Dataset Information

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

ACCESS DATA

Publications

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

Similar Datasets

Project description:Study objectiveAlthough fluid resuscitation is recommended by the Society of Critical Care Medicine Surviving Sepsis Campaign Guidelines, risks of volume overload persist.The objective of this systematic review is to assess the effects of a restrictive fluid resuscitation approach in the septic patient both during and after the initial resuscitation period (30 ml/kg).DesignA systematic review and meta-analysis with trial sequential analysis (TSA) of randomized controlled trials was conducted. Two blinded reviewers independently assessed and included studies that evaluated adult patients with sepsis involving a comparator group with an effective restrictive fluid resuscitation approach. The primary outcome was mortality. Secondary outcomes included rates of acute kidney injury (AKI), renal replacement therapy (RRT), ventilator days, intensive care unit (ICU) and hospital length of stay (LOS), duration of vasopressor therapy, and limb (or digital) ischemia.SettingPubMed and Medline databases were queried for the search.PatientsA total of eight trials in 2375 patients were included.InterventionEffective restrictive fluid resuscitation compared with standard of care.Measurements and main resultsThe risk of bias was high in six studies and low in two studies, and all studies implemented fluid restriction after a 30-ml/kg infusion of fluids. Fluid restriction did not significantly reduce mortality in all studies compared to usual care (37% vs. 40% with usual care; risk ratio [RR] 0.90, 95% confidence interval [CI] 0.76-1.06, p = 0.23, I2 = 24%) or by TSA findings. There were no significant differences in rates of AKI or RRT (5 studies), LOS in ICU (4 studies) or hospital (3 studies), duration of vasopressor therapy (6 studies), or incidence of limb or digital ischemia (3 studies). However, fluid restriction significantly reduced ventilator days as evaluated in seven studies (mean difference - 1.25 days, 95% CI -1.92 to -0.58 days, p = 0.0003, I2 = 90%).ConclusionThis study demonstrated that a restrictive resuscitation strategy in sepsis resulted in no difference in mortality but may reduce ventilator days. Larger randomized trials are required to determine the optimal management of fluids in patients with sepsis.

Project description:ObjectiveTo assess the effects of fluid therapy with hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin on mortality, kidney injury, bleeding, and serious adverse events in patients with sepsis.DesignSystematic review with meta-analyses and trial sequential analyses of randomised clinical trials.Data sourcesCochrane Library, Medline, Embase, Biosis Previews, Science Citation Index Expanded, CINAHL, Current Controlled Trials, Clinicaltrials.gov, and Centerwatch to September 2012; hand search of reference lists and other systematic reviews; contact with authors and relevant pharmaceutical companies.Study selectionEligible trials were randomised clinical trials comparing hydroxyethyl starch 130/0.38-0.45 with either crystalloid or human albumin in patients with sepsis. Published and unpublished trials were included irrespective of language and predefined outcomes.Data extractionTwo reviewers independently assessed studies for inclusion and extracted data on methods, interventions, outcomes, and risk of bias. Risk ratios and mean differences with 95% confidence intervals were estimated with fixed and random effects models.ResultsNine trials that randomised 3456 patients with sepsis were included. Overall, hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin did not affect the relative risk of death (1.04, 95% confidence interval 0.89 to 1.22, 3414 patients, eight trials), but in the predefined analysis of trials with low risk of bias the relative risk of death was 1.11 (1.00 to 1.23, trial sequential analysis (TSA) adjusted 95% confidence interval 0.95 to 1.29, 3016 patients, four trials). In the hydroxyethyl starch group, renal replacement therapy was used more (1.36, 1.08 to 1.72, TSA adjusted 1.03 to 1.80, 1311 patients, five trials), and the relative risk of acute kidney injury was 1.18 (0.99 to 1.40, TSA adjusted 0.90 to 1.54, 994 patients, four trials). More patients in the hydroxyethyl starch group were transfused with red blood cells (1.29, 1.13 to 1.48, TSA adjusted 1.10 to 1.51, 973 patients, three trials), and more patients had serious adverse events (1.30, 1.02 to 1.67, TSA adjusted 0.93 to 1.83, 1069 patients, four trials). The transfused volume of red blood cells did not differ between the groups (mean difference 65 mL, 95% confidence interval -20 to 149 mL, three trials).ConclusionIn conventional meta-analyses including recent trial data, hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin increased the use of renal replacement therapy and transfusion with red blood cells, and resulted in more serious adverse events in patients with sepsis. It seems unlikely that hydroxyethyl starch 130/0.38-0.45 provides overall clinical benefit for patients with sepsis.

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.

