Randomised trials of human albumin for adults with sepsis: systematic review and meta-analysis with trial sequential analysis of all-cause mortality.
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ABSTRACT:
SUBMITTER: Patel A
PROVIDER: S-EPMC4106199 | biostudies-literature | 2014 Jul
REPOSITORIES: biostudies-literature
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Randomised trials of human albumin for adults with sepsis: systematic review and meta-analysis with trial sequential analysis of all-cause mortality.
Patel Amit A Laffan Michael A MA Waheed Umeer U Brett Stephen J SJ
BMJ (Clinical research ed.) 20140722
<h4>Objective</h4>To assess the efficacy and safety of pooled human albumin solutions as part of fluid volume expansion and resuscitation (with or without improvement of baseline hypoalbuminaemia) in critically unwell adults with sepsis of any severity.<h4>Design</h4>Systematic review and meta-analysis of randomised clinical trials, with trial sequential analysis, subgroup, and meta-regression analyses.<h4>Data sources</h4>PubMed, PubMed Central, Web of Science (includes Medline, Conference Proc ...[more]
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Project description:BackgroundSepsis affects millions of people and imposes a substantial economic and social burden worldwide. However, the role of human albumin in the management of septic patients remains unclear.MethodsEMBASE, PubMed, and Cochrane Library databases were searched. Randomized controlled trials regarding the use of human albumin in septic patients were eligible. The overall mortality and the intensive care unit (ICU), in-hospital/28-day, and 90-day mortality were pooled, respectively. Subgroup analyses were performed according to target population, type and dose of human albumin, and type of control group. Risk ratios (RRs) was calculated.ResultsTwenty-four randomized controlled trials were finally included. Meta-analysis showed that human albumin cannot decrease the overall (RR = 1.02, P = .56), ICU (RR = 1.06, P = .65), in-hospital/28-day (RR = 1.01, P = .68), and 90-day (RR = 1.01, P = .65) mortality of total patients. Subgroup analyses showed that human albumin both cannot significantly decrease the overall, ICU, in-hospital/28-day, and 90-day mortality of sepsis and septic patients. Additionally, 20% human albumin (RR = 0.89, P = .03) and high daily dose of human albumin (RR = 0.90, P = .03) might benefit for the survival of patients with septic shock.ConclusionsBased on the current evidence, the general use of human albumin to improve the survival of septic patients cannot be recommended.
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Project description:OBJECTIVE:We aim to synthesise up-to-date randomised trials to investigate the effects of levosimendan on mortality and clinical outcomes in severe sepsis and septic shock. METHODS:A collection of databases including PubMed, EMBASE, Cochrane Central Register and Web of Science were searched updated to August 2017. Randomised trials were included when they pertain to the use of levosimendan in severe sepsis or septic shock compared with any category of inotropes, or as an adjunct to standard therapy with mortality reported. The primary outcome was mortality, and the secondary outcomes were clinical performances including serum lactate, cardiac function, vasopressor requirement and fluid infusion. RESULTS:A total of 10 studies with 1036 patients were included in this meta-analysis. The results revealed that levosimendan could not reduce mortality significantly in severe sepsis and septic shock (OR 0.89, 95% CI 0.69 to 1.16, P=0.39). Levosimendan use could reduce serum lactate more effectively, and enhance cardiac contractibility with increased cardiac index and left ventricular ejection fraction. However, its use could also increase fluid infusion but not reduce norepinephrine dose. No significant benefit in mortality could be observed of levosimendan versus dobutamine use, or in patients with proven cardiac dysfunction. CONCLUSIONS:Current evidence is not sufficient to support levosimendan as superior to dobutamine or as an optimal adjunct in severe sepsis and septic shock. More large-scale randomised trials are necessary to validate levosimendan use in sepsis.
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Project description:BackgroundEpidemiologic data have shown an increasing incidence and declining mortality rate in sepsis. However, confounding effects due to differences in disease classification might have contributed to these trends. To assess if a declining mortality over time could be supported by data derived from high-quality prospective studies, we performed a meta-analysis using data from randomised controlled trials (RCTs) on sepsis. The primary aim was to assess whether the mortality in sepsis trials has changed over time. The secondary aim was to investigate how many of the included trials could show efficacy of the studied intervention regarding 28-day mortality.MethodsWe searched PubMed for RCTs enrolling patients with severe sepsis and septic shock, published between 2002 and 2016. The included trials were assessed for quality and sorted by date of first inclusion. A meta-analysis was performed to synthesise data from the individual sepsis trials.ResultsOf 418 eligible articles, 44 RCTs on sepsis were included in the analysis, enrolling 13,315 patients in the usual care arm between 1991 and 2013. In this time period, mortality decreased by 0.42% annually (p = 0.04) to give a total decline of 9.24%. In subgroup analyses with adjustments for APACHE II, SAPS II and SOFA scores, the observed time trend was not significant (p = 0.45, 0.23 and 0.98 respectively). Only four of the included trials showed any efficacy with regard to mortality.ConclusionsData from RCTs show a declining trend in 28-day mortality in severe sepsis and septic shock patients during the years from 1991 to 2013. However, when controlling for severity at study inclusion, there was no significant change in mortality over time. The number of trials presenting new treatment options was low.Trial registrationPROSPERO CRD42018091100 . Registered 27 August 2018.
