The effect of goal-directed therapy on mortality in patients with sepsis - earlier is better: a meta-analysis of randomized controlled trials

Introduction

The Surviving Sepsis Campaign guidelines recommend goal-directed therapy (GDT) for the early resuscitation of patients with sepsis. However, the findings of the ProCESS (Protocolized Care for Early Septic Shock) trial showed no benefit from GDT for reducing mortality rates in early septic shock. We performed a meta-analysis to integrate these findings with existing literature on this topic and evaluate the effect of GDT on mortality due to sepsis.

Methods

We searched the PubMed, Embase and CENTRAL (Cochrane Central Register of Controlled Trials) databases and reference lists of extracted articles. Randomized controlled trials comparing GDT with standard therapy or usual care in patients with sepsis were included. The prespecified primary outcome was overall mortality.

Results

In total, 13 trials involving 2,525 adult patients were included. GDT significantly reduced overall mortality in the random-effects model (relative risk (RR), 0.83; 95% confidence interval (CI), 0.71 to 0.96; P =0.01; I² = 56%). Predefined subgroup analysis according to the timing of GDT for resuscitation suggested that a mortality benefit was seen only in the subgroup of early GDT within the first 6 hours (seven trials; RR, 0.77; 95% CI, 0.67 to 0.89; P =0.0004; I² = 40%), but not in the subgroup with late or unclear timing of GDT (six trials; RR, 0.92; 95% CI, 0.69 to 1.24; P =0.59; I² = 56%). GDT was significantly associated with the use of dobutamine (five trials; RR, 2.71; 95% CI, 1.20 to 6.10; P =0.02).

Conclusions

The results of the present meta-analysis suggest that GDT significantly reduces overall mortality in patients with sepsis, especially when initiated early. However, owing to the variable quality of the studies, strong and definitive recommendations cannot be made.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0570-5) contains supplementary material, which is available to authorized users.     

Risk factors for lung infection in stroke patients: a meta-analysis of observational studies

Background: The aims of this meta-analysis were to evaluate the risk factors associated with lung infections in stroke patients and to provide evidence for prevention decisions. Methods: We searched the Embase, PubMed, EBSCO and Web of Science databases to collect studies from January 2000 to July 2015. Results: The meta-analysis identified 23 risk factors for lung infections in stroke patients, and the top 5, ranked by order according to odds ratio values (95% confidence interval), were as follows: multiple vertebrobasilar stroke, 22.99 (4.04, 130.83); National Institutes of Health Stroke Scale score >15 points, 14.63 (8.54, 25.08); mechanical ventilation, 10.20 (7.15, 14.57); nasogastric tube use, 9.87 (6.21, 15.70); and dysphagia, 7.50 (2.60, 21.65). Conclusion: Preventive measures should be taken against these risk factors to reduce the incidence of lung infection.     

The influence of esmolol on septic shock and sepsis: A meta-analysis of randomized controlled studies

Background

Esmolol may have some potential in treating septic shock and sepsis. However, the results remain controversial. We conduct a systematic review and meta-analysis to explore the efficacy of esmolol in patients with septic shock and sepsis.

Effect of a multifaceted educational intervention for anti-infectious measures on sepsis mortality: a cluster randomized trial

Purpose

Guidelines recommend administering antibiotics within 1 h of sepsis recognition but this recommendation remains untested by randomized trials. This trial was set up to investigate whether survival is improved by reducing the time before initiation of antimicrobial therapy by means of a multifaceted intervention in compliance with guideline recommendations.

Methods

The MEDUSA study, a prospective multicenter cluster-randomized trial, was conducted from July 2011 to July 2013 in 40 German hospitals. Hospitals were randomly allocated to receive conventional continuous medical education (CME) measures (control group) or multifaceted interventions including local quality improvement teams, educational outreach, audit, feedback, and reminders. We included 4183 patients with severe sepsis or septic shock in an intention-to-treat analysis comparing the multifaceted intervention (n = 2596) with conventional CME (n = 1587). The primary outcome was 28-day mortality.

