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Clinical Nutrition (Edinburgh, Scotland) Jun 2024The aim of this network meta-analysis (NMA) was to investigate the effects of different dietary supplements on the mortality and clinical status of adults with sepsis. (Meta-Analysis)
Meta-Analysis
AIM
The aim of this network meta-analysis (NMA) was to investigate the effects of different dietary supplements on the mortality and clinical status of adults with sepsis.
METHODS
We searched PubMed, EMBASE, and the Cochrane Library Central Register of Controlled Trials until February 2023. The inclusion criteria were: 1) randomized controlled trials (RCT)s; 2) adults suffering sepsis or septic shock; 3) evaluation of short- or long-mortality; and 4) publications between 1994 and 2023. The general information of studies and details of interventions were extracted. The primary outcome was short-term mortality (<90 days), and the secondary outcomes were long-term mortality (≥90 days), length of ICU and hospital stays, and duration of mechanical ventilation (MV). The risk of bias of RCTs was assessed using the Cochrane risk of bias tool 2 (ROB2). A random effect NMA was performed to rank the effect of each intervention using a frequentist approach.
RESULTS
Finally, 56 RCTs with 5957 participants met the criteria. Approximately, one-third of RCTs were low risk of bias. NMA analysis revealed that there was no treatment more effective in short- or long-term mortality than control or other interventions, except for magnesium (RR: 0.33, 95% CI: 0.14, 0.79; GRADE = low) and vitamin C (RR: 0.81, 95% CI: 0.67, 0.99; low certainty evidence), which had beneficial effects on short-term mortality. Moreover, eicosapentaenoic acid, gamma-linolenic acid, and antioxidants (EPA + GLA + AOs) combination was the most effective, and magnesium, vitamin D and vitamin C were the other effective approaches in terms of duration of MV, and ICU length of stay. There was no beneficial dietary supplement for hospital stay in these patients.
CONCLUSIONS
In septic patients, none of the dietary supplements had a substantial effect on mortality except for magnesium and vitamin C, which were linked to lower short-term mortality with low certainty of evidence. Further investigation into high-quality studies with the use of dietary supplements for sepsis should be highly discouraged.
Topics: Humans; Dietary Supplements; Sepsis; Network Meta-Analysis; Shock, Septic; Randomized Controlled Trials as Topic; Treatment Outcome; Length of Stay; Adult; Respiration, Artificial
PubMed: 38663051
DOI: 10.1016/j.clnu.2024.03.030 -
Emerging Microbes & Infections Dec 2023Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) bacteremia can have poor clinical outcomes. Thus, determining the predictors of mortality from... (Meta-Analysis)
Meta-Analysis Review
Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) bacteremia can have poor clinical outcomes. Thus, determining the predictors of mortality from ESBL-PE bacteremia is very important. The present systematic review and meta-analysis aimed to evaluate studies to determine predictors associated with ESBL-PE bacteremia mortality. We searched PubMed and Cochrane Library databases for all relevant publications from January 2000 to August 2022. The outcome measure was mortality rate. In this systematic review of 22 observational studies, 4607 patients with ESBL-PE bacteremia were evaluated, of whom 976 (21.2%) died. The meta-analysis showed that prior antimicrobial therapy (RR, 2.89; 95% CI, 1.22-6.85), neutropenia (RR, 5.58; 95% CI, 2.03-15.35), nosocomial infection (RR, 2.46; 95% CI, 1.22-4.95), rapidly fatal underlying disease (RR, 4.21; 95% CI, 2.19-8.08), respiratory tract infection (RR, 2.12; 95% CI, 1.33-3.36), Pitt bacteremia score (PBS) (per1) (RR, 1.35; 95% CI, 1.18-1.53), PBS ≥ 4 (RR, 4.02; 95% CI, 2.77-5.85), severe sepsis (RR, 11.74; 95% CI, 4.68-29.43), and severe sepsis or septic shock (RR, 4.19; 95% CI, 2.83-6.18) were found to be mortality predictors. Moreover, urinary tract infection (RR, 0.15; 95% CI, 0.04-0.57) and appropriate empirical therapy (RR, 0.39; 95% CI, 0.18-0.82) were found to be a protective factor against mortality. Patients with ESBL-PE bacteremia who have the aforementioned require prudent management for improved outcomes. This research will lead to better management and improvement of clinical outcomes of patients with bacteremia caused by ESBL-PE.