Project description:ObjectiveTo evaluate the benefits and harms of antithrombin III in critically ill patients.DesignSystematic review and meta-analysis of randomised trials.Data sourcesCENTRAL, Medline, Embase, International Web of Science, LILACS, the Chinese Biomedical Literature Database, and CINHAL (to November 2006); hand search of reference lists, contact with authors and experts, and search of registers of ongoing trials.Review methodsTwo reviewers independently selected parallel group randomised clinical trials comparing antithrombin with placebo or no intervention and extracted data related to study methods, interventions, outcomes, bias risk, and adverse events. Disagreements were resolved by discussion. Trials in any type of critically ill patients in intensive care were eligible. All trials, irrespective of blinding or language status, that compared any antithrombin III regimen with no intervention or placebo were included. Trials were considered to be at low risk of bias if they had adequate randomisation procedure, blinding, and used intention to treat analysis. Risk ratios with 95% confidence intervals were estimated with fixed and random effects models according to heterogeneity.Main outcome measuresMortality, length of stay in intensive care or hospital, quality of life, severity of sepsis, respiratory failure, duration of mechanical ventilation, incidence of surgical intervention, intervention effect among various populations, and adverse events (such as bleeding).Results20 trials randomly assigning 3458 patients met inclusion criteria. Eight trials had low risk of bias. Compared with placebo or no intervention, antithrombin III did not reduce overall mortality (relative risk 0.96, 95% confidence interval 0.89 to 1.03). No subgroup analyses on risk of bias, populations of patients, or with and without adjuvant heparin yielded significant results. Antithrombin III increased the risk of bleeding events (1.52, 1.30 to 1.78). Heterogeneity was observed in only a few analyses.ConclusionAntithrombin III cannot be recommended for critically ill patients based on the available evidence.

Project description:ObjectivesTo assess the benefits and harms of cannabinoids in participants with pain.DesignSystematic review of randomised clinical trials with meta-analysis, Trial Sequential Analysis, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.Data sourcesThe Cochrane Library, MEDLINE, Embase, Science Citation Index, and BIOSIS.Eligibility criteria for selecting studiesPublished and unpublished randomised clinical trials comparing cannabinoids versus placebo in participants with any type of pain.Main outcome measuresAll-cause mortality, pain, adverse events, quality of life, cannabinoid dependence, psychosis, and quality of sleep.ResultsWe included 65 randomised placebo-controlled clinical trials enrolling 7017 participants. Fifty-nine of the trials and all outcome results were at high risk of bias. Meta-analysis and Trial Sequential Analysis showed no evidence of a difference between cannabinoids versus placebo on all-cause mortality (RR 1.20; 98% CI 0.85 to 1.67; P = 0.22). Meta-analyses and Trial Sequential Analysis showed that cannabinoids neither reduced acute pain (mean difference numerical rating scale (NRS) 0.52; 98% CI -0.40 to 1.43; P = 0.19) or cancer pain (mean difference NRS -0.13; 98% CI -0.33 to 0.06; P = 0.1) nor improved quality of life (mean difference -1.38; 98% CI -11.81 to 9.04; P = 0.33). Meta-analyses and Trial Sequential Analysis showed that cannabinoids reduced chronic pain (mean difference NRS -0.43; 98% CI -0.72 to -0.15; P = 0.0004) and improved quality of sleep (mean difference -0.42; 95% CI -0.65 to -0.20; P = 0.0003). However, both effect sizes were below our predefined minimal important differences. Meta-analysis and Trial Sequential Analysis indicated that cannabinoids increased the risk of non-serious adverse events (RR 1.20; 95% CI 1.15 to 1.25; P < 0.001) but not serious adverse events (RR 1.18; 98% CI 0.95 to 1.45; P = 0.07). None of the included trials reported on cannabinoid dependence or psychosis.ConclusionsCannabinoids reduced chronic pain and improved quality of sleep, but the effect sizes are of questionable importance. Cannabinoids had no effects on acute pain or cancer pain and increased the risks of non-serious adverse events. The harmful effects of cannabinoids for pain seem to outweigh the potential benefits.

Project description:BackgroundThere is insufficient evidence to support the use of acupuncture for mild cognitive impairment (MCI), and there is no consensus on its efficacy. This review aimed to determine the acupuncture effect in patients with MCI.MethodsRelevant and potentially eligible randomized controlled trials (RCTs) of acupuncture for MCI were obtained from four Chinese databases, four English databases, and additional resources up to 1 August 2022. The primary outcome was the improvement in overall cognitive function (OCF). Secondary outcomes were improved memory function (MF) and activities of daily living (ADLs). The revised Cochrane collaboration risk of bias (ROB) assessment tool (ROB 2.0) was applied to evaluate their methodological quality. The Review Manager software v 5.4 was used for analyses. Trial sequential analysis (TSA) 0.9.5.10 β software was used to estimate the required sample size and test the reliability of the pooled outcome. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool.ResultsThis meta-analysis included 11 RCTs with a total of 602 patients. The methodological quality of all trials was moderate. Low-quality evidence showed that acupuncture significantly improved OCF (Mini-Mental State Examination (MMSE): mean difference (MD) = 1.22, 95% confidence interval (CI): 0.78-1.66; the Montreal Cognitive Assessment Scale (MoCA): MD = 1.22, 95% CI: 0.47-1.97). In subgroup analyses, it was revealed that acupuncture significantly increased OCF in patients with MCI when compared to conventional medicine (CM) and sham acupuncture (SA). TSA's findings indicated that the evidence of improving OCF with acupuncture for patients with MCI was conclusive. Meanwhile, there is no statistical difference in the improvement of MF and ADL between acupuncture and CM. TSA showed that the evidence of improving MF and ADL for patients who had MCI and received acupuncture was inconclusive. The shreds of evidence of improving MF and ADL were ranked from low to critically low.ConclusionAcupuncture appears to be an effective clinical application method for improving OCF in patients with MCI. However, due to low-quality evidence, more relevant and high-quality research is needed in this field.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021291284, PROSPERO, No. CRD42021291284.

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.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets