Standard Total Parenteral Nutrition Research Articles

Physicochemical Compatibility of Amiodarone with Parenteral Nutrition.

Y-site administration of total parenteral nutrition (TPN) and drugs is frequently required in the intensive care setting. Amiodarone is commonly administered by continuous intravenous infusion and subject to be co-administered via a Y-site with TPN. The aim of this study is to determine the physicochemical stability of amiodarone Y-site administered with TPN. Two standard TPN and 2 amiodarone solutions were designed. The 2 TPN differed in the lipid source (Lipofundin MCT/LCT® 20% or SMOFlipid® 20%). The 2 amiodarone solutions were prepared at different concentrations (900 mg and 1200 mg in 250mL of dextrose 5% in water). Each TPN and amiodarone solutions ran at a rate that simulated a 24-hour Y-site infusion to obtain different admixture samples. Each sample was then visually examined and further tested to determine the mean lipid droplet size distribution by dynamic light scattering and amiodarone concentrations by HPLC. No alterations were detected by visual inspection. Average droplet size remained below 500 nm (252.5 ± 5.9 nm for Lipofundin MCT/LCT® TPN and 327.7± 14.4 nm for SMOFlipid® TPN). For the samples obtained after running 900 mg and 1200 mg amiodarone solutions with TPN, the concentrations observed at 24 hours were 0.4491 ± 0.0111 mg/mL and 0.5773 ± 0.0214 mg/mL, respectively. These results represent approximately 100% of the zero-time concentrations and are within ±15% of the predicted values. No degradation products were observed in the chromatograms. Amiodarone is physicochemically compatible with standard TPN via a Y-site administration at the tested amiodarone concentrations.

Physical stability of an all-in-one parenteral nutrition admixture for preterm infants upon mixing with micronutrients and drugs

ObjectivesThe main objective was to investigate Y-site compatibility of intravenous drugs with one standard total parenteral nutrition (TPN) admixture for preterm infants. Since micro-precipitation was observed in the water phase...

Comparison of 2 Perioperative Management Protocols and Their Influence on Postoperative Recovery after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Standard Parenteral Nutrition, Selective Bowel Decontamination and Suprapubic Catheters?

Background: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is associated with considerable postoperative morbidity, including ileus and infectious complications. Perioperative care is believed to be an important factor for the development and treatment of postoperative morbidity. Patients and Methods: Data on case-matched patients from a retrospective database of 2 Dutch HIPEC centres was compared. Patient selection and procedures were identical in both hospitals although perioperative management items differ slightly. In centre B, immediate total parenteral nutrition (TPN), suprapubic urine bladder catheter placement (SPCs) and selective decontamination of the digestive-tract are standard care for CRS-HIPEC patients, while in centre A, they are not. Results: From a total of 223 patients, 68 consecutive patients from centre B were compared to 68 matched patients from centre A. TPN was administered to 54.4% of patients in centre A because of prolonged ileus, whereas it was standard of care in centre B. In all, 105 (77.2%) patients experienced postoperative complications including 17.6% who had a grades III–IV complication. The incidence of grade III-V complications was 18 (26.4%) in centre A and 8 (11.8%) in centre B (p = 0.03). Median hospital stay was 12 days (7–84) in A and 11(6–80) in centre B (p = 0.546). Conclusions: Gastrointestinal recovery after CRS-HIPEC seems to take longer as compared to other surgical procedures. Between the 2 centres, a significant difference in severe complications was found, while standard TPN, selective bowel decontamination and SPCs were the only identified differences in perioperative care.

MON-LB283: Effects by Overnight Standard TPN on Amino Acid Transporters in the Human Rectus Abdominis Muscle

MON-LB283: Effects by Overnight Standard TPN on Amino Acid Transporters in the Human Rectus Abdominis Muscle

Preoperative overnight parenteral nutrition (TPN) improves skeletal muscle protein metabolism indicated by microarray algorithm analyses in a randomized trial.

