Total Parenteral Nutrition Regimen Research Articles

Superior Mesenteric Artery Syndrome: A Vicious Cycle?

CASE REPORT Superior mesenteric artery syndrome (SMAS) is a rare syndrome where the third part of the duodenum is compressed between the abdominal aorta and the superior mesenteric artery (SMA).1 The loss of the intervening mesenteric fat pad causes the aortomesenteric angle to decrease from its normal value of 38°–65° to less than 25°, decreasing the aortomesenteric distance to less than 10 mm and causing duodenal compression. Its incidence in the general population is between 0.1% and 0.3% with a female predominance.2 A 22-year-old woman presented to the emergency department of our hospital with complaints of vomiting and a marked decrease in appetite for the past 4 months. The vomiting was nonbilious and nonprojectile and would only occur postprandially. She also reported past episodes of watery diarrhea associated with anorexia and experienced intermittent episodes of fever, documented at 101°F–102°F. Since the start of her symptoms, she had lost 27 kg. An upper abdominal computed tomography scan in both plain and contrast films revealed significant gastric distention, distention of the duodenum up to the second and third parts, and a relatively collapsed small bowel distal to the presumed crossing of SMA (Figure 1). The computed tomography scan displayed downward inclination of SMA and significant compression of the left renal vein between the abdominal aorta and SMA, confirming the existence of left renal vein entrapment syndrome in our case (Figure 2). In addition, there was a reduced aortomesenteric angle of 11.8°, and a distance of 8 mm was observed (Figure 3). In lieu of the above findings, SMAS was suspected. The patient initially received conservative treatment and was started on nasogastric feeding tube. Owing to intolerance, a total parenteral nutrition regimen was used to stabilize the patient's weight. Only 2 kg were gained by the patient over the course of 4 weeks. Her symptoms continued to worsen despite her slight weight gain. Having failed to achieve a satisfactory outcome with conservative management, an exploratory laparotomy was performed. The peritoneal cavity was exposed through a midline skin incision. There was gross distention of the second part of the duodenum, and the third part of the duodenum was compressed. Owing to grossly dilated duodenum, the decision was taken to perform gastrojejunostomy instead of duodenojejunostomy. Stapled posterior gastrojejunostomy was performed to bypass the compressed duodenum, and an anastomosis was made between the stomach and the proximal loop of the jejunum (Figure 4). The intraperitoneal drain was kept in place. An uneventful recovery followed the patient's extubation.Figure 1.: Computed tomography scan showing compression of the third part of the duodenum. Arrow is pointing toward the compressed duodenum.Figure 2.: Computed tomography scan showing compression of the left renal vein. Arrow is pointing towards the compressed left renal vein.Figure 3.: Computed tomography scan showing compression of the third part of the duodenum. Angle denoting a reduced aortomesenteric angle value of 11° (normally>38°).Figure 4.: Computed tomography scan after gastrojejunostomy displaying the anastomosis made between the stomach and the proximal loop of the jejunum. Arrow pointing towards the anastomotic site.This case report presents an early preoperative diagnosis of a rare disease entity based on its radiological presentations. When women with a low body mass index present with chronic, refractory symptoms of the upper digestive system, SMAS should be suspected. It can also often be confused with other etiologies of mega duodenum such as diabetes mellitus, systemic lupus erythematosus, amyloidosis, myotonic dystrophy, scleroderma, and chronic idiopathic intestinal pseudo-obstruction. This necessitates the need of a multidisciplinary approach based on symptoms to diagnose SMAS by clinicians. DISCLOSURES Author contributions: A. Jawed collected patient information and followed up after discharge and wrote the manuscript. A. Jawed wrote the manuscript. ME Anis identified the case and treated the patient, revised the manuscript, and is the article guarantor. MA Qadeer and Z. Abbas revised the manuscript. Financial disclosure: None to report. Informed consent was obtained for this case report.

The Effect of High Glucose Intake on Weight Gain in Very Low Birth Weight Neonates: A Randomized Controlled Trial.

