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Intravenous fat infusions are a standard component of total parenteral nutrition (TPN). We studied the effects of withholding fat infusions in trauma patients requiring TPN. Polytrauma patients receiving TPN were randomized to receive a standard fat emulsion dose (L) or to have fat infusions withheld (NL) for the first 10 days of TPN. The two groups received the same amino acid and carbohydrate dose (isonitrogenous, nonisocaloric). Clinical outcome parameters were measured. T-cell function was assessed by measuring lymphokine activated killer and natural killer cell activity. Demographics including Injury Severity Score (27 +/- 8; 30 +/- 9) and APACHE II scores (23 +/- 6; 22 +/- 5) were similar for the L (n = 30) and NL (n = 27) groups, respectively. Differences (p < 0.05) were found in length of hospitalization (L = 39 +/- 24; NL = 27 +/- 16), intensive care unit length of stay (L = 29 +/- 22; NL = 18 +/- 12), and days on mechanical ventilation (L = 27 +/- 21; NL = 15 +/- 12). The L group had a higher number of infections (72 in 30) than the NL group (39 in 27) and T-cell function was depressed in this group. Intravenous fat emulsion infusions during the early postinjury period increased susceptibility to infection, prolonged pulmonary failure, and delayed recovery in critically injured patients. It is not clear whether the improved outcome in the NL group was directly related to withholding the fat infusions or due to the hypocaloric nutritional regimen (underfeeding) these patients received.