Topics: Humans; Enterobacteriaceae Infections; Enterobacteriaceae; Bacteremia; Sepsis; beta-Lactamases; Anti-Bacterial Agents; Retrospective Studies; Treatment Outcome
PubMed: 37219067
DOI: 10.1080/22221751.2023.2217951 -
Clinical Chemistry and Laboratory... Apr 2024Sepsis is a life-threatening condition implicating an inadequate activation of the immune system. Platelets act as modulators and contributors to immune processes.... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Sepsis is a life-threatening condition implicating an inadequate activation of the immune system. Platelets act as modulators and contributors to immune processes. Indeed, altered platelet turnover, thrombotic events, and changes in thrombopoietin levels in systemic inflammation have been reported, but thrombopoietin-levels in sepsis and septic-shock have not yet been systematically evaluated. We therefore performed a meta-analysis of thrombopoietin (TPO)-levels in patients with sepsis.
METHODS
Two independent reviewers screened records and full-text articles for inclusion. Scientific databases were searched for studies examining thrombopoietin levels in adult sepsis and septic-shock patients until August 1st 2022.
RESULTS
Of 95 items screened, six studies met the inclusion criteria, including 598 subjects. Both sepsis and severe sepsis were associated with increased levels of thrombopoietin (sepsis vs. control: standardized mean difference 3.06, 95 % CI 1.35-4.77; Z=3.50, p=0.0005) (sepsis vs. severe sepsis: standardized mean difference -1.67, 95 % CI -2.46 to -0.88; Z=4.14, p<0.0001). TPO-levels did not show significant differences between severe sepsis and septic shock patients but differed between sepsis and inflammation-associated non-septic controls. Overall, high heterogeneity and low sample size could be noted.
CONCLUSIONS
Concluding, increased levels of thrombopoietin appear to be present both in sepsis and severe sepsis with high heterogeneity but thrombopoietin does not allow to differentiate between severe sepsis and septic-shock. TPO may potentially serve to differentiate sepsis from non-septic trauma and/or tissue damage related (systemic) inflammation. Usage of different assays and high heterogeneity demand standardization of methods and further large multicenter trials.
Topics: Adult; Humans; Shock, Septic; Thrombopoietin; Sepsis
PubMed: 38037809
DOI: 10.1515/cclm-2023-0792 -
Cureus Oct 2023The optimal fluid management strategy for patients with sepsis remains a topic of debate. This meta-analysis aims to evaluate the impact of restrictive versus liberal... (Review)
Review
The optimal fluid management strategy for patients with sepsis remains a topic of debate. This meta-analysis aims to evaluate the impact of restrictive versus liberal fluid regimens on mortality, adverse events, and other clinical outcomes in patients with sepsis. We systematically reviewed 11 randomized controlled trials published between 2008 and 2023, comprising a total of 4,121 participants. The studies assessed 90-day mortality, 30-day mortality, adverse events, hospital length of stay, ICU admission rate, mechanical ventilation, ventilator-free days, ICU-free days, and vasopressor-free days. Quality assessments indicated minimal bias across the studies. The meta-analysis showed no statistically significant difference in 90-day mortality between restrictive and liberal fluid regimens (OR, 0.93; 95% CI, 0.80 to 1.70; P=0.30). Similar results were observed for 30-day mortality (OR, 0.73; 95% CI, 0.30 to 1.80; P=0.50). Adverse events were comparable between the two groups (OR, 0.81; 95% CI, 0.55 to 1.19; P=0.28). Furthermore, there were no significant differences in hospital length of stay (OR, 0.47; 95% CI, -0.85 to 1.80; P=0.48) or ICU admission rate (OR, 1.09; 95% CI, 0.66 to 1.77; P=0.75) between the restrictive and liberal fluid regimens. Regarding mechanical ventilation and ventilator-free days, no significant distinctions were observed (OR, 0.87; 95% CI, 0.65 to 1.17; P=0.48; OR, 0.99; 95% CI, -0.17 to 2.15; P=0.09, respectively). ICU-free days and vasopressor-free days also showed no significant differences between the two groups (OR, 0.97; 95% CI, -0.28 to 2.21; P=0.13; OR, -0.38; 95% CI, -1.14 to 0.37; P=0.32, respectively). This comprehensive meta-analysis of clinical trials suggests that restrictive and liberal fluid management strategies have comparable outcomes in patients with sepsis, including mortality, adverse events, and various clinical parameters. However, most studies favored restrictive fluid regimen over liberal approach regarding the number of vasopressor-free days, need for mechanical ventilation, adverse events, 30-day mortality, and 90-day mortality in sepsis patients.
