Vitamin C in Sepsis - Fails!
The headlines in the news 2017 were remarkable indeed: "Doctor believes he has found the cure for sepsis..." or "Doctor says improvised 'cure' for sepsis has had remarkable results".
Dr. Paul Marik described his observation in an interview in 2017, where he mentions several cases of sepsis that have almost miraculously responded to the application of vitamin c (watch here: Interview on WAVY TV). He even continues, that since then they see "the same thing over and over again". This implicated that these results were reproducible. He finally stated that the current data at that stage were "impressive" and that there was enough basic science to show that it works.
Vitamin C has many interesting properties that theoretically could be on benefit in sepsis. (read here: Crit☁ post on Vitamin C). Its application was already proposed for the treatment of other diseases like the common cold of Influenza. Despite some moderate positive influence observed, these results could not be reproduced in trials.
While the news picked up on this story as a miracle drug, Paul Marik et al. published their results of a before-and-after single-centre, retrospective cohort study in Chest 2017. In this paper, they compared 47 patients with sepsis that received the metabolic cocktail (Vitamin C 1.5g 6-hourly, hydrocortisone 50mg 6-hourly and thiamine 200mg 12-hourly) to 47 patients which did not - notably in a non-double-blinded, non-randomized fashion. Their results showed overall hospital mortality of 8.5% with the 'cocktail' and 40.4% without its application.
This publication was reason enough to launch a small war of faith about sense and nonsense of this cocktail for sepsis.
The VITAMINS Trial - First Failure
Since 2017 a tiny bunch of studies were published, many of them with significant limitations like a small number of patients, often not randomized-controlled and with conflicting results.
Nabil Habib T, Ahmed I (2017) Early Adjuvant Intravenous Vitamin C Treatment in Septic Shock may Resolve the Vasopressor Dependence. Int J Microbiol Adv Immunol. 05(1), 77-81.
Shin et al. J Clin Med. 2019 Jan; 8(1): 102.
Fowler et al. JAMA. 2019 Oct 1;322(13):1261-1270.
Fujii et al. have just now published the first more substantial and rigorous trial taking a closer look at the influence on vitamin c in sepsis.
They performed an
international, multicenter, randomized-controlled open label trial
In which they enrolled 211 patients with septic shock admitted to an ICU.
Treatment with Vitamin C 1.5g 6-hourly IV, hydrocortisone 50mg 6-hourly IV and thiamin 200mg 12-hourly IV
Hydrocortisone 50mg 6-hourly IV only.
No difference in time alive and time free of vasopressors (primary endpoint) and
No difference 28 days or 90 days mortality (secondary endpoint)
This first study on a larger scale, unfortunately, disappoints. More trials are on the way and might give a clearer picture of this topic to come to a final decision eventually.
For the moment it is appropriate to state:
Just as a reminder: Guidelines recommend against the routine use of glucocorticoids in patients with sepsis. However, corticosteroid therapy is appropriate in patients with septic shock that is refractory to adequate fluid resuscitation and vasopressor administration.
Fujii et al. JAMA. Published online January 17, 2020. doi:10.1001/jama.2019.22176