The University of Toledo Translation Journal of Medical Sciences 
Internal Medicine Abstract, Department of Medicine Research Symposium UTJMS 2023 May 5; 11(1):e1-e2 

Clinically Significant Gastrointestinal 
Bleeding Using Proton Pump Inhibitors or 
Histamine Type-2 Receptor Antagonists in 
Patients Intubated for Over 48 Hours: A 
Systematic Review and Meta-Analysis 
W. Khokher, MD1*, N. Kesireddy, MD1, S. Iftikhar, MD1, A. Beran, MD1, Z.
Abuhelwa, MD1, S. Malhas, MD1, T. Saif, MD1, R. Assaly, MD2

1Division of Internal Medicine, Department of Medicine, The University of Toledo, 
Toledo, OH 43614 
2Division of Pulmonary and Critical Care Medicine, Department of Medicine, The 
University of Toledo, Toledo, OH 43614 

*Corresponding author: Waleed.Khokher@utoledo.edu

Published: 05 May 2023 

Introduction: The use of stress ulcer prophylaxis (SUP) is routine in the intensive care unit (ICU) to 
prevent serious deleterious effects of gastrointestinal bleeding (GIB). Aim of our investigation was to 
perform a literature review and meta-analysis to compare the effectiveness of proton pump inhibitors 
(PPIs) to histamine type-2 receptor antagonists (H2RAs) in a selective high risk patient population that 
has been mechanically ventilated for over 48 hours.   

Methods: Comprehensive search of published studies indexed in PubMed/MEDLINE, EMBASE, and 
the Cochrane Central Register of Controlled Trials to obtain randomized controlled trials (RCTs) that 
evaluated the use of PPIs and H2RAs in patients intubated for >48 hours. Primary outcome was the 
occurrence of clinically significant or overt GIB (CS/O-GIB). Secondary outcomes were occurrence of 
ventilator associated pneumonia (VAP), ICU mortality, and ICU length of stay (LOS).     

Results: Seven RCTs involving 27905 patients that were mechanically ventilated for >48 hours were 
including in the meta-analysis. Rate of CS/O-GIB was significantly lower in patients receiving PPIs 
compared to H2RAs while intubated (1.6% vs. 2.5%, RR 0.59, 95% CI 0.45-0.79, P = 0.0003, I2= 31%). 
There was no significant difference between the two groups in-terms of rate of VAP, ICU morality, and 
ICU LOS.    

https://dx.doi.org/10.46570/utjms.vol11-2023-704 

https://dx.doi.org/10.46570/utjms.vol11-2023-704
mailto:Waleed.Khokher@utoledo.edu


https://dx.doi.org/10.46570/utjms.vol11-2023-704 UTJMS 11(1):e1-e2 

https://dx.doi.org/10.46570/utjms.vol11-2023-704 2 ©2023 UTJMS 

Conclusion: This meta-analysis demonstrates that PPIs in patients mechanically ventilated for over 48 
hours are more effective in preventing CS/O-GIB when compared to H2RAs, without leading to a 
significant increase in the rate of VAP. 

https://dx.doi.org/10.46570/utjms.vol11-2023-704
https://dx.doi.org/10.46570/utjms.vol11-2023-704