CONSENSUS SESSION FOR APPROPRIATE MANAGEMENT OF BLEEDINGNONMALIGNANT GASTRODUODENAL ULCERSden_970 19..21

BLEEDING PEPTIC ULCERS: THE CURRENT MANAGEMENT

Philip Wai Yan Chiu

Department of Surgery, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China

Bleeding peptic ulcer remains the commonest cause of emergency hospital admission worldwide and carries a mortality ofup to 10%. Ulcer rebleeding is one of the important risk factors for mortality, and numerous strategies were examined toprevent ulcer rebleeding including the performance of scheduled second endoscopy and adjunctive proton pump inhibitorinfusion. This article reviews the current management of bleeding peptic ulcer, including the prediction of clinical outcomesfor bleeding peptic ulcer; the use of second-look endoscopy and adjunctive proton pump inhibitor infusion for preventionof rebleeding; and potential future development in achieving better primary endoscopic hemostasis with the use ofendoscopic suturing.

Key words: bleeding peptic ulcers, proton pump inhibitor infusion, second-look endoscopy.

INTRODUCTION

Bleeding peptic ulcer remains the main cause of hospitaliza-tion among patients with acute non-variceal upper gas-trointestinal hemorrhage. Acute gastrointestinal hemorrhageresults in 250 000–300 000 hospital admissions in the USAand in the UK per year and the annual admissions for uppergastrointestinal bleeding are between 50 and 150 per 100 000adults.1,2 Endoscopic therapy revolutionized the managementof bleeding peptic ulcer to a non-surgical approach. This ledto a significant improvement in the clinical outcomes forbleeding peptic ulcer.3,4 Despite the advances in endoscopictreatment, bleeding-ulcer-related mortality had consistentlystayed at around 10%.5–7 Several postulations could explainthe lack of improvement in the mortality. Sung et al. con-ducted a systematic review and found that although there is areduction in the worldwide incidence of peptic ulcer disease,the number of complicated ulcer disease cases requiring hos-pitalization remained static.8 This may be related to anincrease in usage of aspirin for cardiovascular diseases andnon-steroidal anti-inflammatory drugs for degenerative dis-eases.9,10 Moreover, patients who sustain complications frompeptic ulcer disease tend to be older with multipleco-morbidities.11 Hence, severe bleeding or episodes ofrebleeding after primary endoscopic hemostasis are less tol-erable for them. Numerous strategies have been advocated toprevent ulcer rebleeding. This article reviews the currentstrategies in managing bleeding peptic ulcers with a focus onpredicting clinical outcomes and prevention of rebleeding.

PREDICTION OF CLINICAL OUTCOMES FORPEPTIC ULCER BLEEDING

From a database review of 3220 patients who presented tothe Prince of Wales Hospital with peptic ulcer bleeding, wefound that patients who were older than 70, with multiplecomorbidities, systolic blood pressure below 100 mmHg,hematemesis on presentation, in-hospital bleeding, ulcerrebleeding and need for surgery were predictors of mortal-ity.12 Peptic ulcer rebleeding necessitates salvage by surgery,which may result in significant morbidities and mortality.13

We compared the outcomes of salvage surgery after failedendoscopic therapy for bleeding peptic ulcers over a periodof 10 years and found that a recent 5-year cohort consisted ofa larger proportion of patients with multiple comorbiditieswho were in-hospital bleeders. Moreover, the rates of com-plication and mortality were also higher in the recentcohort.14 Preventing ulcer rebleeding would be crucial notonly to avoiding a second episode of catastrophic bleeding,but it also reduced the need for salvage surgery, which carriedsignificant risk of complications and mortality. Differentstrategies have been explored to prevent ulcer rebleeding,including the performance of scheduled second endoscopyand the adjunctive use of proton pump inhibitor (PPI) infu-sion after therapeutic endoscopy.

PREVENTION OF PEPTIC ULCERREBLEEDING: SCHEDULED

SECOND ENDOSCOPY

Scheduled second endoscopy aims to identify peptic ulcersinadequately treated at primary endoscopy or ulcers withpersistent stigmata of recent hemorrhage. Controversyabounds on the effectiveness of scheduled second endoscopyin preventing ulcer rebleeding. Although two prospectiverandomized studies showed second endoscopy to have nobenefit, they were criticized for having a small sample size.15,16

Saeed et al. conducted a prospective randomized study

Correspondence: Philip Wai Yan Chiu, Department of Surgery, Princeof Wales Hospital, The Chinese University of Hong Kong, 30-32Ngan Shing Street, Shatin, Hong Kong, China. Email: philipchiu@surgery.cuhk.edu.hk

Conflicts of interest: The authors have no conflicts of interest todeclare.

