CURRICULUM VITAE

Nama : Prof. Dr. H. Iswan A.Nusi, Sp.PD-KGEH, FACG.

Tgl lahir : Gorontalo 28 Pebruari 1950
Alamat : Jl. Semolowaru Selatan XII No 12. Telp. 031-5941500
Surabaya-60119
Isteri : Hj. Zohra Deu
Anak : 1. AKBP .Rachmad I. Nusi,SIK. Mh.
2. Mayor Inf. Mohamed I. Nusi, SH.
3. Dr.Nurlaella I. Nusi, SpOG.

Pendidikan : - FK. Unair 1978.

- Spesialis Peny Dalam, 1989
- Gastroentero-Hepatologi , Rotterdam 1993
- Gastroenterologi – Endoscopy, Hongkong 1996.
- Brevet Konsultan GEH / KGEH, 1997
Jabatan / : Guru Besar I Penyakit Dalam FK Unair, Surabaya
Pekerjaan : - Kepala Puskesmas Dulalowo, Gorontalo, 1979-1984
- Kepala Dinas Pembinaan Kes Kota Gorontalo, 1980-1984
- Kepala SubDep. Divisi Gastroentero-Hepatologi FK.Unair. 2009-sekarang

Organisasi : - IDI, PAPDI, PGI-PEGI-PPHI.

- Ketua Umum Gab PPHI-PGI –PEGI Cab Surabaya.
- Ketua Umum Pusat Gastro Hepatologi FK Unair -RSUD Dr Soetomo, Surabaya.
- Wakil Ketua Umum PB. PGI,2013-2016.
- Dewan Pertimbangan Keahlian Konsultan
1 Gastroentero-Hepatologi Nasional.
- Ketua Dewan Guru Besar Gastroenterologi-Hepatologi Indonesia, 2016- 2019.
 THE ROLE OF PROTON PUMP
INHIBITOR IN UPPER GI BLEEDING

PROF.Dr. Iswan A. Nusi, SpPD, K-GEH, FACG.

Gastrointestinal Endoscopyc Center

Division Of Gastroentero-Hepatology
Depart of Internal Medicine ,Faculty of Med Airlangga University-
Dr Soetomo Hospital
Surabaya
Konker PAPDI , IJEN HOTEL Malang : 15 Juli 2017.
OUTLINE :
• Introduction
• Epidemiology
• The Current Etiology Trend
• Diagnosis
• Management
 INTRODUCTION
• Upper gastrointestinal (UGI) bleeding is common, costly,
and potentially lifethreatening.
• It must be managed promptly and appropriately to
prevent adverse outcomes
• More people are admitted to the hospital for UGI
bleeding than for congestive heart failure or deep vein
thrombosis.
• In the United States, the annual rate of hospitalization for
UGI bleeding is estimated to be 165 per 100,000—more
than 300,000 hospitalizations per year, at a cost of $2.5
billion
 Definitions
• Upper GI bleed – arising
from the esophagus,
stomach, or proximal
duodenum
• Mid-intestinal bleed –
arising from distal
duodenum to ileocecal
valve
• Lower intestinal bleed –
arising from colon/rectum
OUTLINE :
• Introduction
• Epidemiology
• The Current Etiology Trend
• Diagnosis
• Management
Causes of Esophago-Gastro-
Duodenal Bleeding
Varices
Mallory Weiss
Esophagitis
Gastric Ulcer NSAID’s/
Aspirin

Neoplasm

Duodenal Acute
Ulcer Gastritis
Arterio-Venous
Malformation
 Common Etiologies

Upper GI Bleed Lower GI Bleed

• PUD – 55 % • Diverticular disease – 30%
• Varices – 14 % • Colitis – 18%
• AVMs – 6% – Ischemic
– Inflammatory
• Mallory Weiss Tears – 5%
– Infectious
• Tumors/Erosions – 4%
• Neoplasms – 10%
• Dieulafoy’s lesions – 1%
• AVMs – 8%
• Others 15%
• Hemorrhoids – 5%
• Others – 20%
Khilani et all, Emerg Med 37(10):27-32, 2005
OUTLINE :
• Introduction
• Epidemiology
• The Current Etiology Trend
• Diagnosis
• Management
 The frequent causes of Upper GI Tract Bleeding in patients who
undergo Endoscopy Examination in Cipto Mangunkusumo Hospital
2001-2005

Causes Total Cases Percentage(%)

