September 5, 2020

Background: Over the past few years, corticosteroids have gained traction in the treatment of patients with ARDS and septic shock.  Trials such as APROCCHSS and ADRENAL have shown that the use of corticosteroids is associated with more rapid resolution of shock, weaning from mechanical ventilation in septic shock, and, potentially lower mortality. The RECOVERY trial, the largest RCT to date on the use of corticosteroids in COVID-19, showed treatment with dexamethasone (6mg/d for 10 days)  had an absolute mortality reduction of 11% in patients receiving mechanical ventilation   (IMV) (NNT = 9), 3.5% decreased mortality in patients requiring O2 but not IMV (NNT = 29) and an overall mortality reduction 3% (NNT = 3) compared to usual care alone.  However, there was a signal toward harm (not statistically significant) in patients not receiving respiratory support. In the September 2020 issue of JAMA, there were 3 RCTs (REMAP-CAP, CoDEX, & CAPE COVID) assessing corticosteroid therapy in critically ill patients with COVID-19, as well as a prospective meta-analysis. All 3 RCTs halted enrollment in June 2020 after the RECOVERY trial press release.  The prospective meta-analysis from the WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) working group pooled data from 7 trials (RECOVERY, REMAP-CAP, CoDEX, CAPE COVID, and 3 additional trials) with roughly 1700 patients. In this post we will review the REMAP-CAP, CoDEX, and CAPE COVID trials, as well as the prospective meta-analysis.

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)?