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Cited by 234Clinical Nutrition and GastroenterologySepsis Diagnosis and TreatmentVitamin C and Antioxidants Research

Antioxidant micronutrients in the critically ill: a systematic review and meta-analysis

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Manzanares, William, Dhaliwal, Rupinder, Jiang, Xuran, Murch, Lauren, Heyland, Daren K·2012·Critical Care
DOI 10.1186/cc11316PMC PMC3681395
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Abstract

Introduction: Critical 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. Methods: We 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. Results: A 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 μg 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 μg had no effect on mortality (RR 0.94, 95% CI 0.67 to 1.33, P = 0.75). Conclusions: Supplementation with high dose trace elements and vitamins may improve outcomes of critically ill patients, particularly those at high risk of death.

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Cited by

Sorted by citations

Authors
Manzanares, W., Dhaliwal, R., Jiang, X., Murch, L., & Heyland, D. K.
Affiliations
  • Universidad de la República de Uruguay (UY)
  • Kingston General Hospital (CA)
  • Queen's University (CA)
Corresponding author
Heyland, Daren K
ORCID
Venue
Critical Care
Publisher
Springer Science and Business Media LLC
Published
2012-04-25
Volume
16
Issue
2
Pages
R66-R66
ISSN
1364-8535 (ISSN-L)
DOI
10.1186/cc11316
PMC
PMC3681395
OpenAlex
W2113670582
Cited by
234
References
82
Citations by year
2026: 4 · 2025: 11 · 2024: 5 · 2023: 21 · 2022: 12 · 2021: 14 · 2020: 17 · 2019: 14 · 2018: 13 · 2017: 16 · 2016: 20 · 2015: 30 · 2014: 34 · 2013: 18 · 2012: 5
FWCI
3.39
Type
journal article
Language
en
Open access
Licence
Locations
  • Critical Care (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Clinical Nutrition and Gastroenterology
  • Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
  • Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
Keywords
antioxidant micronutrients, critical illness, oxidative stress, vitamin supplementation, selenium, trace elements, mortality, mechanical ventilation duration, infection, ICU length of stay, antioxidant status, critically ill adults, systemic inflammation, organ failure, mortality risk stratification, dose-response relationship
MeSH terms
Antioxidants, Humans, Randomized Controlled Trials as Topic, Critical Illness, Oxidative Stress, Micronutrients

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