Steroids in sepsis: another swing of the pendulum in our clinical trials

Jean-Louis Vincent

doi:10.1186/cc6861

Abstract

Many studies have been conducted to try and find interventions to treat patients with severe sepsis, but with little success. In several cases, initial apparent beneficial effects have not been confirmed in later trials. The story of steroids in sepsis is one example of this pendulum effect, with initial success in the study by Annane et al. tempered by the more recent negative results of the Corticus study. The reasons for this pendulum effect are likely related, at least in part, to issues of clinical trial design and the way in which clinical trials in intensive care unit patients are developed, conducted and assessed needs to be critically reassessed.

Highlights

The search for effective interventions in sepsis has, in several cases, been associated with rather inconsistent results from clinical studies, as the pendulum seems to swing from a benefit effect through no effect to potential harm and all the way back to benefit, leaving the practicing clinician with a real therapeutic dilemma
With Schumer demonstrating that treatment with one or two doses of intravenous dexamethasone (3 mg/kg) or methylprednisolone (30 mg/kg) was associated with reduced mortality compared with saline treatment in patients with septic shock [1]
In the late 1990s, several studies were published suggesting a role for much smaller, so-called stress, doses of steroids in reducing vasopressor requirements in patients with septic shock [6-8]. These results led to a study by Annane and colleagues in which patients with relative adrenal insufficiency – as assessed by nonresponse to a corticotropin test – who were treated with hydrocortisone (50 mg intravenously every 6 hours) and fludrocortisone (50 μg orally daily) for 7 days had a reduced mortality compared with nonresponders treated with placebo [9]

Summary

Introduction

The search for effective interventions in sepsis has, in several cases, been associated with rather inconsistent results from clinical studies, as the pendulum seems to swing from a benefit effect through no effect to potential harm and all the way back to benefit, leaving the practicing clinician with a real therapeutic dilemma. The story of steroids in sepsis is one example of this pendulum effect, with initial success in the study by Annane et al tempered by the more recent negative results of the Corticus study.

Results

Conclusion