Total Parenteral Nutrition Infusion Research Articles

Tunneled Central Venous Catheter Sepsis: Risk Factors in a Pediatric Hospital

All tunnelled central venous catheters (TCVC) placed at the Alberta Children's Hospital in Calgary, Alberta, between November 1984 and July 1987, were retrospectively reviewed to study the association of catheter infection with a number of factors including age, diagnosis, catheter use, and areas caring for children. One hundred children received 130 silastic catheters placed for a total of 17,861 days. Each catheter survived a median of 100 days. Thirty-one episodes of catheter sepsis were identified (one episode for each 576 days of catheter use). Children under 2 years of age had more than two times the risk of catheter infection (p less than 0.01). Children with malabsorption had a greater risk (45.7%) than did those with infection (25.0%) or cancer (15.5%). The use of catheters for total parenteral nutrition (TPN) or for multiple purposes markedly increased the risk of catheter infection. The risk of infection of TCVC appears to be great in the young child, in particular, in those requiring TPN or multiple intravenous infusions. Use of TCVC in these children should be avoided if possible.

Failure of intravenous infusions in neonates

The median life expectancy (survival) of 286 peripheral intravenous infusion sites in 105 babies in a children's intensive care unit was 36 h. Unadjusted univariate survival analysis revealed that dextrose infusions and the initial infusions received by a baby had longer survival than total parenteral nutrition (TPN) infusions and later infusions respectively. Also infusions with cloxacillin and penicillin survived for longer than average while infusions with phenytoin had reduced survival. Gestational age, weight, infusion site, other drugs, co-infusion of Intralipid with TPN solutions and neutralization of TPN did not influence survival of infusions. Multivariate survival analysis confirmed the findings for TPN and penicillin but not for cloxacillin, phenytoin or later infusions. Multivariate analysis also suggested that survival was improved with ampicillin and aminophylline and worse for leg sites, for older babies and for infusions in which the fluids were given at greater rates. It also indicated that neutralization of TPN improved survival.

Infusion of Total Parenteral Nutrition via the Umbilical Artery

The administration of total parenteral nutrition through umbilical artery catheters in 48 neonates (birth weight 1.7 +/- 0.58 kg) was compared with administration via central venous catheters in 26 infants (birth weight 2.05 +/- 0.89 kg). There was no significant difference in the amount of calories delivered (72 +/- 12 vs 78 +/- 18 cal/kg/day) or in the mean daily weight gain (16.6 +/- 13.3 vs 18 +/- 13.9 g/day). The incidence of sepsis was significantly lower in the umbilical artery catheter group (10.4% vs 15.4%) but there was no significant difference in the rate of infection when adjustment was made for number of days of catheter life (1 per 224 days of catheter life in the umbilical artery group vs 1 per 199 days in the central venous catheter group). Other major complications included transient hypertension in 2 (4%) of the 48 umbilical artery catheter infants and in 1 (3.8%) of the central venous catheter group, aortic thrombosis in 1 (2%) of the 48 umbilical artery catheter infants and a tricuspid vegetation in 1 (3.8%) of the central venous catheter group. Results suggest that the umbilical artery is a reasonable route for the infusion of total parenteral nutrition in low birth weight infants who require arterial access for blood gas analysis. Use of the umbilical artery catheter for parenteral alimentation may avoid the need for surgical placement of central venous lines and the risk of the attendant complications. Nevertheless, safer routes and improved methods of infusion of parenteral infusion must continue to be developed.

Lipid-Free Total Parenteral Nutrition and Macrophage Function in Rats

Certain lipids are immunosuppressive when used for nutritional support, while other lipids and nutritional additives may enhance immunologic function. We hypothesized that total parenteral nutrition (TPN) may be immunosuppressive irrespective of lipids. Twenty-four rats underwent central vein catheterization and received either intravenous saline solution and oral chow or TPN alone. At 7 or 14 days, the animals were killed. Splenic and bone marrow macrophages were isolated and cultured in either M199 medium alone or were stimulated with Escherichia coli lipopolysaccharide. The supernatants were tested for prostaglandin E2 and C3. The splenic prostaglandin E2 levels were significantly higher in the TPN group following lipopolysaccharide stimulation at 7 days but not at 14 days. Administration of TPN to rats, even without lipids, may be immunosuppressive through the release of prostaglandin E2 from splenic macrophages following a septic challenge. This effect appears to be abolished after 14 days of TPN infusion.