Loss of muscle mass is associated with increased risk of morbidity and mortality in hospitalized patients. Uncertainties of treatment efficiency by short‐term artificial nutrition remain, specifically improvement of protein balance in skeletal muscles. In this study, algorithmic microarray analysis was applied to map cellular changes related to muscle protein metabolism in human skeletal muscle tissue during provision of overnight preoperative total parenteral nutrition (TPN). Twenty‐two patients (11/group) scheduled for upper GI surgery due to malignant or benign disease received a continuous peripheral all‐in‐one TPN infusion (30 kcal/kg/day, 0.16 gN/kg/day) or saline infusion for 12 h prior operation. Biopsies from the rectus abdominis muscle were taken at the start of operation for isolation of muscle RNA. RNA expression microarray analyses were performed with Agilent Sureprint G3, 8 × 60K arrays using one‐color labeling. 447 mRNAs were differently expressed between study and control patients (P < 0.1). mRNAs related to ribosomal biogenesis, mRNA processing, and translation were upregulated during overnight nutrition; particularly anabolic signaling S6K1 (P < 0.01–0.1). Transcripts of genes associated with lysosomal degradation showed consistently lower expression during TPN while mRNAs for ubiquitin‐mediated degradation of proteins as well as transcripts related to intracellular signaling pathways, PI3 kinase/MAPkinase, were either increased or decreased. In conclusion, muscle mRNA alterations during overnight standard TPN infusions at constant rate altered mRNAs associated with mTOR signaling; increased initiation of protein translation; and suppressed autophagy/lysosomal degradation of proteins. This indicates that overnight preoperative parenteral nutrition is effective to promote muscle protein metabolism.

GLP-2 Prevents Intestinal Mucosal Atrophy and Improves Tissue Antioxidant Capacity in a Mouse Model of Total Parenteral Nutrition.

We investigated the effects of exogenous glucagon-like peptide-2 (GLP-2) on mucosal atrophy and intestinal antioxidant capacity in a mouse model of total parenteral nutrition (TPN). Male mice (6–8 weeks old) were divided into three groups (n = 8 for each group): a control group fed a standard laboratory chow diet, and experimental TPN (received standard TPN solution) and TPN + GLP-2 groups (received TPN supplemented with 60 µg/day of GLP-2 for 5 days). Mice in the TPN group had lower body weight and reduced intestinal length, villus height, and crypt depth compared to the control group (all p < 0.05). GLP-2 supplementation increased all parameters compared to TPN only (all p < 0.05). Intestinal total superoxide dismutase activity and reduced-glutathione level in the TPN + GLP-2 group were also higher relative to the TPN group (all p < 0.05). GLP-2 administration significantly upregulated proliferating cell nuclear antigen expression and increased glucose-regulated protein (GRP78) abundance. Compared with the control and TPN + GLP-2 groups, intestinal cleaved caspase-3 was increased in the TPN group (all p < 0.05). This study shows GLP-2 reduces TPN-associated intestinal atrophy and improves tissue antioxidant capacity. This effect may be dependent on enhanced epithelial cell proliferation, reduced apoptosis, and upregulated GRP78 expression.

Parenteral nutrition-associated liver injury and increased GRP94 expression prevented by ω-3 fish oil-based lipid emulsion supplementation.

