ACUTE RESPIRATORY DISTRESS ACUTE RESPIRATORY DISTRESS SYNDROME ( ARDS )SYNDROME ( ARDS )

Oea Khairsyaf

Acute Respiratory Distress Acute Respiratory Distress SyndromeSyndrome

Acute Respiratory Distress Acute Respiratory Distress SyndromeSyndrome

• ““Non-cardiogenic Pulmonary Oedema”Non-cardiogenic Pulmonary Oedema”– Ashbaugh, Bigelow et al, 1967Ashbaugh, Bigelow et al, 1967

• ““Adult Respiratory Distress Syndrome”Adult Respiratory Distress Syndrome”– Petty and Ashbaugh, 1971Petty and Ashbaugh, 1971

• ““Shock Lung”Shock Lung”– Staub, 1974Staub, 1974

• ““Acute Respiratory Distress Syndrome”Acute Respiratory Distress Syndrome”– American-European Consensus Committee, American-European Consensus Committee,

19921992

Defenisi

Consensus Conference Definitions for Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS)Consensus Conference Definitions for Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS)

waktwaktuu

OxsigenasiOxsigenasi

(astrup)(astrup)X-rayX-ray

Tekanan Tekanan arteri arteri

pulmonalepulmonale

ALI ALI KriteriKriteriaa

AkutAkut PaOPaO2 2 / FIO/ FIO22 ≤ ≤ 300 mmHg300 mmHg

(fraksi oksigen (fraksi oksigen 21%)21%)

InfiltratInfiltrat

bilateralbilateral≤ ≤ 18 mmHg18 mmHg

ARDS ARDS KriteriKriteriaa

AkutAkut PaOPaO2 2 / FIO/ FIO22 ≤ ≤ 200 mmHg 200 mmHg (fraksi oksigen (fraksi oksigen 21%)21%)

InfiltratInfiltrat

BilateralBilateral≤ ≤ 18 mmHg18 mmHg

ETIOLOGI ARDSETIOLOGI ARDS

• Asma bronkial • PPOK• Pneumonia• Aspirasi makanan• Pulmonary

contusion• Near-drowning• Inhalational injury• DLL

• Sepsis• Severe trauma

with shock • Drug overdose• Acute pancreatitis• Transfusion of

blood products

SECARA LANGSUNG TIDAK LANGSUNG

Acute Respiratory Distress SyndromeAcute Respiratory Distress Syndrome

Gambaran klinis:Gambaran klinis: Awal “shock” responsif terhadap resusitasi.Awal “shock” responsif terhadap resusitasi. Periode latent : beberapa jam, biasanya Periode latent : beberapa jam, biasanya

beberapa hari (12-48 jam).beberapa hari (12-48 jam). Insidious tachypnoea, pasien jadi gelisah .Insidious tachypnoea, pasien jadi gelisah . Paru Paru tidal volume kecil, napas cepat, tidal volume kecil, napas cepat,

hipoksemia refrakter.hipoksemia refrakter. Mula-mula alkalosis respiratorik Mula-mula alkalosis respiratorik asidosis asidosis

respiratorikrespiratorik Ventilasi mekanis Ventilasi mekanis

PatogenesisPatogenesisPatogenesisPatogenesis

3 fase dari lung injury:3 fase dari lung injury:1.1. Fase exudatif ( edema and Fase exudatif ( edema and

perdarahan )perdarahan )

2.2. Fase inflammatory and repairFase inflammatory and repair

3.3. Fase fibrotic Fase fibrotic

Acute Respiratory Distress SyndromeAcute Respiratory Distress Syndrome

Exudative Phase, 0-5 hari.Exudative Phase, 0-5 hari. Ruang alveoli terisi cairan, protein dan inflammatory Ruang alveoli terisi cairan, protein dan inflammatory

cells.cells. Necrosis sel-sel pneumocyte type 1, fibrin, platelet Necrosis sel-sel pneumocyte type 1, fibrin, platelet

thrombi.thrombi.

Inflammatory Phase, 5-10 hari.Inflammatory Phase, 5-10 hari. Proliferasi fibroblasts dan sel-sel pneumocyte type 2.Proliferasi fibroblasts dan sel-sel pneumocyte type 2. Squamous metaplasia dan pembentukan hyaline Squamous metaplasia dan pembentukan hyaline

membranes.membranes.