This study aims at evaluating the effect of high glucose intake as a component of total parenteral nutrition on birth weight (BW) regain in very low birth weight neonates. Ninety newborns with BW <1500 g were randomized to control or experimental groups. Both groups received the same total parenteral nutrition regimens except glucose intake provided by dextrose water (DW) serum: 7 to 15 g/kg/d (10% DW) in the former versus 8.75 to 18.75 g/kg/d (12.5% DW) in the latter. Body weight as the primary outcome was monitored until the BW was regained. Results revealed that neonates who received 12.5% DW regained BW significantly faster (10.98 ± 2.46 vs 13.24 ± 4.03 days, P = .024) and needed lesser duration of respiratory support (5.34 ± 2.11 vs 7.17 ± 3.19 days, P = .003). As the proposed intervention can reduce neonatal intensive care unit admission duration, it mitigates risks of health care-associated infections, while favorably affecting the health economy.

Non-Surgical Interventions for Hospitalized Adults with Class II or Class III Obesity: A Scoping Review.

Adult inpatients with Class II or III obesity and comorbidities have a high health burden with frequent hospitalizations. Surgical risk and patient choice can be contraindications to bariatric surgery, which is considered the gold standard treatment. The best approach to non-surgical management for this adult inpatient group is currently unknown. The aim of this scoping review was to summarize current research in the inpatient setting. The unpublished literature and six electronic database searches identified 4,582 articles, with 12 articles (reporting on 10 studies) eligible and included. The literature on the interventions and their key components in the non-surgical care of the adult inpatient with Class II or III obesity were mapped identifying service provision successes and gaps. The articles reported on intensive lifestyle interventions, comparison of oxygen administration regimes, total parenteral nutrition regimens, and pre-surgical rapid weight loss. Study designs included evaluation (n=1), before–after intervention studies (n=3), and randomized/non-randomized controlled trials (n=6). The classification of obesity as a chronic disease is not universal resulting in reduced inpatient treatment options. Recommendations for consumers, practitioner practice, health policy-makers and future research priorities are reported. Further research in the development of cost-effective inpatient models of care is indicated.

Does the use of fish oil-based lipid emulsion in the clinical setting of total parenteral nutrition and lipid rescue therapy interfere with common laboratory analytes on Roche Cobas 6000?

Lipaemic interference on automated analysers has been widely studied using soy-based emulsion such as Intralipid. Due to the greater adoption of fish oil-based lipid emulsion for total parenteral nutrition in view of improved clinical outcomes, we seek to characterize the optical properties of SMOFlipid 20% (Fresenius Kabi, Bad Homburg, Germany), a fish oil-based emulsion, on the Roche Cobas 6000 chemistry analyser (Roche Diagnostic, Basel, Switzerland). Various amounts of SMOFlipid were spiked into pooled serums. We plotted Roche Cobas Serum Index Gen.2 Lipaemia Index (L-index) against the amount of SMOFlipid added. We then studied the interference thresholds for aspartate aminotransferase, alanine aminotransferase, albumin and renal panel analytes using SMOFlipid. We subjected five levels of spiked lipaemia to high-speed centrifugation and analysed the specimens pre- and post-centrifugation. To postulate whether fish oil-based lipid emulsion interferes with laboratory results in the clinical setting, we calculated concentrations of SMOFlipid post-lipid rescue therapy and steady-state concentration of a typical total parenteral nutrition regime using pharmacokinetic principles. SMOFlipid optical behaviour is similar to Intralipid using the Serum Index Gen.2 L-index, with 1 mg/dL of SMOFlipid representing 1 unit of L-index. Manufacturer-stated interference thresholds are accurate for alanine aminotransferase, aspartate aminotransferase, albumin, urea and creatinine. High-speed centrifugation at 60 min 21,100g facilitates the removal of fish oil-based SMOFlipid. Based on the interference thresholds we verified and pharmacokinetics parameters provided by SMOFlipid manufacturer, total parenteral nutrition may not interfere with chemistry analytes given sufficient clearance, but lipid rescue therapy will interfere. Further studies assessing lipaemic interference on immunoassays are needed.

