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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
Lancet 2007; 369:1553-65
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
Lancet 2007; 369:1553-65
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