ABSTRACTObjective:Parenteral nutrition in infants with gastrointestinal disorders can be lifesaving, but it is also associated with parenteral nutrition–associated liver disease. We investigated the effects of incorporating ω-3 fish oil in a parenteral nutrition mixture on signs of parenteral nutrition–associated liver disease and explored the mechanism involved in this process.Methods:Seven-day-old New Zealand rabbits were divided into 3 groups of 8, and for 1 week they were infused via the right jugular vein with standard total parenteral nutrition with soybean oil (TPN-soy) or TPN with ω-3 fish oil–based lipid emulsion (TPN-FO), or naturally nursed with rabbit milk (control). Serum and liver tissues were analyzed for serological indicators and pathology, respectively. Reverse-transcriptase polymerase chain reaction was used to evaluate the messenger RNA levels of the endoplasmic reticulum stress chaperone protein glucose-regulated protein 94 (GRP94) in liver tissues and GRP94 protein levels were compared through immunohistochemistry and Western blot assays.Results:TPN-soy animals had significantly higher serum total bilirubin, direct bilirubin, and γ-glutamyl transpeptidase and lower serum albumin than the controls (P < 0.01, each) or the TPN-FO group, which were similar to the controls (P < 0.01 cf. TPN). Damage to liver tissues of the TPN-FO group was much less than that of the TPN-soy group. GRP94 messenger RNA and protein levels in liver tissues of TPN-soy animals were significantly higher than that of the controls or TPN-FO rabbits, which were similar to the controls.Conclusions:Incorporating ω-3 fish oil in parenteral nutrition emulsion greatly prevented liver dysfunction and liver tissue damage in week-old rabbit kits, possibly by preventing endoplasmic reticulum stress.

Is additional enrichment of diet in branched-chain amino acids or glutamine beneficial for patients receiving total parenteral nutrition after gastrointestinal cancer surgery?

Total Parenteral Nutrition (TPN) is necessary in patients unable to receive oral or enteral feeding for a period of at least 7 days. Branched-chain amino acids (BCAA): valine (Val), leucine (Leu), and isoleucine (Ile) are essential amino acids, which are important regulators in protein metabolism. They are also the main nitrogen source for glutamine synthesis in muscles. In this process they undergo irreversible degradation and cannot be reutilised for protein synthesis. In catabolic states, like cancers, glutamine demand increases and therefore also its utilisation, which can decrease the level of BCAA required for Gln synthesis. The purpose of this study was to evaluate the necessity of BCAA or glutamine-enriched TPN in patients after gastrointestinal cancers surgery. Our aim was to investigate changes of plasma BCAA and glutamine concentrations in patients operated for colorectal, small intestine or pancreatic cancer and who are either receiving TPN or not in the postoperative period. Free amino acids plasma concentrations were determined by the ion-exchange chromatography. Surgery in the control group caused a decrease in Val, Ile and Leu concentrations in the postoperative period. In TPN patients this depression was inhibited beginning from the third day after surgery, except for Val and Leu in colorectal cancer group. In control and TPN patient groups, Gln concentration decreased after the surgery and subsequently increased beginning from the third day after the operation. Gastrointestinal cancer patients' surgery results in decrease in BCAA concentrations. Standard TPN exerts a beneficial effect on the BCAA level in patients with pancreatic and small intestine cancer. In colorectal cancer such TPN should be enriched with Leu and Val.

OHP-082 Use of Standard Protocols For Total Parenteral Nutrition in a Tertiary University Hospital

BackgroundOne of the clinical pharmacist’s main functions in parenteral nutrition is to ensure the quality and safety of the solutions prepared. It is too laborious to do this with each...

Determinants of Urea Production and Mineral Retention in Parenterally Fed Preterm Infants

