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Vitamin C supplementation in the critically ill: A systematic review and meta-analysis.

ABSTRACT: Background:Low plasma levels of vitamin C are associated with adverse outcomes, including increased mortality, in critically ill patients. Several trials have suggested that the administration of intravenous vitamin C in this setting may have beneficial effects, such as reducing the incidence of organ failure and improving survival. However, these studies have generally involved combination therapies consisting of vitamin C along with other antioxidants, confounding the effects of vitamin C alone. The primary objective of this meta-analysis is to investigate the effects of isolated intravenous supplementation of vitamin C in adults with critical illness. Methods:A database search was conducted for studies on the use of intravenous vitamin C in adult patients with critical illness. The primary outcome assessed was mortality at the longest follow-up time available. Secondary outcomes were the duration of mechanical ventilation, duration of vasopressor support, fluid requirements, and urine output in the first 24 h of intensive care unit admission. Results:Five studies (four randomized controlled trials and one retrospective review) enrolling a total of 142 patients were included in this meta-analysis. Compared with controls, the administration of intravenous vitamin C was associated with a decreased need for vasopressor support (standardized mean difference -0.71; 95% confidence interval (-1.16 to -0.26); p = 0.002) and decreased duration of mechanical ventilation (standardized mean difference -0.5; 95% confidence interval (-0.93 to -0.06); p = 0.03), but no difference was found in mortality (odds ratio 0.76; 95% confidence interval (0.27 to 2.16); p = 0.6). Trends were also noted toward decreased fluid requirements and increased urine output. No adverse effects were reported. Conclusion:The administration of intravenous vitamin C may lead to vasopressor sparing effects and a reduced need for mechanical ventilation in the critically ill, without affecting overall mortality. However, these results should be interpreted in light of the limitations of the primary literature and should serve as a preview of upcoming trials in this area.

SUBMITTER: Zhang M

PROVIDER: S-EPMC6196621 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Vitamin C supplementation in the critically ill: A systematic review and meta-analysis.

Zhang Michael M Jativa David F DF

SAGE open medicine 20181019

<h4>Background</h4>Low plasma levels of vitamin C are associated with adverse outcomes, including increased mortality, in critically ill patients. Several trials have suggested that the administration of intravenous vitamin C in this setting may have beneficial effects, such as reducing the incidence of organ failure and improving survival. However, these studies have generally involved combination therapies consisting of vitamin C along with other antioxidants, confounding the effects of vitami ...[more]

PMID: 30364374

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Project description:IntroductionGlutamine (GLN) has been suggested to have a beneficial influence on outcomes of critically ill patients. However, recent large-scale trials have suggested harm associated with GLN supplementation. Recently, systematic reviews on the use of parenteral GLN have been published; however, less information is available on the role of enteral GLN. Therefore, the aim of this systematic review was to study the effects of enteral GLN supplementation in patients with critical illness.MethodsWe identified randomized controlled trials conducted from 1980 to 2014 with enterally administered GLN in adult critically ill patients. Studies of parenteral GLN only or combined enteral-parenteral GLN were excluded. The methodological quality of studies was scored, and trial data were statistically combined. We examined a priori the treatment effects in subgroups of trials of burn and trauma patients.ResultsA total of 11 studies involving 1079 adult critically ill patients and enteral GLN supplementation were identified. Enteral GLN supplementation was not associated with a reduction of hospital mortality (risk ratio [RR] 0.94, 95% confidence interval [CI] 0.65-1.36; p = 0.74), infectious complications (RR 0.93, 95% CI 0.79-1.10; p = 0.39) or stay in the intensive care unit (weighted mean difference [WMD] -1.36 days, 95% CI -5.51 to 2.78; p = 0.52). However, there was a significant reduction in hospital stay (WMD 4.73 days, 95% CI -8.53 to -0.90; p = 0.02). In the subset of studies of patients with burns, enteral GLN supplementation was associated with significant reductions in hospital mortality (RR 0.19, 95% 0.06-0.67; p = 0.010) and hospital stay (WMD -9.16, 95% CI -15.06 to -3.26; p = 0.002). There was no effect in trauma patients.ConclusionsEnteral GLN supplementation does not confer significant clinical benefit in critically ill patients, with the exception of reduced hospital stay. There may be a significant benefit in patients with burns, but data are sparse and larger randomized trials are warranted to confirm this effect.