Addition of l-glutamine to total parenteral nutrition and its effects on portal insulin and glucagon and the development of hepatic steatosis in rats

Infusion of total parenteral nutrition (TPN) with excess carbohydrate calories leads to hepatic steatosis in rats and is associated with an elevated portal insulin/glucagon molar ratio. Previously we have shown that adding glucagon to TPN prevents and reverses hepatic steatosis in rats, possibly by increasing hepatic lipid export. It has been reported that steatosis is eliminated in rats by the addition of l-glutamine to TPN. In this study, we examined the effect of glutamine on portal insulin and glucagon levels and the development of hepatic steatosis. Adult rats ( n = 19) received internal jugular catheters: Group 1 ( n = 6), saline (3 cc/hr) and chow ad libitum; Group 2 ( n = 7), 25% dextrose base TPN; Group 3 ( n = 6), 25% dextrose base TPN with 2% glutamine. The infusion rate of TPN was 1.2 cc/100 g body wt/hr. Daily nitrogen balance was determined and at 7 days, portal venous blood was drawn for insulin and glucagon radioimmunoassay, livers were removed for histology and lipid content determination, and the small intestines were removed for mucosal protein and DNA content determination. Panlobular vacuolization of the hepatocytes was noted on histology in Group 2 (TPN) while Group 1 (chow) and Group 3 (TPN + glutamine) showed normal liver morphology. Hepatic lipid content was significantly elevated in Group 2 ( P < 0.05). The portal insulin/glucagon molar ratio was increased because of excessive portal venous insulin in Group 2 (TPN). In contrast, portal glucagon was significantly elevated while the insulin/glucagon ratio and hepatic lipid content did not increase above control levels in the glutamine-supplemented Group 3 rats. The results suggest that addition of l-glutamine to hypertonic dextrose TPN prevents the development of hepatic steatosis, possibly by stimulating glucagon secretion and thus lowering the portal insulin/glucagon ratio and increasing hepatic lipid export.

Long-term parenteral nutrition in unrestrained nonhuman primates: an experimental model

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.

USE OF ENDOTOXIN RETENTIVE INTRAVENOUS FILTERS WITH PAEDIATRIC TOTAL PARENTERAL NUTRITION SOLUTIONS

We studied the retention of endotoxin released in a clinically relevant form by senescent bacteria during filtration of amino acid-based total parenteral nutrition (TPN) solutions by the PALL Intravenous Set Saver Filter (ELD96). The ELD96 was shown to be capable of providing an effluent free of detectable endotoxin (less than 0.125 endotoxin unit-equivalents/ml) when challenged with 10(6) total cells of Pseudomonas aeruginosa during simulated clinical TPN infusion. Parallel control experiments showed that endotoxin was released from the test organism and penetrated through conventional intravenous (i.v.) solution filters.

Small bowel resection‐associated urinary calcium loss in rats on long‐term total parenteral nutrition

This study was designed to study the effects of small bowel resection on daily urinary excretion patterns, plasma and bone levels of magnesium, phosphorus and calcium in rats on long-term total parenteral nutrition (TPN). Male Sprague-Dawley rats weighing 300 to 350 g were randomly divided into two groups with six rats in each group. Control consists of rats whose small intestines were transected but anastomosed. Resected rats had 70% of their small intestine removed. After intestinal resection and transection, rats were infused with a balanced TPN solution for 17 days. Resected rats excreted significantly more calcium than transected rats during the first 10 days of TPN infusion. Peak excretion occurred between day 3 and 4 followed by a trend toward a slightly higher than normal level of calcium excretion between days 10 and 17. Urinary losses of phosphorus and magnesium were not influenced by bowel resection. Plasma and tibia calcium, phosphorus and magnesium levels were not altered. The effects of small bowel resection on urinary calcium loss is specific and our data demonstrate the involvement of gut in regulating urinary calcium excretion and suggest that gut may play a significant role in TPN induced metabolic bone disease.

SMALL SCALE PRODUCTION OF TOTAL PARENTERAL NUTRITION INFUSIONS

The lay-out of a small-scale production facility for the preparation of total parenteral nutrition infusions is presented. Its concept and the configuration of the production equipment and the operational procedures are explained. The cleaning and sterilization process are also described.