Received 14 December 2009; accepted 29 January 2010.

Digestive Endoscopy (2010) 22 (Suppl. 1), S19–S21 doi:10.1111/j.1443-1661.2010.00970.x

© 2010 The AuthorJournal compilation © 2010 Japan Gastroenterological Endoscopy Society

investigating selective second-look endoscopy for patientswho were categorized as having a high risk of rebleeding withthe Baylor score.17 Second endoscopy was found to be effec-tive in preventing ulcer rebleeding (0% against 24%). Ourgroup conducted a prospective randomized study consistingof 194 patients with bleeding peptic ulcer and found thatscheduled second endoscopy significantly reduced the risk ofrebleeding from 13.8% to 5%.18 A recent systematic reviewshowed that routine second-look endoscopy with thermalcoagulation therapy reduced peptic ulcer rebleeding.19

However, this effect was not observed with the use of injec-tion therapy alone. In general, second-look endoscopyreduces rebleeding without effect on the mortality and needfor surgery. Selective second-look endoscopy may benefithigh-risk patients.20

PREVENTION OF PEPTIC ULCERREBLEEDING: ADJUNCTIVE PROTON PUMP

INHIBITOR INFUSION

The adjunctive use of PPI maintains a sustainable low acidicenvironment in the stomach. The low acidity stabilizes clotformation on the bleeding vessel underneath the ulcer crater,thus reducing the risk of rebleeding.21 Our group reported alarge prospective randomized trial comparing adjunctiveintravenous omeprazole and a placebo in the prevention ofpeptic ulcer rebleeding after therapeutic endoscopy.22

Among 240 patients who presented with peptic ulcer bleed-ing, the rate of rebleeding was 6.7% in the PPI group com-pared with 22.5% in the placebo group. Leontiadis et al.reported the largest systematic review on the use of PPI afterendoscopic therapy for bleeding peptic ulcer.23 A total of4373 patients were recruited in 24 prospective randomizedcontrolled studies, and PPI was shown to significantly reducerebleeding. The pooled rates of rebleeding were 10.6% forPPI and 17.3% for the control group. The use of PPI alsosignificantly reduced the need for surgery, which was 6.1% inthe PPI group and 9.3% in the control group. The meta-analysis pointed out that only Asian studies have shown areduction in ulcer mortality in the PPI group, and that theeffect of reduction on rebleeding and the need for surgery arequantitatively greater in Asian studies.

PREVENTION OF PEPTIC ULCERREBLEEDING: IMPROVEMENT IN

THE SECURITY OF PRIMARYENDOSCOPIC HEMOSTASIS

Current methods of endoscopic hemostasis include injectionand thermal and mechanical therapy. Meta-analysis confirmsthat combination therapy is superior to single treatment inreducing peptic ulcer rebleeding.24 However, the rate ofrebleeding after combination therapy would be around 10%.A further improvement in the security of primary endoscopichemostasis would be another way to prevent rebleeding. Sur-gical plication to over-sew the bleeding vessel beneath theulcer base can lead to a secure hemostasis irrespective of thestability of clot plug on the bleeding vessel.14 Thus an endo-scopic suture plication device might be able to achieve abetter ulcer hemostasis. The Eagle Claw endoscopic suturingdevice (Olympus,Tokyo, Japan) was examined for hemostasis

in massively bleeding ulcer models in six pigs.25 A median oftwo plications would be necessary to achieve hemostasis forall the surgically constructed ulcer models. The mean timetaken to achieve hemostasis was 6 minutes 56 seconds. Onpost-mortem examination, 10 of the 14 plications remainedintact in the ulcer base.

CONCLUSIONS

Bleeding peptic ulcers remained the commonest cause forhospitalization with significant mortality. Ulcer rebleedingand need for surgery were predictors to mortality. Bothscheduled second endoscopy and adjunctive high-dose PPIinfusion were important strategies for preventing ulcerrebleeding after primary endoscopic hemostasis. The adjunc-tive use of high-dose PPI infusion may alleviate the workloadfor endoscopists and the discomfort of patients undergoingsecond-look endoscopy, and should be the preferred strategyafter primary endoscopic hemostasis.26 An endoscopic sutureplication device may improve primary hemostasis and reduceulcer rebleeding.

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© 2010 The AuthorJournal compilation © 2010 Japan Gastroenterological Endoscopy Society