Randomized, Prospective Trial of Antioxidant Supplementation in Critically Ill Surgical Patients

  title={Randomized, Prospective Trial of Antioxidant Supplementation in Critically Ill Surgical Patients},
  author={Avery B. Nathens and Margaret J. Neff and Gregory J. Jurkovich and Patricia Klotz and Katherine Farver and John T. Ruzinski and Frank A. Radella and Iris A Garc{\'i}a and Ronald V. Maier},
  journal={Annals of Surgery},
ObjectiveTo determine the effectiveness of early, routine antioxidant supplementation using &agr;-tocopherol and ascorbic acid in reducing the rate of pulmonary morbidity and organ dysfunction in critically ill surgical patients. Summary Background DataOxidative stress has been associated with the development of the acute respiratory distress syndrome (ARDS) and organ failure through direct tissue injury and activation of genes integral to the inflammatory response. In addition, depletion of… 

Figures and Tables from this paper

Influence of early antioxidant supplements on clinical evolution and organ function in critically ill cardiac surgery, major trauma, and subarachnoid hemorrhage patients

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.

Vitamin C supplementation in the critically ill: A systematic review and meta-analysis

The administration of intravenous vitamin C may lead to vasopressor sparing effects and a reduced need for mechanical ventilation in the critically ill, without affecting overall mortality.

Mechanical Ventilation Antioxidant Trial.

Enteral administration of antioxidants is a simple, safe, inexpensive, and effective intervention that decreases the duration of mechanical ventilation in critically ill adults.

Analysis of oxidative stress-related markers in critically ill polytrauma patients: An observational prospective single-center study.

Investigation of several biomarkers associated with increased oxidative stress in critically ill polytrauma patients and the effect of antioxidant treatment on the clinical outcome found decreasing the level of oxidative stress by antioxidant substances significantly correlated with a better prognosis and outcome in patients.

Correlation of the oxygen radical activity and antioxidants and severity in critically ill surgical patients – study protocol

This study aims to assess the usefulness of oxygen free radical and antioxidant concentrations to predict the disease severity and mortality in a cohort of critically ill surgical patients.

Antioxidant supplementation in sepsis and systemic inflammatory response syndrome

Three antioxidant nutrients have demonstrated clinical benefits and reached level A evidence: a) selenium improves clinical outcome (infections, organ failure); b) glutamine reduces infectious complication in large-sized trials; and c) the association of eicosapentaenoic acid and micronutrients has significant anti-inflammatory effects.

Vitamin C Administration to the Critically Ill: A Systematic Review and Meta‐Analysis

Current evidence does not support supplementing critically ill patients with vitamin C, but a moderately large treatment effect may exist, but further studies, particularly of monotherapy administration, are warranted.

Antioxidant micronutrients in the critically ill: a systematic review and meta-analysis

Supplementation with high dose trace elements and vitamins may improve outcomes of critically ill patients, particularly those at high risk of death.

Antioxidant supplementation for the treatment of acute lung injury: a meta-analysis.

Conflicting evidence makes it impossible to recommend the routine use of antioxidant supplementation in critically ill patients, says this meta-analysis.

ABC’s of Vitamin Supplementation in Critical Illness

It is proposed that antioxidant vitamins, such as vitamins A and C, may minimize oxidative stress and improve clinical outcomes and few large, randomized trials specifically investigating the role of vitamin supplementation in the critically ill patient population are available.



Antioxidant Therapy in the Prevention of Organ Dysfunction Syndrome and Infectious Complications after Trauma: Early Results of a Prospective Randomized Study

Preliminary data may support a role for the use of this antioxidant mixture to decrease the incidence of multiorgan dysfunction syndrome and infectious complications in the severely injured patient.

Decreased antioxidant status and increased lipid peroxidation in patients with septic shock and secondary organ dysfunction.

These data indicate decreased antioxidant status in the face of enhanced free radical activity, and suggest potential therapeutic strategies involving antioxidant repletion.

Plasma fatty acid changes and increased lipid peroxidation in patients with adult respiratory distress syndrome.

During intensive care treatment, patients with ARDS decrease their percentage plasma concentrations of total plasma linoleic acid, but increase their percentage concentrations of oleic and palmitoleic acids, suggestive of severe oxidative stress leading to molecular damage to lipids.

N-acetylcysteine enhances recovery from acute lung injury in man. A randomized, double-blind, placebo-controlled clinical study.

Intravenous NAC treatment during 72 h improved systemic oxygenation and reduced the need for ventilatory support in patients presenting with mild-to-moderate acute lung injury subsequent to a variety of underlying diseases.

Antioxidant treatment with N‐acetylcysteine during adult respiratory distress syndrome: A prospective, randomized, placebo‐controlled study

It is documented that N-acetylcysteine acts as an anticoagulant and perhaps decreases pulmonary fibrin uptake during ARDS and might be of benefit in ARDS.

A randomized trial of replacement antioxidant vitamin therapy for neutrophil locomotory dysfunction in blunt trauma.

It is concluded that antioxidant replacement therapy significantly improves the PMN locomotory abnormality in blunt trauma.


The data suggests that the attenuation of acute lung injury by NAC in the authors' rodent model is related to free radical scavenging and inhibition of the neutrophil oxidative burst, rather than by an effect on inflammatory cell migration.

Plasma concentrations of cytokines, their soluble receptors, and antioxidant vitamins can predict the development of multiple organ failure in patients at risk.

There is a marked increase in anti-TNF activity and a decrease of antioxidant defense in patients at risk of developing multiple organ failure and the predictive value of plasma concentrations of circulating TNF-soluble receptors and vitamin C in this type of patient needs further evaluation.

Safety of bronchoalveolar lavage in patients with adult respiratory distress syndrome.

It is concluded that FOB and BAL can be performed safely and are reasonably well-tolerated in patients with ARDS.

A trial of antioxidants N-acetylcysteine and procysteine in ARDS. The Antioxidant in ARDS Study Group.

The findings suggest that repletion of glutathione may safely be accomplished with NAC or OTZ in patients with acute lung injury/ARDS and such treatment may shorten the duration of acute lung Injury, but larger studies are needed to confirm this.