Reversal of hepatic steatosis in rats by addition of glucagon to total parenteral nutrition (TPN)

Infusion of total parenteral nutrition (TPN) with excess carbohydrate calories leads to hepatic steatosis in rats that is associated with an elevated portal insulin/glucagon molar ratio. Previously we have shown that adding glucagon to TPN prevents hepatic steatosis in rats. In this study we attempted to reverse the steatosis by adding glucagon to TPN after 1 week of TPN alone. Adult rats ( n = 28) received internal jugular catheters: Group 1 ( n = 7), saline (3 cc/h) and chow ad libitum; Group 2 ( n = 7), 25% dextrose base TPN solution for 1 week; Group 3 ( n = 7), 25% dextrose base TPN for 2 weeks; Group 4 ( n = 7), 25% dextrose base TPN for 1 week and then glucagon (15 μg/100 g/day) added to TPN for the second week. The infusion rate of TPN was 1.2 ml/100 g/hr (40% kcal > control). At 7 days (Group 2) and 14 days (Groups 1, 3, and 4) portal and peripheral venous blood levels were drawn for insulin and glucagon radioimmunoassay, blood glucose determination, and liver function tests; livers were removed for histology and lipid content determination. Blood glucose was equivalent among all groups. Liver function tests were within normal limits. Panlobular vacuolization of the hepatocytes was noted on histology in Groups 2 and 3. Hepatic lipid content was significantly elevated in Group 3. The portal insulin/glucagon molar ratio was increased because of excessive portal venous insulin in Groups 2 and 3 ( P < 0.05 by ANOVA). In contrast, portal venous insulin and the insulin/glucagon molar ratio did not increase in Group 4 and hepatic lipid infiltration was absent when glucagon was added to the TPN solution after 1 week of TPN solution alone. The results suggest that the addition of glucagon to hypertonic dextrose TPN is not only protective in preventing hepatic steatosis, but may reverse steatosis, possibly by increasing hepatic lipid export.

The effect of total parenteral nutrition on vasogenic edema development following cold injury in rats

Total parenteral nutrition (TPN) has been shown to decrease mortality and to increase the rate of recovery in head-injured patients. However, a recent short-term animal experiment has raised concern over the potential enhancement of vasogenic edema by TPN. The experiment described here was undertaken to examine longer-term effects of TPN infusion on vasogenic edema development. Twenty-four rats received an infusion of a TPN solution (35% glucose) or 0.9% saline at 4 ml/kg/hr for 4 or 26 hours following cold injury. In the 4-hour experiment, TPN increased the serum glucose level to 772 +/- 57 mg/dl compared to 160 +/- 14 mg/dl in the saline-treated animals (p = 0.0001) and increased serum osmolality to 312 +/- 3 mOsm/kg compared to 291 +/- 3 mOsm/kg in the saline-treated group (p = 0.0006). In the 26-hour experiment, TPN-infused rats were also hyperglycemic and hyperosmotic by 4 hours postinjury and remained hyperglycemic at 26 hours postinjury (serum glucose level 374 +/- 97 mg/dl compared to 141 +/- 3 mg/dl in saline-treated animals; p = 0.0371). Although by 26 hours the TPN-infused rats appeared hyperosmotic compared to the saline-treated rats, high variability in the TPN group prevented statistical confirmation of this observation (serum osmolality 337 +/- 35 mOsm/kg in the TPN group compared to 287 +/- 6 mOsm/kg in the saline group). A three-way analysis of variance with repeated measures was used to analyze the effect of infusion (saline vs. TPN), time (4 vs. 26 hours), and cold injury on the specific gravity of the five brain regions studied. Cold injury significantly increased edema development in the injured versus uninjured hemisphere for every region studied (p less than or equal to 0.0034, all five regions), and edema development increased significantly between 4 and 26 hours in three of the five regions (p less than or equal to 0.0207, all three regions). The infusion fluid was not a significant factor in any of the analyses. In conclusion, TPN infusion produced hyperglycemia and hyperosmolality in cold-injured rats but did not enhance vasogenic edema development in any brain region studied.

The compatibility of calcium phosphate in paediatric TPN infusions.

The addition of calcium phosphate to total parenteral nutrition (TPN) infusions is investigated with particular reference to factors affecting the solubility of the salt. Recommendations are made about the most appropriate method for adding calcium phosphate to paediatric and neonatal TPN products.

Energy expenditure after infusion of glucose-based total parenteral nutrition.

