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Peran N Acetyl Cystein

Pada PPOK Eksaserbasi Akut


Dr Donni Irfandi Alfian, Sp.P
PDPI KALTIM

Global Strategy for Diagnosis, Management and Prevention of COPD

Definition of COPD

COPD, a common preventable and treatable


disease, is characterized by persistent airflow
limitation that is usually progressive and
associated with an enhanced chronic
inflammatory response in the airways and the
lung to noxious particles or gases.
Exacerbations and comorbidities contribute to
the overall severity in individual patients.
2013 Global Initiative for Chronic Obstructive Lung Disease

Global Strategy for Diagnosis, Management and Prevention of COPD

Mechanisms Underlying
Airflow Limitation in COPD
Small Airways Disease

Parenchymal Destruction

Airway inflammation
Airway fibrosis, luminal plugs
Increased airway resistance

Loss of alveolar attachments


Decrease of elastic recoil

AIRFLOW LIMITATION
2013 Global Initiative for Chronic Obstructive Lung Disease

Global Strategy for Diagnosis, Management and Prevention of COPD

Burden of COPD

COPD is a leading cause of morbidity and


mortality worldwide.

The burden of COPD is projected to increase


in coming decades due to continued
exposure to COPD risk factors and the aging
of the worlds population.

COPD is associated with significant economic


burden.

2013 Global Initiative for Chronic Obstructive Lung Disease

Global Strategy for Diagnosis, Management and Prevention of COPD

Risk Factors for COPD


Genes
Exposure to particles
Tobacco smoke
Occupational dusts, organic
and inorganic

Indoor air pollution from


heating and cooking with
biomass in poorly ventilated
dwellings
Outdoor air pollution

Lung growth and development


Gender
Age
Respiratory infections
Socioeconomic status
Asthma/Bronchial
hyperreactivity
Chronic Bronchitis

2013 Global Initiative for Chronic Obstructive Lung Disease

Global Strategy for Diagnosis, Management and Prevention of COPD

Risk Factors for COPD

Genes

Infections
Socio-economic
status

Aging Populations
2013 Global Initiative for Chronic Obstructive Lung Disease

PATOGENESIS COPD
Noxious particles and
gases
Host factors
Antioxidants

Lung Inflamation

Oxidative stress

Antiproteinase

Proteinase

COPD pathology

Repair mechanism

PROBLEM UTAMA
RESPIRASI PADA PPOK
1. OXIDATIVE STRESS
Basic problem di tingkat selluler

2. Mukostasis (stagnasi mukus)


Timbul manifestasi klinis

3. Bacterial adherence
Timbul kolonisasi bakteri pada saat eksaserbasi Akut

Vicious Circle COPD

( Chronic Obstructive Pulmonary Disease )


Initiating Factors
(viral infection, smoking, etc)

Impaired
mucociliary
clearance
Damaged to
airways
epithelium

Proggress of
COPD

Altered elastase
anti-elastase
balance

Bacterial Colonisation
(Bacterial Adhesion)

Bacterial Product

LPS, Histamine, Protease

Increased Oxidative
Stress (oxidant)

(consumption of antioxidant)

Increased elastolytic
activity

Inflammatory
Response

(Am. Rev. Resp. Dis 1992,


146:1067-83 modified after Cole
& Wilson)

Problem RESPIRASI pada


Umum-nya
1. Perburukan fungsi faal paru
2. Eksaserbasi akut PPOK (masalah kedaruratan)
Kolonisasi bakteri, virus (purulen, demam >
38oC/Common Cold Symptom)

3. Peningkatan Simptom Klinis Kegawatan Paru


Sesak napas
Sulit ekspektorasi (dahak)
Batuk-batuk

Problem Pasien PPOK


4. Sifat PPOK : Irreversible & Slowly Progressive

SOCIAL DEATH
(Faisal Yunus93, ERS98)
Pasien tidak mampu melakukan aktivitas sosial
Disability of Lung Function
FEV1 <30% Predicted Value < 750 ml.

Pengobatan PPOK
(ERS95, PDPI2010)

Strategi :
Terapi
Alasan
Bronkhodilator Terjadi proses fibrosis,metaplasia sel goblet dan

hipertropi
otot polos yang menyebabkan
obstruksi jalan napas

Antiinflamasi

Antioksidan

Terjadi inflamasi pada sel-sel kelenjar dan otot polos


selama napas
Sel inflamasi merelease oksidan yang memperburuk
PPOK.

Terjadi peningkatan oksidan yang berasal dari


sel inflamasi dan inhalan yang berimplikasi
pada progresivitas PPOK.

