May 18, 2020

Background: Getting the basics right in all illness is vital. In sepsis, this means appropriate use of antibiotics, judicious fluid resuscitation, and early identification.  Vasopressor support is also essential in the sickest sepsis patients (i.e. septic shock). Should the metabolic cocktail (thiamine, vitamin C and hydrocrotisone) be part of that initial package? We’ve previously reviewed the key articles in this area: CITRIS-ALI, VITAMINS, and the original before and after Marik trial. Now we have our next RCT, the HYVCTTSSS trial. From a pathophysiologic standpoint, Vitamin C levels are thought to be low in critically ill patients with sepsis. Vitamin C is an antioxidant that prevents vascular endothelial damage and helps maintain microvascular integrity. Additionally, it is a cofactor for catecholamine synthesis which helps maintain vascular tone and cardiac output.  Glucocorticoids have been shown to reduce time to shock relief and length of ICU stay, but not mortality. The addition of thiamine can help promote oxalate decomposition, which reduces vitamin C metabolites from depositing and crystalizing in kidneys.  While these medications are cheap, the more important question is do they improve patient-oriented outcomes? The previous literature on whether this translates to patient oriented benefits has been mostly negative thus far.

January 27, 2020

Background: The combination of vitamin C, hydrocortisone and thiamine in sepsis has been a topic of hot debate in the past couple years.  There is a hypothetical pathophysiological basis to make an argument for the use of this combination of medications, but as with anything it is important to ensure there are no untoward effects either. In Dr. Marik’s before and after study [1] we saw some pretty amazing results showing that treatment reduced hospital mortality  by 31.9% (Treatment Group 8.5% vs Control Group 40.4%). Too good to be true?  Well in short, YES…the major issues with this study were it was not a randomized controlled trial, had a small sample size, was a single center study, and had significant selection bias.  Well we finally have our first randomized controlled trial evaluating the “metabolic cocktail” in a general population of septic shock adult patients.

November 25, 2019

Background: In 2016, Paul Marik published a study in Chest [2] demonstrating a decrease in hospital mortality of 32% for sepsis patients treated with vitamin C, thiamine and hydrocortisone.  The Marik protocol(as it has come to be known), entails IV vitamin C 1.5g q6hr for 4d + IV hydrocortisone 50mg q6hr for 7d + IV thiamine 200mg q12hr x4d. The authors’ hypothesis was that vitamin C, hydrocortisone, and thiamine have synergistic effects that reverse vasoplegic shock and potentially limit the duration of vasopressor treatment resulting in a reduction in organ and limb ischemia from vasopressors themselves.  Although the results of the study are promising, it is important to remember that this was only a hypothesis generating study.  We have been waiting for a randomized clinical trial to recreate the results of this study and finally we have our first of many… CITRIS-ALI. This randomized trial looks to see if high-dose vitamin C could reduce organ failure and biomarkers of inflammation and vascular injury in patients with sepsis and ARDS.

April 7, 2017

Background: The overall mortality in sepsis has decreased quite a bit in the last decade or so, however for a subset of patients, like those with Septic Shock, the mortality still remains high (as high as 50%).  There have been hundreds of studies trying to identify the holy grail to decrease mortality further, but one has not been found thus far.  Marik PE et al [1] published a study in Chest 2016 that has found a potential front runner.  In addition, the authors go on to say, in order to have an impact on a global scale, treatments would not only need to be effective, but also cheap, safe, and readily available; the authors of the following paper may have found just that..
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