Management of GERD : From

Basic Theory to Clinical Practice

dr. Sahat Salim, SpPD
 Outline

 Pengertian GERD
 Epidemiologi
 Patofisiologi
 Diagnosis
 Tatalaksana
 Peran PPI
 3

GERD
Normal

“ GERD is a condition which develops

when the reflux of stomach contents
causes troublesome symptoms
Backflow of acid and
stomach contents into
the oesophagus
Lower oesophageal sphincter
(closed)

GERD

and/or complications1

The term ‘GERD’ should be used to include all individuals who are exposed to to the risk of
” Lower oesophageal sphincter
(open)

physical complications from gastroesophageal reflux, or who experience clinically significant

impairment of health-related well-being
(quality of life), due to reflux-related symptoms, after adequate reassurance
of the benign nature of their symptoms.2

GERD = gastroesophageal reflux disease.

1. Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R, and the Global Consensus Group. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006;101:1900–1920.
2. Dent J, Brun J, Fendrick AM, et al. An evidence-based appraisal of reflux disease management — the Genval workshop report. Gut. 1999;44(Suppl 2):S1–S16.
 4
Gejala Utama GERD

 Rasa panas seperti terbakar dan lebih sering dikenal

dengan istilah heart burn
 Regurgitasi seperti mulut terasa pahit dan adanya
sesuatu yang berbalik arah dari esophagus dan
dirasakan di rongga mulut.

Vakil N et al. Am J Gastroenterol 2006; 101:1900-1920

 5

GERD prevalence is underestimated1

H e a rtb u rn s u ffe rs (% )

100

80 56%
(95% CI 51.9-
60.1%)
44%
60 (95% CI 55-63%)

40
18%
(95% CI 14.8-21.2%)
20

0
Consulted a physician Consulted a pharmacist Used antacids

Adapted from Louisa E, et al, 2002.

A study conducted on 2000 people living in Belgium, selected randomly after stratification, were interviewed face to face, the primary
question was about presence over the previous 12 months of a burning sensation in the epigastric and/or retrosternal region.

CI = confidence interval; GERD = gastroesophageal reflux disease.

1. Louis E, DeLoozeb D, Deprez P, et al. Heartburn in Belgium: prevalence, impact on daily life, and utilization of medical resources. Eur J Gastroenterol Hepatol. 2002;14(3):279-284.
 6

GERD is a common and significant problem: US

study1

Percent of change in the proportion of patients with GERD between 2006 and 2016 using universal Explorys
dataset (A) and Healthcare system dataset (B).

A 5
* * B *
* * 5
*
* *
* *
Percent change (%)

0
*

Percent change (%)

0

-5
-5

-10
* -10
*
-15
15-19 20-29 30-39 40-49 50-59 60-69 ≥70 years
-15
Age groups 15-19 20-29 30-39 40-49 50-59 60-69 ≥70 years
Age groups

Adapted from Yamasaki T, et al, 2018.

BMI = body mass index; GERD = gastroesophageal reflux disease; PPI = proton pump inhibitor.
*P<0.001.
Explorys was used to evaluate datasets at a “Universal” and Healthcare system in northern Ohio to determine if trends at a local level reflected those at a universal level.
A large nationwide database cohort study using the Explorys dataset was performed, where, the proportion of GERD as well as several variables such as age, sex, race, BMI, and treatment with a PPI were evaluated during an 11-year period from 2006 to
2016. Using Explorys, we examined the universal patient population in the universal dataset and compared it with the patient population of a large Healthcare system in Ohio.
1. Yamasaki T, Hemond C, Eisa M, Ganocy S, Fass R. The changing epidemiology of gastroesophageal reflux disease: are patients getting younger? J Neurogastroenterol Motil. 2018:24(4):559-569.
 Prevalence of GERD in several
Countries – Updated 2018

Countries
North America 18.1-27.8%
Europe 8.8-25.9%
East Asia 2.5-7.8%
Middle East 8.7-33.1%
Australia 11.6%
South America 23%

As risk factors for GERD increasingly affect the general population, concerns
have been raised that more young individuals will develop GERD and its
potential consequences.

