Ascorbic Acid and Thiamine Effect in Septic Shock

Sepsis is a complex disease involving life-threatening organ dysfunction caused by a dysregulated host response to infection and is still associated with unacceptably high mortality. Sepsis management should be undertaken as a medical emergency and focused on timely intervention, including early identification and treatment of infection through appropriate antimicrobial therapy and source control when applicable as well as reversing hemodynamic instability through fluid resuscitation and vasopressor use if necessary. Despite these supportive therapies, morbidity and mortality have remained high, suggesting the need for adjuvant therapies for inflammatory and oxidative stress in patients with sepsis; however, no agents have been proven to definitely improve survival.

Vitamin C plays a role in mediating inflammation through antioxidant activities and is also important as a cofactor/co-substrate for the synthesis of endogenous adrenaline, cortisol, and vasopressin. Recently, several clinical trials have reported the positive effects of vitamin C on outcomes in sepsis or septic shock. During sepsis, vitamin C prevents neutrophil-induced lipid oxidation and protects against the loss of the endothelial barrier. Early intravenous supplementation is therefore needed to limit loss of microcirculation and oxidation of lipids. Thiamine is also a key cofactor for glucose metabolism, the generation of ATP (adenosine triphosphate), and the production of NADPH. Considering acute consumption in the hypermetabolic state, thiamine supplementation might be a reasonable therapeutic adjunct for patients with sepsis and was added to reduce the risk of renal oxalate crystallization. These findings led to a recent before-and-after study showing that treatment of sepsis with a combination of vitamin C, hydrocortisone, and thiamine prevented organ dysfunction and reduced the mortality rate.

The aim of this study is to evaluate the efficacy of early metabolic resuscitation with combination therapy using vitamin C and thiamine in improving organ function and survival in patients with septic shock.

Inclusion criteria

• Adult patients (> 18 years)
• Septic shock: sepsis with persisting hypotension requiring vasopressors to maintain a mean arterial pressure ≥65 mm Hg and a serum lactate level >2 mmol/L despite adequate volume resuscitation. Sepsis is defined as clinically suspected or confirmed infection with acute organ failure identified as an acute change in total SOFA score with 2 points or more.

Exclusion criteria

• Transferred patients from other hospitals after application of vasopressors or mechanical ventilation
• Patients who signed a "Do not attempt resuscitation" order or who had set limitations on invasive care
• Patients who have a terminal, unresponsive illness and survival discharge is not expected (metastatic terminal cancer, etc.)
• Patients who experienced cardiac arrest before enrollment or when death is anticipated within 24 hours despite maximal treatment
• Patients who take more than 1g of Vitamin C per day before enrollment or who take supplemental thiamine
• Pregnant woman
• Known Glucose-6-phosphate dehydrogenase deficiency
• Patients with a history of hypersensitivity to vitamin C or thiamine
• Known Mediterranean anemia
• Known hyperoxaluria
• Known cystinuria
• Acute gout attack
• Known oxalate renal stone
• Patients who meet the inclusion criteria 24 hours after emergency department arrival or when enrollment is delayed more than 24 hours after diagnosis of septic shock
• Inability or refusal of a subject or legal surrogate to give informed consent