Early enteral administration of a formula (Impact) supplemented with arginine, nucleotides, and fish oil in intensive care unit patients: results of a multicenter, prospective, randomized, clinical trial.

OBJECTIVE: To determine if early enteral feeding, in an intensive care unit (ICU) patient population, using a formula supplemented with arginine, dietary nucleotides, and fish oil (Impact), results in a shorter hospital stay and a reduced frequency of infectious complications, when compared with feeding a common use enteral formula (Osmolite.HN). DESIGN: A prospective, randomized, double-blind, multicenter trial. SETTING: ICUs in eight different hospitals. PATIENTS: Of 326 patients enrolled in the study, 296 patients were eligible for analysis. They were admitted to the ICU after an event such as trauma, surgery, or sepsis, and met a risk assessment screen (Acute Physiology and Chronic Health Evaluation II [APACHE II] score of > or = 10, or a Therapeutic Intervention Scoring System score of > or = 20) and study eligibility requirements. Patients were stratified by age (< 60 or > or = 60 yrs of age) and disease (septic or systemic inflammatory response syndrome). INTERVENTIONS: Patients were enrolled and full-strength tube feedings were initiated within 48 hrs of the study entry event. Enteral feedings were advanced to a target volume of 60 mL/hr by 96 hrs of the event. One hundred sixty-eight patients were randomized to receive the experimental formula, and 158 patients were randomized to receive the common use control formula. MEASUREMENTS AND MAIN RESULTS: Both groups tolerated early enteral feeding well, and the frequency of tube feeding-related complications was low. There were no significant differences in nitrogen balance between groups on study days 4 and 7. Patients receiving the experimental formula had a significant (p = .0001) increase in plasma arginine and ornithine concentrations by study day 7. Plasma fatty acid profiles demonstrated higher concentrations of linoleic acid (p < .01) in the patients receiving the common use formula and higher concentrations of eicosapentaenoic and docosahexaenoic acid (p < .01) in the patients receiving the experimental formula. The mortality rate was not different between the groups and was significantly (p < .001) lower than predicted by the admission severity scores in both feeding groups. In patients who received at least 821 mL/day of the experimental formula, the hospital median length of stay was reduced by 8 days (p < .05). In patients stratified as septic, the median length of hospital stay was reduced by 10 days (p < .05), along with a major reduction in the frequency of acquired infections (p < .01) in the patients who received the experimental formula. In the septic subgroup fed at least 821 mL/day, the median length of stay was reduced by 11.5 days, along with a major reduction in acquired infections (both p < .05) in the patients who received the experimental formula. CONCLUSIONS: Early enteral feeding of the experimental formula was safe and well tolerated in ICU patients. In patients who received the experimental formula, particularly if they were septic on admission to the study, a substantial reduction in hospital length of stay was observed, along with a significant reduction in the frequency of acquired infections.

Effect of different dietary triglycerides on liver fatty acids and prostaglandin synthesis by mouse peritoneal cells.

The effect of dietary triglycerides varying in fatty acid composition on the tissue fatty acids and prostaglandin synthesis was studied in mice. The dietary fats were medium-chain triglycerides (rich in C8:0 and C10:0), structured lipids (rich in 12:0), high oleic sunflower oil (rich in 18:1), corn oil (rich in n-6 polyunsaturated fatty acids), and menhaden oil (rich in n-3 polyunsaturated fatty acids) fed at 5% by weight in refined diets. The medium chain fatty acids C8 to C12 from medium-chain triglycerides and structured lipids did not accumulate in liver phospholipids. However, long-chain fatty acids from the dietary fats were incorporated into liver lipids, with n-3 polyunsaturated fatty acids replacing arachidonic acid. The synthesis of 6-keto-prostaglandin F1 alpha and prostaglandin E2 by peritoneal cells in response to intraperitoneal injection of zymosan decreased as the arachidonic acid levels were decreased. When the same dietary fats were added to the refined, fat-free diets, at 7.5 wt% levels, together with 2.5 wt% of safflower oil to provide essential fatty acids, only the long-chain fatty acids from the dietary fats were incorporated into the liver lipids. The arachidonic acid in liver lipids was enhanced after supplementation of diets with safflower oil. However, the reduction in prostaglandin synthesis by peritoneal cells in response to intraperitoneal injection of zymosan was similar to that observed when 5% fat was fed. The data suggest that dietary fats of defined composition, with or without added essential fatty acids, may be useful as alternate fat sources in parenteral nutrition in reducing inflammatory responses mediated via prostaglandins.

Improvement in immune function in ICU patients by enteral nutrition supplemented with arginine, RNA, and menhaden oil is independent of nitrogen balance.

Hypermetabolism and multiple organ failure syndrome (MOFS) after trauma, surgery, or sepsis is associated with accelerated catabolism, the rapid onset of malnutrition, and immune system failure. Current nutritional support, enteral or parenteral, can achieve an acceptable nutritional response but appears unable to improve immune function. Nutrients such as arginine, refined menhaden oil, and RNA have been found to have immune-stimulating properties. This randomized blind prospective trial compared two nutritionally complete enteral formulas, one supplemented with arginine, menhaden oil, and RNA, on the disease-specific effects of anergy and suppression of in vitro tests of immune function in intensive-care patients and the nutritional outcome of nitrogen balance. After 7-10 days of enteral nutrition in patients with persistent sepsis syndrome, both formulas were associated with the achievement of net nitrogen retention and improved visceral protein status but with nonresolution of anergy. However, the supplemented formula was associated with marked stimulation of in vitro lymphocyte proliferative responses and a significant reduction in 3-methylhistidine excretion. Six and 12-mo follow-up data demonstrated no long-term effects. Nutrients targeted to effect the disease-induced in vitro suppression of immune function in MOFS appear to achieve that end independent of the nutritional outcome of nitrogen balance and without adverse clinical outcome.

Omega 3 polyunsaturated fatty acids as modulators of cellular function in the critically ill.

Continued improvement in outcome in ICU patients with the hypermetabolism-organ failure syndrome require a better understanding of the disease process. Current research is focusing on altered regulation at the cell membrane and nuclear levels. Cell culture models have provided insight into one possible mechanism, that of altered cell-cell communication with dysregulation of the associated parenchyma. Alteration of the PUFA content of the membrane of macrophages with omega 3 PUFA can be easily induced and maintained, and can alter cell membrane physical characteristics and how the membrane responds to LPS-stimulated prostanoid release. There is also an associated alteration in the release of monokine. These changes are associated with improvements in T lymphocyte response to antigen and in outcome from septic peritonitis. The precise mechanisms through which these effects occur are the subject of investigations, as are the clinical implications. Nonetheless, nutrient pharmacology with omega 3 PUFA may be a promising area of research that will have clinical applicability in ICU patients.