The Role of Nebulized

Salbutamol with Ipratropium Bromide in

Management Therapy of Acute Asthma

Wiwien Heru Wiyono

Department of Pulmonology & Respiratory Medicine

Faculty of Medicine Universitas Indonesia / Persahabatan Hospital
Jakarta
Chronic Respiratory Disease
• Chronic diseases of the airways and other structures of the lung
• The most common are: asthma & chronic obstructive
pulmonary disease (COPD)
• Prevalence in Indonesia based on RISKESDAS 2013: 4,5%
(asthma) & 3,7% (COPD)
• COPD affects about 65 million people worldwide and estimated
to become the third leading cause of death worldwide in 2030
(WHO).
ASTHMA
• Chronic lung disease that is characterized by inflamed and
narrowed airways.
• Recurring periods of wheezing, chest tightness, shortness of
breath, and coughing. The coughing often occurs at night or
early in the morning.
• Asthma affects people of all ages, but it most often starts
during childhood. In the United States, more than 25 million
people are known to have asthma. About 7 million of these
people are children.
ASTHMA
• Common case
• Potentially serious chronic disease
• CAN BE EFFECTIVELY TREATED achieve good control of the disease
Stepwise approach to asthma treatment (GINA 2017)
SALBUTAMOL
&
IPRATROPIUM
BROMIDE
Salbutamol
• Short-acting β2 adrenoreceptor-selective agonist
• Considered essential bronchodilator drugs in the treatment of bronchial
asthma, both as symptoms-relievers and, in combination with inhaled
corticosteroids, as disease-controllers
• Nowadays, they are considered as first-line medications in the treatment of
airway narrowing, the hallmark feature of bronchial asthma and chronic
obstructive pulmonary disease (COPD)
• Available in various dosage forms: oral, inhalation, IV
Salbutamol
• Mechanism of action: trigger direct relaxation of airway smooth muscle
by binding to β2 adrenoreceptor.
Ipratropium
• Short-acting anticholinergic bronchodilator
• Studies of concomitant use of ipratropium and other agents such as β2-
adrenoceptor agonists, theophylline, or sodium cromoglycate, have usually
shown a greater response in many patients than with single drug therapy,
as might be expected from the different mechanisms of action of these
groups of drugs
• Evidence available from randomized trials and from two meta-analyses
confirms the benefit of the addition of inhaled ipratropium to inhaled
beta2-agonist therapy in the treatment of acute asthma exacerbation in
children and adults
Ipratropium
• Mechanism of action: ipratropium exert their bronchodilating action
because of their antimuscarinic properties. It antagonizes the actions of
acetylcholine at parasympathetic, postganglionic, effector cell
junctions by competing with acetylcholine for M3.
 ®

Salbutamol + Ipratropium
Sympathetic Parasympathetic
Pathway
+ Pathway ®

Beta agonists
Anti cholinergic
Atrovent

Beta 2 Cholinergic
receptors receptors

SUPERIOR BRONCHODILATION
“It therefore appears that in acute severe asthma it is beneficial to use drugs which
act in different ways: salbutamol stimulating beta-adrenoceptors and Ipratropium
bromide blocking parasympathetic receptors”

1. Ward M. J. et al. Br. J. Dis. (1985) 79, 374 - 373.

Inhalation drug delivery
• Pulmonary route of administration has proven to be effective in local and
systemic delivery of miscellaneous drugs and biopharmaceuticals to treat
pulmonary and non-pulmonary diseases
• Successful pulmonary administration requires a harmonic interaction
between the drug formulation, the inhaler device, and the patient
Inhalation drug delivery: advantages
• Smaller doses than those for systemic treatment
• Rapid onset of drug action
• Drug delivery is targeted to the respiratory system for local pulmonary
effect
• Systemic side effects are fewer and less severe than with oral parenteral
therapy
• Rapid absorption due to the huge surface area of the respiratory
endothelium
Inhalation drug delivery: devices
INHALER DEVICES

MDI DPI SMI

Nebulizer
(metered-dose inhaler) (dry powder inhaler) (soft mist inhaler)
Nebulizer
• A device that uses forced air to turn
medication into a fine mist that can easily be
breathed into the lungs
• Often prescribed for children and people who
may not be able to breathe in deeply enough
to use an inhaler.
• For some people —and with some medications
— nebulizers are the most effective way of
delivering inhaled medications.
Nebulizer: advantages
• May be used at any age
• No specific inhalation technique required
• May dispense drugs not available with
pMDIs or DPIs
• Some very severe asthmatics get more relief
with nebulized medicines as compared to the
usual inhaler devices
 Penilaian Eksaserbasi Asma
GINA 2017
PENILAIAN AWAL Apakah salah satu dari hal berikut ini ada?
A: airway B: breathing C: circulation Mengantuk, kebingungan, Silent chest

TIDAK
YA

Triase lebih lanjut dengan status klinis

Konsul ke ICU, mulai SABA dan O2,
berdasarkan pada fitur terburuk dan siapkan pasien untuk intubasi

RINGAN atau SEDANG BERAT

Bicara dalam kalimat Bicara dalam kata
Lebih suka duduk daripada berbarin Duduk membungkuk
g Gelisah
Tidak gelisah Frekuensi pernapasan > 30 x/ me
Frekuensi pernapasan meningkat nit
Otot aksesori tidak digunakan Otot aksesori digunakan
Denyut nadi 100-120 x/menit Denyut nadi > 120 x/menit
O2 saturasi ( udara kamar ) 90-95 % O2 saturasi (udara kamar ) < 90
PEF > 50 % prediksi atau terbaik %
PEF ≤50 % prediksi atau terbaik

Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (Updated 2017).
Tatalaksana Eksaserbasi Asma
GINA 2017
RINGAN atau SEDANG BERAT
Beta 2 agonist kerja singkat
Beta 2 agonist kerja singkat
Ipratropium bromida
Pertimbangkan ipratropium bromida
Atur O2 untuk mempertahankan sat
Atur O2 untuk mempertahankan satu
urasi 93–95% (anak 94-98%)
rasi 93–95% (anak 94-98%)
Kortikosteroid oral atau IV
Kortikosteroid oral
Pertimbangkan magnesium IV
Pertimbangkan ICS dosis tinggi

Jika terus memburuk, obati dengan Konsul ke ICU, mulai SABA dan O2,
kriteria berat dan nilai ulang untuk ke ICU dan siapkan pasien untuk intubasi

NILAI KEMAJUAN KLINIS SECARA BERKALA

UKUR FUNGSI PARU
pada semua pasien 1 jam sesudah pengobatan awal

FEV 1 atau PEF 60-80% FEV1 atau PEF < 60%

(prediksi atau terbaik)
dan ada perbaikan gejala
SEDANG
Pertimbangkan untuk dipulangkan
(prediksi atau terbaik)
Atau kurangnya respon klinis
BERAT
Lanjutkan perawatan seperti di atas d
an lakukan penilaian ulang secara ber
kala

Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (Updated 2017).
O’Driscoll BR Nebulized Salbutamol with & without Ipratropium Brom
ide, Lancet June 24, 1418-1420 (1989)
Summary
1. Asthma is chronic lung disease that is characterized by
inflamed and narrowed airways.
2. Acute asthma or exacerbation is worsening in symptom
s and lung function from the patients usual status
3. Salbutamol with ipratropium bromide are used in acute
asthma attack
4. Combination of salbutamol and ipratropium bromide gi
ve benefit than salbutamol alone