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Life sciences · Review
PLOS One · October 30, 2026
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Background Sepsis continues to be a major contributor to death among critically ill individuals and places a heavy strain on healthcare resources. In addition to causing systemic inflammation and affecting hemodynamics, sepsis has a significant effect on the gastrointestinal system, leading to complications like stress ulcers and notable gastrointestinal bleeding (GIB), which worsen patient outcomes. While stress ulcer prophylaxis (SUP) has traditionally been included in sepsis treatment protocols, the concept of applying it universally is being increasingly scrutinized due to the absence of definitive mortality advantages and the risk of adverse effects, such as hospital-acquired pneumonia. Nevertheless, there is a notable gap in synthesized research that specifically addresses the independent risk factors for stress ulcers in sepsis patients. Methods We carried out a systematic review in accordance with PRISMA standards, exploring eight databases (CNKI, Wanfang, VIP, Sinomed, PubMed, Web of Science, Embase, and Cochrane Library) from their inception until September 1, 2026. We included observational analytical studies (either cohort or case-control) that examined factors linked to stress ulcers or significant gastrointestinal bleeding in adult patients with sepsis. Two researchers independently handled the selection of studies, extraction of data, and evaluation of quality using the Newcastle-Ottawa Scale. Due to the limited number of studies for each association between associated factors and outcomes, a narrative synthesis was utilized. Results A total of six studies encompassing 131,568 individuals suffering from sepsis or septic shock were analyzed. The incidence rates of stress ulcers or gastrointestinal bleeding (GIB) varied between 2.0% and 32.3%. The identified associated factors were divided into three categories: patient-related (older age, history of GIB, cirrhosis, HIV, cancer/immunosuppression), disease-related (coagulopathy, kidney impairment, high BUN levels, severity of illness scores, source of infection), and treatment-related (mechanical ventilation, use of anticoagulants, corticosteroid therapy, duration of ICU stay). Specifically for stress ulcer, factors such as respiratory failure, high BUN levels, shock, and increased HMGB1/TLR2/TLR4 levels were found to be independently linked to a higher odds. Conclusions In summary, the likelihood of developing stress ulcers and gastrointestinal bleeding in patients with sepsis is shaped by a variety of factors related to the patient, their illness, and the treatments they receive. Key indicators that consistently emerge include issues with blood coagulation, the presence of shock, the need for mechanical ventilation, liver and kidney dysfunction, the severity of the disease, and any previous occurrences of gastrointestinal bleeding. These results advocate for tailored strategies for stress ulcer prophylaxis based on individual risk rather than a one-size-fits-all approach, offering crucial insights for precise clinical decision-making. Additional high-quality research is essential to confirm and enhance the understanding of these associated factors. Registration PROSPERO ( CRD420251242849 )