Project description:BACKGROUNDVitamin D deficiency (VDD) has been hypothesized not only to be common but also to represent a potentially modifiable risk factor for greater illness severity and clinical outcome during critical illness. The objective of this systematic review was to determine the frequency of VDD in pediatric critical illness and its association with clinical outcomes.METHODSMEDLINE, Embase, and CENTRAL were searched through December 12, 2016, with no date or language restrictions. The primary objective was to estimate the prevalence of VDD in the pediatric intensive care unit (PICU) and compare vitamin D status with healthy control populations. Secondary objectives were to evaluate whether VDD is associated with mortality, increased illness severity, PICU interventions, and patient clinical course. Random effects meta-analysis was used to calculate pooled VDD event rate, compare levels with those of control subjects, and evaluate for associations between VDD and clinical outcome.RESULTSAmong 2700 citations, 17 studies meeting study eligibility were identified. The studies reported a total of 2783 critically ill children and had a median sample size of 120 (range 12-511). The majority of studies used a 25-hydroxyvitamin D [25(OH)D] level less than 50 nmol/L to define VDD, and the pooled VDD prevalence was 54.8 (95% CI 45.4-63.9). Average 25(OH)D levels were significantly lower in PICU patients than in healthy control subjects (pooled difference -17.3 nmol/L, 95% CI -14.0 to -20.6). In a meta-analysis calculation, we found that VDD was associated with increased mortality (OR 1.62, 95% CI 1.11-2.36), illness severity, and need for PICU interventions.CONCLUSIONSApproximately 50% of critically ill children have VDD at the time of PICU admission, defined as a blood total 25(OH)D concentration under 50 nmol/L. VDD was further determined to be associated with greater illness severity, multiple organ dysfunction, and mortality in the PICU setting. Clinical trials are required to determine if optimization of vitamin D status improves patient outcome.TRIAL REGISTRATIONPROSPERO, CRD42016026617 . Registered on 11 January 2016.

Project description:BackgroundIt is currently unclear whether parenteral selenium supplementation should be recommended in the management of critically ill patients. Here we conducted a systematic review and meta-analysis to assess the efficacy of parenteral selenium supplementation on clinical outcomes.Methods/principal findingsRandomized trials investigating parenteral selenium supplementation administered in addition to standard of care to critically ill patients were included. CENTRAL, Medline, EMBASE, the Science Citation Index, and CINAHL were searched with complementary manual searches. The primary outcome was all-cause mortality. Trials published in any language were included. Two authors independently extracted data and assessed trial quality. A third author was consulted to resolve disagreements and for quality assurance. Twelve trials were included and meta-analysis was performed on nine trials that recruited critically ill septic patients. These comprised 965 participants in total. Of these, 148 patients (30.7%) in the treatment groups, and 180 patients (37.3%) in control groups died. Parenteral selenium treatment significantly reduced all-cause mortality in critically ill patients with sepsis (relative risk [RR] 0.83, 95% CI 0.70-0.99, p = 0.04, I(2) = 0%). Subgroup analyses demonstrated that the administration schedule employing longer duration (RR 0.77, 95% CI 0.63-0.94, p = 0.01, I(2) = 0%), loading boluses (RR 0.73, 95% CI 0.58-0.94, p = 0.01, I(2) = 0%) or high-dose selenium treatment (RR 0.77, 95% CI 0.61-0.99, p = 0.04, I(2) = 0%) might be associated with a lower mortality risk. There was no evidence of adverse events.Conclusions/significanceParenteral selenium supplementation reduces risk of mortality among critically ill patients with sepsis. Owing to the varied methodological quality of the studies, future high-quality randomized trials that directly focus on the effect of adequate-duration of parenteral selenium supplementation for severe septic patients are needed to confirm our results. Clinicians should consider these findings when treating this high-risk population.Systematic review registrationPROSPERO 2011; CRD42011001768.

