Impact of high-dose antioxidants on outcomes in acutely injured patients
ABSTRACT The profound oxidative stress that occurs following injury results in significant depletion of many endogenous antioxidants (vitamin C, E, selenium). Increasing evidence suggests antioxidant supplementation reduces infectious complications and organ dysfunction following injury and hemorrhagic shock. The purpose of this study was to evaluate the impact of high-dose antioxidant administration on the mortality rate of acutely injured patients.
In October 2005, we implemented a 7-day high-dose antioxidant protocol for acutely injured patients admitted to our trauma center. A retrospective cohort study, evaluating all patients admitted to the trauma service between October 2005 and September 2006 following protocol implementation (AO+), was performed. The comparison cohort (AO-) was made up of those patients admitted in the year prior to protocol implementation.
A total of 4,294 patients met criteria (AO+, N = 2,272; AO-, N = 2022). Hospital (4 vs 3 days, P < .001) and ICU (3 vs 2 days, P = .001) median length of stays were significantly shorter in the AO+ group. Mortality was significantly lower in the AO+ group (6.1% vs 8.5%, P = .001), translating into a 28% relative risk reduction for mortality in patients exposed to high-dose antioxidants. After adjusting for age, gender, and probability of survival, AO exposure was associated with even lower mortality (OR 0.32, 95% CI 0.22-0.46). Patients with an expected survival <50% benefited most (OR 0.24, 95% CI 0.15-0.37).
A high-dose antioxidant protocol resulted in a 28% relative risk reduction in mortality and a significant reduction in both hospital and ICU length of stay. This protocol represents an inexpensive intervention to reduce mortality/morbidity in the trauma patient.
SourceAvailable from: Jennifer Ann Mcarthur
Article: The Role of Selenium in Sepsis[Show abstract] [Hide abstract]
ABSTRACT: Selenium is a key component of many important enzyme systems, including the glutathione peroxidase (GPX) family of enzymes. Glutathione peroxidases are primarily involved in repairing cell membranes damaged by lipid peroxidation caused by reactive oxygen species. The glutathione peroxidases may also have an anti-inflammatory role. Sepsis is known to cause a significant degree of oxidative stress. The selenium containing glutathione peroxidases play an important role in neutralizing the oxidative damage from sepsis. Selenium supplementation to patients with sepsis shows a potential to improve important outcomes such as mortality and organ dysfunction. However, larger more definitive trials are needed to define the optimal dosing and timing of supplementation. OXIDATIVE STRESS IN SEPSIS Reactive oxygen species (ROS) have many diverse roles in biological systems including the stimulation of cell proliferation, maintenance of vascular tone, and migration and signaling of inflammatory cells to sites of inflammation. Under normal conditions of health, there is a delicate balance between the ROS, and the body's scavenging systems for these potentially harmful mediators. However, significant oxidative stress occurs during sepsis and septic shock when there is activation of granulocytes and endothelial cells resulting in an oxidative burst and overabundance of ROS. The body's endogenous antioxidant mechanisms and ROS scavenging systems are overwhelmed resulting in protein oxidation, lipid peroxidation leading to cellular membrane damage, and DNA damage all of which result in irreversible cellular damage and contribute to the multiple organ dysfunction observed in sepsis. The oxidative stress observed in sepsis is evident by several studies. Total plasma antioxidant capacity (TAC) is a measure of the cumulative ability of a patient's antioxidant systems to scavenge free radicals. Investigators have demonstrated that while TAC between septic patients and healthy volunteers are similar, TAC levels decline over time in the septic patients suggesting a loss in the ability of septic patients to scavenge the ROS. In vitro studies in which human umbilical vein endothelial cells are treated with plasma from patients with septic shock have demonstrated that high amounts of ROS are produced  and intracellular glutathione stores, the most abundant antioxidant, are depleted . The amount of ROS produced correlated to the severity of illness and pretreatment with n-acetylcysteine or glutathione decreased ROS production and cell death .The Open Inflammation Journal 10/2011; 4(1). DOI:10.2174/1875041901104010115
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ABSTRACT: Mortality rates among the severely injured remain high. The successful treatment of hemorrhagic shock relies on expeditious control of bleeding through surgical ligation, packing, or endovascular techniques. An important secondary concern in hemorrhaging patients is how to respond to the lost blood volume. A single method that is able to adequately address all needs of the exsanguinating patient has not yet been agreed upon, despite a large growth of knowledge regarding the causative factors of traumatic shock. A review of relevent literature was performed. Many different trials are currently underway to discriminate ways to improve outcomes in the severely injured and bleeding patient. This paper will review: (1) recent advances in our understanding of the effects hemorrhagic shock has on the coagulation cascade and vascular endothelium, (2) recent research findings that have changed resuscitation, and (3) resuscitation strategies that are not widely used but under active investigation.European Journal of Trauma and Emergency Surgery 12/2014; 40(6):641-656. DOI:10.1007/s00068-014-0416-5 · 0.38 Impact Factor
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ABSTRACT: Vitamin C is not only an essential nutrient involved in many anabolic pathways, but also an important player of the endogenous antioxidant defense. Low plasma levels are very common in critical care patients and may reflect severe deficiency states. Vitamin C scavenges reactive oxygen species such as superoxide and peroxynitrite in plasma and cells (preventing damage to proteins, lipids and DNA), prevents occludin dephosphorylation and loosening of the tight junctions. Ascorbate improves microcirculatory flow impairment by inhibiting tumor-necrosis-factor-induced intracellular adhesion molecule expression, which triggers leukocyte stickiness and slugging. Clinical trials in sepsis, trauma and major burns testing high-dose vitamin C show clinical benefit. Restoration of normal plasma levels in inflammatory patients requires the administration of 3 g/day for several days, which is 30 times the daily recommended dose. The recent research on the modulation of oxidative stress and endothelial protection offer interesting therapeutic perspectives, based on the biochemical evidence, with limited or even absent side-effects.