Meta-analysis assessing the effectiveness of intravenous vitamin C in patients with sepsis and septic shock.
Ontology highlight
ABSTRACT:
SUBMITTER: Tariq MA
PROVIDER: S-EPMC9732199 | biostudies-literature | 2022 Nov
REPOSITORIES: biostudies-literature
Publications
Meta-analysis assessing the effectiveness of intravenous vitamin C in patients with sepsis and septic shock.
Tariq Muhammad Ali MA Amin Hamza H Ali Uzair U
Acute and critical care 20221021 4
Similar Datasets
Project description:ObjectivesVitamin C deficiency is common among patients with sepsis and has been associated with poor clinical outcomes. Nevertheless, the effect of intravenous (IV) vitamin C for the treatment of sepsis remains controversial. The purpose of this meta-analysis was to evaluate the effect of IV vitamin C in patients with sepsis or septic shock.MethodsElectronic databases (PubMed, Embase, Scopus, and Cochrane Library) were searched from inception through May 25, 2022 for randomized controlled trials evaluating the effect of IV vitamin C treatment in patients with sepsis. The primary outcome was short-term mortality, and secondary outcomes including the duration of vasopressor, length of intensive care unit (ICU) stay, and Sequential Organ Failure Assessment (SOFA) score after vitamin C treatment. Subgroup analyses were performed based on the type of disease, dose and duration of IV vitamin C.ResultsA total of 10 studies were included, with a total sample of 755 septic patients. The IV vitamin C was associated with a significant reduction in the short-term mortality (OR 0.51, 95% CI 0.37-0.69, I 2 = 0%) and duration of vasopressor (MD -27.88, 95% CI -49.84 to -5.92, I 2 = 95%). The length of ICU stay (MD -0.68, 95% CI -2.13 to 0.78, I 2 = 74%) and SOFA score (MD -0.05, 95% CI -1.69 to 1.58, I 2 = 86%) were not significantly different between two groups.ConclusionIn patients with sepsis or septic shock, the IV vitamin C reduced the short-term mortality rate and duration of vasopressor, with no effect on the length of ICU stay and SOFA score. Further trials are required to explore the optimal dosage and duration of IV vitamin C.Systematic review registrationhttps://inplasy.com/inplasy-2022-6-0013/, identifier INPLASY202260013.
| S-EPMC9366349 | biostudies-literature
Project description:The objective of this study was to investigate the efficacy of vitamin C in patients experiencing sepsis and septic shock. The PubMed, Embase and Cochrane Library databases were searched for randomized controlled trials (RCTs) about vitamin C treatments for critically ill patients suffering from sepsis and septic shock from inception until December 31, 2019. The primary outcome was mortality, and the secondary outcomes were the ICU length of stay and the dose of vasopressors. A meta-analysis of nine RCTs with a total of 584 patients (301 in the intervention group and 283 in the control group) was conducted. There were significant differences between the vitamin C group and the control group in 28-day mortality (fixed effects OR = 0.60 95% CI [0.42, 0.85], p = 0.004) and in the dose of vasopressors (SMD = -0.88 95% CI [-1.48, -0.29], p = 0.003); however, the ICU length of stay was the same between the two groups (SMD = -0.33 95% CI [-0.87, 0.20] p = 0.23). This meta-analysis demonstrated that the use of vitamin C (compared with placebo) led to a reduction in ICU mortality and a reduction in the dose of vasopressors in patients with septic shock. However, the ICU length of stay was not significantly different between the two groups. Therefore, multicentre and high-quality RCTs are needed to further clarify the safety and effectiveness of vitamin C among patients with sepsis and septic shock.