A Retrospective Look at TPN with Pancreatitis: Do Recommendations Match Guidelines? (P12-036-19)

ObjectivesThe objective of this project was to assess if best practice guidelines for the use of total parenteral nutrition (TPN) in pancreatitis are being followed at a university teaching hospital. MethodsThis retrospective study was an exploratory analysis of de-identified data pulled from a university teaching hospital clinical data repository and electronic medical records for patients who had a diagnosis of pancreatitis between the years of 2014 and 2018. Variables of interest included diagnosis, reason for initiating TPN, diet order, past medical history, age, gender, and race. Feeding modalities were compared to best practice guidelines for nutrition support initiation in pancreatitis provided by the American Society for Parenteral and Enteral Nutrition (ASPEN), European Society for Parenteral and Enteral Nutrition (ESPEN), American Pancreatic Association and the International Association of Pancreatology (IAP/APA), Best Practice in Surgery group at the University of Toronto, and the American College of Gastroenterology (ACG). ResultsA total of 57 patients were admitted between 2014 and 2018 with the diagnosis of pancreatitis. Chart reviews of each patient were assessed for an initial nutrition regimen of either enteral nutrition (EN) or TPN. Of the 57 patients started on nutrition support, 12 patients (21%) received a trial of EN prior to starting TPN. After exclusion of eight patients who had a diagnosis of either ileus, small bowel obstruction (SBO) or bowel perforation, there were 37 (65%) patients who were started on TPN initially without an EN trial. ConclusionsDespite best practice guidelines from multiple groups advocating for EN over TPN, it was found that TPN appears to be a first line feeding strategy in the majority of patients admitted with or who developed pancreatitis at this hospital. Development of an interdisciplinary nutrition support team at this hospital is recommended to facilitate adherence to best practices regarding treatment of patients with pancreatitis. Funding SourcesNot Applicable.

The Effect of Individualized Versus Standardized Parenteral Nutrition on Body Weight in Very Preterm Infants.

BackgroundThis study was designed to evaluate whether standardizing total parenteral nutrition (TPN) is at least non-inferior to TPN with individualized composition in premature infants with a gestational age (GA) < 32 weeks.MethodsIn this retrospective cohort study, all preterm born in or transferred to Maxima Medical Center (MMC) within 24 hours after birth with a GA < 32 weeks were included. The individualized group (2011) was compared to the partially standardized group (2012) and completely standardized group (2014) consequently. The primary endpoint was difference in growth. Secondary endpoints included differences in electrolyte concentrations.ResultsA total of 299 preterm were included in this study. When comparing weight gain, the infants in the (partially) standardized group demonstrated significantly (P < 0.05) less weight loss during the first days of life and grew faster subsequently in the following days than the individualized TPN regimen. Furthermore, significant differences in abnormal serum sodium, chloride, calcium, creatinine, magnesium and triglycerides values were demonstrated.ConclusionTPN with a (partially) standardized composition revealed to be at least non-inferior to TPN with an individualized composition.

A global perspective of the roles of the pharmacist in the NICU.

To describe pharmacist practice and roles performed in the neonatal intensive care unit (NICU) worldwide and to map these findings along the medicines management pathway (MMP). Quasi-systematic review. Google Scholar, Medline/PubMed and Embase were searched utilising the selected MeSH terms. Thirty sources of information were reviewed. Overall, pharmacist practice in the NICU involves a wide-range of roles, with the most commonly reported involving patient medication chart review, therapeutic drug monitoring and the provision of medication information. Studies highlight that pharmacist contribution to total parenteral nutrition (TPN) regimens and patient medication chart review is beneficial to patient outcomes. Roles beyond the regular scope of practice included involvement in immunisation programmes and research. Most of the data were collected from the USA (13 of 30), followed by the UK (6 of 30) and reports from other countries. The American, British, South African and Australian articles have reported very similar roles, with a pharmacist firmly integrated into the overall structure of the NICU team. The literature identifies that there is insufficient evidence to describe what roles are currently performed in NICUs worldwide. This is due to the lack of recently published articles leading to a large gap in knowledge in understanding what contemporary pharmaceutical services in the NICU comprise. Further research is required to address these gaps in knowledge, and identify the impact of the pharmacist's role on neonatal patient outcomes as well as to determine how to better resource NICUs to access pharmacy services.

