The purpose of the present paper is to provide a rationale for
zinc supplementation as a potential therapeutic agent in
critically ill patients by describing its role in health and disease, conducting a systematic review of current randomized trials in
critical care, considering optimum route and dose of administration, and making recommendations for future research. Normal
zinc homeostasis is required for a functional immune system, adequate
antioxidant capacity,
glucose homeostasis, and wound healing. In addition,
zinc is a required cofactor for many
enzymes,
transcription factors, and replication factors. In non-
critically ill patients,
zinc supplementation has been associated with an improvement in markers of immune function. In
critically ill patients, only 4 randomized trials have examined the effect of
zinc supplementation on clinical outcomes. When all 4 studies were aggregated,
zinc supplementation was associated with a nonsignificant reduction in mortality (relative risk = 0.63, 95% confidence intervals 0.25-1.59, P = .33) and
length of stay in
intensive care (-0.35 days, -0.85 to 0.15; P = .17). Thus, because of the paucity of clinical data, there is inadequate evidence to recommend the routine use of high-dose
zinc supplementation in the
critically ill. A first step would be to determine the optimal dose that has a maximal positive effect on underlying inflammatory, immunologic, and metabolic processes yet is safe and tolerated by
critically ill patients. Subsequently, large, rigorously designed, randomized trials are required to elucidate the efficacy of such doses of
zinc supplementation in this patient population.