Glucocorticosteroids for sepsis: systematic review with meta-analysis and trial sequential analysis

Abstract

Introduction Glucocorticosteroids (steroids) are widely used for sepsis patients. However, the potential benefits and harms of both high and low dose steroids remain unclear. A systematic review of randomised clinical trials with meta-analysis and trial sequential analysis (TSA) might shed light on this clinically important question.MethodsA systematic review was conducted according to a published protocol and The Cochrane Handbook methodology including meta-analyses, TSA of randomised clinical trials, and external validity estimation (GRADE). Randomised clinical trials evaluating steroids were included for sepsis patients (systemic inflammatory response syndrome, sepsis, severe sepsis or septic shock) aged >18 years. Cochrane Central Register of Controlled Trials (CENTRAL), PubMed/Medline, Embase, Web of Science and Cinahl were searched until 18 February 2015. No language restrictions were applied. Primary outcomes were mortality at longest follow-up and serious adverse events.ResultsA total of 35 trials randomising 4682 patients were assessed and reviewed in full text. All trials but two had high risk of bias. No statistically significant effect was found for any dose of steroids versus placebo or no intervention on mortality at maximal follow-up [relative risk (RR) 0.89; TSA adjusted confidence interval (CI) 0.74–1.08]. Two trials with low risk of bias also showed no statistically significant difference (random-effects model RR 0.38, 95 % CI 0.06–2.42). Similar results were obtained in subgroups of trials stratified according to high (>500 mg) or low (≤500 mg) dose hydrocortisone (or equivalent) (RR 0.87; TSA-adjusted CI 0.38–1.99; and RR 0.90; TSA-adjusted CI 0.49–1.67, respectively). There were also no statistically significant effects on serious adverse events other than mortality (RR 1.02; TSA-adjusted CI 0.7–1.48). The effects did not vary according to the degree of sepsis. TSA showed that many more randomised patients are needed before definitive conclusions may be drawn.ConclusionEvidence to support or negate the use of steroids in any dose in sepsis patients is lacking. The results of ongoing and future well-designed, large randomised clinical trials are needed.Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-015-3899-6) contains supplementary material, which is available to authorized users.

The effect of physiologic dose of intravenous hydrocortisone in patients with refractory septic shock: a randomized control trial

“…In a systemic review and meta-analysis which was done in 2015, a total of 35 articles were assessed. It included 4682 patients and there was no relation between steroid doses and mortality (24). Death in patients with and without diabetes had a significant difference.…”

Does Low Dose Steroids Confer Benefits in Sepsis and Septic Shock?

“…Finally, TSA suggested that many more randomized patients are needed to draw a conclusion. 43 Although in the CORTICUS trial shock reversal with the LDCs was achieved quickly, there was increased evidence of new sepsis or septic shock in the hydrocortisone group (OR 1.37, p<0.05). 32 They also showed increased rates of hyperglycemia and hypernatremia in the treatment group.…”

Corticosteroid Treatment in Critically Ill Patients

“…There have been previous meta-analyses of steroids within the critical care environment [2][3][4], but, to our knowledge, this is the first using an NMA approach and the first analysis focussing on the effect of the therapeutic agent and regimen. Although all corticosteroids possess the immune, metabolic and fluid homeostatic features of their group, marked differences in the activity of each drug in these features exists.…”

“…Second, do steroids given to all critically ill patients improve outcomes [2]? These questions have been investigated primarily in those patients with septic shock, and sufficient studies have been conducted to allow multiple meta-analyses [2][3][4], including a recently updated Cochrane review [2]. However, not all therapeutic corticosteroids are the same.…”