Rupture of esophageal
280 33.4
varices
Peptic ulcer 225 26.9

Erosive gastritis 219 26.2

None 38 4.5

Others 45 9

Total 807 100

Konsensus Nasional Penatalaksanaan Perdarahan Saluran Cerna Atas Non Varises di Indonesia. 2012
 Etiology
1993 Malignancy
1% Others
2%
Ulcus
Erosive 1%
Gastritis
19%

Variceal
Bleeding
76%

N.Oesman, . dkk, 1993

 The Current Etiology Trend
2008

Others Variceal
Malignancy 15% Bleeding
3% 28%

Ulcus
11%

Erosive
Gastritis
43%

Titong S, Hernomo OK; Iswan AN.,dkk, 2009

 Causes of UGI Bleeding

100% Others

80% Malignancy

60%
Ulcus

40%
Er. Gastritis
20%
Var.
0% Bleeding
1993 2006 2007 2008

Titong S.; Hernomo OK; Iswan AN.,dkk.,2009

Causes of UGI Bleed.Pusat Gastro-Hepatologi
(2008-2010), Data 3 th.
8,
23, 4.20% 6, 1.10% VE :
1.46%
42, 7.68%
GE
145, 26.51%

TUKAK LAMB

TUKAK D
323, 59.05%
KEGANASAN

LAIN2

Iswan Nusi, dkk., 2011.

 Risk factors for ulcers and bleeding
Risk factor

H. pylori • 70-90% in non-bleeding duodenal ulcers

• Lower in bleeding ulcers and gastric ulcers

NSAIDs/ASA • Increased risk of ulcers and bleeding with

(dose dependent) doses as low as 75 mg day ASA

Corticosteroid • Little increased risk when used alone

+ NSAIDs • With NSAIDs increased risk:
• Ulcer complications – 2 x
• GI bleeding – 10 x

Oral anti- • Increased risk of bleeding vs. controls:

coagulants • Alone – 3.3
+/- NSAIDs • With NSAIDs – 12.7
OUTLINE :
• Introduction
• Epidemiology
• The Current Etiology Trend
• Diagnosis
• Management
 DIAGNOSIS

• Upper or Lower?
– History Freebees
– Digital Rectal Exam These can usually make the diagnosis

– Hemoglobin
• Still bleeding?
– Consider NG Lavage
• What’s the etiology?
– Diagnostic Testing
 Diagnostic Testing

• EGD – standard for UGIB

• Barium studies – good to look for lesions/mass
OUTLINE :
• Introduction
• Epidemiology
• The Current Etiology Trend
• Diagnosis
• Management
MANAGEMENT – General Principles
• Risk stratify
– Assess blood loss
– Blatchenford score
– Rockall score (after EGD)
• IV access
• Volume replacement
• ACID SUPPRESSION THERAPY
• ENDOSCOPIC DX- TX.
• Surgery
 Management: Assess Blood Loss
Category % loss HR BP Pulse UOP
Pressure

Stage 1 <15 % < 100 Normal Normal > 30

Stage 2 15-30% > 100 Normal Decreased 20-30

From Advanced Trauma Life Support Guidelines

Stage 3 30- > 120 Decreased Decreased 5-15

40%
HR not useful if patients are Tachycardic means they have If they are hypotensive, you
on AV node blockers lost about 1 liter of blood! are in trouble!

Stage 4 > 40% > 140 Decreased Decreased Negligible

Key Points
 Stratification the risk of Upper GI
Bleeding and Mortality
• Rockall Score
• Blatchford Score
• Endoscopy

Konsensus Nasional Penatalaksanaan Perdarahan Saluran Cerna Atas Non Varises di Indonesia. 2012
 Blatchford admission risk markers
Admission risk marker Score component value
Blood urea (mMol/I)
6.5-8.0 2
8.0-10.0 3
10.0-25.0 4
>25 6
Hemoglobin (g/I) for men
120-130 1
100-120 3
<100 6
Hemoglobin (g/I) for women
100-120 1
<100 6
Systolic blood pressure (mm Hg)
100-109 1
90-99 2
<90 3
Other markers
Pulse>100 per min 1
Presentation with melena 1
Presentation with syncope 2
Hepatic disease 2
Cardiac failure 2 >6
 The Rockall risk score scheme
Value Score
0 1 2 3
Age (years) <60 60-79 >80 －
Shock No shock Tachycardia Hypotension －
(systolic BP100, (systolic BP100, (systolic BP<100)
pulse<100) pulse>100)
Comorbidity No major － Cardiac failure, Renal failure,
comorbidity ischemic heart liver failure,
disease, any disseminated
major malignancy
comorbidity
Diagnosis Mallory-Weiss All other Malignancy of －
tear, no lesion diagnoses upper
identified and no gastrointestinal
SRH tract
Major stigmata of None or dark － Blood in upper －
recent spot only gastrointestinal
hemorrhage tract, adherent
clot, visible or
spurting vessel
Maximum additive score prior to diagnosis=7, maximum additive score following diagnosis=11. BP, blood pressure; SRH,
stigmata of recent hemorrhage
 ROCKALL Score