To determine how weight for gestational age affects urea and mineral excretion by preterm infants receiving total parenteral nutrition (TPN). Daily urine samples were collected from all preterm infants given high calcium TPN, providing 30 kcal/g amino acids, during its first 44 months of use, and from all those given standard TPN, providing 25 kcal/g amino acids, over the previous 24 months. Urine urea and mineral excretion were measured as follows: Urea excretion mmol/kg/day = Urine urea/urine creatinine X creatinine production Creatinine production μmol/kg/day = -2.07 + 2.34 X gestational age in weeks Results: High calcium TPN was evaluated in 52 infants. Urea excretion did not rise with increasing TPN intake. During the first week, urea excretion increased with weight for gestational age, with higher rates in above average than below average weight infants. It also increased with gestational age in above average but not below average weight infants. Below average weight infants had lower potassium and phosphate excretion than those above average. Standard TPN was evaluated in 20 infants. Urea excretion increased with TPN intake to higher levels than on high calcium, and also increased with weight for gestational age. Urea excretion was simple to measure, with remarkably consistent daily results in individuals. Below 30 weeks gestation infants on TPN providing 30 kcal/g amino acids had urea excretion < 0.1 g urea N/kg/day, < 3.5 mmol/kg/day if below average weight, and < 0.12 g urea N/kg/day, < 4.3 mmol/kg/day if above average weight. Below average weight infants retained more potassium and phosphate during the first week than those above average, and their greater requirements were provided by the TPN.

Comparison of standard versus tailored parenteral nutrition in paediatric intensive care

ObjectivePatients in paediatric intensive care (PICU) are often fluid restricted and require a high volume of intravenous infusions, allowing little volume for nutritional intake. Bespoke parenteral nutrition (TPN) is associated...

EFFECTIVENESS AND COST-EFFECTIVENESS OF SUPPLEMENTAL GLUTAMINE DIPEPTIDE IN TOTAL PARENTERAL NUTRITION THERAPY FOR CRITICALLY ILL PATIENTS: A DISCRETE EVENT SIMULATION MODEL BASED ON ITALIAN DATA

The supplementation of alanyl-glutamine dipeptide in critically ill patients necessitating total parenteral nutrition (TPN) improves clinical outcomes, reducing mortality, infection rate, and shortening intensive care unit (ICU) hospital lengths of stay (LOSs), as compared to standard TPN regimens. 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 evaluate the alternatives from the cost perspective of the hospital. Simulated clinical outcomes are death and infection rates in ICU, death rate in general ward, and hospital LOSs. Sensitivity analyses are performed by varying all uncertain parameter values in a plausible range. The internal validation process confirmed the accuracy of the model in replicating observed clinical data. Alanyl-glutamine dipeptide on average results more effective and less costly than standard TPN: reduced mortality rate (24.6% ± 1.6% vs. 34.5% ± 2.1%), infection rate (13.8% ± 2.9% vs. 18.8% ± 3.9%), and hospital LOS (24.9 ± 0.3 vs. 26.0 ± 0.3 days) come at a lower total cost per patient (23,409 ± 3,345 vs. 24,161 ± 3,523 Euro).Treatment cost is completely offset by savings on ICU and antibiotic costs. Sensitivity analyses confirmed the robustness of these results. Alanyl-glutamine dipeptide is expected to improve clinical outcomes and to do so with a concurrent saving for the Italian hospital.

Omega-3 fatty acid improves the clinical outcome of hepatectomized patients with hepatitis B virus (HBV)-associated hepatocellular carcinoma