Yamasaki, 2018. Neurogastroenterol Motil, Vol. 24 No. 4 October

 8
SURVEY PENDUDUK JAKARTA 2006
(1639 ORANG)

7,8
%

www.surveymonkey.com/s/gerdq 
Syam AF, Abdullah M, Rani AA, et. al. National Concencus of GERD. The Indonesian Society of
Gastroenterology. Acta Med Indonesia. 2013
 Prevalence of GERD is underestimated – many individuals do not consult
a physician

Heartburn sufferers (%)

100
n=568
80

60

40

20

0 Consulted a Consulted a Used

physician pharmacist antacids

Robinson et al. Arch Intern Med. 1998;158(21):2373-6.

Louis et al. Eur J Gastroenterol Hepatol. 2002;14(3):279-84
 1

Syam et al, Makara J. Health Res., 2016, 20(2): 35-40

 Methods

 An online survey using Survey

Monkey®

 From August 2013 to June 2015.

 The diagnosis of GERD and its

impact on daily life were determined
based on the GERD Questionnaire
(GerdQ) score

 All possible factors were analyzed to

determine their association with
GERD.
From 2045 subject who completed the survey 57.5% were classified
having GERD  38.7% have a high impact on daily life.
3
Syam et al, Makara J. Health Res., 2016, 20(2): 35-40
 12

Syam et al, Makara J. Health Res., 2016, 20(2): 35-40

 Sprektum klinis GERD
13

“GERD is a condition which develops when the reflux

of stomach content causes troublesome symptoms
and / or complications”

Esophageal Extra-esophageal
Syndromes Syndromes

Proposed
Syndromes
Symptomatic Established Associations
with Esophageal
Syndromes Associations Pharyngitis
Injury
Typical Reflux Reflux Cough Sinusitis
Reflux Esophagitis Idiopathic
Syndrome Reflux Laryngitis
Reflux Stricture
Reflux Chest Reflux Asthma Pulmonary Fibrosis
Barrett’s Esophagus Recurrent Otitis
Pain Syndrome Reflux Dental Eros.
Adenocarcinoma
Media
Vakil N et al. Am J Gastroenterol 2006
14
 GerdQ
 GerdQ : Combination of 3 validated questionnaire
(RDQ, GIS, GSRS)
No Pertanyaan 0 day 1 day 2-3 4-7
days days
1 Heartburn 0 1 2 3
2 Regurgitation Scoring 0Result 1 2 3
3 Epigastric pain 0-7 3No/ low2probability
1 of GERD
0

8-18 Probable of GERD

4 Nausea 3 2 1 0
5 Sleep disturbance 0 1 2 3
induced by heartburn
6 Used antacid 0 1 2 3

Jones RH et al. Aliment Pharmacol Ther. 2009; 30: 1030–1038

 16

Jones RH et al. Aliment Pharmacol Ther. 2009; 30: 1030–1038

 17

Jones RH et al. Aliment Pharmacol Ther. 2009; 30: 1030–1038

 18
Alarm symptom

 Umur 55 tahun pada saat onset

 Penurunan berat badan
 Perdarahan saluran cerna
 Disfagia
 Odinofagia
 Muntah yang terus menerus
 Anemia defisiensi tanpa sebab
 Teraba benjolan atau limpadenopati
 Keluarga dengan Kanker Lambung
Fock KM, Poh CH. J Gastroenterol 2010; 45: 808-815.
 PPI test

PPI dosis tinggi selama 1-2

minggu sambil melihat
respons yang terjadi.

 Test ini dianggap positif jika terdapat

perbaikan dari 50%-75% gejala yang
terjadi

Syam AF, Abdullah M, Rani AA, et. al. National Concencus of GERD. The Indonesian Society of
Gastroenterology. Acta Med Indonesia. 2013
19
 20
pH monitoring 24 hours-impedance

Fock KM, Poh CH. J Gastroenterol 2010; 45: 808-815.

