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Critical Care

, 16:R66

First Online: 25 April 2012Received: 19 December 2011Revised: 13 March 2012Accepted: 25 April 2012


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 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.

ConclusionsSupplementation with high dose trace elements and vitamins may improve outcomes of critically ill patients, particularly those at high risk of death.


CIconfidence interval

COPDchronic obstructive pulmonary disease

C.Randomconcealed randomization

CRRTcontinuous renal replacement therapies

D5Wdextrose 5% in water

ENenteral nutrition

GPxglutathione peroxidase

HAPhospital acquired pneumonia

ICUintensive care unit

IEDsimmune-enhancing diets

ITTintention to treat


LOSlength of stay

MODSmultiple organ dysfunction syndrome

Nnumber of patients


NACN-acetyl cysteine

NF-kappaBnuclear factor kappa-B

PNparenteral nutrition

RCTrandomized controlled trials

RNSreactive nitrogen species

ROSreactive oxygen species

RRrisk ratio

SIRSsystemic inflammatory response syndrome

SODsuperoxide dismutase

TBSAtotal body surface area

VAPventilator associated pneumonia

WMDweighted mean difference

Electronic supplementary materialThe online version of this article doi:10.1186-cc11316 contains supplementary material, which is available to authorized users.

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Autor: William Manzanares - Rupinder Dhaliwal - Xuran Jiang - Lauren Murch - Daren K Heyland


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