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Risk Factors for Rebleeding in Peptic Ulcer Bleeding: A Second Look at Second-Look Endoscopy

Rebleeding, which occurs in 10–15 % of patients with peptic ulcer bleeding (PUB) [1], is associated with a two- to fivefold mortality increase, depending on the presence of other risk factors [2]. Therefore, identification of the predictors of rebleeding seems meaningful in order to identify high-risk patients needing close observation and rapid treatment in case of the development of rebleeding.

According to previous studies, hemodynamic shock, usually defined as a systolic blood pressure <100 mmHg, often combined with tachycardia >100 beats/min, is the most powerful pre-endoscopic predictor of rebleeding [3, 4]. In a meta-analysis, hemodynamic shock was associated with an odds ratio (OR) of rebleeding of 3.3 [3]. Conversely, studies on the association between anemia and rebleeding have found conflicting results: Some of the existing data indicate that hemoglobin <10 g/L may be associated with an increased risk of rebleeding [3]. Data concerning the risks of transfusion are even more confounded by differing study protocols (e.g., pre- or post-endoscopic transfusion, different categorization of volume) to the point that the rebleeding risk of pre-endoscopic transfusion is unknown. Regarding endoscopic predictors, active bleeding at endoscopy (OR 1.7), ulcer size >2 cm (OR 2.8), posterior duodenal ulcer location (OR 3.8), and high lesser gastric curvature ulcer location (OR 2.9) all predict rebleeding in a meta-analysis [3].

The type of endoscopic treatment applied does also affect the risk of rebleeding. A Cochrane analysis reported that combination of epinephrine injection with a second endoscopic treatment modality reduces the relative risk (RR) of rebleeding or persistent bleeding (RR 0.57) compared to endoscopic treatment with epinephrine alone [5]. Therefore, endoscopic monotherapy with injection of epinephrine should be avoided.

In a meta-analysis based on eight randomized controlled trials (RCTs) published from 1994 to 2006, performance of second-look endoscopy within 16–48 h was associated with a significant reduction in rebleeding rate (OR 0.55) [6]. Generalization of this finding to current practice standards can be questioned because only one of the included studies used endoscopic combination therapy combined with high-dose infusion of proton-pump inhibitors [7]. Furthermore, detailed review of the fully published component studies revealed that a significant reduction in rebleeding was only evident in two studies that included patients with a very high risk of rebleeding (up to 47 % of included patients had hemodynamic shock) [6]. When these two trials were excluded from the meta-analysis, the association between performance of second-look endoscopy and rebleeding became statistically insignificant [6]. In a cost-effectiveness analysis, performance of second-look endoscopy was only cost-effective after therapeutic endoscopy if the risk of rebleeding was greater than 31 % [8].

In this issue of Digestive Diseases and Sciences, Kim et al. [9] published a prospective multicenter study of risk factors for rebleeding among 699 patients with PUB from Forrest classification [10] Ia–IIb ulcers. Using multivariate logistic regression analysis, the authors reported that performance of second-look endoscopy was associated with a lower risk (OR 0.269) of rebleeding. High transfusion volume (above 5 units) and use of nonsteroidal anti-inflammatory drugs (NSAIDs) were both associated with a fourfold increase in risk of rebleeding. The authors concluded that performance of second-look endoscopy seemed to lower the risk of rebleeding in high-risk PUB. Therefore, the authors suggest that routine second-look endoscopy should be considered and more concern should be paid to patients receiving >5 units of transfusion and taking NSAIDs.

The finding that NSAIDs and transfusion may increase the risk of rebleeding confirms previous studies [11, 12], reinforcing the likelihood that these patients are at an increased risk of poor outcome. The validity of the authors’ conclusion on the routine use of second-look endoscopy can be questioned because of limitations in design (non-RCT) and methods, including no clear definition of rebleeding, differences in indications used for performing second-look endoscopy between centers, and incomplete adjustment for confounding factors of relevance.

