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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.

Methods

A 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.

Results

A 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.

Conclusion

Evidence 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.

SUBMITTER: Volbeda M

PROVIDER: S-EPMC4483251 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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

Volbeda M M Wetterslev J J Gluud C C Zijlstra J G JG van der Horst I C C IC Keus F F

Intensive care medicine 20150623 7

<h4>Introduction</h4>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.<h4>Methods</h4>A systematic review was conducted according to a published protocol and The Cochrane Handbook methodology including meta-analyses, TSA of ran ...[more]

PMID: 26100123

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Project description:ObjectiveTo determine whether there is sufficient evidence to conclude that exercise interventions are more effective than no exercise control and to compare the effectiveness of different exercise interventions in relieving pain and improving function in patients with lower limb osteoarthritis.Data sourcesNine electronic databases searched from inception to March 2012.Study selectionRandomised controlled trials comparing exercise interventions with each other or with no exercise control for adults with knee or hip osteoarthritis.Data extractionTwo reviewers evaluated eligibility and methodological quality. Main outcomes extracted were pain intensity and limitation of function. Trial sequential analysis was used to investigate reliability and conclusiveness of available evidence for exercise interventions. Bayesian network meta-analysis was used to combine both direct (within trial) and indirect (between trial) evidence on treatment effectiveness.Results60 trials (44 knee, two hip, 14 mixed) covering 12 exercise interventions and with 8218 patients met inclusion criteria. Sequential analysis showed that as of 2002 sufficient evidence had been accrued to show significant benefit of exercise interventions over no exercise control. For pain relief, strengthening, flexibility plus strengthening, flexibility plus strengthening plus aerobic, aquatic strengthening, and aquatic strengthening plus flexibility, exercises were significantly more effective than no exercise control. A combined intervention of strengthening, flexibility, and aerobic exercise was also significantly more effective than no exercise control for improving limitation in function (standardised mean difference -0.63, 95% credible interval -1.16 to -0.10).ConclusionsAs of 2002 sufficient evidence had accumulated to show significant benefit of exercise over no exercise in patients with osteoarthritis, and further trials are unlikely to overturn this result. An approach combining exercises to increase strength, flexibility, and aerobic capacity is likely to be most effective in the management of lower limb osteoarthritis. The evidence is largely from trials in patients with knee osteoarthritis.Protocol registrationPROSPERO (www.crd.york.ac.uk/prospero/) No CRD42012002267.

Dataset Information

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

Introduction

Methods

Results

Conclusion

Publications

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

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