Upper gastrointestinal bleeding (UGIB) presents as a prevalent clinical challenge, with annual incidence rates ranging from 80 to 150 cases per 100,000 individuals. Guidelines for managing patients with UGIB due to bleeding ulcers recommend a continuous infusion of proton pump inhibitors (PPI). However, studies comparing intermittent dosing of PPI therapy show that this regimen achieves similar clinical benefits. If the clinical efficacy remains equivalent, intermittent dosing will be more cost-effective for patients and the health care system. Our research study aims to analyze the comparative effectiveness of intermittent versus continuous PPI therapy after endoscopic treatment in patients with UGIB, focusing on such endpoints as rebleeding risk at 3-and 7-day mortality rates. Methods: Resources searched included MEDLINE, EMBASE, PUBMED, and the Cochrane Central Register of Controlled Trials databases from January 2010 through December 2023 with the inclusion of meta-analysis, systematic review, review, or ACG guideline recommendations. Results of the analysis show how recommendations regarding high vs. low PPI regimen changed over time: from no difference in regimen in 2010 to recommending continuous regimen in 2012 to declaring insufficient evidence between choosing one regimen over another in 2013 to determine that both regimens were comparable to each other in 2014-2018 and finally to recommending both regimens in 2021. To conclude, our review shows that in patients with bleeding ulcers and high-risk endoscopic findings, intermittent PPI therapy is non-inferior to continuous PPI infusion for three days, seven days bleeding risk or mortality rates; however, it remains challenging to determine the most optimal intermittent regimen due to heterogeneity of RCTs included in meta-analyses, and further trials will need to be performed.
References
[1]
Antunes, C. and Copelin II, E.L. (2023) Upper Gastrointestinal Bleeding. StatPearls, Treasure Island.
[2]
Laine, L., Yang, H., Chang, S.C. and Datto, C. (2012) Trends for Incidence of Hospitalization and Death due to GI Complications in the United States from 2001 to 2009. The American Journal of Gastroenterology, 107, 1190-1195. https://doi.org/10.1038/ajg.2012.168
[3]
Kim, J. (2022) Management and Prevention of Upper GI Bleeding. In: Chessman, K., Richardson, M. and Chant, C., Eds., PSAP-VII Gastroenterology and Nutrition, American College of Clinical Pharmacy, Arlington, VA, 7-26.
[4]
Welage, L.S. and Berardi, R.R. (2000) Evaluation of Omeprazole, Lansoprazole, Pantoprazole, and Rabeprazole in the Treatment of Acid-Related Diseases. Journal of the American Pharmaceutical Association, 40, 52-62. https://doi.org/10.1016/S1086-5802(16)31036-1
[5]
Andriulli, A., Loperfido, S., Focareta, R., Leo, P., Fornari, F., Garripoli, A., Tonti, P., Peyre, S., Spadaccini, A., Marmo, R., Merla, A., Caroli, A., Forte, G.B., Belmonte, A., Aragona, G., Imperiali, G., Forte, F., Monica, F., Caruso, N. and Perri, F. (2008) High-versus Low-Dose Proton Pump Inhibitors after Endoscopic Hemostasis in Patients with Peptic Ulcer Bleeding: A Multicentre, Randomized Study. American Journal of Gastroenterology, 103, 3011-3018. https://doi.org/10.1111/j.1572-0241.2008.02149.x
[6]
Freedberg, D.E., Lebwohl, B. and Abrams, J.A. (2014) The Impact of Proton Pump Inhibitors on the Human Gastrointestinal Microbiome. Clinics in Laboratory Medicine, 34, 771-785. https://doi.org/10.1016/j.cll.2014.08.008
[7]
Laine, L., Shah, A. and Bemanian, S. (2008) Intragastric pH with Oral vs Intravenous Bolus Plus Infusion Proton-Pump Inhibitor Therapy in Patients with Bleeding Ulcers. Gastroenterology, 134, 1836-1841. https://doi.org/10.1053/j.gastro.2008.03.006
