Enteral versus parenteral nutrition in the conservative treatment of upper gastrointestinal fistula after surgery: a multicenter, randomized, parallel-group, open-label, phase III study (NUTRILEAK study).

BACKGROUND: Postoperative upper gastrointestinal fistula (PUGIF) is a devastating complication, leading to high mortality (reaching up to 80%), increased length of hospital stay, reduced health-related quality of life and increased health costs. Nutritional support is a key component of therapy in such cases, which is related to the high prevalence of malnutrition. In the prophylactic setting, enteral nutrition (EN) is associated with a shorter hospital stay, a lower incidence of severe infectious complications, lower severity of complications and decreased cost compared to total parenteral nutrition (TPN) following major upper gastrointestinal (GI) surgery. There is little evidence available for the curative setting after fistula occurrence. We hypothesize that EN increases the 30-day fistula closure rate in PUGIF, allowing better health-related quality of life without increasing the morbidity or mortality. METHODS/DESIGN: The NUTRILEAK trial is a multicenter, randomized, parallel-group, open-label phase III trial to assess the efficacy of EN (the experimental group) compared with TPN (the control group) in patients with PUGIF. The primary objective of the study is to compare EN versus TPN in the treatment of PUGIF (after esophagogastric resection including bariatric surgery, duodenojejunal resection or pancreatic resection with digestive tract violation) in terms of the 30-day fistula closure rate. Secondary objectives are to evaluate the 6-month postrandomization fistula closure rate, time of first fistula closure (in days), the medical- and surgical treatment-related complication rate at 6 months after randomization, the fistula-related complication rate at 6 months after randomization, the type and severity of early (30 days after randomization) and late fistula-related complications (over 30 days after randomization), 30-day and 6-month postrandomization mortality rate, nutritional status at day 30, day 60, day 90 and day 180 postrandomization, the mean length of hospital stay, the patient's health-related quality of life (by self-assessment questionnaire), oral feeding time and direct costs of treatment. A total of 321 patients will be enrolled. DISCUSSION: The two nutritional supports are already used in daily practice, but most surgeons are reluctant to use the enteral route in case of PUGIF. This study will be the first randomized trial testing the role of EN versus TPN in PUGIF. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03742752. Registered on 14 November 2018.

Impact of total parenteral nutrition standardization led by pharmacist on quality in postoperative patients with colorectal cancer.

BACKGROUND/OBJECTIVES: Abdominal surgery significantly affects the structure and function of the gastrointestinal system of patients, total parenteral nutrition (TPN) is an important nutrition support method for postoperative patients. However, in the process of TPN practice, the excessive fat emulsion and compound amino-acid prescriptions ratio are often prescribed by doctors. To address the problem, we developed the computerized TPN prescription management system to promote the personalized provision of TPN. The purpose of this study is to evaluate the intervention effects of the computerized TPN prescription management system, which is designed by pharmacists in the Surgical Department of Abdominal Oncology at Zhejiang Cancer Hospital in July 2015. SUBJECTS/METHODS: The computerized TPN prescription management system applied in Surgical Department of Abdominal Oncology on 1 July 2015. The computerized TPN prescription management system was evaluated by comparing the patients who were treated 3 months after the application of the system with the control subjects who were treated 3 months prior to the application of TPN prescription management system in Surgical Department of Abdominal Oncology. RESULTS: In total, 218 TPN prescription-treated patients with colorectal cancer received surgery treatment were analyzed, including 121 subjects who received the treatment 3 months prior to application of TPN prescription system (IPN period) and 97 subjects who received the treatment after 3 months of the system application (SPN period). The rates of optimized TPN prescriptions are 47.1% and 88.7% prior to and after application of TPN prescription review system, respectively (p < 0.001). In detail, prior to application of TPN prescription review system, abnormal glucose-lipid ratio and nitrogen-calorie ratio are the most common problems, which accounted for 74.3 and 97.9%, respectively (p < 0.01). Whereas the proportion of the insufficient dosage of amino acids is 62 and 96.9%, respectively (p < 0.01). Other problems are insufficient dosage of insulin and excessive fat soluble vitamin supplement. After application of TPN prescription review system, as the glucose-lipid ratio and nitrogen-calorie ratio are set up in fixed range according to the nutrition treatment guidelines, only a small amount of TPN prescriptions have the problem of insufficient dosage of compound amino acid. Furthermore, before and after the application of TPN management software, the gender, age, performance status (PS) score and BMI index of the two groups of colorectal cancer patients were not statistically different (p > 0.05). There were significant differences in albumin and prealbumin between the two groups after operation (p < 0.05), and there was a significant difference in total protein (p < 0.001). There were significant differences in alanine aminotransferase and indirect bilirubin between liver and kidney function (p < 0.01), and there were significant differences in aspartate aminotransferase and total bilirubin (p < 0.05). Other total cholesterol, L-γ-glutamyl transferase, direct bilirubin and creatinine were not statistically different (p > 0.05). Blood routine (WBC, Hb and lymphocyte), length of stay and recurrence rate were not statistically different (p > 0.05). CONCLUSIONS: The application of TPN management software not only standardized the doctor's TPN medical advice, but also improved the qualified rate of TPN doctor's advice, thus ensuring the safety of the patient's medication. It also had a positive effect on postoperative recovery of colorectal cancer patients, and ensured the efficacy of the treatment of patients. In addition, it reduced the workload of the pharmacist's audit prescription and improved the efficiency of the audit prescription, and further emphasized the role and value of pharmacists.