Fibroproliferative Phase, 10 hari sampai sembuh Fibroproliferative Phase, 10 hari sampai sembuh atau mati.atau mati. Fibrosis interstital dan intra-alveolar.Fibrosis interstital dan intra-alveolar. Thrombosis dan obliterasi vaskuler.Thrombosis dan obliterasi vaskuler. Collagen paru meningkat.Collagen paru meningkat.

Alveolar / capillaryAlveolar / capillarypermeabilitypermeability

Pulmonary OedemaPulmonary Oedema

ARDS / ALIARDS / ALI

Precipitating EventPrecipitating Event

Inflammatory ResponseInflammatory ResponseNeutrophil activationNeutrophil activation

Neutrophils in BALNeutrophils in BALHistology appearancesHistology appearances

Protein levels in BALProtein levels in BAL

ROSROSReactive Oxygen SpeciesReactive Oxygen Species

Superoxide / HydroxylSuperoxide / Hydroxyl

Lung Water Lung Water

Pathogenesis ARDS / ALIPathogenesis ARDS / ALI

Patogenesis ARDS / ALIPatogenesis ARDS / ALI

REDOX BalanceREDOX Balance

Generation ofGeneration ofOxidantOxidantspeciesspecies

AntioxidantAntioxidant ProtectionProtection

ROSROSHH22OO22

Superoxide (O2Superoxide (O2.-.-))Hydroxyl radical (OHHydroxyl radical (OH--))RNSRNSNitric oxide (NO)Nitric oxide (NO)Peroxynitrite (ONOOPeroxynitrite (ONOO--))

Superoxide dismutaseSuperoxide dismutaseCatalaseCatalaseGlutathioneGlutathioneTransferrinTransferrinCeruloplasminCeruloplasminVit EVit EVit CVit CBeta-caroteneBeta-carotene

NormalNormal

Patogenesis ARDS / ALIPatogenesis ARDS / ALI

Oxidative StressOxidative Stress

ROS formation &ROS formation &Oxidative damageOxidative damage

Depletion ofDepletion ofantioxidantsantioxidants

The Pathogenesis of ARDS / ALIThe Pathogenesis of ARDS / ALIThe Pathogenesis of ARDS / ALIThe Pathogenesis of ARDS / ALI

ROSROSRNSRNS

Molecular DamageMolecular Damageand Dysfunctionand Dysfunction

Alveolar / capillaryAlveolar / capillarypermeabilitypermeability

Pulmonary OedemaPulmonary Oedema

ARDS/ALIARDS/ALI

Ventilatory supportVentilatory supportInhaled NOInhaled NO

signallingsignalling

InflammatoryInflammatorymediatorsmediators

InflammatoryInflammatorymediatorsmediators

Precipitating EventPrecipitating Event

Inflammatory ResponseInflammatory Response(Respiratory Burst)(Respiratory Burst)

Predisposition?Predisposition?

Faktor-faktos seluler dan humoral pada ALI/ARDS

Faktor-faktos seluler dan humoral pada ALI/ARDS

• Neutrophils.Neutrophils.– ROS dan proteases.ROS dan proteases.– Resting, activated, primed and unresponsive.Resting, activated, primed and unresponsive.

• Cytokines (polypeptides).Cytokines (polypeptides).– TNF-TNF-, macrophages, monocytes, neutrophils., macrophages, monocytes, neutrophils.– IL-1IL-1, macrophages, endothelial cells, macrophages, endothelial cells– GM-CSF, monocytes, macrophages, fibroblasts GM-CSF, monocytes, macrophages, fibroblasts

epithelial, endothelial dan smooth muscle cells.epithelial, endothelial dan smooth muscle cells.• Chemokines (chemotactic cytokines).Chemokines (chemotactic cytokines).

– IL-8.IL-8.• Eicosanoids (prostaglandin, leucotrienes, Eicosanoids (prostaglandin, leucotrienes,

thromboxanes), complement, endotoxins, thromboxanes), complement, endotoxins, adhesion molecules, PAF, endothelins, NO.adhesion molecules, PAF, endothelins, NO.