Should endoscopists perform routine second-look endoscopy in all patients with Forrest I–IIb ulcers? Based on the current literature, I believe the answer is “no.” There is evidence supporting that performance of second-look endoscopy in patients with a very high risk of rebleeding is associated with a reduced rate of rebleeding, a reduced need for surgery, and saving of net costs [6, 8]. In my view, second-look endoscopy can be considered in selected patients with high risk of rebleeding, in particular if the primary endoscopic treatment was suboptimal (e.g., monotherapy with epinephrine, compromised lesion visualization). Well-powered RCTs demonstrating a clinically significant effect of second-look endoscopy in an updated setting are needed before routine use of this procedure in all patients with Forrest I–IIb lesions can be recommended.

References

  1. Rosenstock SJ, Møller MH, Larsson H, et al. Improving quality of care in peptic ulcer bleeding: nationwide cohort study of 13,498 consecutive patients in the Danish Clinical Register of Emergency Surgery. Am J Gastroenterol. 2013;108:1449–1457.

    Article  PubMed  Google Scholar 

  2. Rockall TA, Logan RF, Devlin HB, Northfield TC. Risk assessment after acute upper gastrointestinal haemorrhage. Gut. 1996;38:316–321.

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  3. García-Iglesias P, Villoria A, Suarez D, et al. Meta-analysis: predictors of rebleeding after endoscopic treatment for bleeding peptic ulcer. Aliment Pharmacol Ther. 2011;34:888–900.

    Article  PubMed  Google Scholar 

  4. Elmunzer BJ, Young SD, Inadomi JM, Schoenfeld P, Laine L. Systematic review of the predictors of recurrent hemorrhage after endoscopic hemostatic therapy for bleeding peptic ulcers. Am J Gastroenterol. 2008;103:2625–2632.

    Article  PubMed  Google Scholar 

  5. Vergara M, Bennett C, Calvet X, Gisbert JP. Epinephrine injection versus epinephrine injection and a second endoscopic method in high-risk bleeding ulcers. Cochrane Database Syst Rev. 2014;10:CD005584.

    PubMed  Google Scholar 

  6. El Ouali S, Barkun AN, Wyse J, et al. Is routine second-look endoscopy effective after endoscopic hemostasis in acute peptic ulcer bleeding? A meta-analysis. Gastrointest Endosc. 2012;76:283–292.

    Article  PubMed  Google Scholar 

  7. Chiu PW, Joeng H, Choi C, et al. The effect of scheduled second endoscopy against intravenous high dose omeprazole infusion as an adjunct to therapeutic endoscopy in prevention of peptic ulcer rebleeding—a prospective randomized study [abstract]. Gastroenterology. 2006;130:A121.

    Google Scholar 

  8. Imperiale TF, Kong N. Second-look endoscopy for bleeding peptic ulcer disease: a decision-effectiveness and cost-effectiveness analysis. J Clin Gastroenterol. 2012;46:e71–e75.

    PubMed Central  Article  PubMed  Google Scholar 

  9. Kim SB, Lee SH, Kim KO, et al. Risk factors associated with rebleeding in patients with high risk peptic ulcer bleeding: focusing on the role of second look endoscopy. Dig Dis Sci (Epub ahead of print). doi:10.1007/s10620-015-3846-y.

  10. Forrest JA, Finlayson ND, Shearman DJ. Endoscopy in gastrointestinal bleeding. Lancet. 1974;2:394–397.

    Article  CAS  PubMed  Google Scholar 

  11. Vreeburg EM, de Bruijne HW, Snel P, Bartelsman JW, Rauws EA, Tytgat GN. Previous use of non-steroidal anti-inflammatory drugs and anticoagulants: the influence on clinical outcome of bleeding gastroduodenal ulcers. Eur J Gastroenterol Hepatol. 1997;9:41–44.

    Article  CAS  PubMed  Google Scholar 

  12. Restellini S, Kherad O, Jairath V, Martel M, Barkun AN. Red blood cell transfusion is associated with increased rebleeding in patients with nonvariceal upper gastrointestinal bleeding. Aliment Pharmacol Ther. 2013;37:316–322.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Stig Borbjerg Laursen.

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Laursen, S.B. Risk Factors for Rebleeding in Peptic Ulcer Bleeding: A Second Look at Second-Look Endoscopy. Dig Dis Sci 61, 332–333 (2016). https://doi.org/10.1007/s10620-015-3919-y

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