Iatrogenic Wernicke encephalopathy in a patient with severe hyperemesis gravidarum.

BACKGROUND: Hyperemesis gravidarum complicates 0.5-2.0% of pregnancies and may lead to substantial nutritional deficiencies. Total parenteral nutrition can be used in severe cases in an attempt to avoid such deficiencies. Rarely, thiamine deficiency resulting in Wernicke encephalopathy occurs, with significant maternal morbidity. CASE: We present the case of a 30-year-old woman with hyperemesis gravidarum at 13 4/7 weeks of gestation treated with prolonged total parenteral nutrition that lacked thiamine supplementation, resulting in iatrogenic Wernicke encephalopathy. After high-dose intravenous thiamine repletion, she experienced slow resolution of her symptoms. CONCLUSION: Pregnancies complicated by hyperemesis gravidarum treated with total parenteral nutrition represent potential high-risk clinical scenarios for thiamine deficiency. Compositions of total parenteral nutrition are not standardized. Thus, physicians must confirm repletion of all essential components to avoid significant morbidity.

Computer programming: quality and safety for neonatal parenteral nutrition orders.

BACKGROUND: Computerized software programs reduce errors and increase consistency when ordering parenteral nutrition (PN). The purpose of this study was to evaluate the effectiveness of our computerized neonatal PN calculator ordering program in reducing errors and optimizing nutrient intake. MATERIALS AND METHODS: This was a retrospective study of infants requiring PN during the first 2-3 weeks of life. Caloric, protein, calcium, and phosphorus intakes; days above and below amino acid (AA) goals; and PN ordering errors were recorded. Infants were divided into 3 groups by birth weight for analysis: ≤1000 g, 1001-1500 g, and >1500 g. Intakes and outcomes of infants before (2007) vs after (2009) implementation of the calculator for each group were compared. RESULTS: There were no differences in caloric, protein, or phosphorus intakes in 2007 vs 2009 in any group. Mean protein intakes were 97%-99% of goal for ≤1000-g and 1001- to 1500-g infants in 2009 vs 87% of goal for each group in 2007. In 2007, 7.6 per 100 orders were above and 11.5 per 100 were below recommended AA intakes. Calcium intakes were higher in 2009 vs 2007 in ≤1000-g (46.6 ± 6.1 vs 39.5 ± 8.0 mg/kg/d, P < .001) and >1500-g infants (50.6 ± 7.4 vs 39.9 ± 8.3 mg/kg/d, P < .001). Ordering errors were reduced from 4.6 per 100 in 2007 to 0.1 per 100 in 2009. CONCLUSION: Our study reaffirms that computerized ordering systems can increase the quality and safety of neonatal PN orders. Calcium and AA intakes were optimized and ordering errors were minimized using the computer-based ordering program.

XXII Congreso Nacional SENPE: Sevilla, 30 de mayo - 1 de junio de 2007 / No disponible

No disponible

Doubling calcium and phosphate concentrations in neonatal parenteral nutrition solutions using monobasic potassium phosphate.