Project description:IntroductionCritical illness is characterized by oxidative stress, which is a major promoter of systemic inflammation and organ failure due to excessive free radical production, depletion of antioxidant defenses, or both. We hypothesized that exogenous supplementation of trace elements and vitamins could restore antioxidant status, improving clinical outcomes.MethodsWe searched computerized databases, reference lists of pertinent articles and personal files from 1980 to 2011. We included randomized controlled trials (RCTs) conducted in critically ill adult patients that evaluated relevant clinical outcomes with antioxidant micronutrients (vitamins and trace elements) supplementation versus placebo.ResultsA total of 21 RCTs met inclusion criteria. When the results of these studies were statistically aggregated (n = 20), combined antioxidants were associated with a significant reduction in mortality (risk ratio (RR) = 0.82, 95% confidence interval (CI) 0.72 to 0.93, P = 0.002); a significant reduction in duration of mechanical ventilation (weighed mean difference in days = -0.67, 95% CI -1.22 to -0.13, P = 0.02); a trend towards a reduction in infections (RR= 0.88, 95% CI 0.76 to 1.02, P = 0.08); and no overall effect on ICU or hospital length of stay (LOS). Furthermore, antioxidants were associated with a significant reduction in overall mortality among patients with higher risk of death (>10% mortality in control group) (RR 0.79, 95% CI 0.68 to 0.92, P = 0.003) whereas there was no significant effect observed for trials of patients with a lower mortality in the control group (RR = 1.14, 95% 0.72 to 1.82, P = 0.57). Trials using more than 500 ?g per day of selenium showed a trend towards a lower mortality (RR = 0.80, 95% CI 0.63 to 1.02, P = 0.07) whereas trials using doses lower than 500 ?g had no effect on mortality (RR 0.94, 95% CI 0.67 to 1.33, P = 0.75).ConclusionsSupplementation with high dose trace elements and vitamins may improve outcomes of critically ill patients, particularly those at high risk of death.

Project description:ObjectivesTo determine the relation between delirium in critically ill patients and their outcomes in the short term (in the intensive care unit and in hospital) and after discharge from hospital.DesignSystematic review and meta-analysis of published studies.Data sourcesPubMed, Embase, CINAHL, Cochrane Library, and PsychINFO, with no language restrictions, up to 1 January 2015.Eligibility criteria for selection studiesReports were eligible for inclusion if they were prospective observational cohorts or clinical trials of adults in intensive care units who were assessed with a validated delirium screening or rating system, and if the association was measured between delirium and at least one of four clinical endpoints (death during admission, length of stay, duration of mechanical ventilation, and any outcome after hospital discharge). Studies were excluded if they primarily enrolled patients with a neurological disorder or patients admitted to intensive care after cardiac surgery or organ/tissue transplantation, or centered on sedation management or alcohol or substance withdrawal. Data were extracted on characteristics of studies, populations sampled, identification of delirium, and outcomes. Random effects models and meta-regression analyses were used to pool data from individual studies.ResultsDelirium was identified in 5280 of 16,595 (31.8%) critically ill patients reported in 42 studies. When compared with control patients without delirium, patients with delirium had significantly higher mortality during admission (risk ratio 2.19, 94% confidence interval 1.78 to 2.70; P<0.001) as well as longer durations of mechanical ventilation and lengths of stay in the intensive care unit and in hospital (standard mean differences 1.79 (95% confidence interval 0.31 to 3.27; P<0.001), 1.38 (0.99 to 1.77; P<0.001), and 0.97 (0.61 to 1.33; P<0.001), respectively). Available studies indicated an association between delirium and cognitive impairment after discharge.ConclusionsNearly a third of patients admitted to an intensive care unit develop delirium, and these patients are at increased risk of dying during admission, longer stays in hospital, and cognitive impairment after discharge.

