Sepsis - Steroids & APC Flashcards
Low-dose steroids in sepsis study
JAMA 2002 - France
Pts in septic shock requiring pressors randomized to 7d hydrocort (50q6) + fludrocort (50qd) vs placebo
Inadequate adrenal reserve pts had 30% reduced mortality at 28d w/ steroids.
Adequate adrenal reserve pts saw no mortality benefit
Defining inadequate adrenal reserve
<9ug/dl increase in cortisol with cosyntropin stim.
- Measure cortisol
- Give 250ug cosyntropin 30-60min
- Remeasure cortisol 30-60min later
Based on the French study, why do we not use Fludrocortisone?
Likely redundant to hydrocort, which has its own mineralocorticoid activity
Etomidate and HPA axis
Etomidate suppresses cortisol synthesis for up to 1 day
CORTICUS
NEJM 2008
Randomized septic shock pts to hydrocort 50q6 vs placebo x 5 days
No diff in 28d mortality regardless of adeq vs inadeq adrenal reserve
Hydrocort did contribute to faster reversal of shock
What accounts for differences between French study and CORTICUS?
French study had pts w/ more severe septic shock, so you can justify hydrocort use in sicker pts
General recommendations on steroids in sepsis
- If already on steroids, continue
- Consider steroids in all pts with SEVERE septic shock (SBP1h despite IVF) within 8h of shock onset
- Avoid steroids in pts w less severe septic shock
- Avoid cort stim test since cortisol lvls are unreliable in critically ill pts
Sepsis effect on protein C
Sepsis induces tissue factor activation and protein C decrease, leading to pro-coagulant state
Trials looking at APC in Sepsis
- PROWESS: rhAPC reduced mortality, but increases bleeding. Controversial findings.
- ADDRESS: Re-examined PROWESS. Mortality similar, but even more intracranial bleed.
Overall recommendations on APC in Sepsis
Use rhAPC only in pts w/ severe sepsis and APACHE II>25 (high risk of death) and no other risk factors for bleeding (Plts <30)