Resting energy expenditure (REE), carbohydrate balance, and lipogenesis were calculated after administration of glucose-based total parenteral nutrition (TPN) to determine whether the thermic effect of glucose is equal to the energy cost of storing the glucose. Estimated cost of storage as glycogen (5.3%) and fat (19%) was compared with measured increases in REE. Patients with malnutrition received 5% dextrose in water and 6 days of TPN with a low (1.2 times REE, group 1) or high (2.0 times REE, group 2) level of glucose intake. Increases in REE by day 6 were 10% (group 1) and 28% (group 2). The theoretical cost of glucose storage as glycogen and fat accounted for approximately 40% of the measured increase in REE in patients in group 2. The thermic effect of TPN (derived from patients in group 1) accounted for most of the balance. The majority of the thermic effect of high levels of glucose infused with TPN can be explained on the basis of the thermic effect of TPN and glucose storage.

The effect of acute discontinuation of total parenteral nutrition.

The present study was undertaken to assess the impact of acute discontinuation (AD) of total parenteral nutrition (TPN) on serum glucose, insulin, and glucagon levels and on the generation of symptomatic hypoglycemia. Fifty studies were performed in 48 patients. In none of the 30 studies of 1 hour duration nor in the 20 studies of 8 hours duration was there a single episode of symptomatic hypoglycemia. One patient had a glucose below normal (60 mg/dl) during the first hour after AD. Glucose and insulin concentrations were elevated at the start of TPN discontinuation but returned to normal values within 60 minutes and remained there during the successive 7 hours of study. Although glucagon levels were slightly elevated at zero time, no significant decrease occurred. There was no evidence for counter-regulation based on the patterns of glucose and hormone levels. With some restrictions, acute discontinuation is a safe, rapid method of ending a prolonged TPN infusion.

Neutropenia Due to Copper Deficiency in Total Parenteral Nutrition

Copper (Cu) deficiency has been reported both in pediatric and adult patients on total parenteral nutrition (TPN). Manifestations of Cu deficiency are usually hematologic in the adult. A 56-yr-old patient with a history of subtotal gastrectomy underwent massive small bowel resection and partial colectomy in 1977. TPN was initiated. Intravenous (iv) trace mineral supplements were not available in 1977 at our institution. By June 1978, the patient manifested neutropenia with a white blood cell (WBC) count of 2000/mm3 and 39% neutrophils or a total neutrophil count (TNC) of 780/mm3. The serum Cu level at that time was 5 micrograms/dl (normal, 70-140), and the serum zinc (Zn) level was low, although within normal limits. Oral supplementation with Cu and Zn tablets proved ineffective. Twice weekly infusions of fresh frozen plasma were begun in April 1979, and intravenous chromium supplementation started in September 1979, but neither the WBC count nor the TNC improved. Intravenous Cu and Zn were approved in October 1979, and were added to the TPN formula. Within 2 weeks, the WBC count rose to 6300/mm3, and the neutrophils increased to 83% with a TNC of 5229. After 12 weeks, the serum Cu level rose to 80 micrograms/dl. The increase in WBC count and percentage of neutrophils can be attributed to the addition of Cu to the TPN infusate.

Bone and Mineral Status of Patients Beginning Total Parenteral Nutrition

Total parenteral nutrition (TPN) is commonly used to provide nutrition in the seriously ill. Osteomalacia has been described with long-term TPN and the administered solutions and/or vitamin D metabolites have been blamed for the occurrence of osteomalacia. These studies however were performed on patients on long-term TPN programs. We in contrast measured the serum calcium (Ca), ionized calcium (Ca2+), phosphate (Pi), bone GLA protein (BGP), alkaline phosphatase (ALK-P), 25(OH)D, 1,25(OH)2D, the iPTH (carboxyl terminal) in 25 malnourished patients just beginning TPN therapy. The patients ranged from 25 to 80 yr of age and suffered from a variety of diseases. No patient had symptoms, recent fractures, or radiographic evidence of osteomalacia. The results of our study revealed significantly lower 25(OH)D (p less than 0.001), Pi (p less than 0.01), and Ca (p less than 0.01), but higher iPTH (p less than 0.002) values when compared to normals. BGP, 1,25(OH)2D and Ca2+ and ALK-P were not significantly different. We conclude that patients requiring TPN have low serum 25(OH)D values reflecting their nutritional status with a compensatory increase in PTH secretion to maintain their serum Ca2+ levels. The normal BGP levels may indicate depressed bone formation and skeletal resistance to PTH in the very ill patient. The cause of osteomalacia in these patients may therefore be multifactorial and not only related to the TPN infusions.

