Transcript Document

De rol van de MDL-arts bij een bloedend ulcus
Ernst J. Kuipers
Afd. MDL
Erasmus MC Rotterdam
PUB; the role of the gastroenterologist
1. Endoscopic diagnosis and treatment
•
Stop ulcer bleeding
•
Reduce rebleeding risk
2. Risk assessment – rebleeding, mortality
3. Drug treatment
4. Determine the disease etiology
5. Causal treatment to prevent recurrence
Forrest classification
endoscopic
appearance
Forrest class
prevalence
% (range)
recurrent bleeding
% (range)
active bleeding
I
18 (4-26)
55 (17-100)
non-bleeding
visible vessel
IIa
17 (4-35)
43 (0-81)
adherent clot
IIb
17 (0-49)
22 (14-36)
flat spot
IIc
20 (0-42)
10 (0-13)
clean base
III
42 (19-52)
5 (0-10)
Laine et al New Engl J Med 1994;331:717-27
Injectietherapie ulcera
X
X
X
injecties
adrenaline opl. 1:10 000
4 kwadranten rond
bloedingsplek +
ter plaatse bloedingsplek
geen
sclerosantia
alcohol
Increasing the injected volume reduces the risk
of rebleeding
Lin et al Gastrointest Endosc 2002;55:615-9
RCT n =155
epineprine 1:10,000 5-10 ml
13-20 ml
recurrent bleeding
31 %
15 % (p<0.03)
Park et al Gastrointest Endosc 2004;60:875-80
RCT n = 72
epinephrine 10,000 15-25 ml 35- 45 ml
recurrent bleeding
17 %
0 % (p<0.05)
Does a second procedure improve outcome
after epinephrine injection ??
Clavet et al Gastroenterology 2004;126:441-50
16 studies 1673 patients
epinephrine injection + thrombin (2)
sclerosant (5)
ethanol (3)
hemoclip (2)
fibrin glue (1)
heat probe (1)
bipolar coag. (1)
NYAG laser (1)
co-aptive thermocoagulation
gold probe
Conclusion
additional endoscopic treatment after epinephrine injection
reduces
further bleeding (18 % > 11 %)
need for surgery (11 % > 8 %)
mortality ( 5 % > 3 %)
remarks
optimal additional method remains unknown
variable criteria for rebleeding
epinephrine volumes
policy second look endoscopy
more perforations combined therapy (6/558 vs 1/560; n.s.)
PUB; the role of the gastroenterologist
1. Endoscopic diagnosis and treatment
•
Stop ulcer bleeding
•
Reduce rebleeding risk
2. Risk assessment – rebleeding, mortality
3. Drug treatment
4. Determine the disease etiology
5. Causal treatment to prevent recurrence
PPIs: Meta-analyses

1.
2.
3.
Effect on rebleeding for IV PPIs1,2, but…

endoscopic treatment not standardised

differing patient populations (Asian vs non-Asian)

various PPIs and dosing regimens pooled

no reduction of mortality

publication bias3?
Leontiadis et al, BMJ 2005;330:568-70
Leontiadis et al, Aliment Pharmacol Ther 2005;21:1055-61
van Rensburg et al, Canadian DDW 2004, Abstract 147
Asian vs non-Asian populations


1.
2.
3.
4.
5.
6.
Clinical effects of PPIs in PUB studies from

Asia:
positive1, 2

Europe/N America/S Africa:
variable3, 4, 5
Different intragastric pH response to PPI therapy6:

H. pylori prevalence

Parietal cell mass

Drug metabolism
Khuroo et al, NEJM 1997;336:1054-8
Lau et al, NEJM 2000;343:310-6
Hasselgren et al, Scand J Gastroenterol 1997;32:328-33
van Rensburg et al, Canadian DDW 2004, Abstract 147
Jensen et al, Am J Gastroenterol 2004;99:S296, Abstract 903
Leontiadis et al, Aliment Pharmacol Ther 2005;21:1055-61
Recent Clinical Studies in PUB

1.
2.
Two large studies with i.v. pantoprazole

US1 – not completed

Non-US2 – inconclusive

No clarification as to role of IV PPI in PUB

Both randomized, controlled trials, comparing after successful
endoscopic haemostasis:

high-dose i.v. infusion of pantoprazole vs ranitidine

study population: pts at high risk for rebleeding

primary variable: rebleeding during 72 h
Jensen et al, Am J Gastroenterol 2004;99:S296
van Rensburg et al, Canadian DDW 2004, Abstract 147
Non-US high dose pantoprazole iv study
Pantoprazole
Ranitidine
n (ITT)
618
626
Primary variable
11%
14%
p=0.083
- Forrest Ia
11%
35%
p=0.0059
- Gastric ulcers
5.3%
10.6%
p=0.051
van Rensburg et al, Canadian DDW 2004, Abstract 147
2nd look endoscopy ??
Idea
2nd assessment and therapy in patients with persistent
stigmata of recent bleeding in order to prevent rebleeding
randomized controlled trials
Villanueva 1994
n = 104
Saeed 1996
n= 40
Rutgeerts 1997
n = 536
Messmann 1998
n = 105
Chiu 2003
n = 194
meta-analyses
Marmo
Romagnuolo
epinephrine
heat probe
fibrin glue
epinephrine/thrombin-fibrin
epinephrine/heat probe
Conclusion
Second look endoscopy reduces rebleeding risk
No effect on risk of surgery and mortality
remarks
relatively small trials
to demonstrate effect on mortality trial size ~ 14000 !
NNT to prevent one rebleed: 16
PUB; the role of the gastroenterologist
1. Endoscopic diagnosis and treatment
•
Stop ulcer bleeding
•
Reduce rebleeding risk
2. Risk assessment – rebleeding, mortality
3. Drug treatment
4. Determine the disease etiology
5. Causal treatment to prevent recurrence
Etiology of ulcer disease
- H. pylori infection
- NSAID use
- Idiopathic ulcer disease
The proportion of idiopathic ulcer disease among patients with
PUB and the risk of recurrent bleeding in Hong Kong
50
40
30
%
20
10
0
1997
2000
Hp-pos
Idiopathic
Hung et al. Gastroenterology 2005; 129: 1845-50
Recurrent PUB
Idiopathic ulcer disease; etiologic considerations
- Microbes
- Drug use
- Malignancy
- Gastritis syndromes
- Hyperacidic syndromes
- Ischemia
- Specific ulcer types
- Systemic inflammation
- Other conditions
Idiopathic ulcer disease; diagnostic considerations
- Microbes
- histology
- Drug use
- medical history
- Malignancy
- histology
- Gastritis syndromes
- histology + duodenal bx
- Hyperacidic syndromes
- gastrin, secretin test
- Ischemia
- vascular assessment
- Specific ulcer types
- endoscopy
- Systemic inflammation
- histology, colonoscopy
- Other conditions
- medical history
Persistence of PPI use by indication in a Dutch primary care
population
GERD
Non-reflux dyspepsia
H. pylori ass.diseases
With NSAIDs
With aspirin
1.0
0.9
Proportion of persistent users
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
0
92
182
272
366
Treatment time (days)
Based on Erasmus Primary Care Cohort, N = 600.000
van Soest et al. Submitted
488
648
Conclusions
Gastroenterologists have the primary role in PUB:
-
-
Initial diagnosis and treatment
•
Injection therapy
•
Multimodality treatment
PPI treatment
•
efficacy of high-dose continuous PPI remains to be proven
in Caucasian populations
-
2nd look endoscopy not useful, unless perhaps in high-risk
patients
-
Adequate diagnosis and treatment of underlying cause of
ulcer disease mandatory