Prospective double-blind randomized study on the efficacy and safety of an n-3 fatty acid enriched intravenous fat emulsion in postsurgical gastric and colorectal cancer patients.

BackgroundA lipid emulsion composed of soybean oil (long-chain triglycerides, LCT), medium-chain triglycerides (MCT) and n-3 poly-unsaturated fatty acids (PUFAs) was evaluated for immune-modulation efficacy, safety, and tolerance in patients undergoing major surgery for gastric and colorectal cancer.MethodsIn a prospective, randomized, double-blind study, 99 patients with gastric and colorectal cancer receiving elective surgery were recruited and randomly assigned to either the study group, receiving the n-3 PUFAs enriched intravenous fat emulsion (IVFE), or the control group, receiving a lipid emulsion comprised of soybean oil and MCTs (0.8 – 1.5 g · kg-1 · day-1) as part of total parenteral nutrition (TPN) regimen from surgery (day -1) up to post-operative day 7. Safety and efficacy parameters were assessed on day -1 and post-operative visits on day 1, 3, and 7. Adverse events were documented daily and compared between the groups.ResultsPro-inflammatory markers, laboratory parameters, and adverse events did not differ prominently between the 2 groups, with the exception of net changes (day 7 minus day -1) of free fatty acids (FFAs), triglyceride, and high-density lipoprotein (HDL). Net decrease of FFAs was remarkably higher in the study group, while the net increase of triglyceride and decrease of HDL was significantly lower.ConclusionsThe n-3 PUFA-enriched IVFE showed improvements in lipid metabolism. In respect of efficacy, safety and tolerance both IVFE were comparable. In patients with severe stress, there is an inflammation-attenuating effect of n-3 PUFAs. Further, adequately powered clinical trials will be necessary to address this question in postsurgical GI cancer patients.Trial registrationUS ClinicalTrials.gov NCT00798447.

18 TOTAL PARENTERAL NUTRITION DURING NEONATAL CARE OF THE FIRST BITRANSGENIC FEMALE BOVINE CLONE

This work describes the treatment with total parenteral nutrition (TPN) of a 37-day cloned calf after suffering ruminal acidosis by ingestion of milk. Cells for SCNT were obtained by using a bicistronic vector for human lysozyme and lactoferrin. We obtained 7 embryos and 2 pregnancies. Only one fetus was born alive weighing 47 kg and it was presented to the neonatal unit of INTA showing a deep depression, diarrhoea, dehydration (10%), hyperthermia and inability to stand (Table 1). A 20-cm-length 20-Ga-diameter catheter (Arrow) was placed in the jugular vein. Blood samples from catheter and brachial artery showed leukocytosis, hypoglycemia and metabolic acidosis (Table 1). Esophageal tube was placed to remove 5 L of ruminal content and for the administration of 2 L of a solution of sodium bicarbonate (40 g L–1 of water). Saline (NaCl, 9 g L–1), sodium bicarbonate (8.4 g/100 mL) and 10% dextrose were administered IV until dehydration; blood pH and glucose were corrected. Ceftriaxone 1 g IM/12 h (Acantex, Roche) to prevent bacterial translocation, 1.175 mg of flunixin meglumine (PharmaVet) as anti-endotoxic dose and 80 mg of ranitidine IV/12h (Vetanco) to prevent laminitis were also administered. Two litres of bovine plasma were administered during the first 2 days and, after this, we began with a TPN regimen due to lack of sucking reflex and animal anorexia. Kabiven (Fresenius Kabi AV) was administered at 1 g of lipids/kg/24 h by a regimen of 18 drops min–1 to prevent hyperlipidemia at the recommended dose for humans. For this reason, we also administered dextrose 25% 12.5 drops min–1 and amino acids 11.5% 504 mL (Rivero), to reach a dose of 10 g/kg/24 h and 2 g/kg/24 h, respectively. Saline (NaCl, 9 g L–1) and vitamin complex (Rivial Paediatrics, Rivero) was also administered to cover water and vitamin requirements. The TPN therapy lasted 24 days during which the animal regularized its metabolic functions, reversed signs of ruminal acidosis and learned to eat a balanced ration and hay. To our knowledge, no information is available on such a long period of TPN in bovine neonates. This work shows that TPN can increase the survival chances of high risk animals and thus the final efficiency of cloning and transgenesis. Table 1.Clinical and haematological responses to 24-day total parenteral nutrition in a 37-day cloned female calf The authors thank Fresenius Kavi and Rivero Laboratories for their support.