Omega-3 fatty acid supplemented total parenteral nutrition improves the clinical outcome of patients undergoing certain operations; however, its benefits for patients with hepatitis type B virus (HBV)-associated hepatocellular carcinoma (HCC) who have undergone hepatectomy are still not clear. The aim of this study was to evaluate the effect of omega-3 fatty acid supplemented total parenteral nutrition on the clinical outcome of patients with HBV-associated HCC who underwent hepatectomy at our institution. A total of 63 patients with HBV-associated HCC who underwent hepatectomy were included in this study. These patients were randomly assigned to receive standard total parenteral nutrition (the control group, n = 31) or omega-3 fatty acid supplemented total parenteral nutrition (the omega-3 fatty acid group, n = 32) for at least 5 d. The study endpoints were the occurrence of infection-related complications, recovery of liver function and length of hospital stay. The results showed that the omega-3 fatty acid group had a lower infection rate (omega-3 fatty acid, 19.4% vs control, 43.8%, P < 0.05), a better liver function after hepatectomy: alanine transaminase (omega-3 fatty acid, 48.23±18.48 U/L vs control, 73.34±40.60 U/L, P < 0.01), aspartate transaminase (omega-3 fatty acid, 35.77±14.56 U/L vs control, 50.53±24.62 U/L, P < 0.01), total bilirubin (omega-3 fatty acid, 24.29±7.40 mmol/L vs control, 28. 37±8.06 mmol/L, P < 0.05) and a shorter length of hospital stay (omega-3 fatty acid, 12.71±2.58 d vs control, 15.91±3.23 d, P < 0.01). The serum contents of IL-6 (omega-3 fatty acid, 23.98±5.63 pg/mL vs control, 35.55±7.5 pg/mL, P < 0.01) and TNF-α (omega-3 fatty acid, 4.43±1.22 pg/mL vs control, 5.96±1.58 pg/mL, P < 0.01) after hepatectomy were significantly lower in the omega-3 fatty acid group than those of the control group. In conclusion, administration of omega-3 fatty acid may reduce infection rate and improve liver function recovery in HBV-associated HCC patients after hepatectomy. This improvement is associated with suppressed production of proinflammatory cytokines in these patients.

Effects of Branched-Chain Amino Acid Infusions on Liver Regeneration and Plasma Amino Acid Patterns in Partially Hepatectomized Rats

Even though solutions of high branched-chain amino acids (BCAAs) are known to be beneficial to patients with hepatic encephalopathy, data on the effects of BCAA on liver regeneration are limited. Two groups of young adult rats were utilized in this study: standard total parenteral nutrition solutions were administered to group SS (22.59% of BCAAs in total amino acids) and solutions high in BCAAs were given to group HS (34.44% of BCAAs). After 2 days of infusion, 70% partial hepatectomy was performed and the TPN infusions were continued for another 3 days. Liver regeneration was estimated and changes in serum amino acid patterns were determined 3 days after hepatectomy. Thymidine incorporation into liver DNA, in group HS was significantly higher than that in group SS (378±56 vs. 324±38, p=0.032). In group SS, the total concentration of BCAAs decreased (165.11±39.90mg/dL and 145.56±29.53mg/dL, p=0.014) over the experimental period, whereas that of aromatic amino acids (AAAs) increased (226.56±36.5mg/dL and 247.00±48.36mg/dL, p=0.104). However, group HS showed no changes in BCAA or AAA sums over the experimental period. After major hepatectomy, supplementation with high BCAAs helps not only to maintain a stable plasma BCAA/AAA ratio, but also promotes liver regeneration.

Glutamine-Enriched Nutrition Does Not Reduce Mucosal Morbidity or Complications After Stem-Cell Transplantation for Childhood Malignancies: A Prospective Randomized Study

Intravenous glutamine-enriched solution seems to be effective in posttransplant period in decreasing the severity and duration of mucositis. The aim of this randomized study was to determine the benefit of glutamine supplementation both on mucosal morbidity and in posttransplant associated complications. Children undergoing allogeneic hematopoietic stem-cell transplantation (HSCT) for malignant hematological diseases were randomly assigned to standard total parenteral nutrition (S-TPN) or glutamine-enriched (GE)-TPN solution consisting of 0.4 g/kg/day of l-alanine-glutamine dipeptide. This treatment started on the day of HSCT and ended when the patients could orally cover more than 50% of their daily energy requirements. The severity and the rate of post-HSCT mucositis were based on World Health Organization criteria. All the analyses were conducted on intention-to-treat principle. One hundred twenty consecutive patients (83 men; median age, 8.1 years) were enrolled. The mean duration of treatment was 23.5 and 23 days in the two treatment arms. The mean calorie intake was 1538 kcal/d in the S-TPN group and 1512 kcal/d in GE-TPN group. All patients were well nourished before and after HSCT. Mucositis occurred in 91.4% and 91.7% of patients in S-TPN and GE-TPN arm, respectively (P=0.98). Odds ratio adjusted by type of HSCT was 0.98 (95% confidence interval, 0.26-2.63). Type and duration of analgesic treatment, clinical outcome (engraftment, graft versus host disease, early morbidity, and mortality, relapse rate up to 180 days post-HSCT) were not significantly different in the two treatment arms. GE-TPN solution does not affect mucositis and outcome in well-nourished HSCT allogeneic patients.

