Gastroenterology Research and Practice

Gastroenterology Research and Practice / 2013 / Article
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Letter to the Editor | Open Access

Volume 2013 |Article ID 803139 | 2 pages |

High or Nonhigh Doses of Proton Pump Inhibitors for Patients with Peptic Ulcer Bleeding?

Received20 Aug 2012
Accepted26 Dec 2012
Published18 Feb 2013

I read with interest the article entitled “A real world report on intravenous high-dose and nonhigh-dose proton pump inhibitors therapy in patients with endoscopically treated high-risk peptic ulcer bleeding” [1]. In this study, Lu et al. retrospectively analyzed patients receiving nonhighdose (80 mg pantoprazole i.v. bolus followed by i.v. 80 mg per day for 3 days) and high-dose proton pump inhibitors (PPI, 80 mg pantoprazole i.v. bolus followed by 8 mg per hr for 3 days) after obtaining initial hemostasis. After performing case-control matching, they found no statistical difference between the high-dose and nonhigh-dose groups. Therefore, they suggest that both doses of PPI were similar in reducing rebleeding in high-risk patients after successful endoscopic therapy.

This conclusion is different from that in the consensus conference and also in our study [2, 3]. There are several key points that deserve to be mentioned with regards to this study. Lu’s analysis is a retrospective study. Therefore, some important clinical variables could not be adjusted evenly between both groups. As a practice, doctors tend to use a high-dose PPI in high-risk patients after obtaining initial hemostasis. This point is demonstrated in Lu’s study, Table 3. The number of patients with shock is more in the high-dose PPI group than that in the nonhigh-dose group (61.4% versus 46%).

In Lu’s study, the rebleeding rate for the high-dose group (19/70, 27.1%) is much higher than our series (2/50, 4%) and another report (8/120, 6.7%) [2, 4]. This phenomenon may be explained by the high percentage of patients with renal impairment (35/70, 50%). The high proportion of enrolled patients with renal impairment is unusual as compared to the past reports. Because three days after endoscopic therapy are a critical period, high-dose PPI is needed for these three days. After three days, patients usually receive oral intake. However, in Lu’s study, they still gave 80 mg i.v. per day after three days. Thus, utilizing such therapy may waste some economic resources.

In recent few years, there have been some articles supporting the use of low-dose PPI in high-risk patients after endoscopic hemostasis [5]. Many of these articles have pitfalls related to study design, such as the inclusion of patients with low-risk stigmata and the injection of epinephrine alone [6]. In vitro studies revealed that the acid environment impairs platelet function and clot stabilization [7]. Therefore, elevation of intragastric pH is mandatory to prevent rebleeding in patients with peptic ulcer bleeding, which has been confirmed in the consensus conference [2]. In our previous study, we obtained a markedly low rebleeding rate (4%) with a high-dose IV PPI [3]. Further, we found that different IV doses of PPIs have different rebleeding rates (omeprazole 160 mg/day: 9%, 6/67; 80 mg/day: 21.2%, 14/66) [8].

Clearly, there is a bit of a grey zone in identifying stigmata of recent hemorrhage (SRH) [9]. Misinterpretation of SRH can occur for a number of reasons, such as doctors’ experience and academic judgement. Therefore, one strict design (double blind study) is favored in such a clinical trial.


  1. L. S. Lu, S. C. Lin, C. M. Kuo et al., “A real world report on intravenous high-dose and non-high-dose proton-pump inhibitors therapy in patients with endoscopically treated high-risk peptic ulcer bleeding,” Gastroenterology Research and Practice, vol. 2012, Article ID 858612, 7 pages, 2012. View at: Publisher Site | Google Scholar
  2. A. N. Barkun, M. Bardou, E. J. Kuipers et al., “International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding,” Annals of Internal Medicine, vol. 152, no. 2, pp. 101–113, 2010. View at: Google Scholar
  3. H. J. Lin, W. C. Lo, F. Y. Lee, C. L. Perng, and G. Y. Tseng, “A prospective randomized comparative trial showing that omeprazole prevents rebleeding in patients with bleeding peptic ulcer after successful endoscopic therapy,” Archives of Internal Medicine, vol. 158, no. 1, pp. 54–58, 1998. View at: Publisher Site | Google Scholar
  4. J. Y. W. Lau, J. J. Y. Sung, K. K. C. Lee et al., “Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers,” The New England Journal of Medicine, vol. 343, no. 5, pp. 310–316, 2000. View at: Publisher Site | Google Scholar
  5. C. H. Wang, M. H. M. Ma, H. C. Chou et al., “High-dose vs non-high-dose proton pump inhibitors after endoscopic treatment in patients with bleeding peptic ulcer: a systematic review and meta-analysis of randomized controlled trials,” Archives of Internal Medicine, vol. 170, no. 9, pp. 751–758, 2010. View at: Publisher Site | Google Scholar
  6. H. J. Lin, “High or low doses of PPIs for patients with peptic ulcer bleeding?” Archives of Internal Medicine, vol. 170, no. 18, pp. 1699–1700, 2010. View at: Publisher Site | Google Scholar
  7. F. W. Green Jr., M. M. Kaplan, L. E. Curtis, and P. H. Levine, “Effect of acid and pepsin on blood coagulation and platelet aggregation. A possible contributor to prolonged gastroduodenal mucosal hemorrhage,” Gastroenterology, vol. 74, no. 1, pp. 38–43, 1978. View at: Google Scholar
  8. H. J. Lin, W. C. Lo, Y. C. Cheng, and C. L. Perng, “Role of intravenous omeprazole in patients with high-risk peptic ulcer bleeding after successful endoscopic epinephrine injection: a prospective randomized comparative trial,” American Journal of Gastroenterology, vol. 101, no. 3, pp. 500–505, 2006. View at: Publisher Site | Google Scholar
  9. J. Y. W. Lau, J. J. Y. Sung, A. C. W. Chan et al., “Stigmata of hemorrhage in bleeding peptic ulcers: an interobserver agreement study among international experts,” Gastrointestinal Endoscopy, vol. 46, no. 1, pp. 33–36, 1997. View at: Publisher Site | Google Scholar

Copyright © 2013 Yu-Hsi Hsieh and Hwai-Jeng Lin. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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