Results

The 28-day mortality was 35.1% (883 of 2596 patients) in the intervention group and 26.7% (403 of 1587 patients; p = 0.01) in the control group. The intervention was not a risk factor for mortality, since this difference was present from the beginning of the study and remained unaffected by the intervention. Median time to antimicrobial therapy was 1.5 h (interquartile range 0.1–4.9 h) in the intervention group and 2.0 h (0.4–5.9 h; p = 0.41) in the control group. The risk of death increased by 2% per hour delay of antimicrobial therapy and 1% per hour delay of source control, independent of group assignment.

Conclusions

Delay in antimicrobial therapy and source control was associated with increased mortality but the multifaceted approach was unable to change time to antimicrobial therapy in this setting and did not affect survival.

     

Role of statin on mortality outcome in pneumonia patients: A meta-analysis

AIM: To determine the role of statin on mortality outcome in patient with pneumonia.METHODS: For the present meta-analysis, we search the published literatures online through Pub Med, Embase, Scopus and the Cochrane Library databases and the search words used were "statins' ", "bacteraemia", "pneumonia", and "ICU infections". During the online search our focus was on full text articles, peerreviewed, observational cohort or case control studies and randomized controlled trials. Those studies were selected whose outcome was hospital mortality among patients with pneumonia whether or not on statins. In this meta-analysis, 30 d mortality was used as the primary outcome as it has been demonstrated in the previous research that 30 d mortality is primarily because of community acquired pneumonia. As all studies were observational, where statin users were compared with historical rather than randomized controls, odds ratio for in-hospital or all-cause 30 d mortality was used as the primary effect measure used in the meta-analysis.RESULTS: We came across the total 25 studies comprising 35355 patients(2734 statin users and 32621 statin non-users) during the electronic search. Four studies out of 25 were included in the final analysis. In this meta-analysis, when data regarding the use of statin in pneumonia patients on mortality was pooled, its results showed the non-significant effect of the statin on mortality outcome.CONCLUSION: Although statins seems to be useful in the treatment of pneumonia patients but for statistical conclusion, further randomized controlled trials needs to be done or their results still waited to be published of ongoing trials, with the conclusion that presently statins showing no clinical benefit in the pneumonia patients.     

Heparin therapy reduces 28-day mortality in adult severe sepsis patients: a systematic review and meta-analysis

Introduction

There are approximately 19 million new cases of sepsis worldwide each year. Among them, more than one quarter of patients die. We aimed to assess the effects of heparin on short-term mortality in adult patients with sepsis and severe sepsis.

Methods

We searched electronic databases (Medline, Embase, and Cochrane Library databases; the Cochrane Controlled Trials Register) and conference proceedings (Web of Knowledge (Conference Proceedings Citation Index - Science, Conference Proceedings Citation Index - Social Sciences & Humanities)) from inception to July 2014, expert contacts and relevant websites. Controlled trials of heparin versus placebo in sepsis or severe sepsis were identified. In total two reviewers independently assessed eligibility, and four authors independently extracted data; consensus was reached by conference. We used the chi-square test and I² to assess statistical heterogeneity (P <0.05). The primary analysis was based on the fixed-effect model to produce pooled odds ratios with 95% confidence intervals.

Results

A total of nine publications were included in the meta-analysis. Heparin decreased 28-day mortality (n = 3,482, OR = 0.656, 95% CI = 0.562 to 0.765, P <0.0001). According to the meta-analysis of 28-day mortality, heterogeneity was not found among the eight randomized clinical trials (RCTs) (I² = 0.0%). Heparin had no effect on bleeding events in sepsis (seven RCTs, n = 2,726; OR = 1.063; 95% CI = 0.834 to 1.355; P = 0.623; and I² = 20.9%). Subgroup analysis demonstrated that the sample size may be a source of heterogeneity, but experimental design was not.