PubMed: 37899903
DOI: 10.7759/cureus.47783 -
Critical Care Explorations Jul 2024Although clinicians may use methylene blue (MB) in refractory septic shock, the effect of MB on patient-important outcomes remains uncertain. We conducted a systematic... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Although clinicians may use methylene blue (MB) in refractory septic shock, the effect of MB on patient-important outcomes remains uncertain. We conducted a systematic review and meta-analysis to investigate the benefits and harms of MB administration in patients with septic shock.
DATA SOURCES
We searched six databases (including PubMed, Embase, and Medline) from inception to January 10, 2024.
STUDY SELECTION
We included randomized clinical trials (RCTs) of critically ill adults comparing MB with placebo or usual care without MB administration.
DATA EXTRACTION
Two reviewers performed screening, full-text review, and data extraction. We pooled data using a random-effects model, assessed the risk of bias using the modified Cochrane tool, and used Grading of Recommendations Assessment, Development, and Evaluation to rate certainty of effect estimates.
DATA SYNTHESIS
We included six RCTs (302 patients). Compared with placebo or no MB administration, MB may reduce short-term mortality (RR [risk ratio] 0.66 [95% CI, 0.47-0.94], low certainty) and hospital length of stay (mean difference [MD] -2.1 d [95% CI, -1.4 to -2.8], low certainty). MB may also reduce duration of vasopressors (MD -31.1 hr [95% CI, -16.5 to -45.6], low certainty), and increase mean arterial pressure at 6 hours (MD 10.2 mm Hg [95% CI, 6.1-14.2], low certainty) compared with no MB administration. The effect of MB on serum methemoglobin concentration was uncertain (MD 0.9% [95% CI, -0.2% to 2.0%], very low certainty). We did not find any differences in adverse events.
CONCLUSIONS
Among critically ill adults with septic shock, based on low-certainty evidence, MB may reduce short-term mortality, duration of vasopressors, and hospital length of stay, with no evidence of increased adverse events. Rigorous randomized trials evaluating the efficacy of MB in septic shock are needed.
REGISTRATION
Center for Open Science (https://osf.io/hpy4j).
Topics: Methylene Blue; Humans; Shock, Septic; Randomized Controlled Trials as Topic; Length of Stay; Critical Illness
PubMed: 38904978
DOI: 10.1097/CCE.0000000000001110 -
Shock (Augusta, Ga.) Oct 2023Objective: The objective of this study was to provide an in-depth analysis of the advantages and potential research directions concerning the utilization of terlipressin...
Objective: The objective of this study was to provide an in-depth analysis of the advantages and potential research directions concerning the utilization of terlipressin (TP) in combination with norepinephrine (NE) for the management of septic shock. Methods: A systematic search was conducted across five major electronic databases, namely, PubMed, Cochrane, Embase, ScienceDirect, and MEDLINE, using the Boolean method. The search encompassed articles published until May 22, 2023. Randomized controlled trials investigating the efficacy of TP combined with NE in the treatment of patients with septic shock were considered for inclusion. Results: A total of seven trials met the inclusion criteria. The combination therapy of TP and NE exhibited potential benefits in the treatment of adult patients suffering from septic shock. Furthermore, the concurrent administration of TP with NE demonstrated improvements in cardiac output and central venous pressure. However, it is important to acknowledge the presence of certain risks and potential adverse events, including an elevated risk of peripheral ischemia. Conclusions: The available evidence supports the notion that early combination therapy involving NE and TP holds promise in terms of reducing the required dosage of NE, enhancing renal perfusion, and improving microcirculation in patients diagnosed with septic shock.
Topics: Adult; Humans; Norepinephrine; Terlipressin; Shock, Septic; Lypressin; Combined Modality Therapy; Vasoconstrictor Agents
PubMed: 37548701
DOI: 10.1097/SHK.0000000000002204 -
Frontiers in Medicine 2024Methylene blue is an interesting approach in reducing fluid overload and vasoactive drug administration in vasodilatory shock. The inhibition of guanylate cyclase...
