The growth of microorganisms in total parenteral nutrition admixtures

Total nutrient admixtures (TNAs) containing glucose, amino acids, and lipid emulsion in one container and amino acid/dextrose solutions [conventional total parenteral nutrition (TPN) formulations] were studied in a controlled laboratory experiment for their ability to support the growth of microorganisms. Both TNA and conventional TPN formulations for peripheral and central venous administration with standard additives were inoculated with microorganisms to provide 10(1)-10(2) colony-forming units/ml (CFU/ml) of Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans. The admixtures were stored at room temperature and samples for quantitative microbiology were taken at time 0, 6, 12, 24, 48, 72, and 96 hr. K. pneumoniae, E. coli, and P. aeruginosa were able to proliferate in central TNAs, but the growth of these organisms was retarded in conventional TPN solutions. In the peripheral formulations, K. pneumoniae and E. coli proliferated in both the TNA and conventional TPN systems, whereas P. aeruginosa grew well only in the peripheral TNA. S. epidermidis was not able to grow in any admixtures tested; however, C. albicans grew well in all admixtures, but growth was slower in the conventional central TPN. In conclusion, peripheral and central TNAs supported the growth of microorganisms significantly better than conventional TPN solutions.     

Microbial growth patterns in a total parenteral nutrition formulation containing lipid emulsion

Microbial growth of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans was evaluated in a standard amino acid-dextrose-based total parenteral nutrition (TPN) solution, 10% lipid emulsion, and a combined TPN formulation containing amino acids, dextrose, and lipid emulsion. At an initial inoculum of 10(4) CFU/ml, all three bacterial organisms grew well in 10% lipid emulsion, died in the standard solution and grew only minimally or died in the combined formulation. C. albicans grew in all three formulations at an initial inoculum of 10(4) CFU/ml; however, at an initial inoculum of 10(2) CFU/ml, which approximates touch contamination, growth of Candida in the standard and combined formulations was less than 1 log at 24 hr in contrast to the 10% lipid emulsion which showed significant growth greater than 2 log at 24 hr. It is concluded that a 24-hr infusion time is safe for the combined TPN formulation used in this study. This should result in significant cost savings compared to the previously recommended 12-hr infusion time.     

Infection control of parenteral nutrition solutions

Microbial contamination of parenteral nutrition solutions is a preventable cause of in patients receiving nutrition support. The components of the parenteral nutrition solutions have variable microbial growth potential. Crystalline amino acid and dextrose solutions are poor growth media for bacteria but may support fungal growth. Lipid emulsions provide an excellent medium for growth of bacteria and fungal species. Total nutrient admixtures will support microbial growth better than standard parenteral nutrition solutions will but less well than will lipid emulsion alone. Control of infection related to contaminated infusate depends on compounding procedure, quality control, appropriate storage, and procedures to prevent in-use contamination. Guidelines are presented for the preparation and administration of parenteral nutrition infusates that will minimize microbial contamination.     

Postoperative parenteral nutrition with high supply of branched-chain amino acids: effects on nitrogen balance and liver protein synthesis

Branched-chain amino acids (BCAA) stimulate muscle and liver protein synthesis in vitro. The significance of this action in catabolic conditions in vivo remains controversial. The effects of a high supply of BCAA in total parenteral nutrition (TPN) on nitrogen balance and liver protein synthesis were studied in a postoperative rat model. After standard operative trauma TPN was commenced with one of two isocaloric programs (I: 20.1% BCAA and II: 50% BCAA) and continued for 48 hr. The relative rate of liver protein synthesis, measured after TPN in vitro by perfusion with 14C-leucine, was similar in both groups (I: 53.4 +/- 17.3 and II: 49.0 +/- 27.3 arbitrary units of synthesis rate, mean +/- SD). The cumulative nitrogen balance was positive with both regimens and was not improved by the high supply of BCAA (I: 2.02 +/- 0.81 and II: 1.87 +/- 0.63 gN/kg/48 hr mean +/- SD). We conclude that after moderate surgical trauma TPN with a high supply of BCAA offers no advantage over conventional TPN.     

