Systemic Steroids in Severe Sepsis and Septic Shock

Abstract

Despite more than 5 decades of study and debate, the role of corticosteroid treatment in patients with severe sepsis and septic shock remains controversial. Data support a beneficial effect on systemic blood pressure in patients with septic shock. However, the ability of corticosteroid therapy to improve mortality in patients with severe sepsis and septic shock remains controversial, with contradictory results from recent large multicenter clinical trials. Although it appears clear that high-dose corticosteroid treatment provides no benefit and possibly harm in septic patients, the experimental design flaws and biases of recent low-dose (physiologic) steroid treatment trials limit their ability to provide adequate answers to the important questions of which septic patients should be treated, how much steroid to give, and the optimum duration of treatment. Unfortunately, the answer to these important questions is not readily evident based on the current evidence or the application of metaanalysis to the available clinical data. This concise evidence-based review highlights the strengths and weaknesses of the current data to inform the practicing clinician as to which patients are likely to derive significant benefit from corticosteroid treatment, while we await more definitive guidance from future multicenter, prospective, randomized, controlled trials designed to better answer these important therapeutic questions.

Toward Smarter Lumping and Smarter Splitting: Rethinking Strategies for Sepsis and Acute Respiratory Distress Syndrome Clinical Trial Design

“…In the subclass with suppressed glucocorticoid receptor signaling, corticosteroids were independently associated with greater mortality (46). This preliminary work provides a testable hypothesis of which patients with septic shock may benefit from corticosteroids, a therapy that remains controversial because of our current difficulty in identifying which patients will benefit (48).…”

The endothelial glycocalyx: a review of the vascular barrier

“…Prophylactic intra-operative glucocorticoids did not benefit patients undergoing cardiac surgery [49]. Similarly, the role of steroids in sepsis remains unclear: while glucocorticoids improve vasopressor efficacy, it is uncertain whether they benefit patients [50]. No clinical study has specifically examined the impact of steroids on the glycocalyx in patients with sepsis.…”

Implications of the New International Sepsis Guidelines for Nursing Care

“…Although some randomized controlled trials have demonstrated mortality benefit with steroid therapy for patients in vasopressorunresponsive septic shock (hypotension despite fluid resuscitation and vasopressors for more than 60 min), other studies, including a large European multicenter trial (Corticosteroid Therapy of septic shock [CORTICUs]) failed to show a mortality benefit. 24 A review 25 on the use of steroids in adults with septic shock emphasized the importance of study selection for systematic analysis and confirmed the lack of evidence that the use of low-dose hydrocortisone improves the patients' outcome.…”