Download - De rol van de MDL-arts bij een bloedend ulcus Ernst J. Kuipers Afd. MDL Erasmus MC Rotterdam
De rol van de MDL-arts bij een bloedend ulcus
Ernst J. Kuipers
Afd. MDL
Erasmus MC Rotterdam
16-10-2001
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
PUB; the role of the gastroenterologist
Forrest classificationForrest classificationendoscopicendoscopic Forrest class prevalence recurrent bleeding Forrest class prevalence recurrent bleedingappearanceappearance % (range) % (range) % (range) % (range)
active bleedingactive bleeding I 18 (4-26) 55 (17-100)
non-bleedingnon-bleeding visible vesselvisible vessel IIa 17 (4-35) 43 (0-81)
adherent clotadherent clot IIb 17 (0-49) 22 (14-36)
flat spotflat spot IIc 20 (0-42) 10 (0-13)
clean baseclean base III 42 (19-52) 5 (0-10)
Laine et al New Engl J Med 1994;331:717-27
injectiesadrenaline opl. 1:10 0004 kwadranten rondbloedingsplek + ter plaatse bloedingsplek
geensclerosantiaalcohol
X
XX
Injectietherapie ulcera
Lin et al Gastrointest Endosc 2002;55:615-9RCT n =155epineprine 1:10,000 5-10 ml 13-20 mlrecurrent bleeding 31 % 15 % (p<0.03)
Park et al Gastrointest Endosc 2004;60:875-80RCT n = 72epinephrine 10,000 15-25 ml 35- 45 mlrecurrent bleeding 17 % 0 % (p<0.05)
Increasing the injected volume reduces the risk of rebleeding
Does a second procedure improve outcomeafter epinephrine injection ??
Clavet et al Gastroenterology 2004;126:441-50
16 studies 1673 patientsepinephrine injection + thrombin (2)
sclerosant (5) ethanol (3) hemoclip (2) fibrin glue (1) heat probe (1) bipolar coag. (1) NYAG laser (1)
gold probe
co-aptive thermocoagulation
ConclusionConclusionadditional endoscopic treatment after epinephrine injectionreduces
further bleeding (18 % > 11 %) need for surgery (11 % > 8 %) mortality ( 5 % > 3 %)
remarksoptimal additional method remains unknown variable criteria for rebleeding epinephrine volumes policy second look endoscopymore perforations combined therapy (6/558 vs 1/560; n.s.)
16-10-2001
1. Endoscopic diagnosis and treatmentEndoscopic diagnosis and treatment
• Stop ulcer bleedingStop ulcer bleeding
• Reduce rebleeding riskReduce rebleeding risk
2. Risk assessment – rebleeding, mortalityRisk assessment – rebleeding, mortality
3. Drug treatment
4. Determine the disease etiologyDetermine the disease etiology
5. Causal treatment to prevent recurrenceCausal treatment to prevent recurrence
PUB; the role of the gastroenterologist
PPIs: Meta-analyses
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?
1. Leontiadis et al, BMJ 2005;330:568-702. Leontiadis et al, Aliment Pharmacol Ther 2005;21:1055-613. van Rensburg et al, Canadian DDW 2004, Abstract 147
Asian vs non-Asian populations
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
1. Khuroo et al, NEJM 1997;336:1054-82. Lau et al, NEJM 2000;343:310-63. Hasselgren et al, Scand J Gastroenterol 1997;32:328-334. van Rensburg et al, Canadian DDW 2004, Abstract 1475. Jensen et al, Am J Gastroenterol 2004;99:S296, Abstract 9036. Leontiadis et al, Aliment Pharmacol Ther 2005;21:1055-61
Recent Clinical Studies in PUB
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
1. Jensen et al, Am J Gastroenterol 2004;99:S2962. 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 ??2nd look endoscopy ??
Idea2nd assessment and therapy in patients with persistent stigmata of recent bleeding in order to prevent rebleeding
randomized controlled trialsVillanueva 1994 n = 104 epinephrineSaeed 1996 n= 40 heat probeRutgeerts 1997 n = 536 fibrin glueMessmann 1998 n = 105 epinephrine/thrombin-fibrinChiu 2003 n = 194 epinephrine/heat probe
meta-analyses Marmo Romagnuolo
ConclusionConclusion
Second look endoscopy reduces rebleeding riskNo effect on risk of surgery and mortality
remarksrelatively small trialsto demonstrate effect on mortality trial size ~ 14000 !NNT to prevent one rebleed: 16
16-10-2001
1. Endoscopic diagnosis and treatmentEndoscopic diagnosis and treatment
• Stop ulcer bleedingStop ulcer bleeding
• Reduce rebleeding riskReduce rebleeding risk
2. Risk assessment – rebleeding, mortalityRisk assessment – rebleeding, mortality
3. Drug treatmentDrug treatment
4. Determine the disease etiology
5. Causal treatment to prevent recurrence
PUB; the role of the gastroenterologist
16-10-2001
H. pylori infection
NSAID use
Idiopathic ulcer disease
Etiology of ulcer disease
The proportion of idiopathic ulcer disease among patients with PUB and the risk of recurrent bleeding in Hong Kong
Hung et al. Gastroenterology 2005; 129: 1845-50
16-10-2001
Microbes
Drug use
Malignancy
Gastritis syndromes
Hyperacidic syndromes
Ischemia
Specific ulcer types
Systemic inflammation
Other conditions
Idiopathic ulcer disease; etiologic considerations
16-10-2001
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
Idiopathic ulcer disease; diagnostic considerations
Persistence of PPI use by indication in a Dutch primary care population
Based on Erasmus Primary Care Cohort, N = 600.000van Soest et al. Submitted
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0 92 182 272 366 488 648
Treatment time (days)
Pro
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f p
ersi
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sers
GERD Non-reflux dyspepsia H. pylori ass.diseases With NSAIDs With aspirin
16-10-2001
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