Pressure ulcers are common in older adults, especially those confined to a bed or a wheelchair. After these wounds have formed, they become difficult to treat. Good nutrition is vital for healing. Vitamins A, B, C, and E and the minerals copper, selenium, and zinc all appear to play a major role in facilitating the healing process. Zinc serves as a cofactor for several enzymes that are important for cellular growth and replication. A deficiency of this mineral appears to decrease protein and collagen synthesis, resulting in impairment of wound heal-ing. Interestingly, patients with chronic pressure ulcers, when compared with control subjects, tend to be mildly deficient in zinc.
The efficacy of zinc in improving rates of wound healing remains unclear. Five randomized, placebo-controlled trials and a meta-analysis have been conducted to evaluate the efficacy of zinc supplementation in patients with chronic leg ulcers. With one exception, these trials did not demonstrate a statistically significant benefit of zinc for all patients with pressure ulcers. Although statistically significant results were not achieved in some subgroups, a potential improvement in wound healing was noted in each of the five trials.
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In addition, two of these studies compared the efficacy of zinc therapy in zinc-deficient patients with that of patients with normal zinc serum concentrations. The patients with low baseline zinc concentrations demonstrated a statistically significant improvement in wound healing, whereas patients who were not considered to be deficient in zinc attained no such benefit.
Zinc therapy, although relatively safe when used appropriately, may produce some bothersome adverse effects. Orally administered zinc can directly irritate the gastrointestinal tract, sometimes causing vomiting and diarrhea, especially when high doses are used. Excessive zinc supplementation also has the potential for adverse effects on wound healing. This paradoxical finding is thought to be the result of two separate mechanisms:
• The negative effect on tissue repair may be secondary to an impairment of neutrophil and lymphocyte function.
• Excess zinc may compromise the ability of copper and calcium—two other important minerals in the wound-healing process—to access the wound.
Zinc is implicated in contributing to several drug-drug interactions. When given within two to four hours of fluoro-quinolones or tetracyclines, concomitant zinc administration results in the chelation or binding of these antibiotics within the gastrointestinal tract. Absorption of the antibiotic can be significantly decreased, with total drug exposure subsequently diminished. As a result, therapy may fail and the risk of acquired antibiotic resistance may increase.
As mentioned earlier, zinc supplementation in patients with leg ulcerations has not demonstrated improved wound healing unless patients were zinc-deficient. “Normal” plasma zinc concentrations are generally within the range of 70 to 130 mcg/dl. Although serum levels do not necessarily reflect total body stores, conventional wisdom suggests that zinc therapy might be recommended in patients with baseline serum levels below 100 mcg/dl. It is believed that serum concentrations below this value are associated with impaired wound healing.
Supplementation with 220 mg of zinc sulfate (50 mg of elemental zinc) orally, dosed one to three times daily, is recom-mended. Because of the impending risks of dose-related side effects, drug-drug interactions, and the difficulties inherent in multiple daily doses, we favor the empirical use of once-daily dosing for periods of two to three months. After this time, total body stores of zinc should be at or close to repletion. After zinc stores are replete, the mineral’s biological half-life of 250 days should help to negate the occurrence of acute-onset deficiency.
One reasonable algorithm to employ is to check zinc levels before the initiation of therapy and to begin treatment only when the levels are approximately 100 mcg/dl or lower. If the wound is not adequately healed after six to 12 weeks of zinc supplementation, zinc levels should be checked again. An assessment of zinc levels can cost an institution approximately $20.00 to $25.00 and can cost the patient or third-party payer nearly $80.00 (T. Morrow, personal communication, February 2003).
A more cost-effective approach might be to treat patients empirically for six to eight weeks without regard to baseline zinc values and to check zinc levels only in the event of poor wound healing. If zinc concentrations have normalized in the presence of a nonhealing wound, other cofactors and conditions are probably the culprits. In such cases, treatment with zinc should be discontinued. If the ulcer has healed, zinc therapy can be stopped without the need for a post-treatment level assessment.
Zinc appears to play a major role in facilitating the healing process. To date, zinc supplementation has benefited patients with pressure ulcers only when zinc deficiency was present. When used inappropriately, zinc can hinder the healing process. In addition, zinc can become one more unnecessary drug that increases the complexity of patients’ drug regimens and that enhances the probability of iatrogenic drug-related effects. Practitioners should prescribe zinc with caution so that supplementation with this mineral does not become an impediment to the optimal treatment of patients.