Luminal Clinical

Abstract

Background and Aim: Upper gastrointestinal bleeding (UGIB) is a common gastrointestinal emergency and carries high morbidity and mortality. There are multiple risk factors for poorer outcomes, including malnutrition. Ascorbic acid is a water-soluble vitamin present in most plant foods. Dietary deficiency leads to scurvy, which may alter the natural history of UGIB through impaired tissue and mucosal integrity. Traditionally thought to be rare in developed countries, vitamin C deficiency (VCD) is now well described in patients with pneumonia, sepsis, and coronavirus disease 2019. There is a paucity of literature investigating the prevalence and clinical significance of VCD in patients with UGIB;interim findings reported by our group suggested a prevalence of >30%. The aim of this study was to establish the prevalence of VCD in patients presenting with UGIB and its association with clinical outcomes. Methods: We conducted a prospective cohort study of adult patients presenting with UGIB to two metropolitan tertiary hospitals in Melbourne, Australia, over a 12-month period (March 2020 to March 2021). Fasting vitamin C levels were obtained on admission. Patients were risk-stratified using the AIMS65 score, and baseline demographic data and outcomes were recorded. The primary outcome was the prevalence of VCD (serum vitamin C level < 23 μmol/L) and severe VCD (<12 μmol/L). Secondary outcomes included a composite endpoint of adverse events (AE), comprising inpatient death, intensive care unit (ICU) admission, rebleeding, surgery, angioembolization, or massive transfusion (≥4 units of red cells). Multivariate logistic regression was used to determine the association between vitamin C levels and the secondary endpoints. Subgroup analyses were performed in variceal and non-variceal UGIB and high-risk (AIMS65, ≥2) and low-risk (AIMS65, 0-2) UGIB. Results: A total of 227 patients were included. The median age was 65 years (IQR, 54-78), 145 (63.9%) were male, and the median AIMS65 score was 1 (IQR, 1-2). The etiology of UGIB was variceal bleeding in 20.3%, peptic ulcer disease in 44.1%, and other causes in 35.7%. The mean vitamin C level was 40 ± 26 μmol/L. In terms of patient outcomes, inpatient mortality was 4%, ICU admission occurred for 11.9%, and mean length of stay (LOS) was 7.7 ± 9.7 days. Red cell transfusion was required in 63.4% of patients, with a mean requirement of 2.2 ± 2.8 units. VCD was identified in 74 patients (32.6%), with severe deficiency in 32 (14.1%). VCD was associated with significantly higher in-hospital mortality (9.5% vs 1.3%, P = 0.01), prolonged LOS (10.8 vs 6.2 days, P < 0.01), rebleeding (17.6% vs 7.88%, P = 0.05), and a higher composite endpoint of AE (77% vs 54.9%, P < 0.01). On multivariate logistic regression, high-risk UGIB (odds ratio [OR], 3.24;95% CI, 1.42-7.42), VCD (OR, 2.28;95% CI, 1.11-4.71), and chronic liver disease (OR, 11.66;95% CI, 2.92-46.64) were all independently associated with the composite endpoint of AE. In subgroup analysis, VCD was associated with a significantly increased composite endpoint of AE in patients with non-variceal (74% vs 51%, P < 0.01) and low-risk (66% vs 44%, P = 0.04) UGIB. Conclusion: VCD is highly prevalent in patients with UGIB and associated with poorer outcomes, including higher mortality, rebleeding, and LOS. Interventional studies are required to determine the impact of early vitamin C supplementation on clinical outcomes.