Treatment with growth hormone, somatostatin and insulin in combination with hypocaloric parenteral nutrition in gastrointestinal cancer patients after surgery

Objective The metabolic response to gastrointestinal cancer in patients undergoing surgery is associated with hypermetabolism and insulin resistance. The potential use of synergetic anabolic hormones in conjunction with hypocaloric parenteral nutrition ( HPN) has become a significant area of investigation. The current study was performed to determine the clinical efficiency and safety of combined hormone therapy in addition to HPN in gastrointestinal cancer patients. Methods One hundred patients with the nutrition risk screening ( NRS) score of 3 or 4 undergoing surgery for gastrointestinal cancer were randomized into two groups. The patients in the control group received standard total parenteral nutrition (TPN) and systemic insulin. The patients in the study group received HPN and systemic insulin in addition to the pretreatment of recombinant human growth hormone ( r-hGH) and octreotide. Clinical efficiency and safety were evaluated by the measurement of hormones and protein metabolites, immune function, clinical outcome,and adverse events. Follow-ups were performed to determine the influence on prognosis. Results Treatment with r-hGH, octreotide, and insulin in combination with HPN significantly increased protein synthesis , immune function and metabolic tolerance, decreased infectious complications, and shortened postoperative hospital stays, but did not increase the risk of tumor development and recurrence in the study group compared to the control group. Conclusion The proper short-term perioperative administration of growth hormone,somatostatin,and insulin in combination with HPN can overcome the postoperative stress response through the increase of protein synthesis to improve immune function in gastrointestinal cancer patients after surgery. Key words: Hypocaloric parenteral nutrition; Recombined human growth hormone; Somatostatin ,cancer

The Inflammatory Modulation Effect of Glutamine-Enriched Total Parenteral Nutrition in Postoperative Gastrointestinal Cancer Patients

The objective of this study is to explore the inflammatory modulation effect of glutamine-enriched total parenteral nutrition (TPN) by investigating the alterations of inflammation-related cytokines in gastrointestinal (GI) cancer patients postoperatively. Fifty GI cancer patients received postoperative 7 days of isocaloric and isonitrogenous TPN after operation. They were randomly divided to receive either glutamine-enriched TPN or standard TPN. The inflammation-related cytokines including interleukin-6, interleukin-10, and tumor necrosis factor-α were also determined. Records of nutritional assessments, inflammatory status, and postoperative complications were compared between the two groups. Of 50 enrolled patients, 25 patients were classified as the intervention group, and the control group also comprised 25 patients. The differences of gender, age, primary GI malignancies, and hematological and biochemical data between the two compared groups were not statistically significant (all P > 0.05). Compared with standard TPN, a higher serum prealbumin level and better nitrogen balance were observed in glutamine-enriched TPN (P = 0.039 and 0.048 respectively). A significantly lower serum interleukin-6 level was found in comparing glutamine-enriched with standard TPN (P = 0.01), but not in interleukin-10 (P = 0.374) and tumor necrosis factor-α levels (P = 0.653). Moreover, a significant lower serum C-reactive protein level was detected in glutamine-enriched TPN compared with standard TPN (P = 0.013). Indeed, four cases of postoperative infectious complications were noted in the control group, but no postoperative infectious complications were observed in the interventional group (P = 0.037). Our present study shows that glutamine-enriched TPN may be beneficial in improving the inflammatory status and decreasing the infectious morbidity in postoperative GI cancer patients.

