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

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Treatment time (days)

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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