| S-EPMC10358524 | biostudies-literature
Project description:IntroductionIntravenous crystalloid fluid resuscitation forms a crucial part of the early intervention bundle for sepsis and septic shock, with the Surviving Sepsis Campaign guidelines recommending a 30 mL/kg fluid bolus within the first hour. Compliance with this suggested target varies in patients with comorbidities such as congestive heart failure, chronic kidney disease and cirrhosis due to concerns regarding iatrogenic fluid overload. However, it remains unclear whether resuscitation with higher fluid volumes puts them at greater risk of adverse outcomes. Thus, this systematic review will synthesise evidence from existing studies to assess the effects of a conservative as compared with a liberal approach to fluid resuscitation in patients at greater perceived risk of fluid overload due to comorbid conditions.Methods and analysisThis protocol was registered on PROSPERO and has been drafted following the checklist of Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. We will search MEDLINE, MEDLINE Epub Ahead of Print and In-Process, In-Data-Review & Other Non-Indexed Citations, Embase, Embase Classic, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science Core Collection, CINAHL Complete and ClinicalTrials.gov. A preliminary search of these databases was performed from their inception to 30 August 2022. The risk of bias and random errors will be assessed using the revised Cochrane risk-of-bias tool for randomised clinical trials and the Newcastle-Ottawa Scale for case-control and cohort studies. If a sufficient number of comparable studies are identified, we will perform a meta-analysis applying random effects model. We will investigate heterogeneity using a combination of visual inspection of the funnel plot as well as the Egger's test.Ethics and disseminationNo ethics approval is required for this study since no original data will be collected. The findings will be disseminated through peer-reviewed publication and conference presentation.Prospero registration numberCRD42022348181.
| S-EPMC10230890 | biostudies-literature
Project description:Introduction:Vasoplegia is common and associated with a poor prognosis in patients with sepsis and septic shock. Vitamin C therapy in combination with vitamin B1 and glucocorticoid, as well as monotherapy in various doses, has been investigated as a treatment for the vasoplegic state in sepsis, through targeting the inflammatory cascade. However, the combination effect and the relative contribution of each drug have not been well evaluated. Furthermore, the best combination between the three agents is currently unknown. We are planning a systematic review (SR) with network meta-analysis (NMA) to compare the different treatments and identify the combination with the most favourable effect on survival.Methods and analysis:We will include all randomised controlled trials comparing any intervention using intravenous vitamin C, vitamin B1 and/or glucocorticoid with another or with placebo in the treatment of sepsis. We are interested in comparing the following active interventions. Very high-dose vitamin C (≥12 g/day), high-dose vitamin C (≥6 g/day), vitamin C (<6 g/day); low-dose glucocorticoid (<400 mg/day of hydrocortisone (or equivalent)), vitamin B1 and combinations of the drugs above. The primary outcome will be all-cause mortality at the longest follow-up within 1 year but 90 days or longer postrandomisation. All relevant studies will be sought through database searches and trial registries. All reference selection and data extraction will be conducted by two independent reviewers. We will conduct a random-effects NMA to synthesise all evidence for each outcome and obtain a comprehensive ranking of all treatments. We will use the surface under the cumulative ranking curve and the mean ranks to rank the various interventions. To differentiate between the effect of combination therapies and the effect of a component, we will employ a component NMA.Ethics and dissemination:This SR does not require ethical approval. We will publish findings from this systematic review in a peer-reviewed scientific journal and present these at scientific conferences.Prospero registration number:CRD42018103860.
| S-EPMC6858173 | biostudies-literature
Project description:BackgroundTo update a meta-analysis of randomized controlled trials (RCTs) and further explore the outcome of IV vitamin C (IVVC) administration in sepsis or septic shock patients.MethodsThis study is a meta-analysis of RCTs. The RCTs of vitamin C therapy in sepsis or septic shock were searched in PubMed, EMBASE and Clinical Trials.gov from inception to January 16, 2023. We registered the protocol with PROSPERO (CRD42022354875). The primary outcome was delta Sequential Organ Failure Assessment (SOFA) score at 72-96 h. Two reviewers independently assessed RCTs according to eligibility criteria: (1) study type: RCT; (2) patient population: patients ≥ 18 years with sepsis or septic shock; (3) intervention: IVVC at any doses as monotherapy or combined with thiamine or and hydrocortisone compared with standard of care, no intervention or placebo (defined as control group); (4) the RCT described short-term mortality or SOFA score. Then, two authors independently extracted related information from RCTs.ResultsEighteen RCTs (n = 3364 patients) were identified in this meta-analysis. There were significant effects in the delta SOFA score from baseline to 72-96 h (MD, - 0.62; 95% CI, - 1.00 to - 0.25; p = 0.001) and the duration of vasopressor use (MD, - 15.07; 95% CI, - 21.59 to - 8.55; p < 0.00001) with IVVC therapy. Treatment with IVVC was not shown to improve short-term mortality (OR, 0.89; 95% CI, 0.77 to 1.04; p = 0.14); nevertheless, dose at 25-100 mg/kg/d subgroup associated with a significant reduction in short-term mortality (OR, 0.80; 95% CI, 0.65 to 0.97; p = 0.03). An increase adverse event was observed in IVVC therapy (OR, 1.98; 95% CI, 1.06 to 3.68; p = 0.03).ConclusionIn this meta-analysis, IVVC in sepsis or septic shock patients significantly improved delta SOFA score and reduced the duration of vasopressor use, whereas it was not associated with reduction in short-term mortality and had higher adverse events.
