Published Paper Details:

Sepsis, a life-threatening organ dysfunction due to a dysregulated host response to infection, continues to pose a significant clinical challenge despite advances in supportive care. The review synthesizes findings from randomized controlled trials and cohort studies to evaluate the impact of vitamin C--administered alone or in combination with thiamine and hydrocortisone--on key outcomes such as mortality, organ dysfunction (SOFA scores), vasopressor requirements, and safety profiles. The evidence regarding vitamin C monotherapy is mixed: several meta-analyses suggest possible reductions in mortality and improvements in SOFA scores and vasopressor duration, but these findings are not consistently statistically significant, and some large trials even indicate potential harm. Combination therapies, particularly the "metabolic resuscitation cocktail" (vitamin C, thiamine, hydrocortisone), have not demonstrated significant mortality benefit in high-quality trials, though modest improvements in organ dysfunction metrics are observed. Vitamin C is generally well tolerated, but rare adverse effects--such as increased renal replacement therapy or hypernatremia--have been reported in certain studies, warranting caution in patients with specific comorbidities. Substantial heterogeneity in dosing regimens, timing, patient populations, and study design complicates interpretation, and the overall certainty of evidence for major outcomes remains low to moderate according to GRADE criteria. Current guidelines do not recommend routine intravenous vitamin C use in sepsis outside of clinical trials. The review underscores the need for large, well-designed randomized studies to identify patient subgroups most likely to benefit, determine optimal dosing strategies, and clarify the role of vitamin C--alone or in combination--in improving clinically significant outcomes in sepsis. This systematic literature review critically examines the efficacy and safety of intravenous vitamin C administration in the management of sepsis and septic shock.