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VITAMINS for Septic Shock? Hydrocortisone, Ascorbic Acid, and Thiamine for Septic Shock

February 5, 2020

Written by Sam Parnell

Spoon Feed
A combination of vitamin C, thiamine, and hydrocortisone does not appear to lead to improved outcomes or more rapid resolution of septic shock compared to hydrocortisone alone.

Why does this matter?
Sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, is one of the leading causes of death for patients worldwide. Recent studies have suggested that vitamin C and thiamine supplementation may improve outcomes for patients in septic shock. Does it?

The effect of VITAMINS for septic shock was shockingly underwhelming…
The VITAMINS study was a multicenter, international, open-label, randomized clinical trial of 211 patients with septic shock comparing a combination of IV vitamin C (1.5 g every 6 hours), hydrocortisone (50 mg every 6 hours), and thiamine (200 mg every 12 hours) to IV hydrocortisone (50 mg every 6 hours) alone. There was no significant difference in the primary outcome of time alive and free of vasopressors up to 7 days (122.1 hours [IQR, 76.3-145.4 hours] in the intervention group and 124.6 hours [IQR, 82.1-147.0 hours] in the control group).

In addition, there was no statistically significant difference in 9/10 secondary outcomes including all-cause mortality at 28 and 90 days, 28-day cumulative vasopressor-free days, 28-day ventilation-free days, 28-day cumulative renal replacement therapy-free days, 28-day ICU-free days, survival to discharge, or hospital length of stay. The only secondary outcome that was statistically significant was change in SOFA score at day 3 which was greater in the intervention group than in the control group (median, –2 [IQR, –4 to 0] vs –1 [IQR, –3 to 0], respectively; difference, –1.0 [95% CI, –1.9 to –0.1]; P = .02). However, these secondary findings should be interpreted cautiously as this trial was underpowered to detect differences in the secondary outcomes.

This study was unblinded and was unable to assess the individual effects of vitamin C or thiamine for patients with septic shock. Nevertheless, these results suggest that a combination of vitamin C, thiamine, and hydrocortisone does not lead to more rapid resolution of septic shock than hydrocortisone alone. I don’t routinely give vitamin C or thiamine to patients with septic shock, and based on this study, I will not be changing my practice anytime soon.

Another Spoonful
See what EM Nerd, PulmCrit, REBEL EM, The Bottom Line, and EM Lit of Note had to say about VITAMINS.

Effect of Vitamin C, Hydrocortisone, and Thiamine vs Hydrocortisone Alone on Time Alive and Free of Vasopressor Support Among Patients With Septic Shock: The VITAMINS Randomized Clinical Trial. JAMA. 2020 Jan 17. doi: 10.1001/jama.2019.22176. [Epub ahead of print]

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