ABSTRACT
INTRODUCTION: Systemic inflammation triggered by bacterial products like lipopolysaccharides (LPS) in the circulation is an important factor leading to decompensation in patients with chronic liver disease (CLD). High-density lipoprotein cholesterol (HDL-C) has a significant role in innate immune response to LPS in the circulation and could therefore increase the risk for decompensation in patients with CLD. In this study, we have explored the role of HDL-C as a prognostic marker for decompensation. METHODS: This was a prospective, observational, cohort study where consecutive patients with CLD were included. Patients with cholestatic liver disease and hepatocellular carcinoma were excluded. Fasting lipids were measured in all patients at the time of recruitment. Each patient was carefully followed up for development of decompensation events such as new-onset/worsening ascites, hepatic encephalopathy, or variceal bleed during follow-up. RESULTS: A total of 170 patients were included (mean age 60 ± 11.5 years, M : F = 6 : 1). At the end of follow-up, 97/170 patients (57%) had decompensation events. Mean HDL-C levels were significantly lower among patients with decompensation (27.5 ± 15 mg/dL vs. 43.5 ± 13.9 mg/dL; p value 0.004). Using ROC analysis, cut-off for HDL-C of 36.4 mg/dL was identified. On multivariate analysis, HDL-C (OR = 6.072; 95% CI 2.39-15.39) was found to have an independent association with risk of decompensation. CONCLUSIONS: HDL-C level (<36.4 mg/dL) is a reliable marker for risk of decompensation and can be a useful addition to existing prognostic scoring systems in CLD. It can be a valuable tool to streamline treatment protocols and prioritise liver transplantation.
ABSTRACT
BACKGROUND: Sepsis remains a leading cause of death worldwide despite advances in management strategies. Preclinical and observational studies have found mortality benefit with high-dose vitamin C in sepsis. Our study aims to prospectively evaluate the effect of intravenous hydrocortisone, vitamin C [ascorbic acid (AA)], and thiamine (HAT) administration in reducing inpatient all-cause mortality among patients with septic shock. MATERIALS AND METHODS: Our single-center, prospective, open-label, randomized controlled trial recruited patients with admitting diagnosis of septic shock and assigned eligible patients (1:1) into either intervention (HAT) or control group (routine). The HAT group received intravenous combination of vitamin C (1.5 g every 6 hours), thiamine (200 mg every 12 hours), and hydrocortisone (50 mg every 6 hours) within 6 hours of onset of septic shock admission. The treatment was continued for at least 4 days, in addition to the routine standard of care provided to the control group. Thiamine and hydrocortisone use in control arm was not restricted. Vitamin C levels were estimated at baseline and at the end of the 4 days of treatment for both groups. The primary outcome evaluated was mortality during inpatient stay. RESULTS: Among 90 patients enrolled, 88 patients completed the study protocol. The baseline characteristics between the HAT (n = 45) and the routine (n = 43) groups were comparable. The all-cause mortality in the HAT cohort was 57% (26/45) compared to 53% (23/43) in the routine care group (p = 0.4, OR 1.19, 95% CI 0.51-2.76). The time to reversal of septic shock was significantly lower in the HAT (34.58 ± 22.63 hours) in comparison to the routine care (45.42 ± 24.4 hours) (p = 0.03, mean difference -10.84, 95% CI -20.8 to -0.87). No significant difference was observed between the HAT and the routine care with respect to changes in sequential organ failure assessment (SOFA) scores at 72 hours (2.23 ± 2.4 vs 1.38 ± 3.1), the use of mechanical ventilation (48% vs 46%), and mean Vasoactive Inotropic Score (7.77 ± 12.12 vs 8.86 ± 12.5). CONCLUSION: Intravenous administration of vitamin C, thiamine, and hydrocortisone did not significantly improve the inpatient all-cause mortality among patients with septic shock. CLINICAL SIGNIFICANCE: HAT protocol does not reduce hospital mortality but decreases time to shock reversal in septic shock. HOW TO CITE THIS ARTICLE: Mohamed ZU, Prasannan P, Moni M, Edathadathil F, Prasanna P, Menon A, et al. Vitamin C Therapy for Routine Care in Septic Shock (ViCTOR) Trial: Effect of Intravenous Vitamin C, Thiamine, and Hydrocortisone Administration on Inpatient Mortality among Patients with Septic Shock. Indian J Crit Care Med 2020;24(8):653-661.
