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

Consensus Conference Definitions for Acute Lung Injury (ALI)

and Acute Respiratory Distress Syndrome (ARDS)
wakt
u

Oxsigenasi
(astrup)

X-ray

Tekanan
arteri
pulmonale

ALI
Kriteri
a

Akut

PaO2 / FIO2
300 mmHg
(fraksi oksigen
21%)

Infiltrat
bilateral

18 mmHg

ARDS
Kriteri
a

Akut

PaO2 / FIO2
200 mmHg
(fraksi oksigen
21%)

Infiltrat
Bilateral

18 mmHg

ETIOLOGI ARDS
SECARA LANGSUNG

Asma bronkial
PPOK
Pneumonia
Aspirasi makanan
Pulmonary
contusion
Near-drowning
Inhalational injury
DLL

TIDAK
LANGSUNG

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:
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

ROS
Reactive Oxygen Species
Superoxide / Hydroxyl

Inflammatory Response
Neutrophil activation

Neutrophils in BAL
Histology appearances

Alveolar / capillary
permeability

Protein levels in BAL

Pulmonary Oedema

ARDS / ALI

Lung Water

Patogenesis ARDS / ALI

REDOX Balance
Generation of
Oxidant
species
ROS
H2O2
Superoxide (O2.-)
Hydroxyl radical (OH-)
RNS
Nitric oxide (NO)
Peroxynitrite (ONOO-)

Antioxidant
Protection

Normal

Superoxide dismutase
Catalase
Glutathione
Transferrin
Ceruloplasmin
Vit E
Vit C
Beta-carotene

Patogenesis ARDS / ALI

Oxidative Stress
Depletion of
antioxidants

ROS formation &

Oxidative damage

The Pathogenesis of ARDS / ALI

Predisposition?
Inflammatory
mediators

signalling

Precipitating Event
Inflammatory Response
(Respiratory Burst)

ROS
RNS
Molecular Damage
and Dysfunction

Inflammatory
mediators

Alveolar / capillary
permeability
Pulmonary Oedema

ARDS/ALI

Ventilatory support
Inhaled NO

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;342:1334-13

Hyaline membr

Exudative phase
(A & D)

Collagen

Fibrosing-alveolitis phase
(B, C & E)

Ware LB, Matthay MA. N Engl J Med 2000;342:1334-1

Exudative phase

Fibrosing-alveolitis phase

Ware LB, Matthay MA. N Engl J Med 2000;342:1334-13

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%