Selected ultratrace elements in total parenteral nutrition solutions

Ultratrace elements are potentially essential (eg. boron, molybdenum, nickel, and vanadium) or toxic (eg, aluminum and cadmium) in humans. Long-term total parenteral nutrition (TPN) patients can inadvertently receive significant amounts of ultratrace elements present as contaminants in TPN solutions. We determined the intake of selected ultratrace elements from a standard TPN solution and compared it with the amount reported to be absorbed from food in normal subjects. Contamination of TPN solutions with ultratrace elements was widespread and variable. The daily intakes of Mo, Ni, V. and Cd from this contamination were comparable to the amounts reported to be absorbed through the gastrointestinal tract in normal subjects. Al intake was high; B intake was low, approximately 10% of the amount absorbed by normal subjects. Thus, TPN solutions are contaminated with significant amounts of ultratrace elements. The biological significance of the intravenous infusion of these ultratrace elements is unclear and requires further investigation, particularly in home TPN patients.     

Parenteral (glucose or glucose-lipid) vs enteral repletion in malnourished primates: a controlled crossover study

Nutritional repletion with glucose-based total parenteral nutrition (TPN), mixed-substrate (58% lipid, 42% glucose) TPN, and mixed-substrate total enteral nutrition (TEN) was studied in four adult male chair-adapted primates using a crossover design. After 10 d nutritional depletion animals were repleted for 10 d with one of three isocaloric isonitrogenous diets. TPN Diets I and II were identical except that I provided all nonprotein calories as glucose while II provided 58% nonprotein calories as lipid and 42% as glucose. Animals were randomized to I or II as their first repletion treatment. The 20-d depletion-repletion cycle was repeated with the other TPN diet after a 30-d rest period of caged free-feeding. After another 30-d rest period, animals underwent a third 10-d depletion and were repleted with 10 d of TEN (Diet III, identical to II in composition). The three diets resulted in similar weight gain, positive nitrogen balance and fluid balance, and increase in total iron-binding capacity.     

Hyperalimentation-associated neonatal cholestasis: effect of oral gentamicin

The effect of oral gentamicin on the incidence of parenteral nutrition-associated cholestasis in preterm infants less than 1500 g birth weight was assessed retrospectively. Of 24 patients on parenteral nutrition for more than 10 days, 12 infants who received oral gentamicin (group I) for prophylaxis against neonatal necrotizing enterocolitis were compared to 12 infants who did not (group II). Both mean and peak direct bilirubin levels were significantly higher in group II. The increase in both mean and peak direct bilirubin levels after initiation of total parenteral nutrition (TPN) was significant in group II only. The incidence of cholestasis was significantly higher in group II than in group I. These results suggest that oral gentamicin may have a protective effect against parenteral nutrition-associated cholestasis in the newborn preterm infant.     

Trace element contamination of total parenteral nutrition. 2. Effect of storage duration and temperature.

BACKGROUND: Patients who receive home total parenteral nutrition (TPN) frequently are supplied with solutions up to 30 days in advance of anticipated use. The purpose of this study was to determine the stability of trace elements relative to time and temperature conditions, in a typical adult TPN solution stored in a usual home environment by examining variations in delivery of intended trace elements and inadvertent trace element contamination. METHODS: Trace element concentrations were determined using inductively coupled plasma-mass spectrometry technology. The effect of the delivery apparatus, storage duration (36 hours or 30 days) after compounding, and storage temperature (4 degrees C or 20 degrees C) were examined. RESULTS: The delivery apparatus contaminated the delivered TPN solution with cobalt but did not alter trace elements formulated into the TPN solution. Storage duration and temperature significantly decreased three (Zn, Cu, and Mn) of the six trace elements formulated into the TPN solution. Higher temperatures and longer duration of storage accelerated this decrease. Boron, Al, V, Ti, Ba, Sr, and CO were the trace elements that appeared as contaminants during storage. Boron, Al, V, and Ti contamination decreased with higher temperatures and longer duration of storage. CONCLUSIONS: Longer storage duration and higher storage temperature progressively reduced the deliverable concentrations of trace elements specifically formulated into the TPN solution and also of those trace elements that were not formulated into the TPN solution but that appeared as contaminants.     