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Project description:BackgroundChronic pain in adults is a frequent clinical symptom with a significant impact on patient well-being. Therefore, sufficient pain management is of utmost importance. While tramadol is a commonly used pain medication, the quality of evidence supporting its use has been questioned considering the observed adverse events. Our objective will be to assess the benefits and harms of tramadol compared with placebo or no intervention for chronic pain.Methods/designWe will conduct a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis to assess the beneficial and harmful effects of tramadol in any dose, formulation, or duration. We will accept placebo or no intervention as control interventions. We will include adult participants with any type of chronic pain, including cancer-related pain. We will systematically search the Cochrane Library, MEDLINE, EMBASE, Science Citation Index, and BIOSIS for relevant literature. We will follow the recommendations by Cochrane and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The risk of systematic errors ('bias') and random errors ('play of chance') will be assessed. The certainty of evidence will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.DiscussionAlthough tramadol is often being used to manage chronic pain conditions, the beneficial and harmful effects of this intervention are unknown. The present review will systematically assess the current evidence on the benefits and harms of tramadol versus placebo or no intervention to inform clinical practice and future research.Systematic review registrationPROSPERO CRD42019140334.
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Project description:ObjectiveTo investigate the association between cholesterol lowering interventions and risk of death from suicide, accident, or trauma (non-illness mortality).DesignMeta-analysis of the non-illness mortality outcomes of large, randomised clinical trials of cholesterol lowering treatments.Studies reviewed19 out of 21 eligible trials that had data available on non-illness mortality. INTERVENTIONS REVIEWED: Dietary modification, drug treatment, or partial ileal bypass surgery for 1-10 years.Main outcome measureDeaths from suicides, accidents, and violence in treatment groups compared with control groups.ResultsAcross all trials, the odds ratio of non-illness mortality in the treated groups, relative to control groups, was 1.18 (95% confidence interval 0.91 to 1.52; P=0.20). The odds ratios were 1.28 (0.94 to 1.74; P=0.12) for primary prevention trials and 1.00 (0.65 to 1.55; P=0.98) for secondary prevention trials. Randomised clinical trials using statins did not show a treatment related rise in non-illness mortality (0.84, 0.50 to 1.41; P=0.50), whereas a trend toward increased deaths from suicide and violence was observed in trials of dietary interventions and non-statin drugs (1.32, 0.98 to 1.77; P=0.06). No relation was found between the magnitude of cholesterol reduction and non-illness mortality (P=0.23).ConclusionCurrently available evidence does not indicate that non-illness mortality is increased significantly by cholesterol lowering treatments. A modest increase may occur with dietary interventions and non-statin drugs.
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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.
| S-EPMC10634281 | biostudies-literature
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.
| S-EPMC3573769 | biostudies-literature
Project description:ObjectiveTo determine whether patients with severe sepsis or septic shock could benefit from a strict and early goal-directed therapy (EGDT) protocol recommended by Surviving Sepsis Campaign (SSC) Guidelines.MethodsMEDLINE/PubMed, EMBASE/OVID and Cochrane Central Register of Controlled Trials (CENTRAL) were searched between March 1983 and March 2015. Eligible studies evaluated the outcomes of EGDT versus usual care or standard therapy in patients with severe sepsis or septic shock. The primary outcomes were mortality within 28 days, 60 days and 90 days. Included studies must report at least one metric of mortality.Results5 studies that enrolled 4303 patients with 2144 in the EGDT group and 2159 in the control group were included in this meta-analysis. Overall, there were slight decreases of mortality within 28 days, 60 days and 90 days in the random-effect model in patients with severe sepsis or septic shock receiving EGDT resuscitation. However, none of the differences reached statistical significance (RR=0.86; 95% CI 0.69 to 1.06; p=0.16; p for heterogeneity=0.008, I(2)=71%; RR=0.94; 95% CI 0.81 to 1.10; p=0.46; p for heterogeneity=0.16, I(2)=43%; RR=0.98; 95% CI 0.88 to 1.10; p=0.75; p for heterogeneity=0.87, I(2)=0%, respectively).ConclusionsThe current meta-analysis pooled data from five RCTs and found no survival benefit of EGDT in patients with sepsis. However, the included trials are not sufficiently homogeneous and potential confounding factors in the negative trials (ProCESS, ARISE and ProMISe) might bias the results and diminish the treatment effect of EGDT. Further well-designed studies should eliminate all potential source of bias to determine if EGDT has a mortality benefit.
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