Note : Pemberian antibiotik hanya pada saat eksaserbasi akut COPD (AECOPD) (NLHEP98 &
ERS;95)

Global Strategy for Diagnosis, Management and


Prevention of COPD, 2013: Chapters

Definition and Overview

Diagnosis and Assessment

Therapeutic Options

Manage Stable COPD

Manage Exacerbations

Manage Comorbidities

UPDATED 2013

2013 Global Initiative for Chronic Obstructive Lung Disease

Global Strategy for Diagnosis, Management and Prevention of COPD

Manage Exacerbations
An exacerbation of COPD is:
an acute event characterized by a

worsening of the patients respiratory


symptoms that is beyond normal dayto-day variations and leads to a
change in medication.

2013 Global Initiative for Chronic Obstructive Lung Disease

Global Strategy for Diagnosis, Management and Prevention of COPD

Manage Exacerbations: Key Points


The most common causes of COPD exacerbations
are viral upper respiratory tract infections and
infection of the tracheobronchial tree.
Diagnosis relies exclusively on the clinical
presentation of the patient complaining of an acute
change of symptoms that is beyond normal day-today variation.

The goal of treatment is to minimize the impact of


the current exacerbation and to prevent the
development of subsequent exacerbations.
2013 Global Initiative for Chronic Obstructive Lung Disease

Global Strategy for Diagnosis, Management and Prevention of COPD

Manage Exacerbations: Key Points


Short-acting inhaled beta2-agonists with or without
short-acting anticholinergics are usually the
preferred bronchodilators for treatment of an
exacerbation.
Systemic corticosteroids and antibiotics can shorten
recovery time, improve lung function (FEV1) and
arterial hypoxemia (PaO2), and reduce the risk of
early relapse, treatment failure, and length of
hospital stay.
COPD exacerbations can often be prevented.
2013 Global Initiative for Chronic Obstructive Lung Disease

Consequences Of COPD Exacerbations


Negative
impact on
quality of life

Impact on
symptoms
and lung
function

EXACERBATIONS
Accelerated
lung function
decline

Increased
economic
costs
Increased
Mortality

2013 Global Initiative for Chronic Obstructive Lung Disease

Global Strategy for Diagnosis, Management and Prevention of COPD

Manage Exacerbations: Assessments


Arterial blood gas measurements (in hospital): PaO2 < 8.0
kPa with or without PaCO2 > 6.7 kPa when breathing room air
indicates respiratory failure.

Chest radiographs: useful to exclude alternative diagnoses.

ECG: may aid in the diagnosis of coexisting cardiac problems.


Whole blood count: identify polycythemia, anemia or
bleeding.

Purulent sputum during an exacerbation: indication to begin


empirical antibiotic treatment.

Biochemical tests: detect electrolyte disturbances, diabetes, and


poor nutrition.

2013:Global
for Chronic Obstructiveduring
Lung Diseasean exacerbation.
Spirometric tests
notInitiative
recommended

Global Strategy for Diagnosis, Management and Prevention of COPD

Manage Exacerbations: Treatment Options


Oxygen: titrate to improve the patients hypoxemia with a
target saturation of 88-92%.
Bronchodilators: Short-acting inhaled beta2-agonists with or
without short-acting anticholinergics are preferred.
Systemic Corticosteroids: Shorten recovery time, improve
lung function (FEV1) and arterial hypoxemia (PaO2), and
reduce the risk of early relapse, treatment failure, and length
of hospital stay. A dose of 30-40 mg prednisolone per day for
10-14 days is recommended.

2013 Global Initiative for Chronic Obstructive Lung Disease

Global Strategy for Diagnosis, Management and Prevention of COPD

Manage Exacerbations: Treatment Options

Antibiotics should be given to patients with:


Three cardinal symptoms: increased
dyspnea, increased sputum volume, and
increased sputum purulence.
Who require mechanical ventilation.

2013 Global Initiative for Chronic Obstructive Lung Disease

Global Strategy for Diagnosis, Management and Prevention of COPD

Manage Exacerbations: Treatment


Options

Noninvasive ventilation (NIV) for patients


hospitalized for acute exacerbations of
COPD:
Improves respiratory acidosis, decreases
respiratory rate, severity of dyspnea,
complications and length of hospital stay.
Decreases mortality and needs for
intubation.
GOLD Revision 2011

2013 Global Initiative for Chronic Obstructive Lung Disease

Global Strategy for Diagnosis, Management and Prevention of COPD

Manage Exacerbations: Indications for


Hospital Admission

Marked increase in intensity of symptoms


Severe underlying COPD
Onset of new physical signs
Failure of an exacerbation to respond to initial
medical management
Presence of serious comorbidities
Frequent exacerbations
Older age
Insufficient home support
2013 Global Initiative for Chronic Obstructive Lung Disease

PERANAN NAC

DALAM MENGATASI

Problem Respirasi

Dosis / Hari

ANTIOXIDANT

Idiopathic Pulmonary Fibrosis

I.C.U.

Activity
MUCOLYTIC

I.V. INFUS.

