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Endoscopic Therapy for Bleeding Ulcers: An Evidence-Based Approach Based on Meta-Analyses of Randomized Controlled Trials

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The aim of this study was to determine appropriate endoscopic treatment of patients with bleeding ulcers by synthesizing results of randomized controlled trials. We performed dual independent bibliographic database searches to identify randomized trials of thermal therapy, injection therapy, or clips for bleeding ulcers with active bleeding, visible vessels, or clots, focusing on results from studies without second-look endoscopy and re-treatment. The primary end point was further (persistent plus recurrent) bleeding. Compared with epinephrine, further bleeding was reduced significantly by other monotherapies (relative risk [RR], 0.58 [95% CI, 0.36–0.93]; number-needed-to-treat [NNT], 9 [95% CI, 5–53]), and epinephrine followed by another modality (RR, 0.34 [95% CI, 0.23–0.50]; NNT, 5 [95% CI, 5–7]); epinephrine was not significantly less effective in studies with second-look and re-treatment. Compared with no endoscopic therapy, further bleeding was reduced by thermal contact (heater probe, bipolar electrocoagulation) (RR, 0.44 [95% CI, 0.36–0.54]; NNT, 4 [95% CI, 3–5]) and sclerosant therapy (RR, 0.56 [95% CI, 0.38–0.83]; NNT, 5 [95% CI, 4–13]). Clips were more effective than epinephrine (RR, 0.22 [95% CI, 0.09–0.55]; NNT, 5 [95% CI, 4–9]), but not different than other therapies, although the latter studies were heterogeneous, showing better and worse results for clips. Endoscopic therapy was effective for active bleeding (RR, 0.29 [95% CI, 0.20–0.43]; NNT, 2 [95% CI, 2–2]) and a nonbleeding visible vessel (RR, 0.49; [95% CI, 0.40–0.59]; NNT, 5 [95% CI, 4–6]), but not for a clot. Bolus followed by continuous-infusion proton pump inhibitor after endoscopic therapy significantly improved outcome compared with placebo/no therapy (RR, 0.40 [95% CI, 0.28–0.59]; NNT, 12 [95% CI, 10–18]), but not compared with histamine2-receptor antagonists. Thermal devices, sclerosants, clips, and thrombin/fibrin glue appear to be effective endoscopic hemostatic therapies. Epinephrine should not be used alone. Endoscopic therapy should be performed for ulcers with active bleeding and nonbleeding visible vessels, but efficacy is uncertain for clots. Bolus followed by continuous-infusion intravenous proton pump inhibitor should be used after endoscopic therapy.

Section snippets

Methods

The study type we defined for inclusion was randomized controlled trials that compared one of the included interventions with no therapy or with a second included intervention. Studies with pseudorandomization (eg, day of the week, odd vs even patient number) were not included.

The population defined for inclusion was patients presenting with bleeding from a gastric or duodenal ulcer and found to have active bleeding, a nonbleeding visible vessel, or a clot at endoscopy. Because patients with

Results

The MEDLINE search produced 2044 citations and the Cochrane Central Registry search produced 1432 citations. A review of titles and abstracts led to 92 articles considered to be potentially relevant for full review. A review of the 92 full articles revealed 74 articles (75 studies) for inclusion.8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58,

Discussion

Meta-analyses dating back to the early l990s documented that endoscopic therapy overall was effective for patients with bleeding ulcers.91, 100 However, those analyses were driven by results from modalities that are not generally used at present (laser and monopolar electrocoagulation). Many more studies comparing endoscopic hemostatic therapies with no therapy or with one another have been published in the intervening years.

We sought to broadly address the major clinically relevant questions

Summary of Recommendations

  • Epinephrine injection alone should not be used.

  • Thermal therapy, sclerosant therapy, clips, and thrombin/fibrin glue all appear to be effective endoscopic hemostatic therapies.

  • Epinephrine injection before these therapies may be beneficial, especially for the actively spurting ulcer, but data supporting such a benefit are extremely limited.

  • Endoscopic therapy should be used for ulcers with active bleeding and nonbleeding visible vessels.

  • The role of endoscopic therapy for ulcers with adherent clots

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  • Cited by (0)

    The authors disclose the following: L.L. is a consultant for AstraZeneca, Novartis, Santarus, Eisai, and Merck and received research Support from TAP and GlaxoSmithKline. No support was received for this project.

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