| S-EPMC10012592 | biostudies-literature
Project description:BackgroundThe objective of this study was to evaluate the clinical efficacy of thiamine and vitamin C with or without hydrocortisone coadministration on the treatment of sepsis and septic shock.MethodsMEDLINE, EMBASE and CENTRAL databases were searched for randomized controlled trials (RCTs) that made a comparative study between the combination therapy of vitamin C and thiamine with or without hydrocortisone and the administration of placebo in patients with sepsis or septic shock. Two reviewers independently performed study selection, data extraction and quality assessment. Both short-term mortality and change in the sequential organ failure assessment (SOFA) score from baseline (delta SOFA) were set as the primary outcomes. Secondary endpoints included intensive care unit (ICU) mortality, new onset of acute kidney injury, total adverse events, ICU and hospital length of stay, duration of vasopressor usage and ventilator-free days. Meanwhile, trial sequential analysis was conducted for primary outcomes.ResultsEight RCTs with 1428 patients were included in the current study. The results showed no significant reduction of short-term mortality in sepsis and septic shock patients who received combination therapy of vitamin C and thiamine with or without hydrocortisone compared to those with placebo {risk ratio (RR), 1.02 [95% confidence interval (CI), 0.87 to 1.20], p = 0.81, I 2 = 0%; risk difference (RD), 0 [95% CI, -0.04 to 0.05]}. Nevertheless, the combination therapy was associated with significant reduction in SOFA score [mean difference (MD), -0.63, (95% CI, -0.96 to -0.29, p < 0.001, I 2 = 0%] and vasopressors duration (MD, -22.11 [95% CI, -30.46 to -13.77], p < 0.001, I 2 = 6%). Additionally, there were no statistical differences in the pooled estimate for other outcomes.ConclusionsIn the current meta-analysis, the combination therapy of vitamin C and thiamine, with or without hydrocortisone had no impact on short-term mortality when compared with placebo, but was associated with significant reduction in SOFA score among patients with sepsis and septic shock.
| S-EPMC8660008 | biostudies-literature
Project description:BackgroundIntravenous vitamin C administration in septic shock may have a sparing effect on vasopressor requirements, and vitamin C's enzyme cofactor functions provide a mechanistic rationale. Our study aimed to determine the effect of intravenous vitamin C administration on vasopressor requirements and other outcomes in patients with septic shock.MethodsThis was a double-blind, randomised placebo-controlled trial in 40 patients with septic shock who were randomised (1:1) to receive intravenous vitamin C (at a dose of 25 mg/kg of body weight every 6 h) or placebo (intravenous 5% dextrose) for up to 96 h, or until death or discharge. The primary outcome was intravenous vasopressor requirements (dose and duration), and secondary outcomes included Sequential Organ Failure Assessment (SOFA) scores, intensive care unit (ICU) and hospital length of stay, and mortality. In addition, blood samples were collected to determine vitamin C kinetics and inflammatory marker concentrations.ResultsMedian plasma vitamin C concentrations were deficient at baseline (9.2 [4.4, 12] µmol/L) and increased to 408 (227, 560) µmol/L following 72 h of intervention. The mean duration of intravenous vasopressor infusion in the vitamin C group was 48 (95% CI 35-62) hours and in the placebo group was 54 (95% CI 41-62) hours (p = 0.52). The dose of vasopressor delivered over time was comparable between the two groups, as were SOFA scores (p > 0.05). The median ICU length of stay in the intervention group was 3.8 (2.2, 9.8) days versus 7.1 (3.1, 20) days in the placebo group (p = 0.12). The median hospital length of stay for the vitamin C group was 18 (11, 35) days versus 22 (10, 52) days for the placebo group (p = 0.65). Mortality was comparable between the two groups (p > 0.05). Of the inflammatory markers, neutrophil counts were elevated in the vitamin C group relative to placebo by 72 h (p = 0.01). C-reactive protein and myeloperoxidase concentrations were elevated at baseline, however, the two groups were comparable over time (p > 0.05).ConclusionsOur pilot study indicated that intravenous vitamin C did not provide significant decreases in the mean dose or duration of vasopressor infusion. Further research that takes into account the potential impact of intervention timing, dose and duration, and location of trial, may provide more definitive evidence.Trial registrationACTRN12617001184369 (11/8/2017).
