Association of Vitamin C, Thiamine, and Hydrocortisone Infusion With Long-term Cognitive, Psychological, and Functional Outcomes in Sepsis Survivors

Abstract

ImportanceSepsis is associated with long-term cognitive impairment and worse psychological and functional outcomes. Potential mechanisms include intracerebral oxidative stress and inflammation, yet little is known about the effects of early antioxidant and anti-inflammatory therapy on cognitive, psychological, and functional outcomes in sepsis survivors.ObjectiveTo describe observed differences in long-term cognitive, psychological, and functional outcomes of vitamin C, thiamine, and hydrocortisone between the intervention and control groups in the Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) randomized clinical trial.Design, Setting, and ParticipantsThis prespecified secondary analysis reports the 6-month outcomes of the multicenter, double-blind, placebo-controlled VICTAS randomized clinical trial, which was conducted between August 2018 and July 2019. Adult patients with sepsis-induced respiratory and/or cardiovascular dysfunction who survived to discharge or day 30 were recruited from 43 intensive care units in the US. Participants were randomized 1:1 to either the intervention or control group. Cognitive, psychological, and functional outcomes at 6 months after randomization were assessed via telephone through January 2020. Data analyses were conducted between February 2021 and December 2022.InterventionsThe intervention group received intravenous vitamin C (1.5 g), thiamine hydrochloride (100 mg), and hydrocortisone sodium succinate (50 mg) every 6 hours for 96 hours or until death or intensive care unit discharge. The control group received matching placebo.Main Outcomes and MeasuresCognitive performance, risk of posttraumatic stress disorder and depression, and functional status were assessed using a battery of standardized instruments that were administered during a 1-hour telephone call 6 months after randomization.ResultsAfter exclusions, withdrawals, and deaths, the final sample included 213 participants (median [IQR] age, 57 [47-67] years; 112 males [52.6%]) who underwent long-term outcomes assessment and had been randomized to either the intervention group (n = 108) or control group (n = 105). The intervention group had lower immediate memory scores (adjusted OR [aOR], 0.49; 95% CI, 0.26-0.89), higher odds of posttraumatic stress disorder (aOR, 3.51; 95% CI, 1.18-10.40), and lower odds of receiving mental health care (aOR, 0.38; 95% CI, 0.16-0.89). No other statistically significant differences in cognitive, psychological, and functional outcomes were found between the 2 groups.Conclusions and RelevanceIn survivors of sepsis, treatment with vitamin C, thiamine, and hydrocortisone did not improve or had worse cognitive, psychological, and functional outcomes at 6 months compared with patients who received placebo. These findings challenge the hypothesis that antioxidant and anti-inflammatory therapy during critical illness mitigates the development of long-term cognitive, psychological, and functional impairment in sepsis survivors.Trial RegistrationClinicalTrials.gov Identifier: NCT03509350

Thiamine for Septic Shock: Take Your Vitamins?

“…Thiamine replacement can reduce lactate concentrations in critically ill patients ( 7 ) and appeared to benefit certain patients with septic shock at increased risk for thiamine deficiency; however, the potential benefits and risks have yet to be fully understood ( 8 – 10 ).…”

Ascorbic acid modulates immune responses through Jumonji‐C domain containing histone demethylases and Ten eleven translocation (TET) methylcytosine dioxygenase

“…[121,122] Although Intravenous ascorbic acid led to reduction of cytokine storm in acute respiratory distress syndrome may be due to attenuation of IL-1β, IL-6, IL-8, and TNFα expression and JMJD3-mediated polarization of anti-inflammatory M2 macrophages (ARDS) [59,[123][124][125] in the VICTAS study, survivors of sepsis who were treated early in the ICU with vitamin C, hydrocortisone and thiamine, had cognitive, psychological, and functional results that were either unaltered by the regimen or worsened compared to those who received placebo at the 6-month follow-up. [126] Intravenous vitamin C has a higher risk of death or persistent organ dysfunction in adults with sepsis receiving vasopressor therapy. [127] In individuals with septic shock, ascorbic acid monotherapy was unable to reduce mortality.…”

Error in the Byline

“…In the Original Investigation titled “Association of Vitamin C, Thiamine, and Hydrocortisone Infusion With Long-term Cognitive, Psychological, and Functional Outcomes in Sepsis Survivors: A Secondary Analysis of the Vitamin C, Thiamine, and Steroids in Sepsis Randomized Clinical Trial,” published February 28, 2023, Ms Kiehl’s name should be listed as Amy L. Kiehl, MA. This article has been corrected …”