BACKGROUND
Methylene blue is an interesting approach in reducing fluid overload and vasoactive drug administration in vasodilatory shock. The inhibition of guanylate cyclase induced by methylene blue infusion reduces nitric oxide production and improves vasoconstriction. This systematic review and meta-analysis aimed to assess the effects of methylene blue administration compared to placebo on the hemodynamic status and clinical outcomes in patients with sepsis and septic shock.
METHODS
The authors specifically included randomized controlled trials that compared the use of methylene blue with placebo in adult patients with sepsis and septic shock. The outcomes were length of intensive care unit stay, hemodynamic parameters [vasopressor use], and days on mechanical ventilation. We also evaluated the abnormal levels of methemoglobinemia. This systematic review and meta-analysis were recorded in PROSPERO with the ID CRD42023423470.
RESULTS
During the initial search, a total of 1,014 records were identified, out of which 393 were duplicates. Fourteen citations were selected for detailed reading, and three were selected for inclusion. The studies enrolled 141 patients, with 70 of them in the methylene blue group and 71 of them in the control group. Methylene blue treatment was associated with a lower length of intensive care unit stay (MD -1.58; 95%CI -2.97, -0.20; = 25%; = 0.03), decreased days on mechanical ventilation (MD -0.72; 95%CI -1.26, -0.17; = 0%; = 0.010), and a shorter time to vasopressor discontinuation (MD -31.49; 95%CI -46.02, -16.96; = 0%; < 0.0001). No association was found with methemoglobinemia.
CONCLUSION
Administering methylene blue to patients with sepsis and septic shock leads to reduced time to vasopressor discontinuation, length of intensive care unit stay, and days on mechanical ventilation.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023423470, CRD42023423470.
PubMed: 38698779
DOI: 10.3389/fmed.2024.1366062 -
Frontiers in Nutrition 2023An increasing number of studies indicate that vitamin C (VC) reduces the mortality of adult septic patients, while some articles suggest otherwise. We performed this...
BACKGROUND
An increasing number of studies indicate that vitamin C (VC) reduces the mortality of adult septic patients, while some articles suggest otherwise. We performed this systematic review and meta-analysis to resolve the discrepancies in reported results concerning the efficacy of VC in septic patients.
METHODS
We comprehensively searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled trials for randomized controlled trials (RCTs) evaluating the efficacy of intravenous VC (IVVC) on adult septic patients published from inception to November 28, 2022. The quality of outcomes for eligible studies was assessed using the Recommendations Assessment, Development, and Evaluation methodology. The results were analyzed using the pooled mean difference (MD) or risk ratio (RR) and 95% confidence intervals (CIs).
RESULTS
Twenty-two studies (3,570 adult septic patients) were included. IVVC treatment did not improve 28-day mortality compared to the control group (RR, 0.92; 95% CI, 0.81-1.04; = 26%; evidence risk, moderate). IVVC monotherapy decreased mortality (RR, 0.69; 95% CI, 0.52-0.93; = 57%), whereas combination therapy did not affect mortality (RR, 1.03; 95% CI, 0.90-1.17; =0%). IVVC had a trend to decrease the mortality of septic patients (RR, 0.83; 95% CI, 0.69-1.00; = 33%) but did not affect septic shock patients (RR, 1.01; 95% CI, 0.85-1.21; = 18%). IVVC reduced the duration of vasopressor use (MD, -8.45; 95% CI, -15.43 to -1.47; evidence risk, very low) but did not influence the incidence of AKI, ICU length of stay, duration of mechanical ventilation.
CONCLUSIONS
IVVC treatment did not improve the 28-day mortality in septic patients. Subgroup analysis indicated that VC had a trend to decrease the 28-day mortality in patients with sepsis but not septic shock. IVVC monotherapy, rather than combination therapy, decreased the 28-day mortality in septic patients. The findings imply that Hydrocortisone, Ascorbic acid, Thiamine (HAT) combination therapy is not superior to IVVC monotherapy for septic patients. These findings warrant further confirmation in future studies, which should also investigate the mechanisms underlying the enhanced efficacy of IVVC monotherapy in septic patients.
SYSTEMATIC REVIEW REGISTRATION
https://inplasy.com/.
