April 8, 2021

Background: Since the publication of the before and after Marik trial [1] published in 2016, there have been six randomized clinical trials trying to answer the question of the utility of the metabolic cocktail (Vitamin C, thiamine, and hydrocortisone) in septic shock (See table below). Although, each was of various methodological rigor only one had a positive primary outcome (i.e. ORANGES). It is important to note that the primary outcome of the ORANGES trial was changed after full data collection (and likely analysis) was complete (See the REBEL EM analysis HERE). We now have our 7th RCT on this topic.

October 12, 2020

Background: The only well-established treatments for sepsis and septic shock are antibiotic therapy and source control.  Septic shock, the most severe form of sepsis, is characterized by circulatory and cellular metabolism abnormalities.  There have been a host of randomized controlled trials evaluating the use of vitamin C, thiamine, and corticosteroids (i.e. metabolic cocktail) to help mitigate dysregulated host responses in the hopes of improving patient-oriented outcomes. Thus far none of the randomized trials have shown improvements in mortality and shown mixed results with shock reversal (see tables below).

October 10, 2020

From Oct 6th – 8th, 2020, Haney Mallemat (@CriticalCareNow) and his team put on an absolutely amazing online critical care conference called ResusX Rewired.  ResusX is a conference designed by resuscitationists to provide clinicians with the most up to date skills and knowledge to help make a difference in your patients' lives.  Haney and his crew made a combination of short-format, high-yield lectures, and completely customizable small group sessions with procedural demos seem easy.  There were so many high-quality speakers and pearls that I learned from this conference that I wanted to archive them here in one post for reference and to share with our readers/followers.

September 14, 2020

Background: Though it’s been stated numerous times on this blog, it bears repeating: the pillars of sepsis care remain early identification of sepsis, early appropriate empiric antibiotics, source control, and supportive care. The focus should be on getting the basics right but, it is important to evaluate whether other adjunctive therapies can help decrease mortality in a common and frequently fatal condition. Ascorbic acid and thiamine deficiency have been described in patients with sepsis and are thought to be due to reduced intake and increased metabolic demands.  Corticosteroids have had mixed results but seem to improve shock reversal in patients with septic shock based on best available evidence (Link is HERE). There have been a slew of RCTs evaluating this metabolic cocktail (vitamin C, thiamine, & corticosteroids) in recent months. Though biologically plausible, this treatment approach has not been shown to improve patient-oriented outcomes.

July 16, 2020

Background: The cornerstones of sepsis management continues to include early identification, early appropriate empiric antibiotics, definitive source control, and vasopressors to support end organ perfusion. There have been multiple studies looking at the co-administration of hydrocortisone, ascorbic acid, and thiamine (known as HAT therapy or the metabolic cocktail) to help reduce mortality and reverse shock. Despite the original Marik study showing an association between HAT therapy and a 31.9% overall decrease in mortality and a 3-fold decrease in time to vasopressor discontinuation in patients presenting with severe sepsis and septic shock, the mortality benefit has not been reproduced in subsequent randomized clinical trials.  Studies focused specifically on the use of corticosteroids have demonstrated reduced time on vasopressors in patients in septic shock.  The bigger question is does vitamin C and thiamine add anything additional to help improve mortality (The ORANGES Trial)?