Stress Ulcer Prophylaxis in Critical Care: Evidence, Risk Stratification, and Clinical Implications

Stress-related mucosal damage (SRMD) is a common complication in critical care medicine. The necessity of stress ulcer prophylaxis (SUP) is debated due to advancements in supportive care and challenges in accurately stratifying bleeding risk. This narrative review evaluates contemporary evidence on stress ulcer prophylaxis in critically ill patients, with emphasis on bleeding risk stratification and implications for clinical practice. To construct this narrative review, we searched Embase and PubMed for randomized controlled trials (RCTs) evaluating SUP in adult intensive care unit (ICU) populations. The Population, Intervention, Comparison, and Outcome (PICO) framework was used to guide the search through March 2026. Major trials, relevant subgroup analyses, meta-analyses, and contemporary international clinical practice guidelines were reviewed to contextualize trial-level findings. Large randomized controlled trials demonstrated that acid-suppressive therapy reduces the incidence of clinically significant gastrointestinal bleeding (GIB), without demonstrating a mortality benefit. Inconsistent definitions of risk factors for GIB limit reproducibility and reduce the precision of pooled risk estimates. Meta-analyses confirmed a reduction in GIB and highlighted clinical heterogeneity. Current guidelines recommend stress ulcer prophylaxis for patients with high-risk presentations. However, these recommendations remain conditional due to the absence of a multivariable prediction model. Despite current uncertainty regarding the effects of stress ulcer prophylaxis on gastrointestinal bleeding prevention and mortality, it is recommended to consider SUP in selected critically ill patients based on individual risk assessment. In parallel, clinicians should optimize supportive measures, including early enteral nutrition, hemodynamic stabilization, and discontinuation of prophylaxis once the patient is clinically stable. Further prospective research is needed to guide individualized prophylaxis and avoid unnecessary treatment in low-risk populations.