BACKGROUND: Premature infants require high intakes of Ca and P to mimic fetal accretion rates. With the current phosphate salt used, adequate amounts cannot be provided due to the precipitation of Ca and P in TPN solutions. OBJECTIVE: To compare monobasic potassium phosphate (monobasic regimen) and monobasic plus dibasic potassium phosphate (dibasic regimen) on calcium phosphate solubility in 5 amino acid products, and to determine whether solubility differences observed in these products can be explained by buffering capacity. METHODS: TPN solutions were prepared according to standard clinical practice. The following amino acid products were used at 3% concentrations: Primene, Vamin N, TrophAmine, Aminosyn-PF, and Travasol. Dextrose 10%, standard electrolytes, heparin, vitamins and trace elements were added. Calcium (as gluconate) and phosphate (as monobasic or dibasic regimen) were added in one-to-one molar ratios from 0-45 mmol/L. Solutions were inspected macroscopically and microscopically for precipitation under three conditions: immediately, 24 h after preparation at room temperature, and 3 h later in a 37 degrees C water bath. Buffering capacity was determined for each amino acid product by titrating with standardized 0.1 M NaOH. RESULTS: Variations in Ca:P solubility and buffer capacity exist between amino acid solutions. With Primene and Vamin no macroscopic or microscopic precipitation was detected up to 45 mmol/L using monobasic regimen, compared to 25 mmol/L using dibasic regimen with Trophamine. Buffer capacity did not account for the solubility differences observed between the five amino acid products, which were related to the pH of the final solution. CONCLUSIONS: These data will allow clinicians to double the current concentrations of calcium and phosphate in neonatal TPN solutions using monobasic regimen. Although this is particularly relevant to situations when fluid intake is restricted, the effect of the acid load needs to be investigated in extremely low birth weight infants.

Selenium and zinc levels in surgical patients receiving total parenteral nutrition.

The zinc and selenium levels of 40 surgical patients were monitored pre- and post-TPN. The initial selenium level was low normal, and the initial zinc level was also low. Both selenium and zinc are potent antioxidants involved in cellular defense against free radicals. Surgical patients are at risk for selenium and zinc deficiencies secondary to both increased needs and losses. TPN blood work protocols should include monitoring of selenium and zinc with supplementation of the nutrient solutions, as required.

Total parenteral nutrition for patients receiving antineoplastic therapy at a regional oncology unit: a two-year study.

The aim of this prospective study was to establish the exact role parenteral nutrition has in the provision of nutritional support to patients receiving antineoplastic therapy. The diagnosis, reasons for implementation, method of delivery and duration of nutritional support were determined. The outcome of nutritional support was established by the percentage change in weight and alteration in body mass index during the period of nutritional support. The results indicate that parenteral nutrition can successfully maintain the body weight of patients who are unable to receive enteral nutrition whilst receiving antineoplastic treatment. However, it is recommended that the provision of parenteral nutrition is evaluated at regular intervals and alternative feeding methods via the enteral feeding route are accessed as soon as possible.

Calcium and phosphate solubility curves for parenteral nutrient solutions containing Vaminolact.

Calcium and phosphate incompatibility in the total parenteral nutrient (TPN) solutions is a common problem especially in neonates. Their combinations in TPN admixture must be tested before use. We here investigated the compatibility of calcium and phosphate in TPN solutions containing a newborn amino acid product, Vaminolact. The TPN test-solutions contained 10 per cent dextrose, 1, 2, or 3 per cent Vaminolact, 4 mmole/L of magnesium sulphate and various combinations of calcium gluconate and dipotassium phosphate. Precipitations and crystallizations were inspected visually and microscopically after 24 hours standing at room temperature. Solubility curves were made by plotting the maximum concentrations of calcium and phosphate at which both were still compatible in the solution. Such curves are extremely helpful for clinicians and pharmacists to administer maximum calcium and phosphate dose for individual patient requirement.

A total parenteral nutrition solution supplemented with a nucleoside and nucleotide mixture sustains intestinal integrity, but does not stimulate intestinal function after massive bowel resection in rats.

The effects of supplementing a total parenteral nutrition solution with a nucleoside and nucleotide mixture on mucosal adaptive processes after massive bowel resection were studied. Male Wistar rats (n=30) underwent 80% small intestine resection, were randomized into two groups and received either standard total parenteral nutrition (TPN) or TPN supplemented with a nucleoside and nucleotide mixture (2.5 mL.kg-1.d-1). An additional five rats, fed a nonpurified diet and not resected, were used as controls. After 4 or 7 d, rats were killed and samples were collected for mucosal indices and intestinal enzymatic activities (disaccharidases and diamine oxidase). After massive small bowel resection and TPN, residual jejunal mucosal wet weights, villus heights, protein and RNA contents on d 4 and 7, and total wet weights and DNA contents on d 7 were significantly lower than in the control group. Administration of the nucleoside and nucleotide mixture resulted in significantly higher residual jejunal total and mucosal weights, proteins, DNA, RNA contents, and the ratio of proliferating cell nuclear antigen positive cells per crypt than did the standard TPN solution on d 7. However, disaccharidase and diamine oxidase activities were not affected by supplementation with the nucleoside and nucleotide mixture. Our data suggest the supplementation of a nucleoside and nucleotide mixture to a TPN solution can attenuate the initial mucosal atrophy and improve intestinal cell turnover after massive bowel resection, but the supplementation has little effect on enterocyte enzymatic activities.

