Impact of High‐Dose Antioxidants on Outcomes in Acutely Injured Patients

Collier, Bryan R.; Giladi, Aviram M.; Dossett, Lesly A.; Dyer, Lindsay; Fleming, Sloan B.; Cotton, Bryan A.

doi:10.1177/0148607108319808

Cited by 92 publications

(53 citation statements)

References 28 publications

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“…This approximates the minimal dose of parenteral ascorbate (1000 mg ascorbate/day) that raises the plasma ascorbate concentration of septic patients into the range of normal plasma levels (35). The dose should be tolerated well, judging from clinical trials that injected 1000-2000 mg ascorbate every 8-24 h for up to 7 days in critically ill surgical or acutely injured patients (5,11,16,39).…”

Section: Vitamin C Dosage and Safetymentioning

confidence: 99%

Evaluation of Vitamin C for Adjuvant Sepsis Therapy

Wilson

2013

Antioxidants & Redox Signaling

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Significance: Evidence is emerging that parenteral administration of high-dose vitamin C may warrant development as an adjuvant therapy for patients with sepsis. Recent Advances: Sepsis increases risk of death and disability, but its treatment consists only of supportive therapies because no specific therapy is available. The characteristics of severe sepsis include ascorbate (reduced vitamin C) depletion, excessive protein nitration in microvascular endothelial cells, and microvascular dysfunction composed of refractive vasodilation, endothelial barrier dysfunction, and disseminated intravascular coagulation. Parenteral administration of ascorbate prevents or even reverses these pathological changes and thereby decreases hypotension, edema, multiorgan failure, and death in animal models of sepsis. Critical Issues: Dehydroascorbic acid appears to be as effective as ascorbate for protection against microvascular dysfunction, organ failure, and death when injected in sepsis models, but information about pharmacodynamics and safety in human subjects is only available for ascorbate. Although the plasma ascorbate concentration in critically ill and septic patients is normalized by repletion protocols that use high doses of parenteral ascorbate, and such doses are tolerated well by most healthy subjects, whether such large amounts of the vitamin trigger adverse effects in patients is uncertain. Future Directions: Further study of sepsis models may determine if high concentrations of ascorbate in interstitial fluid have pro-oxidant and bacteriostatic actions that also modify disease progression. However, the ascorbate depletion observed in septic patients receiving standard care and the therapeutic mechanisms established in models are sufficient evidence to support clinical trials of parenteral ascorbate as an adjuvant therapy for sepsis.

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Section: Vitamin C Dosage and Safetymentioning

confidence: 99%

Evaluation of Vitamin C for Adjuvant Sepsis Therapy

Wilson

2013

Antioxidants & Redox Signaling

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“…An association has been proposed between increased oxidative stress and poor outcomes in the critically ill, suggesting a potential role for antioxidant strategies in the intensive care unit (ICU) (3). Limiting levels of oxidative stress may prevent cellular death, decrease inflammation and reduce morbidity and mortality rates (4); therefore, the antioxidant properties of sedative drugs should be taken into consideration as an important part of ICU remedy strategies, particularly when mechanical ventilation is required.…”

Section: Introductionmentioning

confidence: 99%

A comparison of the effects of midazolam, propofol and dexmedetomidine on the antioxidant system: A randomized trial

Han

Ding

Jiang

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Previous studies on the antioxidant activity of sedatives have predominantly been in vitro investigations that are lacking clinical data, resulting in conclusion without cogency. The aim of the present prospective, randomized study was to use single sedative drugs for anesthesia induction to compare their antioxidant properties. The effects on the antioxidant system of midazolam, propofol and dexmedetomidine were assessed using oxidative stress indicators and micronuclei (MN). Forty-nine patients undergoing esophageal cancer radical prostatectomy were selected. Midazolam, propofol and dexmedetomidine were used to induce anesthesia. Venous blood samples were obtained prior to and at 2 and at 24 h after surgery, and oxidative stress indicators were detected using the appropriate kits. The cytokinesis-block micronucleus cytome assay was executed and the frequencies of MN, nucleoplasmic bridges and nuclear buds were examined. It was found that the use of the three sedatives, respectively, led to a marked increase in the levels of free radical indicators at 2 h after surgery, which then decreased at 24 h after surgery. Furthermore, lower levels of oxidative stress were found following the use of propofol and dexmedetomidine compared with those following midazolam administration, and similar results were obtained regarding the level of MN. It is suggested that propofol and dexmedetomidine exhibit a superior antioxidant function to midazolam.

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“…Recently a large, retrospective review was reported of adults with trauma before and after the initiation of protocolized administration of an antioxidant cocktail containing ascorbic acid, -tocopherol and selenium to all acutely injured patients [24]. Patients who were admitted after the implementation of the antioxidant protocol had improved outcomes including hospital mortality, length of ICU stay and length of hospital stay, with the most significant improvements noted in the sickest patients with a probability of survival <50% [24].…”

Section: Anti-oxidant Treatment Regimens Containing Seleniummentioning

confidence: 99%

The Role of Selenium in Sepsis

McArthur

Quasney²

2011

TOINFJ

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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.Keywords: Selenium, sepsis, oxidative stress, reactive oxygen species, glutathione peroxidase. OXIDATIVE STRESS IN SEPSISReactive 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 [1] and intracellular glutathione stores, the most abundant antioxidant, are depleted [2]. The amount of ROS produced correlated to the severity of illness and pretreatment with n-acetylcysteine or glutathione decreased ROS production and cell death [2].

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Impact of High‐Dose Antioxidants on Outcomes in Acutely Injured Patients

Abstract: 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.

Cited by 92 publications

References 28 publications

Evaluation of Vitamin C for Adjuvant Sepsis Therapy

Evaluation of Vitamin C for Adjuvant Sepsis Therapy

A comparison of the effects of midazolam, propofol and dexmedetomidine on the antioxidant system: A randomized trial

The Role of Selenium in Sepsis

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