Dose of intravenous lipids and rate of bacterial clearance in preterm infants with blood stream infections

Intravenous lipid emulsion (IVLE) is an integral part of the total parenteral nutrition (TPN) regimen in neonates. The use of IVLE during sepsis is the subject of controversy because it may interfere with phagocytosis of microbes by macrophages and may lead to significant hypertriglyceridemia. This paper aims to study the rate of clearance of bacteria in relation to dose of IVLE administered to preterm infants with blood stream infections (BSIs). Preterm infants (mean gestational age ± SD, 32.0 ± 2.5weeks) with culture-proven BSI and receiving TPN were randomized to two groups. The first group (n = 22) was given the usual dose of IVLE according to a standard protocol (starting from 0.5g kg(-1) day(-1) and gradually increased by 1gkg(-1)day(-1) to a maximum of 3.5gkg(-1)day(-1)); in the second group (n = 20), IVLE were restricted at a dose of 1gkg(-1)day(-1). Samples for blood cultures were withdrawn every 24h until a negative culture was obtained. CRP was measured daily until its normalization. Serum triglycerides were monitored daily. The rate of bacterial clearance was significantly more rapid in the restricted-dose IVLE group compared to the standard-dose group [72 (48-120) versus 144 (72-168) h, p = 0.001]. Daily weight increment was significantly greater in the standard-dose IVLE group compared to the restricted-dose IVLE group [25 (6.9-31.9) versus 0.9 (-3.3-11.7) g, p = 0.0001]. The duration of antibiotic use was significantly reduced in the restricted-dose IVLE group compared with the standard-dose IVLE group (10.0 ± 4.5 vs 14.9 ± 5.1days; p = 0.003). The durations of TPN, mechanical ventilation, and hospitalization were not significantly different between groups. Restriction of the dose of IVLE to 1gkg(-1)day(-1) in preterm infants with BSI is associated with earlier negative blood cultures and reduced duration of antibiotic therapy but was associated with a lower daily weight increments.

Inflammatory Response in Preterm Infants Is Induced Early in Life by Oxygen and Modulated by Total Parenteral Nutrition

The i.v. lipid emulsion (LIP) is a source of oxidants, which may stimulate inflammation. Coadministration of parenteral multivitamins (MVP) with LIP prevents lipid peroxidation in light-exposed total parenteral nutrition (TPN). We hypothesized that this modality of TPN administration affects systemic inflammation, which may be modulated by exposure to oxygen. Premature infants were allocated to three TPN regimens: control regimen - MVP coadministered with amino acid/dextrose exposed to ambient light, LIP provided separately (n = 9) - LIP+MVP light exposed (LE): MVP coadministered with light-exposed LIP (n = 9) - LIP+MVP light protected (LP): MVP coadministered with light-protected LIP (n = 8). In LE and LP, amino acid/dextrose was provided separately. On reaching full TPN, infants were sampled for IL-6 and IL-8 in plasma and the redox potential of glutathione in whole blood (E, mV). Data were compared (ANOVA) in infants exposed to low (<0.25) versus high (> or =0.25) FiO2. Patients (mean +/- SD: birth weight 797 +/- 172 g; GA 26 +/- 1 wk) had similar clinical characteristics in TPN groups. Cytokine levels correlated positively (p < 0.01) with FiO2 and E. High FiO2 stimulated an increase (p < 0.01) in cytokines in control regimen, whereas these markers remained unaffected by oxygen in the LE and LP groups. The choice of a TPN admixture may have important consequences on the systemic inflammatory response triggered by an oxidant stress.