Intravenous gamma-glutamyl-tyrosine elevates brain tyrosine but not catecholamine concentrations in normal rats.

A number of clinical situations may benefit from intravenous supplements of tyrosine (Tyr). In total parenteral nutrition (TPN), the supply of Tyr is limited by its poor solubility. In both rats and infants maintained on pediatric TPN, plasma Tyr levels are approximately 30% of normal, and in rat brains Tyr concentrations are similarly reduced. We reported previously that supplementing a TPN solution with the soluble peptide, gamma-glutamyl-Tyr [Glu(Tyr)], normalizes plasma Tyr and doubles brain Tyr in rats. To assess more fully the behavior of intravenous Glu(Tyr) in vivo, 20 mmol/L Glu(Tyr) was infused into the inferior vena cava of rats at rates increased every 2 hours over an 8-hour period (300 to 450 mumol Glu(Tyr)/kg body weight/h). The surgical procedure for catheterization is described. At the maximum rate of infusion, plasma Tyr and Glu(Tyr) concentrations reached mean plateau values of 326 and 252 mumol/L, respectively. Brain Tyr concentrations were 71 and 264 nmol/g wet weight in control rats infused with heparinized saline (SAL group) and rats infused with Glu(Tyr) (PEP group) respectively. No differences were found in concentrations of norepinephrine (NE), dopamine (DA), or homovanillic acid (HVA) in prefrontal cortex (PFC), striatum (STR), or remaining brain (RB) tissue in PEP and SAL rats. We did not detect undergraded Glu(Tyr) in the brain, and less than 0.5% of infused Glu(Tyr) appeared in the urine.

Cysteine supplementation and reduction of total parenteral nutrition-induced hepatic lipid accumulation in the weanling rat.

Total parenteral nutrition (TPN)-induced hepatic steatosis is the most common complication of TPN administration to humans. The mechanism of TPN-induced hepatic steatosis has not been studied in young mammals. The goal of this study was to determine the mechanism of TPN-induced hepatic steatosis in the weanling rat and the effect of supplementation of TPN with choline and/or cysteine on TPN-induced hepatic steatosis. In the weanling rat, we investigated the effect of TPN administration on histologic hepatic steatosis, total hepatic lipid, hepatic acetyl-CoA-carboxylase (ACC--the rate limiting enzyme in fatty acid synthesis) specific activity, and total plasma lipids. TPN administration resulted in a threefold increase in hepatic lipid as compared with control and sham animals (TPN 138 +/- 12 mg/g liver versus control 57 +/- 1), an increase in histologic steatosis (TPN 3.7 versus control 1.3), and a decline in total plasma lipid (TPN 2.1 +/- 0.3 g/L versus control 4.1 +/- 0.3). TPN-induced hepatic steatosis in the weanling rat was not associated with an increase in ACC specific activity (TPN 2.10 +/- 0.33 nmol/min/mg protein versus control 2.85 +/- 0.23). Supplementation of the TPN with choline (15 mg/day) did not significantly lessen hepatic steatosis; however, supplementation of TPN with cysteine (2.5 mg/day) or with cysteine and choline did result in a significant lessening of hepatic lipid content and of histologic steatosis and a normalization of total plasma lipid.(ABSTRACT TRUNCATED AT 250 WORDS)

Are bilirubin and plasma lipid profiles of premature infants dependent on the lipid emulsion infused?

The effect of a lipid emulsion containing long-chain triglycerides (LCT) and supplemented with L-carnitine on plasma lipids and bilirubin in premature neonates on total parenteral nutrition was compared to that of lipid emulsions containing either LCT or a mixture of LCT and medium-chain triglycerides (MCT). In a double-blind randomized study 49 premature neonates received one of the three fat emulsions, given intravenously, over 16-20 h daily for 6 days. Plasma carnitine levels increased significantly in the supplemented group only; the addition of carnitine did not seem to affect any of the parameters studied. Mean plasma triglycerides rose by 193 and 199% in the carnitine-supplemented and the LCT groups, respectively, and by 314% in the MCT/LCT group. On the sixth day of the study free fatty acids were significantly higher in the MCT/LCT group than in the other two groups. Plasma phospholipids and free cholesterol increased (p < 0.05) progressively in all groups and were correlated (r = 0.74, p < 0.001). At the end of the 6-day study all groups showed a similar decline in free and total bilirubin levels despite the significant increase in plasma lipids and free fatty acids resulting from the stepwise increase in lipid load. No correlation was found between free fatty acids and free bilirubin. Since hyperbilirubinemia and hypertriglyceridemia appear to be clinically independent factors, the infusion of lipids should not be withheld from jaundiced infants on total parenteral nutrition.

