Effect of adjunctive granisetron therapy on mortality and hospital stay in patients with sepsis

Background: Sepsis is considered a major cause of mortality. Serotonin (5-HT) has been linked to the pathophysiology of sepsis because of its pro-inflammatory and vasoregulatory properties. Granisetron, a selective 5-HT₃ receptor antagonist, has shown potential anti-inflammatory and organ-protective effects. Aim of the study: To evaluate the effectiveness and safety of adjunctive granisetron therapy in patients with sepsis. Methodology: A prospective, randomized, controlled trial was conducted at Al-Azhar University Hospital, Damietta, enrolling 160 adult patients who fulfilled the diagnostic sepsis criteria. Participants were randomly assigned either intravenous granisetron or a placebo for four days, or until ICU discharge, in addition to standard sepsis management. 28-day all-cause mortality, duration of organ support, length of stay, changes in SOFA scores, trends in inflammatory biomarkers, and safety profiles were recorded. Results: The 28-day mortality rate was lower in the granisetron group compared with placebo (18.2% vs. 26.9%; OR 0.92, 95% CI 0.46–1.85; p = 0.87), although the difference was not statistically significant. Similarly, no significant differences were observed between groups regarding ICU length of stay, SOFA score trajectories, or the incidence of new organ dysfunction. Nonetheless, patients receiving granisetron exhibited favorable trends, including greater reductions in inflammatory biomarkers (IL-6, CRP, PCT) and improvements in liver and renal function parameters. Adverse events were uncommon and comparable between the two groups. Conclusions: Granisetron was safe, accurate, and well-tolerated, supporting its safety in critically ill patients.