The clinical and economic value of the dipeptide alanyl-glutamine in total parenteral nutrition of critically ill patients treated in intensive care units in Italy

Introduction: the supplementation of alanyl-glutamine dipeptide in critically ill patients necessitating total parenteral nutrition (TPN) improves clinical outcomes, reducing mortality, infection rate, and shortening ICU hospital lengths of stay (LOS), as compared to standard TPN regimens. Here we present a pharmacoeconomic evaluation of alanyl-glutamine dipeptide in critically ill patients admitted to Italian Intensive Care Units (ICUs). Methods: a Discrete Event Simulation model that incorporates outcomes rates from 200 Italian ICUs for over 60,000 patients, alanyl-glutamine dipeptide efficacy data synthesized by means of a Bayesian Random-Effects meta-analysis, and national cost data has been developed to evaluated the alternatives from the point of view of the hospital. Simulated clinical outcomes are death and infection rates in ICU, death rate in general ward, and hospital LOSs. One-way and probabilistic sensitivity analyses are performed by varying all uncertain parameter values in a plausible range. Results: alanyl-glutamine dipeptide results more effective and less costly than standard TPN: reduced mortality rate (23.55% ± 15.2% vs 34.50% ± 2.06%), infection rate (15.91% ± 3.95% vs 18.97% ± 3.94%), and hospital LOS (25.47 ± 0.26 vs 26.00 ± 0.27 days) come at a lower total cost per patient (23,922 ± 3,249 vs 24,145 ± 3,361 Euro). Treatment cost is completely offset by savings on ICU and antibiotic costs. The cost/effectiveness acceptability curve indicates an estimated 78% probability of alanyl-glutamine dipeptide resulting dominant and a 90% probability of resulting cost/effective for a willingness to pay up to 1,500 Euro for one patient death avoided. Conclusions: alanyl-glutamine dipeptide is expected to improve clinical outcomes and to do so with a concurrent saving for the hospital.

Gut Responses to Enteral Nutrition in Preterm Infants and Animals

Preterm birth is associated with immature digestive function that may require the use of total parenteral nutrition and special oral feeding regimens. Little is known about the responses to oral food in the preterm neonate and how enteral nutrients affect the immature gastrointestinal tract (GIT). In vivo studies are difficult to perform in laboratory rodents because of their small body size and that of immature organs at birth, and this makes the large farm animals (e.g., pigs, cattle, sheep) more attractive models in this field. In these species, preterm delivery at 88%-95% gestation is associated clinical complications and degrees of GIT immaturity similar to those in infants born at 70%-90% gestation. Studies in both animals and infants indicate that the immature GIT responds to the first enteral food with rapid increases in gut mass and surface area, blood flow, motility, digestive capacity, and nutrient absorption. To a large extent, the enteral food responses are birth independent, and can be elicited also in utero, at least during late gestation. Nevertheless, preterm neonates show compromised GIT structure, function, and immunology, particularly when delivered by caesarean section and fed diets other than mother's milk. Formula-fed preterm infants are thus at increased risk of developing diseases such as necrotizing enterocolitis, unless special care is taken to avoid excessive nutrient fermentation and bacterial overgrowth. The extent to which results obtained in preterm animals (most notably the pig) can be used to reflect similar conditions in preterm infants is discussed.

Soybean Oil Fat Emulsion to Prevent TPN-Induced Liver Damage: Possible Molecular Mechanisms and Clinical Implications

Long-term total parenteral nutrition (TPN) is known to be associated with cholestasis and hepatic steatosis, which can be lethal in infants who cannot be fed orally. The present review focuses on the metabolic complications in the liver that may occur due to the excessive administration of fat-free TPN. We have recently developed an infant rat model of hepatic dysfunction and steatosis induced by overdose of fat-free TPN. In this model, plasma levels of liver enzymes in the fat-free TPN group were found to be significantly higher than in the other groups (i.e., the oral diet and fat-containing TPN groups). Pathological examination showed hepatomegaly and severe fatty changes without cholestasis in the liver of infant rats that received fat-free TPN. We clearly demonstrated that the addition of soybean oil emulsion to the TPN regimen prevented hepatic dysfunction and fatty changes. In the present review, we discuss the molecular mechanism of the hepatic dysfunction induced by fat-free TPN and the role of soybean oil fat emulsion in the TPN regimen. We also discuss the clinical implications of soybean oil-containing TPN solutions and point out the importance of including fat in the TPN regimen in order to prevent the hepatic abnormalities associated with the excessive administration of fat-free TPN.