| S-EPMC8786621 | biostudies-literature
Project description:BACKGROUND:Sepsis is characterized by a complex immune response. This meta-analysis evaluated the clinical effectiveness of intravenous IgM-enriched immunoglobulin (IVIgGM) in patients with sepsis and septic shock. METHODS:Four databases, PubMed, the Cochrane Library, the ISI Web of Knowledge, and Embase, were systematically searched from inception to June 2018 to update the 2013 edition of the Cochrane review by two investigators, who independently selected studies, extracted relevant data, and evaluated study quality. Data were subjected to a meta-analysis and trial sequential analysis (TSA) for the primary and secondary outcomes. Level of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) scale. RESULTS:Nineteen studies comprising 1530 patients were included in this meta-analysis. Pooled analyses showed that the use of IVIgGM reduced the mortality risk of septic patients (relative risk 0.60; 95% confidence interval [CI] 0.52-0.69, I2 = 0%). TSA showed that IVIgGM had a significant effect on mortality. Additionally, the meta-analysis suggested that use of IVIgGM shortened length of mechanical ventilation (mean difference - 3.16 days; 95% CI - 5.71 to - 0.61 days) and did not shorten length of stay in the intensive care unit (mean difference - 0.38 days; 95% CI - 3.55 to 2.80 days). The GRADE scale showed that the certainty of the body of evidence was low for both benefits and IVIgGM. CONCLUSION:Administration of IVIgGM to adult septic patients may be associated with reduced mortality. Treatment effects tended to be smaller or less consistent when including only those studies deemed adequate for each indicator. The available evidence is not clearly sufficient to support the widespread use of IVIgGM in the treatment of sepsis. Trial registration PROSPERO registration number: CRD42018084120. Registered on 11 February 2018.
| S-EPMC6365591 | biostudies-literature
Project description:BackgroundAn 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.MethodsWe 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).ResultsTwenty-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; I2 = 26%; evidence risk, moderate). IVVC monotherapy decreased mortality (RR, 0.69; 95% CI, 0.52-0.93; I2 = 57%), whereas combination therapy did not affect mortality (RR, 1.03; 95% CI, 0.90-1.17; I2 =0%). IVVC had a trend to decrease the mortality of septic patients (RR, 0.83; 95% CI, 0.69-1.00; I2 = 33%) but did not affect septic shock patients (RR, 1.01; 95% CI, 0.85-1.21; I2 = 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.ConclusionsIVVC 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 registrationhttps://inplasy.com/.
| S-EPMC10437115 | biostudies-literature
Project description:For more than two decades, sepsis was defined as a microbial infection that produces fever (or hypothermia), tachycardia, tachypnoea and blood leukocyte changes. Sepsis is now increasingly being considered a dysregulated systemic inflammatory and immune response to microbial invasion that produces organ injury for which mortality rates are declining to 15-25%. Septic shock remains defined as sepsis with hyperlactataemia and concurrent hypotension requiring vasopressor therapy, with in-hospital mortality rates approaching 30-50%. With earlier recognition and more compliance to best practices, sepsis has become less of an immediate life-threatening disorder and more of a long-term chronic critical illness, often associated with prolonged inflammation, immune suppression, organ injury and lean tissue wasting. Furthermore, patients who survive sepsis have continuing risk of mortality after discharge, as well as long-term cognitive and functional deficits. Earlier recognition and improved implementation of best practices have reduced in-hospital mortality, but results from the use of immunomodulatory agents to date have been disappointing. Similarly, no biomarker can definitely diagnose sepsis or predict its clinical outcome. Because of its complexity, improvements in sepsis outcomes are likely to continue to be slow and incremental.
| S-EPMC5538252 | biostudies-other