Dear Readers:

Along with careful diagnosis, alleviating causes of tissue damage, such as pressure, impaired circulation or infection and providing an optimal healing environment, nutrition plays a key role in wound care.^1,2 The role of nutritional supplements becomes increasingly urgent in healing patients with more invasive injuries or conditions that deplete body stores of important nutrients. The articles presented in this Evidence Corner teach us how nutritional supplements support immunologic and healing functions in patients with major burns, and one reminds us that nutrient absorption through the gastrointestinal tract is not always optimal.

Enteral Glutamine Improves Severely Burned Patients’ Recovery
Reference: Peng X,Yan H,You Z,Wang P,Wang S. Glutamine granule-supplemented enteral nutrition maintains immunological function in severely burned patients. Burns. 2006;32(5):589–593.
Rationale: In appropriate concentrations, glutamine fuels immune cell function and nourishes proliferating cells.
Objective: Explore effects of supplementing enteral nutrition with glutamine granules on immunologic function in severely burned patients.
Methods: A double-blind controlled trial randomly assigned patients admitted to a burn intensive care unit (ICU) with 30%–75% total body surface area (TBSA) burns (20%–58% of TBSA full-thickness burns) to receive an enteral diet supplemented with either 0.5 mg/kg per day glutamine (n = 23) or an isocaloric, isonitrogenous control diet containing 0.5 mg/kg per day of glycine as placebo (n = 25) on days 1–14 post burn. Plasma glutamine level, cell immunity function (CD4/CD8 cell ratios, IL-2, lymphocyte transformation ratio, and neutrophil phagocytosis index), and plasma humoral immunity factors (IgA, IgG, IgM, C3, C4) were determined from peripheral blood samples on days 1 and 14. Burn dimensions on day 1 and length of hospital stay were also recorded.
Results: Glutamine and control groups were comparable on day 1 in patient, burn, and immunologic measures, with equally depressed plasma glutamine, and cellular immunity measures compared to those of 10 healthy volunteers (P < 0.01). These values were restored to normal levels after 14 days of enteral glutamine, but not glycine control supplement. There were no significant effects on the humoral immunity function measures with the glutamine diet. Glutamine supplemented patients experienced a shorter average length of hospital stay: 49.6 days compared to 55.7 days in the control group (P < 0.05).
Authors’ Conclusions: Oral or tube-fed enteral glutamine supplements improve depressed immunological cell function following severe burns and associated wound healing, while reducing the length of hospital stay.

Trace Element Supplements Improve Recovery of Severe Burn Patients
Reference: Berger MM, Baines M, Raffoul W, et al. Trace element supplementation after major burns modulates antioxidant status and clinical course by way of increased tissue trace element concentrations. Am J Clin Nutr. 2007;85(5):1293–1300.
Rationale: Trace element deficiencies after major burns are associated with infectious and healing complications that can influence clinical patient outcomes.
Objective: Explore effects of large intravenous doses of trace elements (TE) on circulating and cutaneous TE concentrations, antioxidant status, and clinical outcomes of patients hospitalized with major burns.
Methods: A prospective, randomized, controlled trial compared effects of intravenous (IV) 250 mL over 12 h daily of either TE or vehicle (V) on TE and antioxidant metabolite levels, as well as clinical infection and graft take outcomes of 21 patients with major burns admitted to a burn ICU. Patients were stratified by age (< or ≥ 50 years), total body surface area burned (< or ≥ 50%BSA), and inhalation injury (yes/no). The patients were randomized to receive TE (n = 11) in an IV 0.9% saline solution vehicle mixed with a commercial parenteral supplement given as vehicle (V) to the control group (n = 10). Trace element concentrations were 59 μmol Cu as copper gluconate, 4.8 μmol Se as sodium selenite, and 574 μmol Zn as zinc gluconate. Treatment began within 12 h of injury, continued through days 14 to 20, and included standardized nutritional support following an accepted major burn protocol. Trace element and metabolic biochemistry were reported on periodic blood and urine samples. Skin specimens were harvested from burns and skin graft donor sites of 12 (7 V and 5 TE) patients after 3, 10, and 20 days of supplementation. Measured clinical outcomes included length of mechanical ventilation, ICU and hospital stays, infections requiring new antibiotic therapy during the first 30 days post burn, and graft requirements calculated as the total surface grafted divided by the total body surface surgically excised. Analyses included intent-to-treat patients with statistical significance P = 0.05.
Results: The two groups did not differ on patient or burn characteristics. Mean BSA burned was 44% in V and 45% in TE patients, with mean BSA of 34% and 31%, respectively, requiring surgery. Significantly fewer grafts per unit surgically excised area (P < 0.02) were required for TE patients than for V patients. Trace element patients also experienced fewer median infections per patient (P < 0.01), which were mainly pulmonary (P = 0.03) with no significant differences between groups in cutaneous or other infections, or other clinical outcomes. Trace element supplementation increased plasma levels of Cu, Se, and Zn on days 5–20, Se levels in burned and healthy skin tissue from days 3–20, and restored normal Zn levels to burned tissue by day 20. Plasma and tissue glutathione and related metabolites, which play a selenium-dependent role in intracellular and extracellular antioxidant host defenses, generally paralleled selenium concentrations.
Authors’ Conclusions: Early large copper, selenium, and zinc supplementation is safe and of benefit to patients with major burns, as it reduces the number of infectious complications (mainly pneumonia) and skin grafting requirements with a nonsignificant shorter treatment time in the ICU.

Clinical Perspective
Despite the small number of patients in these two studies, significant effects were reported and suggest parallel benefits of TE and glutamine nutritional supplements in improving immunologic cell function in severely burned patients. Glutamine supplementation reduced length of hospital stay, and an aggregate analysis of two similar studies by Berger et al³ confirmed shorter ICU stay per percent of BSA burned (P = 0.002), in TE-supplemented patients with major burns with fewer antibiotic therapy days (P = 0.021),and nosocomial pulmonary infections (P < 0.001). The Berger et al finding of reduced skin grafting requirements per unit area of surgically debrided burn suggests either a direct effect of TE on healing or a secondary healing benefit due to reduced pulmonary infection. Peng et al did not report any direct healing effects. Selenium was hypothesized to fuel the TE effect, though it may also be fruitful to explore its interactions with zinc or copper or effects on parallel immunologic pathways, as nature rarely responds to challenges via a single nutrient, enzyme, or cytokine. Do these findings generalize to other acute challenges such as trauma, surgery, or infection? Topical zinc was reported as ineffective in healing pilonidal excisions in zinc deficient patients,⁴ but it is unclear whether systemic administration or a multi-trace element approach might have been more effective. Evidence shows that patients with chronic leg ulcers have experienced no consistent healing benefits of oral zinc sulfate—the exception being mixed results in trials of patients with low serum zinc.⁵ While further research is needed to determine effects on chronic wounds or other acute wounds, these compelling benefits of reversing nutrient deficiencies in patients with major burns merit further attention.