Major operative trauma increases peripheral amino acid release during the steady-state infusion of total parenteral nutrition in man.

The effect of major operative trauma on skeletal muscle metabolism was examined in nine patients receiving a constant infusion of calories (1460 kcal/m2/day) and protein (75 gm of amino acids/m2/day) for 5 days before and 4 days after an operation. Compared with the preoperative state, 72 hours after the operation there was a significant rise in arterial levels of glucagon, cortisol, norepinephrine, and inactive triiodothyronine and a drop in concentrations of insulin, active triiodothyronine, and amino acids. Forearm blood flow increased, as well as the efflux from forearm muscle of lactate, taurine, serine, glycine, valine, methionine, isoleucine, leucine, phenylalanine, lysine, arginine, and total amino acid nitrogen (440%). This loss of muscle protein after trauma is associated with increased muscle proteolysis, as measured by increased urinary 3-methylhistidine excretion (83%), and accounts for increased nitrogen loss (54%) from the body. Increased activity of the sympathetic nervous system is manifested by increased levels of epinephrine and norepinephrine, a relative lack of insulin, and increased levels of glucagon. This hormonal milieu plays an important role in the production of hypoaminoacidemia, increased efflux of amino acids and lactate from muscle, and negative nitrogen balance observed in these traumatized patients.

The effects of rate and route of nutrient intake on protein metabolism

Isotopic measurements of protein kinetics are useful for the investigation of metabolic protein disorders during surgical illness. The effects of rate and route (oral vs parenteral) of nutritional substrate intake have not been well defined. Fischer 344 rats were infused with a total parenteral nutrition (TPN) solution at either 25, 100, or 175% of their normal substrate intake or were fed an oral diet ad libitum. After 4 days, [ 15N]glycine was infused at 0.138 mg 15N/hr for 24 hr. Whole-body protein turnover (WPT), synthesis, and catabolism were determined by 15N urea enrichment. Fractional synthesis rates (FSR) of liver and muscle protein were calculated by analyzing 15N tissue enrichment. WPT ( r = 0.93, P < 0.001) and liver FSR ( r = 0.57, P < 0.01) increased linearly with TPN infusion rates. All rats had protein synthesis rates greater than catabolism rates except for the rats infused with 25% TPN. Although caloric intake was the same in rats fed orally and those infused with 100% TPN, the orally fed rats had faster WPT ( P < 0.001), synthesis ( P < 0.05), catabolism ( P < 0.001), and liver FSR ( P < 0.05) than the TPN rats. Muscle FSR was not significantly affected by either the route of feeding or the TPN infusion rate. In this study, rate and route of substrate intake affected protein kinetics in the whole animal and liver, but not in muscle. Rate and route of nutrient intake need to be carefully specified and controlled during isotopic studies of protein kinetics.

Cholestasis Associated with Total Parenteral Nutrition

SummaryIt appears that neonates, especially those with very low birthweights, may be at especially high risk of developing cholestasis associated with total parenteral nutrition (TPN). Within 2 weeks of starting intravenous alimentation, it would appear highly desirable to be able to start at least small enteral feedings to interrupt the physiology of fasting. Such feedings may not have to be of much nutritional benefit to improve cholestasis. Calorie and amino acid intake should be limited to the requirements of the infant being treated. Whether protection of the TPN infusate from light is of benefit remains to be determined. Drug therapies for TPN‐associated cholestasis of infancy have not been proven safe or effective. Additional investigations to further clarify the pathogenesis of this syndrome, and clinical studies of prophylaxis and therapy, are needed to enhance our ability to provide nutritionally effective and metabolically safe parenteral nutrition.

Cholestasis associated with total parenteral nutrition.

It appears that neonates, especially those with very low birthweights, may be at especially high risk of developing cholestasis associated with total parenteral nutrition (TPN). Within 2 weeks of starting intravenous alimentation, it would appear highly desirable to be able to start at least small enteral feedings to interrupt the physiology of fasting. Such feedings may not have to be of much nutritional benefit to improve cholestasis. Calorie and amino acid intake should be limited to the requirements of the infant being treated. Whether protection of the TPN infusate from light is of benefit remains to be determined. Drug therapies for TPN-associated cholestasis of infancy have not been proven safe or effective. Additional investigations to further clarify the pathogenesis of this syndrome, and clinical studies of prophylaxis and therapy, are needed to enhance our ability to provide nutritionally effective and metabolically safe parenteral nutrition.