Treatment with growth hormone, somatostatin, and insulin in combination with hypocaloric parenteral nutrition in gastrointestinal cancer patients after surgery

Objective The metabolic response to gastrointestinal cancer in patients undergoing surgery is associated with hypermetabolism and insulin resistance. The potential use of synergetic anabolic hormones in conjunction with hypocaloric parenteral nutrition (HPN) has become a significant area of investigation. The presented study was performed to determine the clinical efficiency and safety of hormone therapy combined with HPN in patients with gastrointestinal cancer. Methods One hundred patients with a Nutrition Risk Screening score of 3 or 4 undergoing surgery for gastrointestinal cancer were randomized into two groups. The patients in the control group received standard total parenteral nutrition and systemic insulin. The patients in the study group received HPN and systemic insulin in addition to pretreatment with recombinant human growth hormone and octreotide. Clinical efficiency and safety were evaluated by the measurement of hormones and protein metabolites, immune function, clinical outcome, and adverse events. Follow-ups were performed to determine the influence on prognosis. Results Treatment with recombinant human growth hormone, octreotide, and insulin in combination with HPN significantly increased protein synthesis, immune function, and metabolic tolerance, decreased infectious complications, and shortened postoperative hospital stays, but did not increase the risk of tumor development and recurrence in the study group compared with the control group. Conclusion The proper short-term perioperative administration of growth hormone, somatostatin, and insulin in combination with HPN can overcome the postoperative stress response through the increase of protein synthesis to improve immune function in patients with gastrointestinal cancer after surgery.

Arginine-Enriched Total Parenteral Nutrition Improves Survival in Peritonitis by Normalizing NFκB Activation in Peritoneal Resident and Exudative Leukocytes

Enteral nutrition maintains peritoneal defense more effectively than parenteral nutrition, at least partly by preserving NFkappaB activation in peritoneal cells. We hypothesized that arginine (ARG)-enriched parenteral nutrition would normalize NFkappaB activation in peritoneal leukocytes, thereby improving the survival of peritonitis models. A total of 105 ICR mice were randomized to chow (n=33), IV feeding of a standard (STD) total parenteral nutrition (STD-TPN) solution (ARG 0.3%) (n=35), or 1% ARG-TPN solution (n=37), and fed accordingly for 5 days.Experiment 1: Thirty mice were used for intranuclear NFkappaB measurement in peritoneal resident cells (PRCs). After incubation with lipopolysaccharide (LPS: 0, 1, 10 microg/mL) for 30 minutes, intranuclear NFkappaB activity was examined by laser scanning cytometry.Experiment 2: Fifty-one mice were injected with 2 mL of 1% glycogen intraperitoneally. Peritoneal exudative cells (PECs) were obtained at 2 or 4 hours after glycogen administration for NFkappaB measurement. Cytokine (TNFalpha, IL-10) levels in peritoneal lavage fluid were also determined by ELISA.Experiment 3: After 5 days of feeding, 24 mice underwent cecal ligation and puncture. Survival was observed up to 5 days. Experiment 1: Intranuclear NFkappaB levels in the ARG-TPN and chow groups increased dose-dependently after LPS stimulation, while the level in the STD-TPN group was unchanged.Experiment 2: Intranuclear NFkappaB level was significantly higher at 2 hours in the chow than in the STD-TPN group, whereas in the ARG-TPN mice the level was midway between those of the chow and STD-TPN groups. TNFalpha and IL-10 levels of the chow group were significantly higher than those of STD-TPN mice at 2 hours. TNFalpha was significantly higher in the ARG-TPN group than in the STD-TPN group, but the IL-10 level showed no recovery.Experiment 3: Survival times were significantly reduced in the STD-TPN as compared with the chow group, though ARG-TPN improved survival. ARG-enriched TPN is a surrogate for enteral feeding which maintains peritoneal defense by preserving NFkappaB activation in peritoneal resident and exudative leukocytes.

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.