Landmark Papers in Critical Care: steroids for septic shock

When the body is in septic shock, the self-perpetuated inflammatory response can become more dangerous than the infection itself. One of the effects that severe sepsis can have is relative adrenal insufficiency.

One of the classic papers looking at the effect of steroids in septic shock was, fittingly named, “Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock.” The goal of the study was to examine whether a hydrocortisone-fludrocortisone combo could improve mortality in severe septic shock. These were patients who were hypotensive despite being on pressors and getting fluids, and who were mechanically intubated.

Within 8 hours of onset of shock, a 250 microgram ACTH test was administered and then patients were randomized to placebo or hydrocortisone 50 mg IV every 6 hours plus fludrocortisone 50 micrograms PO daily for seven days.

Overall, there was no mortality difference demonstrated between the groups at 28-days. However, in a subgroup analysis, there was a 10% absolute reduction in 28-day mortality in patients that were non-responders to the ACTH test (<9 micrograms/dL change from baseline cortisol) randomized to the treatment group (p=0.04). This was not a super-convincing finding, but did show improvement in the most important metric of any study: mortality.

Steroids in treatment of septic shock remains a controversial issue. Other studies such as the CORTICUS trial did not find any mortality benefit. However, the CORTICUS patients were enrolled within 72 hours, not 8, and in general were not as sick. Meta-analyses conclude that there is most likely a benefit to steroids–specifically, IV hydrocortisone–in patients who are truly in shock, ie, not responding to pressors.

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