[8]
Playford, R.J., Podas, T. and Modlin, I. (1999) Pantoprazole, Prout and the Proton Pump. Journal of Hospital Medicine, 60, 500-504. https://doi.org/10.12968/hosp.1999.60.7.1743
[9]
Shin, J.M. and Sachs, G. (2008) Pharmacology of Proton Pump Inhibitors. Current Gastroenterology Reports, 10, 528-534. https://doi.org/10.1007/s11894-008-0098-4
[10]
Gedda, K., Scott, D., Besancon, M., et al. (1995) Turnover of the Gastric H+, K+-Adenosine Triphosphatase Alpha Subunit and Its Effect on Inhibition of Rat Gastric Acid Secretion. Gastroenterology, 109, 1134-1141. https://doi.org/10.1016/0016-5085(95)90571-5
[11]
Wang, C., Ma, M.H., Chou, H., et al. (2010) 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, 170, 751-758. https://doi.org/10.1001/archinternmed.2010.100
[12]
Wu, L.C., Cao, Y.F., Huang, J.H., Liao, C. and Gao, F. (2010) High-Dose vs Low-Dose Proton Pump Inhibitors for Upper Gastrointestinal Bleeding: A Meta-Analysis. World Journal of Gastroenterology, 16, 2558-2565. https://doi.org/10.3748/wjg.v16.i20.2558
[13]
Laine, L. and Jensen, D.M. (2012) Management of Patients with Ulcer Bleeding. The American Journal of Gastroenterology, 107, 345-360. https://doi.org/10.1038/ajg.2011.480
[14]
Neumann, I., Letelier, L.M., Rada, G., Claro, J.C., Martin, J., Howden, C.W., Yuan, Y. and Leontiadis, G.I. (2013) Comparison of Different Regimens of Proton Pump Inhibitors for Acute Peptic Ulcer Bleeding. Cochrane Database of Systematic Reviews, No.6, CD007999. https://doi.org/10.1002/14651858.CD007999.pub2
[15]
Sachar, H., Vaidya, K. and Laine, L. (2014) Intermittent vs Continuous Proton Pump Inhibitor Therapy for High-Risk Bleeding Ulcers: A Systematic Review and Meta-Analysis. JAMA Internal Medicine, 174, 1755-1762. https://doi.org/10.1001/jamainternmed.2014.4056
[16]
Sgourakis, G., Chatzidakis, G., Poulou, A., Malliou, P., Argyropoulos, T., Ravanis, G., Vagia, A., Kpogho, I., Briki, A., Tsuruhara, H. and Stankovičová, T. (2018) High-Dose vs. Low-Dose Proton Pump Inhibitors Post-Endoscopic Hemostasis in Patients with Bleeding Peptic Ulcer. A Meta-Analysis and Meta-Regression Analysis. Turkish Journal of Gastroenterology, 29, 22-31. https://doi.org/10.5152/tjg.2018.17143
[17]
Loren, L., Barkun, A.N., Saltzman, J.R., Martel, M. and Leontiadis, G.I. (2021) ACG Clinical Guideline: Upper Gastrointestinal and Ulcer Bleeding. The American Journal of Gastroenterology, 116, 899-917. https://doi.org/10.14309/ajg.0000000000001245
[18]
Hung, W.K., Li, V.K., Chung, C.K., et al. (2007) Randomized Trial Comparing Pantoprazole Infusion, Bolus and No Treatment on Gastric pH and Recurrent Bleeding in Peptic Ulcers. ANZ Journal of Surgery, 77, 677-681. https://doi.org/10.1111/j.1445-2197.2007.04185.x
[19]
Khan, R.S., Hadi, Y.B., Chima, N. and Kupec, J. (2020) Skipping the Drip: Intravenous Proton Pump Inhibitor Bolus Therapy Leads to Poor Outcomes in High-Risk Bleeding. Cureus, 12, e8362. https://doi.org/10.7759/cureus.8362
[20]
Chaimoff, C., Creter, D. and Djaldetti, M. (1978) The Effect of pH on Platelet and Coagulation Factor Activities. The American Journal of Surgery, 136, 257-259. https://doi.org/10.1016/0002-9610(78)90241-6
[21]
Green Jr, F.W., Kaplan, M.M., Curtis, L.E., et al. (1978) Effect of Acid and Pepsin on Blood Coagulation and Platelet Aggregation. A Possible Contributor is Prolonged Gastroduodenal Mucosal Hemorrhage. Gastroenterology, 74, 38-43. https://doi.org/10.1016/0016-5085(78)90352-9
[22]
Patchett, S.E., Enright, H., Afdhal, N., et al. (1989) Clot Lysis by Gastric Juice: An in Vitro Study. Gut, 30, 1704-1707. https://doi.org/10.1136/gut.30.12.1704