ventilation, or time in ICUventilation, or time in ICU

Might be useful to treat refractory Might be useful to treat refractory hypoxemia hypoxemia

Optimum timing or duration ?Optimum timing or duration ? Routine use is not recommendedRoutine use is not recommended

Prone PositionProne Position

High-Frequency Oscillatory High-Frequency Oscillatory Ventilation (HFOV) Ventilation (HFOV)

HFOVHFOV

Frequency: 180-600 breaths/min (3-10Hz)

Effect of HFOV on gas exchange in Effect of HFOV on gas exchange in ARDS patientsARDS patients

AJRCCM 2002; 166:801-8

Survival difference of ARDS patients Survival difference of ARDS patients treated with HFOV or CMVtreated with HFOV or CMV

30-day: P=0.057

90-day: P=0.078

AJRCCM 2002; 166:801-8

HFOVHFOV

Complications:Complications: Recognition of a pneumothRecognition of a pneumoth

oraxorax Desiccation of secretionsDesiccation of secretions Sedation and paralysisSedation and paralysis Lack of expiratory filterLack of expiratory filter

Failed to show a mortality Failed to show a mortality benefitbenefit

Combination with other intCombination with other interventions ?erventions ?

Chest 2007; 131:1907-1916

Adjunctive TherapyAdjunctive Therapy

Steroid treatmentSteroid treatment Fluid managementFluid management Extracorporeal membrane oxygenation Extracorporeal membrane oxygenation

(ECMO)(ECMO) Nitric oxideNitric oxide OthersOthers

Steroid therapySteroid therapy

NEJM 2006;354:1671-1684

Increase the number of ventilator-free and Increase the number of ventilator-free and shock-free days during the first 28 dayshock-free days during the first 28 day

Improve oxygenation, compliance and blood Improve oxygenation, compliance and blood pressurepressure

No increase in the rate of infectious No increase in the rate of infectious complicationscomplications

Higher rate of neuromuscular weaknessHigher rate of neuromuscular weakness Routine use of steroid is not supportedRoutine use of steroid is not supported Starting steroid more than 14 days after the Starting steroid more than 14 days after the

onset of ARDS may increase mortalityonset of ARDS may increase mortality

Steroid therapySteroid therapy

NEJM 2006;354:1671-1684

Fluid ManagementFluid Management

NEJM 2006;354:2564-2575

Fluid ManagementFluid Management

NEJM 2006;354:2564-2575

Fluid ManagementFluid Management

NEJM 2006;354:2213-24

Conservative strategy improves lung Conservative strategy improves lung function and shortens the duration of function and shortens the duration of ventilator use and ICU stayventilator use and ICU stay

No significant mortality benefitNo significant mortality benefit The use of pulmonary artery catheter not The use of pulmonary artery catheter not

routinely suggestedroutinely suggested

Fluid ManagementFluid Management

Extracorporeal Membrane Extracorporeal Membrane Oxygenation (ECMO)Oxygenation (ECMO)

No improvement on survival or time on No improvement on survival or time on ventilationventilation

Substantial risk of infection and bleedingSubstantial risk of infection and bleeding Not routinely recommendedNot routinely recommended

Nitric OxideNitric Oxide

Vasodilator Vasodilator Improve oxygenation and pulmonary Improve oxygenation and pulmonary

vascular resistancevascular resistance No improvement on survival No improvement on survival Routine use is not recommendedRoutine use is not recommended

Unproven TreatmentsUnproven Treatments

Ketoconazole Ketoconazole Pentoxyfilline and lisofyllinePentoxyfilline and lisofylline Nutritional modificationNutritional modification AntioxidantsAntioxidants Neutrophil elastase inhibitionNeutrophil elastase inhibition SurfactantSurfactant Liquid ventilation Liquid ventilation

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Conclusions Conclusions The only treatment that shows mortality beThe only treatment that shows mortality be

nefit: nefit: lung-protective ventilation strategylung-protective ventilation strategy Low tidal volume (6ml/Kg), high PEEP, adequLow tidal volume (6ml/Kg), high PEEP, adequ

ate Pplat (<30 cmH2O)ate Pplat (<30 cmH2O) Modalities to improve oxygenation:Modalities to improve oxygenation:

Prone position, steroid, fluid treatment, steroid, Prone position, steroid, fluid treatment, steroid, HFOV, NOHFOV, NO

Combining other treatments:Combining other treatments: Activated protein C, antibiotics, EGDT…etcActivated protein C, antibiotics, EGDT…etc