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)?

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.

March 19, 2020

Background: Vasopressors are often used to improve hypotension and perfusion in an effort to decrease mortality of patients with septic shock. Mean arterial pressure (MAP) of >65mmHg has typically been used to guide vasopressor therapy in most patients and higher targets have been recommended for patients with chronic hypertension or coronary artery disease. Results from the Sepsis and Mean Arterial Pressure (SEPSISPAM) [2] and Optimal Vasopressor Titration (OVATION) [3] pilot trials suggested that increased exposure to vasopressors targeting higher MAPs in older patients (≥65mmHg) may be associated with increased risk of death. We now have the 65 trial [1] which is a randomized clinical trial testing the hypothesis that reducing vasopressor exposure through permissive hypotension (Targeting a MAP of 60 – 65mmHg) among patient ≥65 years of age with vasodilatory hypotension versus usual care in the ICU.

March 2, 2020

Background: The cornerstones of sepsis management include early identification, early antimicrobial administration, and source control.  The Surviving Sepsis Campaign guidelines recommend that blood cultures be drawn before starting antimicrobial therapy, however, obtaining cultures prior to antibiotics may be challenging due to shorter time windows (i.e. 1hr from identification) to initiate antibiotics.  Some may prioritize administering antimicrobial agents before obtaining blood cultures to ensure they meet this core measure. This study (The FABLED Trial) tried to determine the sensitivity of blood cultures obtained both before and after initiation of antimicrobial therapy in patients with severe manifestations of sepsis.

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.

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