Based on clinical observations, we hypothesized that prolonged parenteral nutrition (in contrast to enteral nutrition) is detrimental after major hepatic resection. Male Sprague-Dawley rats (300 to 380 g) anesthetized with intraperitoneal sodium pentobarbital had 70% hepatic resection and jugular vein and gastrostomy catheterizations using aseptic techniques and were divided randomly into three groups: (1) total parenteral nutrition (TPN) (nutrients via central vein), (2) total enteral nutrition (TEN) (identical nutrients via gastrostomy), and (3) standard oral feeding (SOF) (chow and water ad libitum). Unused catheters were plugged. In the first set of experiments (n = 42), nutrient intake was formulated to approximate the nutritional intake of normal rats, 216 kcal/kg/d. Infusate was 15% glucose, 4.5% amino acids, electrolytes, trace minerals, vitamins, and 20% fat emulsion given half-strength the first day, three-fourths strength the second day, and full strength thereafter. On postoperative day 7, surviving rats were killed. Mortality prior to day 7 was very high (68%) in the TPN group and low in the TEN (9%) and SOF (9%) groups (p < 0.005). Among survivors, the serum albumin level was lowest (p < 0.002) and serum bilirubin level (p < 0.025) and wet weight of regenerated liver (p < 0.002) highest in the TPN group. However, the livers in TPN rats appeared pale and were found to be abnormal histologically with markedly diminished glycogen and amphophylic hepatocyte cytoplasm, and their spleens were enlarged (by a factor of two). The high mortality of TPN rats was seen whether the fat emulsion was given as a bolus daily, continuously as part of the infusate, or not included as part of the TPN regimen. In the next series (n = 70), nutrient concentrations, volumes, and rates of infusion were varied. There was a high correlation between caloric (r2 = 0.831, p < 0.0006), glucose (r2 = 0.598, p < 0.02), and amino acid (r2 = 0.619, p < 0.03) intakes and mortality in the TPN group: at 140 kcal/kg/d, none died; at 178 kcal/kg/d, 50% to 62% died; and at 230 kcal/kg/d, 80% died. No TEN rat died. In conclusion, 70% hepatectomized rats fed enterally with nutrients approximating the intake of normal rats do well and survive. In sharp contrast, mortality is very high when identical nutrients are infused parenterally. By reducing the levels of nutrients given parenterally, survival improves significantly.
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