Meta-analysis assessing the effectiveness of intravenous vitamin C in patients with sepsis and septic shock.
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ABSTRACT:
SUBMITTER: Tariq MA
PROVIDER: S-EPMC9732199 | biostudies-literature | 2022 Nov
REPOSITORIES: biostudies-literature
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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
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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: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: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
Project description:BackgroundBaseline characteristics and disease severity of patients with septic shock according to the new Sepsis-3 definition may differ from patients that only comply with the Sepsis-2 definition. We conducted a retrospective cohort study on the ICU of a Belgian tertiary care facility to seek out differences between these two patient groups and to identify variables associated with no longer satisfying the latest definition of septic shock.ResultsOf 1198 patients with septic shock according to the Sepsis-2 consensus definition, 233 (19.4%) did not have septic shock according to the Sepsis-3 shock definition. These patients more often had medical admission reasons and a respiratory infection as cause for the septic shock. They less often had surgery on admission and were less likely to have chronic liver disease (5.6% vs 16.2%, absolute difference 10.6% (95% CI 6.4-14.1%). Patients with septic shock only according to the old definition had significant lower APACHE II and SOFA scores and lower hospital mortality (31.6% vs 55.3%, p < 0.001). In a multivariate analysis, following variables were associated with Sepsis-2 shock patients no longer being defined as such by the Sepsis-3 definition: respiratory infection (OR 1.485 (95% CI 1.56-2.089), p = 0.023), a medical admission reason (OR 1.977 (95% CI 1.396-2.800) and chronic liver disease (OR 0.345 (95% CI 0.181-0.660), p < 0.001).ConclusionsOne in five patients with septic shock according to the Sepsis-2 consensus definition is no longer considered as such when the Sepsis-3 shock criteria are applied. A medical admission reason, a respiratory infection and absence of chronic liver disease are independently associated with no longer being identified as having septic shock by the Sepsis-3 criteria.
| S-EPMC8557229 | biostudies-literature
Project description:ObjectiveTo evaluate mortality from sepsis and septic shock in Korea during the past 10 years, we conducted a systematic review and meta-analysis.MethodsWe searched six databases for studies on mortality from sepsis and septic shock in adult patients. Primary outcomes were 28- or 30-day mortality and in-hospital mortality from sepsis and septic shock. To assess the risk of bias, we used the Newcastle-Ottawa Scale and Risk of Bias 2 tools. The protocol is registered in PROSPERO (No. CRD42022365739).ResultsA total of 61 studies were included. The mortality rates from sepsis and septic shock at 28 or 30 days were 22.7% (95% confidence interval [CI], 20.0%-25.6%; I2=89%) and 27.6% (95% CI, 22.3%-33.5%; I2=98%), respectively, according to the Sepsis-3 criteria. Furthermore, in accordance with the Sepsis-3 criteria, the in-hospital mortality rates were 28.1% (95% CI, 25.2%-31.1%; I2=87%) and 34.3% (95% CI, 27.2%-42.2%; I2=97%), respectively.ConclusionThe mortality rates from sepsis and septic shock in Korea are high. In the case of septic shock, the in-hospital mortality rate is approximately 30%.
| S-EPMC10350360 | biostudies-literature