Search

The question of whether parenteral nutrition adversely affects calcium regulation remains unclear. Human studies of this question have been confounded by uncontrolled variables including the degree to which food is ingested orally; gut absorption; underlying disease; medication adversely affecting bone, including steroids; and aluminum contamination of parenteral nutrients. The present study was undertaken to examine whether parenteral nutrition adversely affects calcium regulation in a nonhuman primate model that allows for control of underlying clinical variables and mobility. With use of this model, it was possible to show weight maintenance and positive nitrogen and calcium balances with parenteral nutrition. There was no demonstrable effect of the animals' wearing a jacket and tether system or of catheterization on calcium regulation. Calciuria in response to parenteral nutrition was elevated initially but diminished by 2 wk of therapy. The calciuria observed resulted from an increased urine-filtered calcium load. Calcium balance with parenteral nutrition was preserved by a diminished fraction of calcium filtered by the kidney being excreted in the urine. The present study suggests that negative calcium balance produced by parenteral nutrition may result from abnormal renal tubular function or disruption of normal parathyroid hormone regulation.

The etiology of bone disease seen in long-term total parenteral nutrition patients is poorly defined. This study examined the question of whether abnormal bone could be induced in otherwise normal weanling rats fed a balanced nutrient solution intravenously. Young adult, male Wag/Rij rats were divided into three groups. One group was fed a commercial liquid research diet, one group received an indwelling jugular catheter and was fed an intravenous elemental solution formulated to be nutritionally complete, and one group received an indwelling catheter but was fed the commercial liquid diet orally. Significant differences were seen between groups in percent bone, femur length, growth-plate width, endosteal label area, periosteal mineral apposition rate, and periosteal and endosteal bone-formation rates. This study suggests that intravenous administration of otherwise adequate nutrients to rats results in altered bone remodeling compared to orally fed cohorts.

A freely mobile jacket and tether system was developed for the investigation of total parenteral nutrition (TPN)-induced metabolic bone disease and complications of prolonged TPN in 12 Macaca fascicularis nonhuman primates. The animals received TPN for 49 +/- 7 d (means +/- SEM), providing 82 +/- 2 kcal.kg-1.d-1. Serum glucose increased from 3.6 +/- 0.2 mmol/L at baseline to 8.3 +/- 1.9 mmol/L (p less than 0.01) during TPN, and serum albumin decreased from 38 +/- 1 g/L at baseline to 29 +/- 1 g/L (p less than 0.001) during 2.75% amino acid TPN and 30 +/- 2 g/L (p less than 0.01) during 5% amino acid TPN infusion. No significant changes were seen in serum prealbumin, total protein, bilirubin, alanine aminotransferase, and 5'-nucleotidase during TPN infusion. Major complications included catheter sepsis, hyperglycemia, diarrhea, and premature death in six animals. Thus, metabolic complications of prolonged TPN support may be investigated in a freely mobile nonhuman primate.

The impact of parenteral nutrition on mineral loss was examined in 11 long-term (10-79 mo) and 6 short-term (1-8 mo) patients. In the long-term patients, there was a significant (p less than or equal to 0.02) urinary loss of calcium and magnesium during infusion compared with periods off infusion. The magnitude of urinary excretion of these minerals was much lower than in previously reported series and in short-term patients. Despite this, in long-term patients the mean bone mass at the spine was lower than normal (p less than 0.001) but mean bone mass at the wrist was not. Current data suggest that hypercalciuria is not a consistent feature of parenteral nutrition. Furthermore, osteopenia is a feature of some long-term parenteral nutrition patients.