Project description:IntroductionTelemedicine extends intensivists' reach to critically ill patients cared for by other physicians. Our objective was to evaluate the impact of telemedicine on patients' outcomes.MethodsWe searched electronic databases through April 2012, bibliographies of included trials, and indexes and conference proceedings in two journals (2001 to 2012). We selected controlled trials or observational studies of critically ill adults or children, examining the effects of telemedicine on mortality. Two authors independently selected studies and extracted data on outcomes (mortality and length of stay in the intensive care unit (ICU) and hospital) and methodologic quality. We used random-effects meta-analytic models unadjusted for case mix or cluster effects and quantified between-study heterogeneity by using I² (the percentage of total variability across studies attributable to heterogeneity rather than to chance).ResultsOf 865 citations, 11 observational studies met selection criteria. Overall quality was moderate (mean score on Newcastle-Ottawa scale, 5.1/9; range, 3 to 9). Meta-analyses showed that telemedicine, compared with standard care, is associated with lower ICU mortality (risk ratio (RR) 0.79; 95% confidence interval (CI), 0.65 to 0.96; nine studies, n = 23,526; I2 = 70%) and hospital mortality (RR, 0.83; 95% CI, 0.73 to 0.94; nine studies, n = 47,943; I² = 72%). Interventions with continuous patient-data monitoring, with or without alerts, reduced ICU mortality (RR, 0.78; 95% CI, 0.64 to 0.95; six studies, n = 21,384; I² = 74%) versus those with remote intensivist consultation only (RR, 0.64; 95% CI, 0.20 to 2.07; three studies, n = 2,142; I2 = 71%), but effects were statistically similar (interaction P = 0.74). Effects were also similar in higher (RR, 0.83; 95% CI, 0.68 to 1.02) versus lower (RR, 0.69; 95% CI, 0.40 to 1.19; interaction, P = 0.53) quality studies. Reductions in ICU and hospital length of stay were statistically significant (weighted mean difference (telemedicine-control), -0.62 days; 95% CI, -1.21 to -0.04 days and -1.26 days; 95% CI, -2.49 to -0.03 days, respectively; I2 > 90% for both).ConclusionsTelemedicine was associated with lower ICU and hospital mortality among critically ill patients, although effects varied among studies and may be overestimated in nonrandomized designs. The optimal telemedicine technology configuration and dose tailored to ICU organization and case mix remain unclear.

Project description:RationaleRespiratory muscle weakness is common in critically ill patients; the role of targeted inspiratory muscle training (IMT) in intensive care unit rehabilitation strategies remains poorly defined.ObjectivesThe primary objective of the present study was to describe the range and tolerability of published methods for IMT. The secondary objectives were to determine whether IMT improves respiratory muscle strength and clinical outcomes in critically ill patients.MethodsWe conducted a systematic review to identify randomized and nonrandomized studies of physical rehabilitation interventions intended to strengthen the respiratory muscles in critically ill adults. We searched the MEDLINE, Embase, HealthSTAR, CINAHL, and CENTRAL databases (inception to September Week 3, 2017) and conference proceedings (2012 to 2017). Data were independently extracted by two authors and collected on a standardized report form.ResultsA total of 28 studies (N = 1,185 patients) were included. IMT was initiated during early mechanical ventilation (8 studies), after patients proved difficult to wean (14 studies), or after extubation (3 studies), and 3 other studies did not report exact timing. Threshold loading was the most common technique; 13 studies employed strength training regimens, 11 studies employed endurance training regimens, and 4 could not be classified. IMT was feasible, and there were few adverse events during IMT sessions (nine studies; median, 0%; interquartile range, 0-0%). In randomized trials (n = 20), IMT improved maximal inspiratory pressure compared with control (15 trials; mean increase, 6 cm H2O; 95% confidence interval [CI], 5-8 cm H2O; pooled relative ratio of means, 1.19; 95% CI, 1.14-1.25) and maximal expiratory pressure (4 trials; mean increase, 9 cm H2O; 95% CI, 5-14 cm H2O). IMT was associated with a shorter duration of ventilation (nine trials; mean difference, 4.1 d; 95% CI, 0.8-7.4 d) and a shorter duration of weaning (eight trials; mean difference, 2.3 d; 95% CI, 0.7-4.0 d), but confidence in these pooled estimates was low owing to methodological limitations, including substantial statistical and methodological heterogeneity.ConclusionsMost studies of IMT in critically ill patients have employed inspiratory threshold loading. IMT is feasible and well tolerated in critically ill patients and improves both inspiratory and expiratory muscle strength. The impact of IMT on clinical outcomes requires future confirmation.

Dataset Information

Vitamin C supplementation in the critically ill: A systematic review and meta-analysis.

Publications

Vitamin C supplementation in the critically ill: A systematic review and meta-analysis.

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