PubMed: 37599680
DOI: 10.3389/fnut.2023.1211194 -
Medicina Intensiva Dec 2023To determine the diagnostic performance of the clinical evaluation of peripheral tissue perfusion in the prediction of mortality. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the diagnostic performance of the clinical evaluation of peripheral tissue perfusion in the prediction of mortality.
DESIGN
Systematic review and meta-analysis.
SETTING
Intensive care unit.
PATIENTS AND PARTICIPANTS
Patients with sepsis and septic shock.
INTERVENTIONS
Studies of patients with sepsis and/or septic shock that associated clinical monitoring of tissue perfusion with mortality were included. A systematic review was performed by searching the PubMed/MEDLINE, Cochrane Library, SCOPUS, and OVID databases.
MAIN VARIABLES OF INTEREST
The risk of bias was assessed with the QUADAS-2 tool. Sensitivity and specificity were calculated to evaluate the predictive accuracy for mortality. Review Manager software version 5.4 was used to draw the forest plot graphs, and Stata version 15.1 was used to build the hierarchical summary receiver operating characteristic model.
RESULTS
Thirteen studies were included, with a total of 1667 patients and 17 analyses. Two articles evaluated the temperature gradient, four evaluated the capillary refill time, and seven evaluated the mottling in the skin. In most studies, the outcome was mortality at 14 or 28 days. The pooled sensitivity of the included studies was 70%, specificity 75.9% (95% CI, 61.6%-86.2%), diagnostic odds ratio 7.41 (95% CI, 3.91-14.04), and positive and negative likelihood ratios 2.91 (95% CI, 1.80-4.72) and 0.39 (95% CI, 0.30-0.51), respectively.
CONCLUSIONS
Clinical evaluation of tissue perfusion at the bedside is a useful tool, with moderate sensitivity and specificity, to identify patients with a higher risk of death among those with sepsis and septic shock.
REGISTRATION
PROSPERO CRD42019134351.
Topics: Humans; Shock, Septic; Sepsis; Sensitivity and Specificity; Intensive Care Units; Perfusion
PubMed: 37419840
DOI: 10.1016/j.medine.2023.05.011 -
Diagnostic and Prognostic Research Aug 2023Numerous biomarkers have been proposed for diagnosis, therapeutic, and prognosis in sepsis. Previous evaluations of the value of biomarkers for predicting mortality due... (Review)
Review
Basal procalcitonin, C-reactive protein, interleukin-6, and presepsin for prediction of mortality in critically ill septic patients: a systematic review and meta-analysis.
BACKGROUND
Numerous biomarkers have been proposed for diagnosis, therapeutic, and prognosis in sepsis. Previous evaluations of the value of biomarkers for predicting mortality due to this life-threatening condition fail to address the complexity of this condition and the risk of bias associated with prognostic studies. We evaluate the predictive performance of four of these biomarkers in the prognosis of mortality through a methodologically sound evaluation.
METHODS
We conducted a systematic review a systematic review and meta-analysis to determine, in critically ill adults with sepsis, whether procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), and presepsin (sCD14) are independent prognostic factors for mortality. We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials up to March 2023. Only Phase-2 confirmatory prognostic factor studies among critically ill septic adults were included. Random effects meta-analyses pooled the prognostic association estimates.
RESULTS
We included 60 studies (15,681 patients) with 99 biomarker assessments. Quality of the statistical analysis and reporting domains using the QUIPS tool showed high risk of bias in > 60% assessments. The biomarker measurement as a continuous variable in models adjusted by key covariates (age and severity score) for predicting mortality at 28-30 days showed a null or near to null association for basal PCT (pooled OR = 0.99, 95% CI = 0.99-1.003), CRP (OR = 1.01, 95% CI = 0.87 to 1.17), and IL-6 (OR = 1.02, 95% CI = 1.01-1.03) and sCD14 (pooled HR = 1.003, 95% CI = 1.000 to 1.006). Additional meta-analyses accounting for other prognostic covariates had similarly null findings.
CONCLUSION
Baseline, isolated measurement of PCT, CRP, IL-6, and sCD14 has not been shown to help predict mortality in critically ill patients with sepsis. The role of these biomarkers should be evaluated in new studies where the patient selection would be standardized and the measurement of biomarker results.
TRIAL REGISTRATION
PROSPERO (CRD42019128790).
PubMed: 37537680
DOI: 10.1186/s41512-023-00152-2