Immediate stimulation of protein metabolism in burned rats by total parenteral nutrition enriched in branched-chain amino acids

The effects of two kinds of total parenteral nutrition (TPN) on energy and protein metabolism were examined in rats subjected to 15% full-thickness scald burns in the absence of septic complications. One type of TPN was enriched in branched-chain amino acids (BCAAs), especially leucine (45% BCAA content), and the other was conventional TPN (21% BCAA content). Burned rats received isocaloric and isonitrogeneous TPN solutions for 48 hr after resuscitation by saline infusion for 24 hr. Liver and rectus abdominis muscle were removed from the rats at 7, 24, 48, and 72 hr. The concentrations of adenine nucleotides, RNA, protein, glucose-6-phosphate, hepatic glycogen, muscle phosphocreatine, and 3-methylhistidine were determined. Metabolic alterations occurred during the period of saline resuscitation (0-24 hr). At 48 hr the RNA and protein levels were significantly more improved in the BCAA-TPN group than in the conventional TPN group. At 72 hr, however, the results for the two groups were similar in most metabolite levels. Thus, BCAA-TPN enriched in leucine rapidly stimulated protein synthesis in the liver and muscle. This rapid effect may make it useful during the initial nutritional management of severe trauma patients.     

Serum concentration of cobalamines during total parenteral nutrition in Crohn's disease

The vitamin B12 status was assessed by measuring the fasting serum (S-) concentration of cobalamines in a consecutive series of 12 patients with Crohn's disease (CD) given total parenteral nutrition (TPN)--nil per os--for between 21 and 97 days (mean, 49 days). At introduction of TPN the S-cobalamine concentration was less than 300 pmol/liter in four patients (group I) and more than 300 pmol/liter in eight (group II). Each day during TPN fat- and water-soluble vitamins, including 2 micrograms of cyanocobalamin, were given. In group I there was a small increase in the S-cobalamine level during the first 2 to 4 weeks of TPN, whereas in group II the values approached the middle of the reference range (190-680 pmol/liter) after 6 to 8 weeks of TPN. It would thus appear that the vitamin regimen studied, including 2 micrograms of cyanocobalamin per 24 hr, is able to maintain the S-cobalamine concentration within the reference range during 6 to 8 weeks of TPN in CD patients with no evidence of vitamin B12 deficiency, and to prevent the development of vitamin B12 deficiency during 2 to 4 weeks of TPN in CD patients with a S-cobalamine level initially below 300 pmol/liter.     

Essential fatty acid deficiency in patients receiving simultaneous parenteral and oral nutrition

Essential fatty acid deficiency is a common finding in patients nourished parenterally with hypertonic glucose and amino acids. In this study, we measured the linoleate concentration in the livers of 3 groups of patients. All the patients had operable upper gastrointestinal tract malignancies. Group I ate the hospital's regular diet ad libitum. Group II were given total parenteral nutrition (TPN), Group III received both enteral and parenteral nutrition and obtained about 35% of their caloric intake from food. The percentage of total liver fatty acids as linoleate were group I, 15.2 +/- 1.2%, group II, 3.7 +/- 1.4%, and group III, 2.8 +/- 1.6%. Data are expressed as the mean +/- 1 SEM. The patients who received 35% of their calories by mouth as food and the patients on TPN were found to be equally depleted in linoleate.     

The incidence and clinical significance of intravenous fat emulsion contamination during infusion

So that the actual contamination rate of intravenous fat emulsions, as well as the type of microbial contamination, could be quantified, 103 bottles of 10% fat emulsion were collected near infusion completion from patients' bedsides. All samples were cultured and compared according to actual hanging time, in addition to the amount and type of microbial contamination. Recovered organisms included Escherichia coli, Staphylococcus epidermidis, diphtheroids, and Micrococcus. Sample analysis failed to demonstrate significant differences in extrinsic microbial contamination rate or organism multiplication between samples infusing for less than or equal to 12 hr and those infusing longer. Although these products support microbial growth, the contaminants introduced into the infusate by environmental or touch contamination yielded minimal colony growth. No patient developed signs or symptoms of bacteremia during the study period. Therefore, infusion of intravenous fat emulsion products over extended periods of time in this study did not increase the risk of developing infectious complications.     

