High-dose antioxidant administration is associated with a reduction in post-injury complications in critically ill trauma patients
Introduction
Severe and sustained oxidative stress from trauma, infection, burn, or other critical illness results in depletion of endogenous antioxidants due to the rapid and massive production of reactive oxygen species (ROS).12, 23 This systemic stress results in wound complications, increased infections, and leads to multiorgan dysfunction (MOD), contributing to increased morbidity and mortality.15, 25, 29 In these patients, serum and tissue levels of antioxidants are markedly decreased.26, 28 Numerous investigators have shown that exogenous supplementation of various antioxidants, including ascorbic acid (vitamin C), α-tocopherol (vitamin E), and selenium, results in systemic and local tissue levels returning to baseline.2, 4, 9
In the burn population, supplementation of various antioxidants in both human and animal models has resulted in decreased organ failure.22, 27, 28, 31 Additionally, copper, selenium, and zinc replacement resulted in shorter hospital stay, reduction of pulmonary infections, as well as lower skin grafting requirements.9, 10 In acute respiratory distress syndrome (ARDS) patients, antioxidants were used along with fish oils to decrease organ failure and ventilator days.19 In critically ill surgical patients, vitamins C and E reduced the incidence of organ failure and shortened intensive care unit (ICU) length of stay.26 Recently, we presented a historical cohort study with sufficient patients and power to show vitamin C, vitamin E, and selenium supplementation in acutely injured patients resulted in a reduction in overall mortality.16
Many well-designed trials have provided great support for antioxidant supplementation, but these studies have been unsuccessful in demonstrating significant reduction in critical illness morbidities and a decrease in overall mortality. Given the recent findings that antioxidant supplementation is associated with a 28% relative risk reduction in mortality, it is important to define potential avenues through which such a reduction could be observed.16 The purpose of this study was to evaluate the impact of high-dose vitamin C, vitamin E, and selenium supplementation on the incidence of post-injury complications in critically injured patients.
Section snippets
Study design and setting
The Vanderbilt University Institutional Review Board approved this study. Vanderbilt University Medical Center is a state verified level I trauma centre that evaluates over 3000 acutely injured patients annually; over 700 patients are admitted to the trauma ICU and require mechanical ventilation for greater than 24 h. Patients are cared for by a group of trauma and critical care trained physicians according to evidence based practice management guidelines for sedation, ventilator weaning,
Demographic and clinical characteristics
Patients in the AO+ group were more likely to be male, older, and have a lower calculated probability of survival by means of TRISS (Table 1). There were no statistical differences in race or Injury Severity Scores (ISS) between AO groups.
Clinical course and durations of care
The overall mortality rate in the AO− group was 8.5% compared to 6.1% in the AO+ group (p < 0.001). Intensive care median length of stay was significantly shorter (p < 0.001) in those patients exposed to high-dose antioxidants compared to those not exposed (2
Discussion
Surviving initial injuries is of primary focus in the care of trauma patients; however, those who survive but continue to undergo systemic inflammation and stress often succumb to multiorgan failure.15, 25, 29 An increased amount of evidence has linked the excess production of reactive oxygen species (ROS) to these systemic complications.11, 21 When they accumulate, ROS injure cell membranes and structural proteins, and induce apoptosis.21, 27 In the normal state, these ROS are neutralised by
Conclusion
Severely injured patients are subject to significant systemic stress resulting in an overwhelming production of ROS and depletion of endogenous antioxidants. These key substrates are thought to be key in preventing additional tissue injury, organ system failure, and the resultant mortality. Following implementation of a high-dose AO protocol in trauma patients, we noted a reduction in respiratory failure, abdominal wall complications, surgical site infections, and overall infectious
Funding
No financial support was used for this study.
Conflicts of interest
The authors of this article have no financial or other conflicts of interest.
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