http://www.fmed.uniba.sk/uploads/media/Rockall_Score_01.pdf
Skor 0-5: tak butuh intervensi; Skor > 6: butuh intervensi
 Risk Factor indicating bad
prognosis in peptic ulcer bleeding
• Age > 60 years old
• Bleeding onset in the hospital
• Comorbid
• Shock or orthostatic hypotension
• Fresh blood in the nasogastric tube
• Coagulopathy
• Ulcer in the upper minor curvatura(near left gastric
artery)
• Posteriof duodenal bulb ulcer(near gastroduodenal
artery)
Konsensus Nasional Penatalaksanaan Perdarahan Saluran Cerna Atas Non Varises di Indonesia. 2012
• Endoscopic findings showed arterial of visible vessel
bleeding.
MANAGEMENT: ACCESS AND VOLUME
• IV Access
– Two large bore peripheral IVs is best
• Volume replacement
– Normal saline
– Blood products
– Consider FFP
Management – Suspected Varices
• Initial stabilization
• Splanchnic Vasoconstricters:
Octreotide/Vasopressin.
• - PPI ??
• TIPS
• Minnesota tube/Blakemoore tube
• Antibiotic prophylaxis
• A whole other talk
Forrest I Active bleeding
Ia Active pulsation 90%
Ib Active oozing 30%

Forrest II Bleeding stigmata

IIa Visible vessel 50%
IIb Clot 20%
IIc Black base <5%

Forrest III No bleeding signs

Clear ulcer base <5%
 ENDOSCOPIC RISK STRATIFICATION
Endoscopic Finding Rebleed Mortality
Active bleeding 55% 11%
Visible vessels 43% 11%
Adherent dot 22% 7%
Flat spots 10% 3%
CLEAN UCLER BASE 5% 2%
Laine et al. NEJM 1994; 331:717
Spurting bleeding
Application of a clip in upper
GI bleeding
Algorith Patient with UGI Bleeding
• MANAGEMENT : ACID SUPPRESSION
 Pathophysiology
• Imbalance between aggressive factors and
defensive factors.
• Underlying diseases: shock, cardiovascular
diseases, liver or renal failure.

Konsensus Nasional Penatalaksanaan Perdarahan Saluran Cerna Atas Non Varises di Indonesia. 2012
 Protective Factors of Gastric Mucous

http://www.intechopen.com/books/gastritis-and-gastric-cancer-new-insights-in-gastroprotection-diagnosis-and-
treatments/protective-effects-of-gastric-mucus
 Pharmacokinetic comparison of five PPIs
Pantoprazole shows a significantly higher AUC in comparison to other PPIs
7.0
6.5
6.0 Pantoprazole 40 mg
5.5 Omeprazole 20 mg
Concentration (µmol/l)

5.0
4.5 Esomeprazole 40 mg
4.0
Esomeprazole 20 mg
3.5
3.0 Rabeprazole 20 mg
2.5
2.0
Lansoprazole 30 mg
1.5
1.0
0.5
0.0
0 2 4 6 8 10 12 14 16 18 20 22 24
Hours after dose

Welage LS et al. Gastroenterology 2002; 122 (Suppl 1): A-202

Pharmacology

Pharmacodynamics
Pantoprazole is the only PPI to also bind
deep within the pump at Cys 822

Clinically, Pantoprazole`s strong binding may result in a longer duration of

action, which has the potential for therapeutic advantages in terms of
prolonged symptom relief
 Role of acid in haemostasis

