Specialty “Immune-Enhancing” Diets
The concept that some nutrients became “conditionally essential” during stress and sepsis (e.g., GLN) or that other substrates such as omega-6 fatty acids could potentially aggravate inflammation through production of proinflammatory products led to the creation of a family of immune-enhancing diets (IEDs). These IEDs contain various combinations of GLN, arginine, omega-3 fatty aids, beta-carotene, and nucleotides. Liquid diets cannot be supplemented with GLN as a free amino acid because of its propensity to degrade into the toxic products pyroglutamate and ammonia after heat sterilization. Free GLN is found only in dry, powdered diets, which require reformulation prior to administration. These diets can be administered via transgastric jejunostomies (TGJs), large-bore (12–18 Fr) jejunostomies, and 7-Fr needle catheter jejunostomies (NCJs), but they tend to clog 5-Fr NCJs.
The rationale for these specific nutrient supplementations has been partly discussed above. Although skeletal muscle production of GLN increases during stress and sepsis, serum and intracellular levels decrease. GLN is a substrate for various immunologic cells and for enterocytes in the unfed state.6 Arginine promotes proliferating T cells after mitogen or cytokine stimulation in vitro and increases natural killer cell cytotoxicity, specific cytolytic T-cell activity, and macrophage tumor cytotoxicity. It also exerts a positive effect on wound healing; stimulates pituitary GH, prolactin, insulin, and IGF-I, and acts as a precursor for nitric oxide, nitrites, and nitrates as well as the growth substances putrescine, spermine, and spermidine, which may be involved in GI tract integrity. Omega-3 PUFAs from fish or canola oil can replace omega-6 PUFAs, such as linoleic acid, found mainly in vegetable oils. Omega-6 fatty acids inhibit killer cell activity, antibody formation, and cell-mediated immune response due to the inhibitory nature of their metabolic end products.10 Animal studies have shown that omega-3 supplementation reduces mortality after burn injury, reduces bacterial translocation compared with other lipids, promotes cell-mediated immunity, increases resistance to infection, reduces inflammation, and reduces mortality following bacterial peritonitis. The administration of RNA via nucleotides improves survival to a septic challenge with Candida albicans, and malnourished animals provided RNA during refeeding from a malnourished state had more rapid improvement in immune function.31 Nucleotide deprivation suppresses helper T-cell and interleukin-2 (IL-2) production, largely due to uracil, since adenine does not prevent this immunosuppression. Clinically, various combinations of these nutrients have been made available in specialty nutrient diets. The majority of clinical studies carried out in critically ill patients, general surgical patient populations, trauma patients, and burn patients suggest an additional benefit with the IEDs over unsupplemented diets.16,17,32,33
Gottschlich et al.34 randomized 50 pediatric and adult patients with burns over 10–89% of their body surface area to diets including a modular feeding supplemented with arginine, cysteine, histidine, and omega-3 fatty acids. A significant reduction in wound infection, length of stay per percent body burn, and total number of infectious complications occurred in this group, with a trend (P = .06) toward reduced pneumonia. More inhalation injuries in the control group as well as more fat and less carbohydrates in the control formula were confounding variables.
Patients with an ATI between 18 and 40 randomized to an IED or a chemically defined diet generated significant increases in total lymphocyte count and T-lymphocyte and T-helper cell numbers as well as fewer intra-abdominal abscesses and less multiple organ failure with the supplemented diet.17 Since a higher nitrogen content in the IED was a confounding variable, a subsequent study randomized patients with an ATI >25 or an ISS >20 to an IED or an isonitrogenous, isocaloric diet.16 Unfed cohorts, eligible for the trial entry but without enteral access, were also prospectively followed. The IED resulted in fewer major septic complications, fewer therapeutic antibiotics, and a shorter hospital stay than in the unfed group or those receiving the control diet. The incidence of intra-abdominal abscess, pneumonia, bacteremia, major wound infections, or any major complication was highest in the unfed population. Complications and antibiotic use with the control diet were between the unfed and IED groups. Administration of a GLN-supplemented enteral diet has also been shown to reduce pneumonia, bacteremia, and sepsis.35 Potential negative effects may also occur with these diets. One study noted an increase in respiratory failure with an IED.36 An increased incidence of respiratory failure in the treatment group at baseline limited the ability to implicate the diet, however.
We institute an IED in patients with an ATI >25 or an ISS >20 (Fig. 60-1) and convert to a standard high-protein enteral diet once the patients are less vulnerable to septic complications, usually within 7–10 days. Patients with less severe injuries receive a high-protein diet.