Conclusions

Heparin may reduce 28-day mortality in patients with severe sepsis, at the same time, there was no increase in the risk of bleeding in the heparin group. We recommend the use of heparin for sepsis and severe sepsis.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0563-4) contains supplementary material, which is available to authorized users.     

Cigarette smoking and abdominal obesity: a meta-analysis of observational studies

Background: Smoking and obesity are two of the leading causes of preventable death in developed countries. We conducted a meta-analysis to examine the association between cigarette smoking and abdominal obesity measured by waist-to-hip circumference ratio (WHR).

Method: Keyword and reference search were conducted in four electronic bibliographic databases: Cochrane Library, Embase, MEDLINE, and Web of Science. Articles were included based on predefined study selection criteria. Random-effect model was performed to estimate the relationship between cigarette smoking and abdominal obesity.

Results: Fifteen studies (116 146 subjects) met the study selection criteria and were included in the meta-analysis. Compared to those who have never smoked, current cigarette smokers who smoke in a regular basis are associated with 0.0113 (95% CI: 0.0081–0.0145, p < 0.001) higher WHR. Publication bias could be present as the sample sizes of individual studies and the effect sizes are negatively correlated (p < 0.01).

Conclusions: In this meta-analysis, we found some preliminary evidence that links cigarette smoking to abdominal obesity. This study has important limitations pertained to observational study design, publication bias, and measurement error. Future research on the casual effect of smoking on abdominal obesity is warranted.     

Selenium supplementation for sepsis: a meta-analysis of randomized controlled trials

Background

Recently, several studies were conducted to investigate the effect of selenium supplementation in septic patients. However, no consistent conclusion was made. Thus, we aimed to systematically summarize the available randomized controlled trials (RCTs) to evaluate the effect of selenium supplementation on important clinical outcomes in septic patients.

Methods

A systematic literature search of Pubmed, Embase, and the Cochrane Central Register of Controlled Trials was conducted (up to August 25, 2012). RCTs were included if they reported the effect of selenium supplementation on the treatment of septic patients. A fixed-effect model was used, and in the case of significant heterogeneity, a random-effects model was employed.

Results

Five studies with a total of 530 patients were included. Pooled analysis showed that selenium supplementation did not reduce all-cause mortality (relative risk [RR] = 0.89, 95% confidence interval [CI]: 0.73-1.07, P = .21), hospital-acquired pneumonia (RR = 1.15, 95% CI: 0.73-1.82, P = .55), or length of intensive care unit stay (weighted mean differences = 2.32 days, 95% CI: − 0.05 to 4.69; P = .05). In addition, no significant difference was observed regarding adverse events between groups (RR = 0.97, 95% CI: 0.72-1.33, P = .87).

Conclusions

The present meta-analysis showed no benefit of selenium supplementation in patients with sepsis. Due to the limited number of RCTs included, more prospective multicenter clinical trials on selenium therapy in septic patients are warranted in the future.     

Impact of cancer on mortality rates in patients with sepsis: A meta-analysis and meta-regression of current studies

BACKGROUNDResearch suggests that approximately 6% of adult patients admitted to hospitals in the United States present with sepsis and there has been a minimal change in the incidence of this condition in the last decade. Furthermore, patients with cancer generally have a higher incidence of sepsis due to immunosuppression caused by cancer or its treatment.AIMTo assess if cancer increases the mortality rates in sepsis patients by pooling evidence from contemporary studies.METHODSPubMed, Embase, and Google Scholar databases were searched from January 1, 2001 to December 15, 2021 for studies comparing outcomes of sepsis patients based on the presence of active cancer. Mortality data were pooled using a random-effects model, with the odds ratio (OR) and 95% confidence interval (CI) calculated. Meta-regression was conducted to assess the influence of confounders on mortality rates.RESULTSNine studies were included. The meta-analysis demonstrated a non-significant tendency towards increased risk of early mortality (OR = 2.77, 95%CI: 0.88-8.66, I² = 99%) and a statistically significantly increased risk of late mortality amongst sepsis patients with cancer as compared to non-cancer sepsis patients (OR = 2.46, 95%CI: 1.42-4.25, I² = 99%). Overall, cancer was found to significantly increase the risk of mortality in sepsis patients (OR = 2.7, 95%CI: 1.07-6.84, I² = 99%). Meta-analysis indicated a statistically significantly increased risk of mortality in patients with solid tumors as well as hematological malignancies. Meta-regression indicated that an increase in the prevalence of comorbid pulmonary and renal diseases increased the risk of mortality in cancer patients with sepsis. Mortality rates increased with an increase in the percentage of patients with urinary tract infections while an inverse relationship was seen for infections of cutaneous origin.CONCLUSIONContemporary evidence indicates that the presence of any cancer in sepsis patients significantly increases the risk of mortality. Scarce data suggest that mortality is equally increased for both solid and hematological cancers. Current evidence is limited by high heterogeneity and there is a need for further studies taking into account several confounding variables to present better evidence.     

