Abstract
IntroductionOxidative stress is involved in the development of secondary tissue damage and organ failure. Micronutrients contributing to the antioxidant (AOX) defense exhibit low plasma levels during critical illness. The aim of this study was to investigate the impact of early AOX micronutrients on clinical outcome in intensive care unit (ICU) patients with conditions characterized by oxidative stress.MethodsWe conducted a prospective, randomized, double-blind, placebo-controlled, single-center trial in patients admitted to a university hospital ICU with organ failure after complicated cardiac surgery, major trauma, or subarachnoid hemorrhage. Stratification by diagnosis was performed before randomization. The intervention was intravenous supplements for 5 days (selenium 270 μg, zinc 30 mg, vitamin C 1.1 g, and vitamin B1 100 mg) with a double-loading dose on days 1 and 2 or placebo.ResultsTwo hundred patients were included (102 AOX and 98 placebo). While age and gender did not differ, brain injury was more severe in the AOX trauma group (P = 0.019). Organ function endpoints did not differ: incidence of acute kidney failure and sequential organ failure assessment score decrease were similar (-3.2 ± 3.2 versus -4.2 ± 2.3 over the course of 5 days). Plasma concentrations of selenium, zinc, and glutathione peroxidase, low on admission, increased significantly to within normal values in the AOX group. C-reactive protein decreased faster in the AOX group (P = 0.039). Infectious complications did not differ. Length of hospital stay did not differ (16.5 versus 20 days), being shorter only in surviving AOX trauma patients (-10 days; P = 0.045).ConclusionThe AOX intervention did not reduce early organ dysfunction but significantly reduced the inflammatory response in cardiac surgery and trauma patients, which may prove beneficial in conditions with an intense inflammation.Trials RegistrationClinical Trials.gov RCT Register: NCT00515736.
Highlights
Oxidative stress is involved in the development of secondary tissue damage and organ failure
The AOX intervention did not reduce early organ dysfunction but significantly reduced the inflammatory response in cardiac surgery and trauma patients, which may prove beneficial in conditions with an intense inflammation
Severity of brain injury was worse in the AOX subgroup compared with placebo patients, as reflected by a lower admission Glasgow Coma Scale (GCS) score (P = 0.11), with more severe SAPS and brain Injury Severity Score (ISS) (P = 0.019) and worse admission neurological sequential organ failure assessment (SOFA) scores (P = 0.012)
Summary
Oxidative stress is involved in the development of secondary tissue damage and organ failure. A network of functionally overlapping antioxidant (AOX) defense mechanisms aims at protecting cells from reactive oxygen and nitric oxide species. It is formed by traceelement-dependent enzymes such as superoxide dismutase, catalase, and glutathione peroxidase (GPX) (selenium, zinc, manganese, copper, and iron), thiol donors, and their. AKI = acute kidney injury; ANOVA = analysis of variance; AOX = antioxidant; BP = bodily pain; CI = confidence interval; CRP = C-reactive protein; EN = enteral nutrition; FiO2 = fraction of inspired oxygen; GCS = Glasgow Coma Scale; GH = general health perception; GPX = glutathione peroxidase; ICU = intensive care unit; ISS = Injury Severity Score; iv = intravenously; MOS SF-36 = Medical Outcome Study Short Form 36-item health survey; PaO2 = arterial partial pressure of oxygen; PF = physical functioning; PN = parenteral nutrition; RP = role functioning-physical; RR = relative risk; SAH = subarachnoid hemorrhage; SAPS = Simplified Acute Physiology Score; SF-36 = Short Form 36-item health survey; SIRS = systemic inflammatory response syndrome; SOFA = sequential organ failure assessment. Micronutrient deficiency favors the persistence of inflammation and the propagation of lipid peroxidation and other free-radical-mediated damage, contributing to organ dysfunction and failure
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