Urea nitrogen excretion in chair-adapted primates

To evaluate the temporal pattern of urea excretion in chair-adapted primates (Macaque fascicularis) on continuous total parenteral nutrition (TPN), two groups of five animals were studied. Group I received continuous TPN (75 glucose kcal; 0.56 g nitrogen; and 100 ml fluid per kg per day) while Group II received a single morning isonitrogenous oral meal along with a continuous isovolemic intravenous infusion of 0.45% saline. Urine was collected hourly in group I for 2 days and every 4 hr in group II for 5 days and analyzed for urea content. Time series analysis revealed no periodicity of urea excretion in either group. Six animals were then studied for a total of 46 TPN days to define the relationship between the urea content of a single 3-hr morning urine aliquot and its respective content in a 24-hr collection. A significant linear relationship was found (r = +0.76, p less than 0.01). However, using this relationship, a reasonable estimate (+20%) of measured 24-hr urea output was achieved only 50% of the time using a single 3-hr urea output. Chair-adapted primates maintained on continuous TPN or a single oral meal with continuous saline infusion do not exhibit a periodic pattern of urea excretion. The variability in 3-hr urinary urea output in the chaired primate on continuous TPN does not consistently permit accurate estimation of the coincident 24-hr urinary urea output.     

Total parenteral nutrition delays platelet engraftment in patients who undergo autologous hematopoietic stem cell transplantation

OBJECTIVES: One of the major challenges in the post-transplant period is nutrition. In this prospective, non-randomized study, total parenteral nutrition (TPN) was given to 31 patients and partial parenteral nutrition (PPN) was given to 30 patients undergoing autologous hematopoietic stem cell transplantation for solid tumors or hematologic malignancies to compare the effects of these parenteral nutrition modalities on post-transplant hematological engraftment, blood chemistry, and supportive therapy requirements. METHODS: All patients in the TPN group and 17 patients in the PPN group received growth factor in the post-transplant period. Both groups did not differ with respect to sex, age, and reinfused CD34(+) cell numbers. RESULTS: After transplantation body mass index and body weight decreased significantly in both groups (P < 0.001). Whereas serum albumin concentrations did not decrease significantly in the TPN group, it fell markedly in the PPN group at the end of parenteral nutrition (P = 0.019). After parenteral nutrition, blood chemistry was also remarkable for serum urea and glucose levels, which were elevated significantly in the TPN group (P < 0.001 and P = 0.03, respectively). Patients receiving TPN had a higher incidence of positive microbial cultures and clinical infection than did patients receiving PPN (64.5% versus 40%, P = 0.05). The most striking result was a delay in platelet engraftment for the TPN group compared with the PPN group (15.54 and 12.93 d, respectively; P = 0.014). This difference was also noted in patients using growth factor in the PPN group (P = 0.017). Parallel to these results, platelet transfusion requirement increased in the TPN group compared with the PPN group (1.93 versus 1.16 U, P = 0.004). Both groups were unremarkable for leukocyte recovery and red blood cell transfusion requirement. CONCLUSIONS: Consequently, TPN has some pitfalls of hyperglycemia, infection tendency, delayed platelet engraftment, and increased platelet transfusion requirement. Therefore, it should not be used as a standard nutrition support for patients undergoing autotransplantation.     

Weight-based ordering: an evaluation of increased guideline use in hospital total parenteral nutrition dosing.