Impairs clot formation

– Impairs platelet aggregation and causes
disaggregation

Accelerates clot lysis

- Predominantly acid-stimulated pepsin

May impair integrity of mucus/bicarbonate barrier

Effect of plasma pH on platelet aggregation

0 pH = 5.9

20 ADP pH = 6.8
Aggregation (%)

40 pH = 7.4

60

80

100
0 1 2 3 4 5
Time (minutes)

Green et al; 1978

 Effect of PPI on gastric pH

Increase intragastric pH
 pH>6.0 for 84-99% of day

No reported tolerance

Continuous infusion (CI) superior to intermittent bolus

administration

Clinical improvements in rebleeding and/or surgery with:

Bolus 80mg + CI 8mg/h
Role of Omeprazole in the treatment of
Upper G I Bleeding
 Binding sites of different PPIs on the proton pump
Cys 822 is the unique additional binding site for Pantoprazole only

Cys 813 Cys 822 Cys 321

Pantoprazole   
Omeprazole   
Esomeprazole   
Lansoprazole   
Rabeprazole   
 = Binding
Sachs G and Shin JM. Drugs Today 2004; 40 (Suppl A): 9–14
 = No binding
 MANAGEMENT : ACID SUPPRESSION
 Applies to UGIB from ulcers

Key Point: PPIs can improve

mortality

Gralnek I.M et al. NEJM 2008

 New Guidelines for Nonvariceal Upper Gastrointestinal Bleeding
An update to the 2003 consensus recommendations
• Early risk stratification using prognostic scales is recommended.
• Endoscopy within 24 hours of presentation is appropriate for most patients.
• Endoscopic therapy using clips or thermal therapy is effective for high-risk lesions.
• Epinephrine injection is a useful adjunct to other endoscopic therapy but is not sufficient
alone.
• Second-look endoscopy is appropriate in some, but not all, high-risk patients.
• Intravenous proton-pump inhibitor (PPI) therapy is indicated in all patients with high-risk
lesions after endoscopic therapy; PPI therapy might downstage the lesion if given before
endoscopy.
• Selected low-risk patients may be discharged immediately after endoscopy, but high-risk
patients should be hospitalized for at least 72 hours.
• Postdischarge use of aspirin or nonsteroidal anti-inflammatory drugs warrants cotherapy with
a PPI.
• Resumption of aspirin therapy in patients who require antithrombotic prophylaxis should not
be delayed because cardiovascular risks outweigh the risk for rebleeding. Use prognostic
scales to assess risk for rebleeding and death.

http://gastroenterology.jwatch.org/cgi/content/full/2010/219/1
Barkun NA et.al. Ann. Intern Med.2010;152: 101-13
 Table 9: Endoscopic Treatment For Non-variceal Upper
Gastrointestinal Bleeding
• Thermal
• Heater probe
• Multipolar electrocoagulation (BICAP,Gold Probe)
• Argon plasma coagulation
• Laser
• Injection
• Adrenaline (1:10000)
• Procoagulants(fibrin glue,human thrombin)
• Sclerosants (ethanolamine, 1% polidoconal)
• Alcohol (98%)
• Mechanical
• Clips
• Band Ligation
• Endoloops
• Staples
• ·utures
• Combination therapy
• Injection plus thermal therapy
• Injection plus mechanical therapy
• Methods rarely used are depicted in italics.

Malaysian Society of Gastroenteroloogy. MANAGEMENT OF NON-VARICEAL UPPER GASTROINTESTINAL BLEEDING. 2003

 Proton Pump Inhibitor for UGI Bleeding
• Initial IV bolus 30 mg followed by continous infussion 6
mg/hr or IV bolus 4-5 x 30 mg until bleeding
stop(3days) then switch to oral PPI double dose/day.

• Type of intravenous PPI: Omeprazole, Lansoprazole,

Pantoprazole, Esomeprazole.

• Type of oral PPI: Omeprazole, Lansoprazole,

Pantoprazole, Rabeprazole, Esomeprazole.
 PPI in active peptic ulcer bleeding

• PPI 4-5x/day iv bolus or continue iv until

bleeding stopped then switch to oral PPI
• PPI increases pH>6, blood clot stabilization
on pH> 6.
 CONCLUTION
• UGI bleeding is a common hospital diagnosis –
Look for it.
• The Current Etiology Trend Of UGI Bleeding in
Surabaya/ Indonesia ? : GE......NSAID.
• Risk factors are the most important part of the
history
• Vital signs can help risk stratify patients
• PPIs can reduce need for surgery, rebleeding,
and death
Thank You