The process and mediators resulting in tissue injury following ischemia and reperfusion are multifactorial, but there is considerable evidence that supports the idea that they include reactive oxygen species. In healthy individuals, a wide range of antioxidant defenses protects against oxidative damage. However, free radicals can accumulate as a result of overwhelming production of inadequate defenses. The latter situation may reflect an inadequate supply of antioxidant micronutrients. Cross-clamping of the aorta during abdominal aortic aneurysmectomy (AAA) leads to ischemia-reperfusion, oxidative stress, cell dysfunction, and injury in the muscles of the lower extremities. Scientists hypothesized that supplementation with micronutrients with antioxidant properties would supplement antioxidant mechanisms and minimize the decreases in muscle strength and physical function, which occur following AAA.
In an attempt to evaluate this process, these researchers conducted a randomized, double-blind, placebo-controlled clinical trial of individuals undergoing AAA. Due to the synergistic and complementary actions of antioxidant micronutrients, investigators chose to supplement patients with a combination of vitamins and trace elements. A two-week period of preoperative supplementation was chosen because of data demonstrating that oral vitamin E supplementation for two weeks achieved increased tissue levels of alpha-tocopherol. Patients of both sex and any age who were identified at least two weeks before elective repair of an infrarenal abdominal aortic aneurysm were eligible to participate in the study. Subjects were randomly assigned to receive either micronutrient (MN) supplementation or placebo in a blocked design. MN supplementation consisted of beta-carotene (10 000 IU/d), vitamin C (1000 mg/d), vitamin E (400 IU/d), selenium (50 microgram/d), and zinc (24 mg/d). The supplement or placebo was taken orally for at least two weeks and not more than three weeks prior to surgery and continued on the morning of surgery and daily during the first postoperative week. Patients were instructed to maintain their routine diets before surgery. Clinical, functional, physiologic, and biochemical endpoints were evaluated. The duration of the surgical procedure and aortic clamping and other clinical variables were recorded. Organ system function was assessed on the first and second postoperative mornings. Pain was evaluated. Assessments of function status (Karnofsky Performance Status [KPS]), cognitive impairment (Mini-Mental State Examination, MMSE), health-related quality of life (HRQL) (SF36 Health Survey) and the ability to conduct physical and instrumental activities of daily living (PADL, IADL) were made at the Pre-Admission Unit visit before surgery and at the scheduled follow-up visit closet to four weeks following the operation. Thirty-six subjects participated in the study.
Handgrip strength decreased following surgery, with no significant difference observed between MN and placebo groups. Intravenous fluid administration, red blood cell transfusions, ICU stay, duration of mechanical ventilation, and hospital stay were similar in MN and placebo groups. There was no 30-day mortality in either group. KPS decreased following surgery, but the decrease did not differ between groups. MMSE did not change following surgery and a full diet was tolerated on postoperative day 6+2 in both groups. The decline in general health following surgery was more marked in the placebo group, and the difference in decline in vitality approached statistical significance.
The investigators concluded that perioperative supplementation with micronutrient with antioxidant properties has limited effects on strength and physical function following major elective surgery.
J. Watters, A. Vallerand, S. Kirkpatrick, et al. Limited effects of micronutrient supplementation on strength and physical function after abdominal aortic aneurysmectomy. Clinical Nutrition 21:321-327 (August, 2002). [Correspondence: James M. Watters, Ottawa Hospital 737 Parkdale Avenue, Ottawa, Ont., Canada K1Y 4E9].
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