IAI SPECIAL EDITION: Meta-analysis of the effectiveness of histamine-2 receptor antagonists as prophylaxis for gastrointestinal bleeding in intensive care unit patients

Authors

  • Fonny Cokro Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia https://orcid.org/0000-0002-9810-1402
  • Juliana Sumartono Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia

DOI:

https://doi.org/10.46542/pe.2022.222.113117

Keywords:

Gastrointestinal bleeding, Histamine-2 receptor, Antagonist, Intensive care unit

Abstract

Background: The risk of upper gastrointestinal bleeding increases in critically ill patients admitted to an intensive care unit (ICU), with 50–77% mortality. Histamine-2 receptor antagonists (H2RAs) are frequently used to prevent gastrointestinal bleeding in ICU patients, but the tests on its effectiveness and safety are still conflicting.        

Objective: To determine the effectiveness and safety of H2RA in preventing gastrointestinal bleeding in ICU patients.    

Methods: Data on randomised controlled trials (RCTs) were collected from the MEDLINE database, ScienceDirect, ClinicalKey, and The Cochrane Library. Two investigators assessed the quality of the trials using the critical appraisal skills program (CASP) checklist for RCT studies, and fixed-effects meta-analysis was carried out using Review Manager software.        

Results: The 12 RCTs showed a reduced risk of gastrointestinal bleeding (RR = 0.40; 95% CI = 0.30 ‒ 0.53; I-square = 38%; p <0.00001) and a decreased number of patients requiring blood transfusion in H2RA group (RR = 0.44; 95% CI = 0.23 ‒ 0.82; I-square = 8%; p = 0.01), and these effects were significantly different from the placebo group. However, there was no significant difference in mortality between the two groups (RR = 0.99; 95% CI = 0.74 ‒ 1.33; I-square = 0%; p = 0.96). Regarding its safety, the administration of H2RAs did not affect the incidence of nosocomial pneumonia (RR = 1.13; 95% CI = 0.82 ‒ 1.55; I-square = 30%; p = 0.46). A sensitivity analysis with a random-effects model was also performed on eight articles with a low risk of bias. The statistical analyses of eight and 12 articles showed the same results—that H2RAs significantly reduced the risk of gastrointestinal bleeding.   

Conclusion: H2RA proves effective and safe in reducing the incidence of gastrointestinal bleeding, but not reducing the mortality in ICU patients.

Author Biographies

Fonny Cokro, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia

Faculty of Medicine and Health Sciences

Juliana Sumartono, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia

Faculty of Medicine and Health Sciences

References

Barbateskovic, M., Marker, S., Granholm, A., Anthon, C.T., Krag, M., Jakobsen, J. C., Perner, A., Wetterslev, J., & Møller, M. H. (2019). Stress ulcer prophylaxis with proton pump inhibitors or histamin-2 receptor antagonists in adult intensive care patients: A systematic review with meta-analysis and trial sequential analysis. Intensive Care Medicine, 45(2), 143–158. https://doi.org/10.1007/s00134-019-05526-z

Daley, R.J., Rebuck, J.A., Welage, L.S., & Rogers, F.B. (2004). Prevention of stress ulceration: Current trends in critical care. Critical Care Medicine, 32(10), 2008–2013. https://doi.org/10.1097/01.CCM.0000142398.73762.20

Huang, H. Bin, Jiang, W., Wang, C. Y., Qin, H. Y., & Du, B. (2018). Stress ulcer prophylaxis in intensive care unit patients receiving enteral nutrition: A systematic review and meta-analysis. Critical Care. https://doi.org/10.1186/s13054-017-1937-1

Krag, M., Perner, A., Wetterslev, J., Wise, M. P., Borthwick, M., Bendel, S., McArthur, C., Cook, D., Nielsen, N., Pelosi, P., Keus, F., Guttormsen, A. B., Moller, A.D., & Møller, M.H. (2015). Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acutely ill adult intensive care patients. Intensive Care Medicine. https://doi.org/10.1007/s00134-015-3725-1

Liu, B. L., Li, B., Zhang, X., Fei, Z., Hu, S. J., Lin, W., Gao, D. K., & Zhang, L. (2013). A randomised controlled study comparing omeprazole and cimetidine for the prophylaxis of stress-related upper gastrointestinal bleeding in patients with intracerebral haemorrhage: Clinical article. Journal of Neurosurgery. https://doi.org/10.3171/2012.9.JNS12170

Nugent, C., Flakson, S., & Terrell, J.M. (2020). H2 Blockers. In Stat Pearls. Treasure Island (FL): StatPearls Publishing

Peura, D.A., & Johnson, L.F. (1985). Cimetidine for prevention and treatment of gastroduodenal mucosal lesions in patients in an intensive care unit. Annals of Internal Medicine. https://doi.org/10.7326/0003-4819-103-2-173

Spirt, M.J. (2004). Stress-related mucosal disease: Risk factors and prophylactic therapy. Clinical Therapeutics. https://doi.org/10.1016/S0149-2918(04)90019-7

Stollman, N., & Metz, D.C. (2005). Pathophysiology and prophylaxis of stress ulcer in intensive care unit patients. In Journal of Critical Care. https://doi.org/10.1016/j.jcrc.2004.10.003

Toews, I., George, A.T., Peter, J.V., Kirubakaran, R., Fontes, L.E.S., Ezekiel, J.P.B., & Meerpohl, J.J. (2018). Interventions for preventing upper gastrointestinal bleeding in people admitted to intensive care units. Cochrane Database of Systematic Reviews, 2018(6). https://doi.org/10.1002/14651858.CD008687.pub2

Zhou, X., Fang, H., Xu, J., Chen, P., Hu, X., Chen, B., Wang, H., Hu, C., & Xu, Z. (2019). Stress ulcer prophylaxis with proton pump inhibitors or histamine 2 receptor antagonists in critically ill adults—A meta-analysis of randomised controlled trials with trial sequential analysis. BMC Gastroenterology, 19(1), 193. https://doi.org/10.1186/s12876-019-1105-y

Downloads

Published

2022-03-31

How to Cite

Cokro, F. ., & Sumartono, J. . (2022). IAI SPECIAL EDITION: Meta-analysis of the effectiveness of histamine-2 receptor antagonists as prophylaxis for gastrointestinal bleeding in intensive care unit patients. Pharmacy Education, 22(2), p. 113–117. https://doi.org/10.46542/pe.2022.222.113117

Issue

Section

Special Edition