- Design
- Post hoc analysis of a double-blind, factorial randomised trial
- Population
- 173 adults with septic shock in UK intensive care units
- Primary outcome
- Interaction of baseline PENK with hydrocortisone on kidney-failure-free days and mortality
- Effect
- High PENK: kidney-failure-free days 11 with hydrocortisone vs 26 with placebo (interaction p = 0.01)
VANISH randomised UK patients with septic shock to vasopressin or norepinephrine, and then to hydrocortisone or placebo. This post hoc analysis measured proenkephalin A (PENK), a marker of kidney function, in 173 of them and split them at 89 pmol/L.
High PENK was associated with higher 28-day mortality (OR 3.24, 95% CI 1.62–6.74). Among the 111 who reached the vasopressor threshold for the hydrocortisone stage, there was an interaction for kidney-failure-free days: with high PENK, median 11 days on hydrocortisone against 26 on placebo; with low PENK, 28 in both. Mortality in high-PENK patients was 50% with hydrocortisone and 32% with placebo, but that interaction was not statistically significant.
This is a small exploratory subgroup analysis and the authors say it needs validation. It is a hypothesis about why steroid trials in sepsis disagree, not a reason to withhold hydrocortisone.
- Keep giving hydrocortisone in septic shock as current guidance recommends.
- Do not use PENK to select patients for steroids; it is not validated for that.
- Monitor kidney function closely in septic shock whether or not steroids are given.
- Watch for a validation study before changing practice.
Why it matters
If confirmed, a biomarker could explain why steroid trials in sepsis keep reaching different conclusions.
Don't overread it
A post hoc subgroup of 111 patients cannot show that hydrocortisone harms anyone; the mortality interaction was not significant.
The statistics, in plain English
An interaction test asks whether a treatment works differently in two groups. Here it was significant for kidney outcomes (p = 0.01) but not for death (p = 0.14). Post hoc subgroup findings in small samples are often not reproduced.
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