Adjuvant recombinant human growth hormone normalizes plasma amino acids in parenterally fed trauma patients.

BACKGROUND: The addition of an anabolic stimulant during intensive nutrition therapy in trauma patients seems to be a reasonable adjuvant for minimizing muscle-mass erosion. The plasma free amino acid pattern is the mirror of the net amino acid metabolism, and we have measured the progressive changes resulting from recombinant human growth hormone therapy in trauma victims during nutritional repletion in the early catabolic flow phase of injury. METHODS: In 20 severely injured (injury severity scale = 31 +/- 2), highly catabolic, and hypermetabolic adult multiple-trauma patients, we have measured the fasting (day 0) plasma amino acid levels (48 to 60 hours after injury before starting the nutrition therapy) and their progressive changes during 7 days of IV nutrition support (total parenteral nutrition, 1.1 x resting energy expenditure calories, 250 mg of nitrogen per kilogram per day) with or without adjuvant recombinant human growth hormone. Group H (n = 10) randomly received daily recombinant human growth hormone (0.15 mg of Somatropin per kilogram per day) and Group C (n = 10) received the vehicle of infusion. RESULTS: Hypoaminoacidemia of trauma is normalized by infusion of recombinant human growth hormone, which indicates its anabolic nature, and this is confirmed in the cumulative nitrogen balance (-281 +/- 139 mg of nitrogen per kilogram per 7 days compared with -809 +/- 151 mg of nitrogen per kilogram per 7 days without recombinant human growth hormone; p < or = .005). This improved nitrogen retention is also reflected in the significantly low blood urea nitrogen levels in the recombinant human growth hormone group, which represents the efficient utilization of the infused amino acids for synthesis of proteins. Elevated plasma insulin-like growth factor-1 levels in Group H compared with those in Group C may also account for this altered amino acid metabolism. CONCLUSIONS: Recombinant human growth hormone treatment in combination with conventional total parenteral nutrition in the immediate posttraumatic period improved nitrogen metabolism and normalized the plasma free amino acid levels.

Parenteral iron dextran therapy: a review.

Iron dextran was introduced more than 30 yr ago for the parenteral treatment of iron deficiency anemia that is refractory to oral therapy. Iron dextran is a preparation of ferric hydroxide complexed with a low molecular weight fraction of dextran. Iron deficiency anemia is one of the most common nutritional deficiency diseases and occurs worldwide secondary to inadequate dietary iron, usually with excessive gastrointestinal blood losses. Repletion of iron stores is often complicated by intolerance to oral iron supplementation and may require parenteral iron. Parenteral iron can be administered via the intramuscular or intravenous route either directly or as an additive to total parenteral nutrition. Both routes of administration can cause various side effects and a test dose is recommended before therapeutic administration to assess the risk for anaphylaxis. Although the efficacy and safety of parenteral iron dextran have been convincingly demonstrated, supplementation may be contraindicated in the setting of infection.

Enhancement of microbiological safety levels of aseptically admixed total parenteral nutrition solutions through low-dose gamma irradiation.

This study was undertaken to determine the effect of low-dose gamma irradiation on aseptically admixed total parenteral nutrition (TPN) solutions to which large inocula of three test bacterial species were added. Microbiological safety levels were quantified in terms of sterility assurance levels (SALs), indicating the probability of contamination occurring expressed as 10-n. The radiation sensitivity (D10 values) of test bacteria in TPN solutions inoculated with a series of bacteria recognized as common contaminants of these products, was determined. Attainable SALs of TPN solutions containing test bacteria were subsequently calculated from the D10 values. Results showed that a minimum absorbed radiation dose as low as 1.5 kGy improved the SAL of aseptically prepared TPN solutions from a probability value of 10(-3) to a value of less than 10(-8) for the microorganisms investigated. At an absorbed dose as high as 8.3 kGy, no measurable changes in amino acid, electrolyte, glucose and lipid components of the solutions were detected. These findings have important implications for the enhancement of microbiological safety levels of aseptically prepared intravenous fluids in general.