Elsevier

Injury

Volume 42, Issue 1, January 2011, Pages 78-82
Injury

High-dose antioxidant administration is associated with a reduction in post-injury complications in critically ill trauma patients

https://doi.org/10.1016/j.injury.2010.01.104Get rights and content

Abstract

Background

We recently demonstrated a high-dose antioxidant (AO) protocol was associated with reduction in mortality. The purpose of this study was to evaluate the impact of AO on organ dysfunction and infectious complications following injury.

Patients and methods

High-dose AO protocol: ascorbic acid 1000 mg q 8 h, α-tocopherol 1000 IU q 8 h, and selenium 200 mcg qd for 7-day course. Retrospective cohort study evaluating all patients admitted after protocol implementation (AO+), October 1, 2005 to September 30, 2006. Comparison cohort (AO−): all patients admitted in the year prior to implementation, October 1, 2004 to September 30, 2005.

Results

2272 patients included in the AO+ group, 2022 patients in the AO− group. Demographics and injury severity were similar. Abdominal compartment syndrome (ACS) (2.9% vs. 0.7%, <0.001), surgical site infections (2.7% vs. 1.3%, p = 0.002), pulmonary failure (27.6% vs. 17.4%, p < 0.001), and ventilator-dependent respiratory failure (10.8% vs. 7.1%, p < 0.001) were significantly less in the AO+ group. Multivariate regression showed 53% odds reduction in abdominal wall complications and 38% odds reduction in respiratory failure in the AO+ group.

Conclusions

Implementation of a high-dose AO protocol was associated with a reduction in respiratory failure and ventilator-dependence. In addition, AO were associated with a marked decrease in abdominal wall complications, including ACS and surgical site infections.

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.

References (31)

  • Z. Balogh et al.

    Both primary and secondary abdominal compartment syndrome can be predicted early and are harbingers of multiple organ failure 105

    J Trauma

    (2003)
  • M.M. Berger et al.

    Copper, selenium, and zinc status and balances after major trauma

    J Trauma

    (1996)
  • H.K. Biesalski et al.

    Antioxidant therapy in critical care—is the microcirculation the primary target?

    Crit Care Med

    (2007)
  • E.M. Bulger et al.

    Intracellular antioxidant activity is necessary to modulate the macrophage response to endotoxin

    Shock

    (2002)
  • E.M. Bulger et al.

    Enteral vitamin E supplementation inhibits the cytokine response to endotoxin

    Arch Surg

    (1997)
  • Cited by (0)

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