Immunorestorative effect of lipid emulsions during total parenteral nutrition

This prospective in vivo cross-over study investigated the effect of Intralipid on immune responses. Twenty-three patients were randomly allocated to receive one of two alternative total parenteral nutrition (TPN) regimens for the first 7 days and the other regimen for the second 7 days. Only one of the regimens included a fat emulsion to provide 50 per cent of the calorific requirement. Immunological studies were performed on days 0, 7 and 14. These included peripheral blood T cell subsets, antibody dependent cellular cytotoxicity and basal and maximal Interleukin 2 production. All immunological parameters were significantly augmented during total parenteral nutrition using the lipid based regimen. No such change was seen during intravenous feeding with carbohydrate based TPN. It is concluded that, far from being immunosuppressive, the incorporation of a fat emulsion into a TPN regimen has immunostimulatory properties.

Effect of branched chain amino acid enrichment of total parenteral nutrition on nitrogen sparing and clinical outcome of sepsis and trauma: A prospective randomized double blind trial

Administration of extra branched chain amino acids (BCAA) has been associated with a nitrogen sparing effect in septic and traumatized patients. Whether nitrogen sparing is associated with decreased morbidity and mortality rates is unknown. We therefore undertook a prospective, randomized, double blind trial investigating the effects of BCAA enrichment of a total parenteral nutrition (TPN) regimen on nitrogen balance, 3-methylhistidine excretion, morbidity as evidenced by disturbances in organ function, severity of sepsis and mortality. One hundred and one patients entered the study; 52 received a standard TPN solution and 49 a BCAA-enriched solution. Both groups received 30 kcal kg-1 body-weight, 15 per cent fat calories and 0.17 g nitrogen kg-1 body-weight. In the BCAA-enriched group, patients received 0.56 g BCAA kg-1 body-weight (50.2 per cent BCAA). Standard group patients received 0.18 g BCAA kg-1 body-weight (15.6 per cent BCAA). Nitrogen balances and 3-methylhistidine excretion were not significantly different between groups. Although morbidity scores tended to decrease during the study no difference was observed between groups. Mortality (early or late), sepsis or stress-related, did not differ significantly between groups. We were not able to confirm the reported beneficial effects of BCAA-enriched TPN solutions for use in septic and traumatized patients.

Effects of different lipid emulsions on lymphocyte function during total parenteral nutrition

A prospective randomized study of the immunological effects of three total parenteral nutrition (TPN) regimens in patients undergoing preoperative parenteral nutrition was conducted. In one regimen the calories were derived solely from glucose. The others were identical except that 50 per cent of the calories were provided as lipid emulsion, in one as long-chain triglycerides (LCT) only while the other contained half the fat as medium-chain triglycerides (MCT) and half as LCT (MCT/LCT). Natural killer (NK) activity and lymphokine-activated killer (LAK) activity were significantly higher after TPN with the MCT/LCT solution. A significant fall in LAK activity occurred after TPN with the LCT solution. The interleukin 2 content in supernatants from activated T lymphocytes was significantly higher after TPN with the LCT-containing solution. Solutions containing LCT and those containing MCT perturb cytokine interactions, but this is less with MCT-containing solutions, which may augment certain responses. These observations may have implications for the design of TPN regimens.

Effects of a medium-chain triacylglycerol/long-chain triacylglycerol fat emulsion containing a reduced ratio of phospholipid to triacylglycerol in pediatric surgical patients