A 27-yr-old gravida 3, para 2 was supported from the 8th week of pregnancy by intermittent daily total parenteral nutrition (TPN) following the loss of her small bowel. Nutrient intake was adjusted by monitoring nitrogen balance and the rate of increase in fetal cranial enlargement. Maternal calcium balance proved difficult to maintain, since massive urinary Ca+2 losses occurred during infusion of nutrients (576 +/- 2 mg/12 hr on TPN compared to 47 +/- 12 mg/12 hr off). This increase in urine Ca+2 was due to depressed Ca+2 reabsorption by the kidney (87.1 +/- .7 vs 98.1 +/- .3%) and increased filtered load (4623 +/- 241 mg/12 hr vs 2591 +/- 329). Initially calcium balance was -180 mg/day. Nitrogen balance assessed by total stool and urine nitrogen was 1.1 g/24 hr, which was judged to be suboptimal. Deficits were corrected by increasing nitrogen intake, lengthening the duration of infusion and the oral administration of elemental calcium during periods off infusion. A normal fetus was delivered vaginally without complications at 351/2 weeks. This patient demonstrates that normal fetal growth and development as well as appropriate maternal weight gain and nitrogen balance can be maintained throughout pregnancy, including the first trimester, by intermittent daily TPN.

D-Lactic acid can accumulate in blood in some patients with intestinal failure, leading to a clinical syndrome of severe acidosis and encephalopathy. The possible impact of parenteral nutrition on its clinical course has not been established. One patient with a severe short-bowel syndrome supported by long-term parenteral nutrition who suffered repeated episodes of ataxia and disorientation associated with elevated serum levels of D-lactate was studied. Results demonstrated no impact of glucose- vs lipid-based parenteral nutrition formulations on total acid production or serum D-lactic acid levels, increased serum D-lactate levels during administration of neomycin, but prompt resolution of both acidosis and clinical symptoms with discontinuation of oral intake. This study confirms the findings of other investigators that D-lactic acidosis may be a significant, heretofore unappreciated complication in patients with severe short-bowel syndrome, and that prompt resolution may be effected with abrupt discontinuation of oral intake. Furthermore, the present study suggests neither a detrimental nor a beneficial effect of parenteral nutrition on this syndrome.

In an attempt to define clinical variables which might predict the whole blood selenium level prior to supplementation, whole blood selenium levels were determined in 21 home parenteral nutrition patients who were not receiving selenium supplementation. These levels were examined for possible correlations by single and multivariant analysis with the following clinical parameters: age at initiation of home parenteral nutrition, months of home parenteral nutrition received, hematocrit, albumin, estimated length of remaining small bowel, kilocalories per kilogram actual body weight infused per day, grams protein per kilogram actual body weight infused per day, and multiple of ideal body weight. Of all the combinations of variables examined, the best correlation obtained was between whole blood selenium levels and the total kilocalories per kilogram body weight per day delivered intravenously (r = -0.89, p less than 0.001). A statistically significant correlation (r = -0.67, p less than 0.01) was also observed between selenium levels and the grams protein per kilogram actual body weight infused per day. However, inclusion of this or additional variables did not increase the predictive value of the equation describing whole blood selenium levels as a function of the calories delivered. The implication of this study is that patients requiring more intensive nutritional support develop lower selenium levels during the course of treatment. Despite these correlations, no single clinical parameter or combination of parameters, however, was of sufficient predictive value to preclude laboratory determination of whole blood selenium values in deciding which patients might benefit from selenium supplementation.

The characteristics of bone disease associated with parenteral nutrition are controversial. To further elucidate the contribution of aluminum deposition to this syndrome and the spectrum of pathology in patients supported by current regimens utilizing crystalline amino acids, quantitative histomorphometry and staining for Al were performed on iliac crest bone biopsies from 26 long-term parenteral nutrition patients and 16 normal volunteers. Compared with normal subjects, median trabecular bone area (TBA) for a group with positive Al staining (n = 14) who were exposed to casein hydrolysate was significantly less (12.9% vs 20.7, p less than 0.05) as was the median rate of bone formation (RBF) (29 micron2 X mm-2 X d-1 vs 360, p less than 0.05). A variety of abnormal histological findings were present in patients without positive aluminum stains (n = 12) who were supported solely by regimens utilizing crystalline amino acids. However, neither decreased TBA (median TBA = 15.3%) nor decreased RBF (median RBF = 126 micron2 X mm-2 X d-1) was uniformly characteristic of the latter patient group.