ACUTE RESPIRATORY DISTRESS SYNDROME ( ARDS ) Oea Khairsyaf

Acute Respiratory Distress Syndrome Defenisi “Non-cardiogenic Pulmonary Oedema” Ashbaugh, Bigelow et al, 1967 “Adult Respiratory Distress Syndrome” Petty and Ashbaugh, 1971 “Shock Lung” Staub, 1974 “Acute Respiratory Distress Syndrome” American-European Consensus Committee, 1992

Tekanan arteri pulmonale Consensus Conference Definitions for Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) waktu Oxsigenasi (astrup) X-ray Tekanan arteri pulmonale ALI Kriteria Akut PaO2 / FIO2 ≤ 300 mmHg (fraksi oksigen 21%) Infiltrat bilateral ≤ 18 mmHg ARDS Kriteria PaO2 / FIO2 ≤ 200 mmHg (fraksi oksigen 21%) Bilateral

ETIOLOGI ARDS Asma bronkial PPOK Pneumonia Aspirasi makanan SECARA LANGSUNG TIDAK LANGSUNG 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

Acute Respiratory Distress Syndrome Gambaran klinis: Awal “shock” responsif terhadap resusitasi. Periode latent : beberapa jam, biasanya beberapa hari (12-48 jam). Insidious tachypnoea, pasien jadi gelisah . Paru  tidal volume kecil, napas cepat,  hipoksemia refrakter. Mula-mula alkalosis respiratorik  asidosis respiratorik Ventilasi mekanis

Patogenesis 3 fase dari lung injury: Fase exudatif ( edema and perdarahan ) Fase inflammatory and repair Fase fibrotic

Acute Respiratory Distress Syndrome Exudative Phase, 0-5 hari. Ruang alveoli terisi cairan, protein dan inflammatory cells. Necrosis sel-sel pneumocyte type 1, fibrin, platelet thrombi. Inflammatory Phase, 5-10 hari. Proliferasi fibroblasts dan sel-sel pneumocyte type 2. Squamous metaplasia dan pembentukan hyaline membranes. Fibroproliferative Phase, 10 hari sampai sembuh atau mati. Fibrosis interstital dan intra-alveolar. Thrombosis dan obliterasi vaskuler. Collagen paru meningkat.

Pathogenesis ARDS / ALI Precipitating Event Inflammatory Response Neutrophil activation ROS Reactive Oxygen Species Superoxide / Hydroxyl Neutrophils in BAL Histology appearances Alveolar / capillary permeability Protein levels in BAL Pulmonary Oedema Lung Water ARDS / ALI

Patogenesis ARDS / ALI REDOX Balance Generation of Antioxidant Oxidant species Antioxidant Protection Superoxide dismutase Catalase Glutathione Transferrin Ceruloplasmin Vit E Vit C Beta-carotene ROS H2O2 Superoxide (O2.-) Hydroxyl radical (OH-) RNS Nitric oxide (NO) Peroxynitrite (ONOO-) Normal

Patogenesis ARDS / ALI Oxidative Stress Depletion of antioxidants ROS formation & Oxidative damage

The Pathogenesis of ARDS / ALI Precipitating Event Predisposition? Inflammatory Response (Respiratory Burst) Inflammatory mediators ROS RNS Ventilatory support Inhaled NO signalling Molecular Damage and Dysfunction Alveolar / capillary permeability Inflammatory mediators Pulmonary Oedema ARDS/ALI

Faktor-faktos seluler dan humoral pada ALI/ARDS Neutrophils. ROS dan proteases. Resting, activated, primed and unresponsive. Cytokines (polypeptides). TNF-, macrophages, monocytes, neutrophils. IL-1, macrophages, endothelial cells GM-CSF, monocytes, macrophages, fibroblasts epithelial, endothelial dan smooth muscle cells. Chemokines (chemotactic cytokines). IL-8. Eicosanoids (prostaglandin, leucotrienes, thromboxanes), complement, endotoxins, adhesion molecules, PAF, endothelins, NO.

Pathogenesis Influx cairan edema kaya protein  alveoli (permeabilitas alveolar-capillary barrier ) Kerusakan Type 2 cells  gangguan epithelial fluid transport  gangguan pengeluaran cairan dan produksi surfactant abnormal Bila kerusakan hebat  gangguan epithelial repair  fibrosis Neutrophils merupakan sel yang dominant Cytokines dan proinflammatory compounds mengawali dan memperkuat respons inflammatory

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

Fibrosing-alveolitis phase Hyaline membr Collagen Exudative phase (A & D) Fibrosing-alveolitis phase (B, C & E) Ware LB, Matthay MA. N Engl J Med 2000;342:1334-1349

Fibrosing-alveolitis phase Exudative phase Fibrosing-alveolitis phase Ware LB, Matthay MA. N Engl J Med 2000;342:1334-1349

ARDS

PENATALAKSANAAN Obati penyakit dasar Antibiotika Kortikosteroid oksigenasi Anti oksidan

Keluaran (outcome) Tahun 1967 - 1979 Tahun 1980 - 1989 Asbaugh (1967) : survival 42% Survival : 18 – 38% Tahun 1980 - 1989 Survival (< 1985) : 32 – 36% Survival (> 1985) : 41 - 52% (European Collaborative Study 41%) Tahun 1990 – 2000 Survival : 41 – 60% NIH ARDS study : mortality 40% vs 30% (penurunan 25%, antara VT 12 mL/kg vs 6 mL/kg)

Outcome Jangka Panjang pada Survivors (1-1,5 tahun pasca ARDS) Sequelae pulmoner Majoritas, fungsi paru kembali hampir normal Gangguan residual: restrictive ventilatory defect (biasanya ringan), Hipertensi pulmoner (ringan), airflow limitation ( bronchial hyperactivity) Gangguan pada exercise testing lebih bermakna (setara pasien COPD berat) Derajat gangguan ~ umur, riwayat merokok, ventlasi mekanis berkepanjangan

Survival 10 tahun terakhir, mortalitas turun  20% Mortalitas: Umur : 75% (≥ 60 th) vs 37% (< 60 th) Faktor resiko : 64% (sepsis) vs 42% (trauma) Penyulit : 86% (sepsis) vs 38% (tanpa sepsis) Response thd PEEP : PaO2/FiO2 > 150 mmHg mortalitas 23%

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