Written by Clay Smith
A combination of hydrocortisone, ascorbic acid, and thiamine did not appear to reduce ventilator or vasopressor-free days or reduce mortality compared with placebo in sepsis patients.
Why does this matter?
We have written extensively on the “metabolic cocktail” of hydrocortisone, ascorbic acid, and thiamine for sepsis. This started with the original case report of this weird sepsis cocktail and has been followed by numerous luscious fruity RCT acronyms: CITRUS ALI, to HYVCTTSSS, to VITAMINS, to VITAMINS for kids, to ORANGES, to ACT.
Approaching the definition of insanity…
This was a multicenter RCT that enrolled 501 patients who had sepsis and respiratory or cardiovascular dysfunction as a result. They received, “intravenous vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) every 6 hours (n = 252) or matching placebo (n = 249) for 96 hours or until discharge from the intensive care unit or death.” For the primary outcome of ventilator and vasopressor-free days, there was no difference: cocktail group 25 days; placebo group 26 days; difference -1 day (95%CI -4 to 2, p = .85). There was also no difference in mortality: cocktail 22%; placebo 24%. The trial lost funding funding and was stopped early administratively. They planned to enroll 2,000 patients. That’s unfortunate, and this study may be underpowered to detect a true difference. However, the original case report by Marik et al was headline-grabbing precisely because the sepsis cocktail appeared to work like a miracle, with drastic mortality reductions. Given the negative results of this study and its many tangy cousins, I think it is probably true that this sepsis cocktail does not improve meaningful sepsis outcomes.
Effect of Vitamin C, Thiamine, and Hydrocortisone on Ventilator- and Vasopressor-Free Days in Patients With Sepsis: The VICTAS Randomized Clinical Trial. JAMA. 2021 Feb 23;325(8):742-750. doi: 10.1001/jama.2020.24505.