ACUTE RESPIRATORY DISTRESS

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

Oxsigenasi Tekanan arteri

waktu X-ray
(astrup) pulmonale

ALI Akut PaO2 / FIO2 ≤ Infiltrat ≤ 18 mmHg

Kriteria 300 mmHg bilateral
(fraksi oksigen
21%)

ARDS Akut PaO2 / FIO2 ≤ Infiltrat ≤ 18 mmHg

Kriteria 200 mmHg Bilateral
(fraksi oksigen
21%)
 ETIOLOGI ARDS
SECARA LANGSUNG TIDAK LANGSUNG

• Asma bronkial • Sepsis

• PPOK • Severe trauma with
shock
• Pneumonia • Drug overdose
• Aspirasi makanan • Acute pancreatitis
• Pulmonary contusion • Transfusion of blood
products
• Near-drowning
• Inhalational injury
• DLL
 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:
1. Fase exudatif ( edema and perdarahan )
2. Fase inflammatory and repair
3. 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 Neutrophils in BAL

ROS Neutrophil activation Histology appearances
Reactive Oxygen Species
Superoxide / Hydroxyl
Alveolar / capillary
permeability Protein levels in BAL

Pulmonary Oedema Lung Water

ARDS / ALI
 Patogenesis ARDS / ALI
REDOX Balance

Generation of Antioxidant
Oxidant Protection
species

ROS Superoxide dismutase

H2O2 Catalase
Superoxide (O2.-) Glutathione
Hydroxyl radical (OH-) Transferrin
RNS Ceruloplasmin
Vit E
Nitric oxide (NO) Normal Vit C
Peroxynitrite (ONOO-)
Beta-carotene
 Patogenesis ARDS / ALI
Oxidative Stress
Depletion of
antioxidants

ROS formation &

Oxidative damage
 The Pathogenesis of ARDS / ALI
Precipitating Event
Predisposition?
Inflammatory Response
Inflammatory (Respiratory Burst)
mediators

ROS
signalling RNS

Molecular Damage
and Dysfunction

Inflammatory
Alveolar / capillary
mediators
permeability

Pulmonary Oedema Ventilatory support

Inhaled NO

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
Hyaline membr Collagen

Exudative phase Fibrosing-alveolitis phase

(A & D) (B, C & E)

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

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
– 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%