术前大剂量他汀类药物预防对比剂肾病的meta分析

目的评价碘对比剂造影术前应用大剂量他汀是否可以预防对比剂肾病。方法检索MEDLINE、EMBASE数据库、中国知网、Corchrane图书馆及二次资源。检索词:对比剂、对比剂肾病、他汀。入选试验满足条件:试验为随机对照试验,试验对象为需要行造影的人群。采用比值比(odds ratio,OR)和95%可信区间(95%confidence interval,CI)作为评价大剂量他汀组和小剂量他汀或安慰剂组对比剂肾病发生率有无差异的指标,用均数差(mean difference,MD)和95%CI作为评价术后血肌酐(SCr)水平有无差异的指标。统计学分析应用RevMan5.0软件。结果在检索到的文章中共有12个实验满足条件,总计2 774例患者。造影术前应用大剂量他汀可减少对比剂肾病发生率(OR=0.44;95%CI=0.34~0.59,P0.01),并较小剂量他汀或安慰剂组术后SCr水平下降(MD=-0.07;95%CI=-0.10~-0.04,P0.01)。结论造影术前应用大剂量他汀减少对比剂肾病的发生。     

依维莫司和佐他莫司两种药物洗脱支架临床安全性和有效性的比较研究

目的关于依维莫司和佐他莫司药物洗脱支架的安全性和有效性一直存在着争议,不同随机对照临床试验(RCT)和观察性研究的结果大相径庭。本研究旨在通过系统综述和荟萃分析的方法比较依维莫司和佐他莫司两类药物洗脱支架的安全性和有效性,为今后临床实践提供指导。方法通过Pubmed,Embase和Cochrane数据库以及Clinicaltrials.gov网站检索了2015年3月之前所有相关文献和摘要。安全性终点事件包括:重大心血管不良(MACE)事件、全因死亡率、非致死性心肌梗死、支架内血栓形成。有效性终点事件包括:靶血管再血管化治疗、靶病变再血管化治疗、靶血管失败率、靶病变失败率。随访时间均大于等于12月。结果最终分析数据来源于8个RCT试验(11 778例患者)和26个观察性研究(34850列患者)。在RCT试验中,依维莫司和佐他莫司药物洗脱支架的安全性和有效性未见明显差异。结论在RCT研究中,依维莫司和佐他莫司药物洗脱支架的安全性和有效性未见明显差异,而在观察性研究和全部数据集合组中,依维莫司药物洗脱支架的安全性和有效性优于佐他莫司药物洗脱支架。对于随机对照临床试验和观察性研究的结果差异有待于进一步研究。     

Hypoalbuminemia and acute kidney injury: a meta-analysis of observational clinical studies

Purpose  

To test the hypothesis that hypoalbuminemia is independently associated with increased risk of acute kidney injury (AKI).     