 Classification Of GERD

21
Hardiyanto, 2016.Journal of Gastroenterology and Hepatology; 31 (Suppl. 3): 7–441
 22
Tatalaksana

Menghilangkan
gejala
Mencegah
komplikasi.
Vakil N, et al. Am J Gastroenterol 2006;101:1900–1920
 23
Modifikasi Gaya Hidup

 Berhenti merokok dan mengonsumsi alcohol

 Menurunkan berat badan
 Diet rendah lemak
 Menghindari makanan yang mengandung coklat dan
keju& makanan dan minuman yang merangsang
pengeluran asam lambung: meminum alkohol, kopi dan
minuman bersoda.

Syam AF, Abdullah M, Rani AA, et. al. National Concencus of GERD. The Indonesian Society of
Gastroenterology. Acta Med Indonesia. 2013
 24
Terapi Medikamentosa

 Menekan produksi asam

 Omeprazole (2 x 20 mg)
lambung sebaik mungkin
 Lansoprazole (2 x 30 mg)
 Pendekatan step down  Pantoprazole (2 x 40 mg)
 Rabeprazole (2 x 20 mg)
 Esomeprazole (2 x 40 mg)

MEMPERTAHANKAN PH >4 ADALAH PENTING

UNTUK PENATALAKSANAAN GERD
Syam AF, Abdullah M, Rani AA, et. al. National Concencus of GERD. The Indonesian Society of
Gastroenterology. Acta Med Indonesia. 2013
 Mekanisme Sekresi Asam
25
Fase Gastrik Fase Sefalik
Makanan di Nervus Vagus
Lambung
Asetilkolin
G-cell

Gastrin H+/K+ ATPase

ECL-cell

Histamin

Hersey, et al. 1995. PHYSIOLOGICAL REVIEWS Vol. 75, No. 1, January 1995
 Mekanisme Sekresi Asam
26
Fase Gastrik Fase Sefalik
Makanan di Nervus Vagus
Lambung
HCl
Asetilkolin
Cl¯

G-cell K+

H+
Gastrin H+/K+ ATPase
ECL-cell
H+

H+

Histamin

Hersey, et al. 1995. PHYSIOLOGICAL REVIEWS Vol. 75, No. 1, January 1995
 Mekanisme Sekresi Asam
27
Fase Gastrik Fase Sefalik
Makanan di Nervus Vagus
Lambung
HCl
Asetilkolin
Cl¯

G-cell K+

H+
Gastrin H+/K+ ATPase
ECL-cell

A
H+

H2 R
H+

Histamin

Hersey, et al. 1995. PHYSIOLOGICAL REVIEWS Vol. 75, No. 1, January 1995
 Mekanisme Sekresi Asam
28
Fase Gastrik Fase Sefalik
Makanan di Nervus Vagus
Lambung HCl
Asetilkolin

)
Cl¯

an
G-cell

I
PP
K+

H+
Gastrin H+/K+ ATPase
ECL-cell
H+

H+

Histamin

Hersey, et al. 1995. PHYSIOLOGICAL REVIEWS Vol. 75, No. 1, January 1995
Konsensus Nasional GERD 2013
Konsensus Nasional GERD 2013
 ACG guidelines 2013
Use of PPIs Recommen- Level of
dation evidence
An 8-week course of PPIs is the therapy of choice for symptom
1. Strong High
relief and healing of erosive esophagitis
PPI therapy should be initiated at once a day dosing, before the first Strong Moderate
2.
meal of the day.
For patients with partial response to once daily therapy, tailored
therapy with adjustment of dose timing and/ or twice daily dosing Strong Low
3.
should be considered in patients with night-time symptoms, variable
schedules, and/ or sleep disturbance
Non-responders to PPI
- should be referred for evaluation
4. In patients with partial response to PPI therapy Conditional Low
- increasing the dose to twice daily therapy or switching to a
different PPI may provide additional symptom relief
Refractory GERD patients with negative testing are unlikely to have
5. Strong Low
GERD and PPI therapy should be discontinued

Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am
J Gastroenterol 2013;108(3):308-328.
 ACG guidelines 2013

Use of PPIs – Maintenance therapy Recommen- Level of

dation evidence

Maintenance PPI therapy should be administered – in

patients who continue to have symptoms after PPI is
1. discontinued Strong Moderate
– in patients with complications including erosive
esophagitis and Barrett’s esophagus
For patients who require long-term PPI therapy, it
2. should be administered in the lowest effective dose, Conditional Low
including on demand or intermittent therapy

Katz PO, et al. Am J Gastroenterol 2013;108:308-328

 Acid Control:

the key to Effective Management of GERD

Berstad A. Scand J Gastroenterol 1970;5:343-8

 The healing of reflux esophagitis is directly related to the duration of intragastric
pH >4
Patients healed after 8 weeks (%)
100

80

60

40

20

0
2 4 6 8 10 12 14 16 18 20 22
Duration intragastric pH >4 (hours)

Adapted from Bell et al. Digestion 1992;51(Suppl 1):59–67

Esomeprazole 40 mg has faster symptom relief in Day 1
for patient with Erosive Esophagitis than other PPIs
 Significantly maintain longer time
intragastric PH > 4 vs Rabeprazole within 24 hour

Chart Title
70.00%
59.60%
60.00%

50.00%
44.60%
40.80%
40.00%
29.60%
30.00%

20.00%

10.00%

0.00%
Day 1 Day 5

Nexium 40 mg Rabeprazole 20 mg

1. Rohss K, Lind T, Wlider-Smith C. Esomeprazole 40 mg provides more effective intragastric acid control than lansoprazole 30 mg, omeprazole 20 mg,pantoprazole 40
mg and rabeprazole 20 mg in patients with gastroesophageal reflux symptoms. Eur J Clin Pharmacol 2004; 60: 531-539
 Newest Technology in PPI
Multiple Unit Pellet System (MUPS)

Acid resistant film

Basic Excipient
Esomeprazole Every individual pellet in the
Esomeprazole MUPS tablet
has an acid resistant enteric
coating, to prevent drug
release and inactivation in the
Advantages of MUPS Formulation: stomach. 
• MUPS has rapid disintegration rate in the
gastrointestinal tract
• MUPS facilitates uniform drug absorption
• MUPS reduces inter-patients variability in drug
absorption and clinical response
• MUPS increases bioavailability
Ozarde YS, Sarvi S, Polshettiwar SA, Kuchekar BS. Multiple-Unit-Pellet System (MUPS): A Novel Approach for Drug Delivery. Drug Invention Today. 2012;4(12): 603-609.
 38

Delivering relief for a wide range of patients

Esomeprazole® MUPS can be taken orally with water

• For adults and adolescents
• Nexium® MUPS tablets of 40 mg and 20 mg

Esomeprazole® MUPS can be dispersed in a glass of non-carbonated water and taken as a drink
• For patients who have difficulty in swallowing

Esomeprazole® MUPS can be administered via a syringe through a gastric tube

• For patients who are unable to swallow e.g hospitalized

MUPS = multiple unit pellet system.

1. Nexium® 20 mg & 40 mg tablets [summary of product characteristics]. ID: AstraZeneca; 2018.
 39
Kesimpulan

 Penyakit GERD saat ini kecenderungannya meningkat dimasyarakat1.

 Manifestasi klinik GERD bisa ekstra esofageal sehingga jarang
terdeteksi lebih awal2
 Tatalaksana utama adalah menghilangkan gejala dan mencegah
komplikasi2.
 Selain terapi medikamentosa yang adekuat perubahan gaya hidup juga
merupakan hal penting untuk kesembuhan pasien dengan penyakit
GERD ini1.
 Pemilihan terapi yang tepat merupakan kunci efektif management
GERD

1. Syam AF, Abdullah M, Rani AA, et. al. National Concencus of GERD. The Indonesian Society of Gastroenterology.
Acta Med Indonesia. 2013
2. Vakil N, et al. Am J Gastroenterol 2006;101:1900–1920
TERIMAKASIH