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.

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.

November 7, 2019

Background: Despite minimal high-quality supporting evidence (Seymour 2017, Liu 2017, Ferrer 2014, Sterling 2015), regulatory bodies have pushed for benchmark times for administration of antibiotics in patients with sepsis. While most clinicians would agree that in patients with septic shock antibiotics should be given as quickly as possible, the same does not hold true for those patients with less severe infections. In the US, the Centers for Medicare and Medicaid Services (CMS) currently mandates that antibiotics be started in patients within 3 hours of onset of new organ dysfunction in patients with systemic inflammatory response syndrome and documented infection. The Surviving Sepsis Campaign (SSC) has even more extreme recommendations stating that antibiotics should be started within 1 hour from triage in septic patients (Levy 2018). Based on prior experience with arbitrary time to antibiotic administration (see community acquired pneumonia), such draconian recommendations are likely to increase inappropriate use of antibiotics, distract clinicians from more important tasks and have minimal effect on patient outcomes. This is likely why the Infectious Disease Society of America (IDSA) declined endorsement of the SSC guidelines. The ridiculous nature of these recommendations has been discussed elsewhere.

Even if the recommendation had some merit, it’s important to ask whether it’s even possible to implement. None of those on the SSC committee work in emergency departments and their understanding of the logistical challenges of such a policy is limited.