A 2022 systematic review and meta-analysis identified 11 randomized controlled trials (RCTs) of 930 adults admitted to the intensive care unit (ICU) with primary neurologic injury to evaluate the efficacy of stress ulcer prophylaxis (SUP) in reducing gastrointestinal bleeding (GIB). Primary neurological conditions included traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracranial hemorrhage (ICH) as well as other conditions. The interventions compared the use of histamine-2-receptor antagonists (H2RAs) or proton pump inhibitors (PPIs) against placebo, no prophylaxis, or each other. Enteral nutrition varied with 6 studies implementing early enteral feeding practices, 4 studies implementing fasting, and the remaining studies lacking data. [1]
A pooled analysis revealed that both PPIs and H2RAs significantly reduced the occurrence of GIB compared to placebo or no prophylaxis, with risk ratios (RR) of 0.37 (95% confidence interval [CI] 0.23 to 0.59; 0<0.001) and 0.42 (95% CI 0.30 to 0.58; p<0.001), respectively. However, no significant difference was observed between PPIs and H2RAs (RR 0.53; 95% CI 0.26 to 1.06; p= 0.07). Despite the observed reduction in GIB, there were no significant differences in 30-day mortality or incidence of nosocomial pneumonia across treatment groups. H2RAs showed similar mortality outcomes as placebo or no treatment (RR 0.77; 95% CI 0.55 to 1.07; p= 0.12), and nosocomial pneumonia rates were not significantly increased with either treatment. Median duration of treatment across all studies was 6 days. The included trials exhibited variability in definitions of GIB, follow-up durations, and feeding practices, and all were classified as high risk of bias, limiting the strength of clinical recommendations. Additionally, small sample sizes and low event rates further constrained the interpretability of the findings. Although suggesting SUP may reduce the incidence of GIB, the data underscore the need for larger, high-quality RCTs focusing on neurocritical populations. [1]
A 2015 meta-analysis investigated the risks and benefits of SUP in adult neurocritical care patients. A total of 8 studies (N= 829) included individuals diagnosed with TBI (n= 288, 4 studies) and intracerebral bleeding (n= 440, 4 studies). TBI regimens included ranitidine 50 mg IV Q6-8H titrated to maintain gastric pH ≥4, 6.25 mg/h continuous IV up to 3-5 days, or cimetidine 300 mg IV Q4H up to 3 weeks. Among all patients, there was a significantly lower incidence of UGI bleeding in treatment versus placebo groups (RR 0.31; CI 0.20 to 0.47; p<0.00001; I2=45%). Subanalyss of TBI studies included the following: UGI bleeding (RR 0.22; 95% CI 0.11 to 0.43), mortality (RR 0.88; 95% CI 0.49 to 1.57), and nosocomial pneumonia (RR 0.75; 95% CI 0.38 to 1.51). [2]
Intracerebral hemorrhage regimens included ranitidine 50 mg IV Q6-8H, omeprazole 40 mg Q12H with cimetidine 300 mg IV Q6H, esomeprazole 40 mg/day, lansoprazole 40 mg/day, ranitidine 150 mg/day, or famotidine 40 mg/day. Subanalysis of intracerebral hemorrhage studies included the following: UGI bleeding (RR 0.31; 95% CI 0.14 to 0.72), mortality (RR 0.63; 95% CI 0.41 to 0.95), and nosocomial pneumonia (RR 0.98; 95% CI 0.29 to 3.31). Overall, the findings suggest that SUP may be more effective than placebo or no prophylaxis for UGI bleeding and all-cause mortality in neurocritical care patients, but the benefits in TBI and intracerebral patients are limited to secondary analyses. [2]