BACKGROUND: In the past, parenteral nutrition in the Calgary Health Region was ordered as volumes of standard solutions, which limited individualization. Ordering total parenteral nutrition (TPN) that falls within macronutrient dosing guidelines may minimize complications associated with TPN, such as hyperglycemia, azotemia, hepatic steatosis, or continued malnutrition and catabolism. The Foothills Medical Centre in Calgary changed to a weight-based ordering system for TPN in 1999. This study's purpose was to determine if this change increased adherence to TPN dosing guidelines. METHODS: Macronutrient doses in TPN solutions ordered as standard solutions were compared with those ordered by weight. Mean protein, dextrose, lipid, and kilocalorie doses and the number of orders deviating from guidelines were examined. RESULTS: Weight-based dosing showed a significant reduction in deviation from guidelines for kilocalorie dose compared with TPN ordered as standard solutions. There also was a significant increase in mean protein dose and reductions in mean dextrose load and mean kilocalorie dose in the weight-based TPN group only, suggesting these changes were caused by the change in ordering method. CONCLUSIONS: Overall, weight-based ordering increased adherence to TPN dosing guidelines. The study did not have the statistical power to show significant differences between weight-based or standard TPN dosing; however, several trends were shown.     

Total parenteral nutrition-induced steatosis: reversal by parenteral lipid infusion

Prolonged use of total parenteral nutrition (TPN) may be associated with hepatic complications, primarily steatosis and cholestasis. A case is reported of an 18-year-old woman with chronic idiopathic intestinal pseudo-obstruction syndrome who was on prolonged home parenteral nutrition without lipid supplementation and developed steatosis. This finding was reversed by addition of lipid emulsion, at a dose of 0.5 g/kg/day, to the parenteral nutrition solution. The lack of lipid supplementation as a possible cause of steatosis, as well as other mechanisms of liver steatosis associated with TPN, are discussed.     

Epidermal growth factor regulates intestinal glutamine uptake during total parenteral nutrition

Sprague Dawley rats were randomised into three groups: group I (chow) were fed rat chow and water ad libitum, group II total parenteral nutrition (TPN) received a standard formula of TPN, and group III (TPN--epidermal growth factor (EGF)) received the same TPN as group II and injections of EGF (0.1 microg/gm body weight) subcutaneously twice daily. Glutamine (GLN) concentrations in tissues and blood were measured by reversed phase high performance liquid chromatography. Gut GLN extraction was calculated by dividing the difference in GLN concentrations (Conc) between the carotid artery (ART) and portal vein (PV) by the arterial concentration [(ART Conc - PV Conc)/ART Conc]. TPN induced a marked reduction of GLN concentration in tissues and blood, and also reduction of gut GLN extraction. When EGF was administered along with TPN, gut GLN concentration did not fall and gut GLN extraction was increased by 15% (TPN - EGF 1 week, P < 0.05). Arterial blood concentration of GLN was increased when TPN and EGF were used for 1 week (P < 0.05 vs control). But EGF did not prevent the GLN concentration of other tissues decreasing during TPN. Our results suggest that EGF can regulate intestinal uptake of GLN during TPN.     

Blood vitamin levels of long-term adult home total parenteral nutrition patients: the efficacy of the AMA-FDA parenteral multivitamin formulation

Although the AMA-FDA parenteral adult multivitamin formula is now widely used, there are no published data on the efficacy of this formulation in maintaining adequate vitamin nutriture in patients on long-term parenteral nutrition. Blood levels of its constituent nutrients were determined in 16 clinically stable home total parenteral nutrition patients with severe gastrointestinal dysfunction, the majority of whom had been on home total parenteral nutrition for 1 to 9 yr and most of whom were ingesting some food orally. The daily formula (MVI-12) was added to the basic total parenteral nutrition formula in 2-day batches; the vitamins were thus infused approximately 3 hr after preparation on day 1 and after 27 hr on day 2. The duration of infusions was from 8 to 16 hr. Blood was drawn approximately 36 hr after completion of the last vitamin infusion. Plasma, trichloroacetic acid-treated plasma, and whole blood were frozen until analyzed for the vitamins by microbiologic or chemical methods. All vitamin levels, except for vitamin D metabolites, were measured four times in each patient between the 4th and 36th wk while receiving daily MVI-12. Single determinations of 25-OH and 1:25 (OH)2 vitamin D were made in eight of the 16 patients between the 61st and 84th wk while on MVI-12. Repeat values during this extended period were also made on five of the patients for vitamins A and E. These values were compared with serum vitamin levels obtained on an earlier formulation (MVI concentrate, Berocca C, and folate each given twice weekly and B12 given once weekly). The AMA-FDA formula given daily maintained blood levels above the lower normal limits for most of its constituent vitamins and vitamin D metabolites for the great majority of stable home total parenteral nutrition adults with unexplained occasional exceptions. However, almost half of the vitamin A levels and some of the pantothenate and biotin values were above the normal range; these tended to be associated with the presence of renal disease. Ascorbic acid and thiamin levels tended to be clustered in the lower normal range. Because of evidence for loss of ascorbic acid standing in total parenteral nutrition solutions for 24 hr prior to infusion, it is recommended that the vitamin formulation be added to the total parenteral nutrition solution just prior to infusion.     