Objective Medium-chain triacylglycerol (MCT) has been shown to provide better nutritional support than long-chain triacylglycerol (LCT). We compared the efficacy of MCT/LCT fat emulsions containing a usual (0.12) or a decreased (0.06) ratio of phospholipid to triacylglycerol (PL:TG) in pediatric patients under surgical stress. Methods Three patient groups ( n = 10 in each) received equivalent amounts of glucose (12 g · kg −1 · d −1) and amino acids (2 g · kg −1 · d −1), but group A received a 10% MCT fat emulsion (PL:TG 0.06), group B received a 20% MCT fat emulsion (PL:TG 0.06), and group C received a 10% MCT/LCT fat emulsion (PL:TG 0.12) in amounts of 1.5 g · kg −1 · d −1 in a randomized study. Total parenteral nutrition was given for 7 d. Blood samples were collected before total parenteral nutrition administration and on days 4 and 7 for determination of various biochemical indexes. Results Serum phospholipid concentrations were significantly higher in group C than in group A or B on days 4 and 7 ( P < 0.05). Serum triacylglycerol and cholesterol concentrations and the very-low-density lipoprotein percentage were also significantly higher in group C than in group A or B on days 4 and 7 ( P < 0.05). The high-density lipoprotein percentage was significantly higher in group B on days 4 and 7 ( P < 0.05). Conclusions In pediatric patients under surgical stress, a total parenteral nutrition regimen containing an MCT/LCT fat emulsion with a decreased PL:TG ratio (0.06) is likely to result in partly better lipid and lipoprotein metabolism than an emulsion containing the usual ratio (0.12).

Role of Soybean Oil Pat Emulsion in the Prevention of Hepatic Xenobiotic Transporter mRNA Up- and Down-Regulation Induced by Overdose of Pat-free Total Parenteral Nutrition in Infant Rats

Total parenteral nutrition (TPN) is associated with cholestasis and hepatic steatosis in human infants. The present study focused on the changes in hepatic xenobiotic transporters associated with overdose of fat-free or fat-containing TPN in infant rats. Three-week-old male Sprague-Dawley rats were divided into three groups: group 1 received an oral diet, group 2 received TPN without fat, and group 3 received TPN with 20% of its calories from fat (soybean oil emulsion). After TPN administration for 4 days, both serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, which are indicators of hepatic dysfunction, in group 2 were significantly higher (p<0.001) than those in the other groups, whereas there were no differences between groups 1 and 3 in either serum AST or ALT levels. The serum bilirubin concentration in group 2 was also markedly higher than that in the other groups. Mdr2, Bsep, Mrp2, Mrp6, Oct1, and Oat2 mRNA levels were decreased in group 2 (fat-free TPN) compared with those in group 1 (oral diet), whereas Mdr1b, Mrp1, and Mrp5 mRNA levels were increased. Specifically, the level of Mdr1b mRNA in group 2 was 16 times higher (p<0.001) than that in group 1. On the other hand, the changes in these mRNA expression levels in group 3 (fat-containing TPN) were smaller than those in group 2, and specifically, the expression levels of Mdr1b, Mrp1, Mrp5, Mrp6, and Oat2 mRNA in group 3 were not significantly different from those in group 1. The results of the present study indicate that including fat in the TPN regimen is very important in preventing the mRNA up- and down-regulation of xenobiotic transporters, which is considered to be the main factor responsible for the abnormal hepatic changes such as cholestasis associated with the excessive administration of fat-free TPN.

Major Role of Soybean Oil in Preventing Decrease in CYP4A1 mRNA Content Relative to PPAR.ALPHA. mRNA Down-Regulation in Infant Rats

Changes in the levels of CYP4A1, PPARalpha, and RXRalpha mRNA expression in the liver following overdose of fat-free or fat-containing total parenteral nutrition (TPN) were studied in 3-week-old male Sprague-Dawley rats. The rats were divided into three groups: group 1, oral diet; group 2, fat-free TPN; and group 3, TPN with 20% of calories from soybean oil emulsion. Levels of CYP4A1, PPARalpha, and RXRalpha mRNA in the fat-free TPN group were significantly lower than those in the other groups. Levels of CYP4A1 and PPARalpha mRNA were strongly correlated (r=0.849), and levels of CYP4A1 and RXRalpha mRNA were weakly correlated (r=0.618). This is the first report of a strong correlation between the levels of CYP4A1 and PPARalpha mRNA following overdose of fat-free or fat-containing TPN in infant rats. Our results also indicate that it is important to include fat in TPN regimens in order to prevent CYP4A1 mRNA down-regulation, which may be related to changes in PPARalpha mRNA levels in the liver.