Prospective observational study of bacteremic pneumococcal pneumonia: Effect of discordant therapy on mortality

STUDY OBJECTIVE: To evaluate the effect of discordant empirical therapy on outcome in bacteremic pneumococcal community-acquired pneumonia. DESIGN: Prospective observational study. SETTING: A 600-bed teaching hospital with a reference area of 400,000 inhabitants. PATIENTS: All patients aged > or =18 yrs with a diagnosis of community-acquired pneumonia whose blood cultures, obtained within the first 48 hrs of hospitalization, demonstrated growth of Streptococcus pneumoniae were included in the study. METHODS: Discordant therapy was defined as failure to administer an antibiotic with in vitro activity against the isolated strain within 24 hrs of hospital admission. The 2002 breakpoints recommended for respiratory infections by the National Committee for Clinical Laboratory Standards were used to classify therapy. RESULTS: A total of 100 patients with bacteremic pneumococcal pneumonia were identified. Penicillin- and macrolide-resistant strains were identified in 29 and 18 cases, respectively. Only two strains had minimum inhibitory concentrations of >2 microg/mL for cephalosporins. Discordant therapy was documented in ten patients, five of whom died. Mortality in patients receiving concordant therapy was 14% (13 of 90). Nursing home residence (odds ratio [OR] = 14.8) and immunocompromise (OR = 11.5) were independently (p <.05) associated with discordant therapy. Risk of discordant therapy was significantly higher (p <.05) when empirical therapy did not include cefotaxime or ceftriaxone (OR = 10.4). Discordant therapy (OR = 27.3), multilobar involvement (OR = 14.2), underlying chronic obstructive pulmonary disease (OR = 9.1), and hospitalization during the previous 12 wks (OR = 7.9) were independently associated (p <.05) with death. The excess mortality for initial discordant therapy was estimated to be 35.6% (95% confidence interval, 3.73-67.4). CONCLUSIONS: Survival in patients with bacteremic community-acquired pneumococcal pneumonia can be improved by avoiding suboptimal therapy. Using the 2002 breakpoints, it is very unlikely that discordant therapy would be given with ceftriaxone or cefotaxime. Clinical outcome is worse in those patients receiving antimicrobial therapy that in vitro testing suggests would be ineffective.     

The effect of statins on mortality from severe infections and sepsis: A systematic review and meta-analysis

PurposeThe aim of this study was to systematically review the literature on the effect of statins on mortality in patients with infection and/or sepsis.Materials and MethodsMEDLINE, EMBASE, PapersFirst, and the Cochrane collaboration and the Cochrane Register of controlled trials were searched and were current as of December 2009. Randomized, double-blind or single-blind, placebo-controlled studies; observational cohort studies (retrospective and prospective); and case-controlled studies were included. Types of participants included adult and pediatric subjects with sepsis or various other types of infection. Exposure was defined as the use of a statin for any indication. The primary outcome chosen was mortality from any cause, and secondary outcomes included 30-day mortality, in-hospital mortality, mortality from pneumonia, mortality from bacteremia, mortality from sepsis, and mortality from mixed infection.ResultsA total of 20 studies were included in the analysis, 18 being cohort studies (12 retrospective, 6 prospective), 1 matched cohort study with 2 case-control studies, and 1 randomized control trial. Meta-analysis for various infection-related outcomes revealed the following pooled odds ratios all in favor of statin use vs non: 0.61 (95% confidence interval [CI], 0.48-0.73) for 30-day mortality (n = 7), 0.38 (95% CI, 0.13-0.64) for in-hospital mortality (n = 7), 0.63 (95% CI, 0.55-0.71) for pneumonia-related mortality (n = 7), 0.33 (95% CI, 0.09-0.75) for bacteremia-related mortality (n = 4), 0.40 (95% CI, 0.23-0.57) for sepsis-related mortality (n = 4), and 0.50 (95% CI, 0.18-0.83) for mixed infection-related mortality (n = 4).ConclusionsThis meta-analysis demonstrated a protective effect for statins in patients with sepsis and/or other infections compared to placebo for various infection-related outcomes. However, our results are limited by the cohort design of the selected studies and the degree of heterogeneity among them, and as a result, further randomized trials are needed to validate the use of statins for sepsis and/or other infections.