Beyond Fluid Therapy: The Role of Vitamin C, Steroids, and Thiamine in Sepsis Management

Sepsis remains a major contributor to mortality among critically ill patients, with sepsis-induced metabolic dysfunction significantly worsening outcomes. As metabolic dysfunction plays a key role in the pathogenesis of sepsis, recent interest has grown around metabolic resuscitation therapies as potential adjuncts to traditional fluid resuscitation strategies. This narrative review evaluates current evidence regarding the role of vitamin C, thiamine, and corticosteroids in improving sepsis outcomes. Early studies suggested that vitamin C may reduce organ dysfunction and vasopressor requirements; however, more recent randomized trials have produced inconsistent results, with some findings even indicating potential harm in certain patient groups. Similarly, the use of corticosteroids in sepsis management has shown mixed outcomes. Thiamine has demonstrated possible renal protective effects and improved lactate clearance, although its impact on mortality and vasopressor needs remains inconclusive. Combination therapy with hydrocortisone, vitamin C, and thiamine (the HAT protocol) has been associated with reduced vasopressor duration but has not consistently improved survival or other major clinical endpoints, despite its apparent safety. Overall, while vitamin C, corticosteroids, and thiamine present a theoretically attractive strategy in sepsis management, clinical results remain debated. Corticosteroids currently have the strongest supporting evidence for use in septic shock, while vitamin C and thiamine remain investigational therapies and are not recommended for routine use outside clinical trials. Future research should explore biomarker-guided, precision-medicine approaches to better identify patients who might benefit most from metabolic resuscitation, and large-scale randomized controlled trials are needed to clarify optimal timing and dosing strategies.