PathogenesisPathogenesis

• Influx cairan edema kaya protein Influx cairan edema kaya protein alveoli alveoli (permeabilitas alveolar-capillary barrier (permeabilitas alveolar-capillary barrier ))

• Kerusakan Kerusakan Type 2 cellsType 2 cells gangguan epithelial gangguan epithelial fluid transport fluid transport gangguan pengeluaran gangguan pengeluaran cairan dan cairan dan produksi surfactant abnormalproduksi surfactant abnormal

• Bila kerusakan hebat Bila kerusakan hebat gangguan epithelial gangguan epithelial repair repair fibrosis fibrosis

• Neutrophils merupakan sel yang dominantNeutrophils merupakan sel yang dominant• Cytokines dan proinflammatory compounds Cytokines dan proinflammatory compounds

mengawali dan memperkuat respons mengawali dan memperkuat respons inflammatoryinflammatory

Ware LB, Matthay MA. Ware LB, Matthay MA. N Engl J MedN Engl J Med 2000;342:1334-1349 2000;342:1334-1349

Ware LB, Matthay MA. Ware LB, Matthay MA. N Engl J MedN Engl J Med 2000;342:1334-1349 2000;342:1334-1349

Exudative phaseExudative phase(A & D)(A & D)

Fibrosing-alveolitis phaseFibrosing-alveolitis phase(B, C & E)(B, C & E)

Hyaline membr Collagen

Ware LB, Matthay MA. Ware LB, Matthay MA. N Engl J MedN Engl J Med 2000;342:1334-1349 2000;342:1334-1349

Exudative phaseExudative phase Fibrosing-alveolitis phaseFibrosing-alveolitis phase

ARDSARDS

PENATALAKSANAAN

Obati penyakit dasar

Antibiotika

Kortikosteroid

oksigenasi

Anti oksidan

Keluaran (outcome)Keluaran (outcome)

• Tahun 1967 - 1979Tahun 1967 - 1979– Asbaugh (1967) : survival 42%Asbaugh (1967) : survival 42%– Survival : 18 – 38%Survival : 18 – 38%

• Tahun 1980 - 1989Tahun 1980 - 1989– Survival (< 1985) : 32 – 36%Survival (< 1985) : 32 – 36%– Survival (> 1985) : 41 - 52% (European Collaborative Survival (> 1985) : 41 - 52% (European Collaborative

Study 41%)Study 41%)

• Tahun 1990 – 2000Tahun 1990 – 2000– Survival : 41 – 60%Survival : 41 – 60%– NIH ARDS study : mortality 40% vs 30% (penurunan NIH ARDS study : mortality 40% vs 30% (penurunan

25%, antara VT 12 mL/kg vs 6 mL/kg)25%, antara VT 12 mL/kg vs 6 mL/kg)

Outcome Jangka Panjang pada Survivors

(1-1,5 tahun pasca ARDS)

Outcome Jangka Panjang pada Survivors

(1-1,5 tahun pasca ARDS)

Sequelae pulmonerSequelae pulmoner

Majoritas, fungsi paru kembali hampir normalMajoritas, fungsi paru kembali hampir normal

Gangguan residual:Gangguan residual:• restrictive ventilatory defect (biasanya ringan),restrictive ventilatory defect (biasanya ringan),• Hipertensi pulmoner (ringan),Hipertensi pulmoner (ringan),• airflow limitation (airflow limitation ( bronchial hyperactivity) bronchial hyperactivity)

Gangguan pada exercise testing lebih Gangguan pada exercise testing lebih bermakna (setara pasien COPD berat)bermakna (setara pasien COPD berat)

Derajat gangguan ~ umur, riwayat merokok, Derajat gangguan ~ umur, riwayat merokok, ventlasi mekanis berkepanjanganventlasi mekanis berkepanjangan

SurvivalSurvival• 10 tahun terakhir, mortalitas turun 10 tahun terakhir, mortalitas turun 20% 20%• Mortalitas:Mortalitas:

– Umur : 75% (≥ 60 th) vs 37% (< 60 th)Umur : 75% (≥ 60 th) vs 37% (< 60 th)– Faktor resiko : 64% (sepsis) vs 42% Faktor resiko : 64% (sepsis) vs 42%

(trauma)(trauma)– Penyulit : 86% (sepsis) vs 38% (tanpa Penyulit : 86% (sepsis) vs 38% (tanpa

sepsis)sepsis)

– Response thd PEEP : PaOResponse thd PEEP : PaO22/FiO/FiO2 2 > 150 > 150 mmHg mortalitas 23% mmHg mortalitas 23%