The solubility of calcium and phosphorus in neonatal total parenteral nutrition solutions.

Precipitation of calcium phosphate in neonatal total parenteral nutrition (TPN) solutions remains a significant problem. Whereas numerous studies have attempted to establish guidelines for maximum concentrations of various combinations that can be mixed, differences in study design and reliance upon subjective visual assessment severely limit their applicability. The purpose of this study was to quantitatively determine calcium and phosphate compatibility in commonly used neonatal TPN solutions containing a final concentration of either 1 or 2% amino acids. The final dextrose concentration was 10%. Electrolytes, heparin, and pediatric vitamins and trace minerals were also added. Calcium gluconate (10%) and potassium phosphate (mono and dibasic) were added by calibrated micropipetors. Calcium concentrations ranged from 5 to 60 mEq/L and phosphate from 5 to 40 mM/L with a minimum of 84 combinations tested for each amino acid concentration. Calcium concentrations were measured in duplicate for each tested combination. Control solutions containing calcium but no phosphate were included to validate the assay methodology. All samples were stored at room temperature for 23.5 hours and then placed in a water bath at 37 degrees C for 30 minutes to simulate incubator conditions encountered during TPN infusion. Calcium determinations were then repeated and precipitation was judged to have occurred whenever calcium concentrations fell below 90% of the initial measured values. These data allowed plotting a calcium and phosphorus reference curve for TPN solutions containing 1 and 2% amino acids based on quantitative assessment. These reference curves should allow pharmacists to avoid compounding TPN solutions that will precipitate, thus saving considerable cost to the pharmacy and preventing complications.     

Stability of imipenem and cilastatin sodium in total parenteral nutrient solution

The chemical stability and compatibility of imipenem-cilastatin sodium (Primaxin) in two different total parenteral nutrient (TPN) solutions was determined. TPN solutions consisted of 4.25% and 5% amino acids with 25% and 35% dextrose, respectively. Imipenem-cilastatin sodium was constituted with 10 ml of sterile water and admixed with 90 ml of TPN solution for a final concentration of 5 mg/ml of each drug. The final solutions were assayed at times 0 (immediately after admixture), 15 min, 30 min, 1, 4, 8, and 24 hr by a stability-indicating high-performance liquid chromatographic assay. Concurrently, test TPN solutions were monitored for pH changes, color changes, and precipitate formation. The potential effect of imipenem-cilastatin sodium on the stability of amino acids and other TPN additives was not evaluated. Imipenem and cilastatin sodium was stable (greater than or equal to 90% recovered) in each TPN solution at 15 min. A significant (greater than or equal to 10%) and steady decrease of imipenem recovery occurred at subsequent sampling times. Cilastatin appeared more stable than imipenem in both TPN solutions. A physical color change from colorless to dark orange appeared in each TPN solution over the 24-hr study period. Imipenem-cilastatin sodium is stable for 15 min in the TPN solutions studied; however, until the stability of the amino acids can be determined, the antibiotic should be administered through a separate line or Y-site while the TPN infusion is interrupted.