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).

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.

June 11, 2020

Background: In end-stage renal disease (ESRD) patients on hemodialysis (HD), infection is the second most common cause of mortality after cardiovascular disease (Sarnik 2000). Because of the systemic inflammation and increased capillary permeability, septic patients are at significant risk for fluid imbalances and frequently require large volumes of crystalloids. The Surviving Sepsis Campaign guidelines provide a strong recommendation with low quality of evidence for administering a 30mL/kg fluid bolus within 3 hours of recognition of sepsis-induced hypoperfusion (Rhodes 2016). Further fluid administration should be guided by hemodynamic assessment (bedside echocardiography, passive leg-raise, etc.). In the general population, this early administration of fluids to patients with hypotension or sepsis-induced hypoperfusion has been associated with improved outcomes. However, there is significant confusion regarding the effects of a large 30mL/kg bolus on ESRD patients due to a lack of studies. While these patients may appear, volume overloaded on physical exam, they may be intravascularly volume deplete. Physicians may be hesitant to administer a large fluid bolus in ESRD patients because of the risk of precipitating cardiogenic shock, pulmonary edema, and respiratory failure. In fact, multiple studies show that patients who have ESRD are less likely to receive the full 30mL/kg fluid bolus compared to non-ESRD patients (Lowe 2018, Truong 2019, Dagher 2015). Furthermore, some studies show equivalent outcomes between ESRD patients who receive the full bolus and those who do not. We will review two studies that examined this topic.

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.

May 11, 2020

“You’re in the emergency department, you have a patient who EMS has brought in from a nursing home…who’s excited? Right, nobody is. And they are brought in for a chief complaint of altered mental status. So they’re concerned about sepsis. This is your initial set of vital signs: febrile, tachycardic, hypotensive. And you’re looking at the patient and you’re looking at their Foley and it looks like somebody put oatmeal into it. You know for a fact that the probability is that they have a urinary tract infection is pretty high. So the next question is: do you do what you normally do, but add steroids?”
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