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CRITICAL CARE AND TRAUMA

The Beneficial Effects of Antioxidant Supplementation in Enteral Feeding in Critically Ill Patients: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial

Ettore Crimi, MD^*, Antonio Liguori, MD, Mario Condorelli, MD, Michele Cioffi, MD, Marinella Astuto, MD^||, Paola Bontempo, MD PhD, Orlando Pignalosa, MD, Maria Teresa Vietri, MD, Anna Maria Molinari, MD, Vincenzo Sica, MD, Francesco Della Corte, MD^*, and Claudio Napoli, MD PhD^,

*Department of Anesthesiology and Intensive Care, University of Eastern Piedmont, Novara, Italy; Coronary Care Unit, Pellegrini Hospital, Naples, Italy; Department of Medicine, University of Naples, Naples, Italy; Division of Clinical Pathology, II University of Naples, Naples, Italy; and ||Department of Anesthesiology and Intensive Care, University of Catania, Catania, Italy

Address correspondence and reprint requests to Ettore Crimi, MD, Department of Anesthesiology and Intensive Care, University of Eastern Piedmont, Novara, Italy, Via Solaroli, 17 Novara 28100, Italy. Address e-mail to etcrimi{at}tin.it

We investigated whether intervention with antioxidant vitamins C and E in enteral feeding influenced oxidative stress and clinical outcome in critically ill patients. Two-hundred-sixteen patients expected to require at least 10 days of enteral feeding completed the study. One-hundred-five patients received enteral feeding supplemented with antioxidants, and 111 control patients received an isocaloric formula. Plasma lipoperoxidation (by thiobarbituric acid reactive substances [TBARS] and prostaglandin F₂ isoprostane levels), low-density lipoprotein (LDL) oxidizability, and LDL tocopherol content were determined at baseline and at the end of the 10-day period. The clinical 28-day outcome was also assessed. Plasma TBARS and isoprostanes were 5.33 ± 1.26 nM/mL and 312 ± 68 pg/mL, respectively, before treatment and 2.42 ± 0.61 nM/mL and 198 ± 42 pg/mL after intervention (P < 0.01 for both comparisons). Antioxidants improved LDL resistance to oxidative stress by approximately 30% (the lag time before treatment was 87 ± 23 min and was 118 ± 20 min after treatment; P < 0.04). There was a significantly reduced 28-day mortality after antioxidant intervention (45.7% in the antioxidant group and 67.5% in the regular-feeding group; P < 0.05). Isoprostanes may provide a sensitive biochemical marker for dose selection in studies involving antioxidants.

IMPLICATIONS: Massive oxidative injury may promote poor clinical outcome in critically ill patients. This study demonstrates that antioxidant intervention is associated with reduced oxidative stress, enhanced antioxidant defenses, and reduced 28-day mortality in critically ill patients.

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