FLUIMUCIL
600 mg x 3

4 Amp / hr

COPD with exacerbation

600 mg x 2

COPD

600 mg x 2

Chronic bronchitis

600 mg x 2

Acute bronchitis
Influenza

600 mg
200 mg x 3
100 mg x 3

1800 mg

Activity

ORAL

HIDONAC 600 -

NAC EFFECTIVENESS

Peranan NAC Pada Masalah


Respirasi Sebagai
1. Mukolitik
2. Anti oksidan

3. Anti-adhesi bakteri
4. Anti inflamasi

MUKOLITIK & MUKOSILIARI KLIREN


1. Direct mucolytic activity
2.Activation of mucociliary clearance

S
S

NAC breaks disulfide chain,


rendering the mucousless viscous
and easier to expectorate

NAC improves the physiological


transport of mucous, facilitating
its removal
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2. NAC sebagai antioksidan & precursor


glutathione (master oxidant)

NAC Memperbaiki penetrasi Antibiotik


(Memperbaiki gejala-gejala klinik)
Menghilangkan media pertumbuhan kuman,
sehingga pengobatan lebih tuntas

Membantu penetrasi antibiotika pada pengobatan


Infeksi saluran nafas yang diserta sekret baik mukoid
maupun purulen

5. NAC

sebagai IMMUNOMODULATOR

Cara kerja lain dari NAC


NAC menurunkan daya attraction AM
dam PMN pada paru
NAC antielastase
Alveolar surfactant : meningkatkan
secretory dari pneumocyte tipe 2 yang
menimbulkan
surfactant
pada
permukaan epithel alveolar

1. Mempertahankan Fungsi Faal Paru Pada Tingkat


Optimal
Menghambat Perburukan Tahunan Fungsi Faal Paru
60

N = 36
P = 0.034

54 ml/tahun

ml/tahun

50
40

30 ml/tahun
30
20
10
0

NAC

Placebo

(Lundback, Swedia 1988 - 1993)

NAC-Fluimucil Menghambat Pasien PPOK jatuh ke


SOCIAL DEATH

2. Mengurangi & Mengatasi Eksaserbasi


Akut PPOK
Mengurangi Insident
Mengurangi Penggunaan Antibiotik
Incidence in 6 months
N = 241

20

P = 0.001
15
10

N = 254
5
0

50

N = 259
P = 0.001

40
30

40%

20
10

NAC

Mencegah dan Mengatasi


Eksaserbasi
(Multicenter Study Group)

800

739
N = 28

600

260
400

N = 27

200

19%

Control

P = 0.088

1000

Jumlah Hari

25

% Pasien bebas eksaserbasi


setelah 6 bulan pengobatan

Placebo

NAC

Mengurangi Eksaserbasi

Placebo
(6 bulan)

NAC

Mengurangi Incident

(G.Boman)

Meningkatkan Effektifitas
(Rasmussen, et al.)

(NAC)

Sasaran Pengobatan COPD

3. Mengurangi simptom klinis & Memperbaiki


Kualitas Hidup
(European Multicenter Study Group)

2,5

ADJUSTED MEANS
CORR. COEFF. = 0.36
P < 0.001

2
Tickness Score

2
1,5

1,5

0,5

0,5

0
0

NAC

2
1,5
1
0,5
0

bulan
Placebo

ADJUSTED MEANS
CORR. COEFF. = 0.28
P < 0.001

2,5

ADJUSTED MEANS
CORR. COEFF. = 0.27
P < 0.001

Difficulty Expectoration Score

2,5

bulan
Placebo

NAC

6
bulan

Placebo

NAC

Batuk

Viscositas Sputum

Difficulty Expectoration

(Multicenter Study Group)

(Multicenter Study Group)

(Multicenter Study Group)

Peningkatan Kadar Glutathione pada


Bronchoalveolar Lavage Setelah Pengobatan
dengan NAC 600 mg/hari
P<0.001

n mol/g

275

200

150

n = 27

100

No NAC

+ NAC

+ NAC

(1-3 jam)

(16-20 jam)
(Bridgeman, 1991)

Safety
Aman dalam dosis tinggi

Aman diberikan pada ibu hamil dan


menyusui (Gustaf A. Dekker, Horowitz)
Metabolit Fluimucil (Cystein, NAC,
Glutathione, SO3), semuanya mempunyai
efek terapis
Tidak menimbulkan efek atherosclerosis,
emboli paru

Peran NAC pada Pasien PPOK


Mengurangi frekuensi dan severitas eksaserbasi
Mengurangi kolonisasi bakteri
Memberikan efek yang menguntungkan pada fungsi paru

Memperbaiki kemampuan ekspektorasi


Memperbaiki gejala-gejala klinis

Mengurangi risiko masuk kembali ke rumah sakit oleh


karena eksaserbasi PPOK
Mengurangi biaya terapi
Mengurangi penggunaan antibiotika

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