Several recent studies have demonstrated that gut mucosal dysfunction, in the form of increased permeability and villous sloughing, occurs early in the absence of enteral feedings. In the critically injured patient, several authors have demonstrated improvements in the catabolic state, specifically through improved nitrogen balance, when enteral nutrition is utilized instead of TPN. Physiological advantages of enteral nutrition over TPN include its stimulation of gallbladder emptying and release of pancreatic secretions, as well as maintenance of gut-associated lymphoid tissue (GALT) and mucosal immune function. The improved gut mucosal integrity noted with enteral feedings is likely responsible for the decreased bowel perforation rate, improved intestinal anastomotic healing, and decreased septic complications. In addition, enteral feeding is significantly less expensive (even when excluding the costs associated with TPN complications) than parenteral formulations.

The intestinal mucosa and submucosa is an area of intense metabolic and immunologic activity, especially in the critically ill and severely injured patient. Utilization of TPN in these patients further
compromises an already tenuous situation, with loss of mucosal mass and weight, increased villous sloughing, and disturbed mucosal enzyme activity. TPN use has been shown to decrease IgA in the gut, as well as in upper respiratory secretions. From a metabolic standpoint, TPN causes metabolic acidosis, hyperglycemia, hyperlipidemia, and significant electrolyte disturbances. In addition, TPN has been associated with hepatic steatosis and cellular injury leading to liver dysfunction and failure. Systemically, the effects of TPN include impairment of leukocyte chemotaxis, impaired phagocytosis, and an attenuated inflammatory response. Other authors, however, have shown TPN associated alterations may actually potentiate the systemic inflammatory state by allowing increased bacterial translocation and increasing free-radical formation. Some studies have demonstrated higher mortality, especially among the critically ill, in those receiving parenteral nutrition compared with enteral feeding, with TPN almost doubling the risk of dying. Of note, the risks of TPN toxicity can be reduced by the addition of low-rate (sometimes referred to as trophic) tube feedings (10 to 30 mL/h).