Conventional Total Parenteral Nutrition Research Articles

Postnatal growth and short-term complications in very low birth weight neonates receiving total parenteral nutrition

Objective: To study the postnatal growth and short-term complications in very low birth weight preterm neonates receiving total parenteral nutrition (TPN). Methods: This prospective, observational study was conducted in the neonatal intensive care unit of a tertiary care hospital in South India. All neonates with birth weight <1250 g and <32 weeks of gestation who received TPN and survived at least 7 days were studied prospectively. Amino acid infusion was started at 1 g/kg/day on day 1 and graded up to 4 g/kg/day. Lipids were started on the day 2 of life at 1 g/kg/day and graded up to 3 g/kg/day. Enteral feeds were introduced within3 days of life. TPN was stopped once enteral feeds reached 100 ml/kg/day. Postnatal growth and biochemical and hematological parameters were also monitored. Results: Time to reach full enteral feeds was 11.3±4.5 days, cumulative weight loss proportion (in %) was 8.5±4.7, and number of days to regain birth weight was 11.1±4.5 days. Mean growth velocity (GV) at 30 days of life and 40 weeks of postmenstrual age (PMA) was 16.37±4.8 g/kg/day and 20.03±5.8 g/day, respectively. Mean GV of appropriate for gestational age (AGA) infants was 3.13 g/kg/day, lower compared to small for GA (SGA) infants at 30 days PMA (p=0.01). However, there was no statistical difference in GV between AGA and SGA infants at 40 weeks of PMA. There was no correlationbetween energy intake on the day 7 and weight and head circumference at 40 weeks of PMA. Hyponatremia was observed in 40.6% infants receiving TPN, and there were no other significant complications. Conclusion: Conventional TPN was associated with favorable postnatal growth until 30 days of postnatal life. However, catch-up growth at 40 weeks of PMA was not satisfactory. Mean GV of AGA infants was found to be lower compared to that in SGA infants at 30 days of postnatal life. Besides hyponatremia, there was no major complication due to TPN in this study.

Total parenteral-nutrition-mediated dendritic-cell activation and infiltration into the small intestine in a rat model

Total parenteral nutrition (TPN) is commonly carried out in the clinical setting. However, effects of TPN on the immune system, including dendritic cells (DC), are not well understood. The purpose of this study was to determine whether TPN affects DC activation and infiltration into the intestinal barrier. Male Wistar rats were given conventional nutrition (CN) or TPN for 7days. DCs were visualized by immunohistochemistry. Levels of nucleotide-binding oligomerization domain protein 2 (NOD2) and high-mobility group box 1 (HMGB1) protein were assessed by Western blot. The number of DCs at the small intestinal barrier was significantly increased in the TPN group (9.2±3.1 cells/microscopic field) compared with the CN group (0.5±0.6 cells/microscopic field; p<0.05), as were protein expression levels of NOD2 and HMGB1. These results suggest that TPN increases activation and infiltration of DCs into the small intestine, potentially involving an increase in NOD2 and HMGB1 levels in the small intestine.

Role of glutamine administration on cellular immunity after total parenteral nutrition enriched with glutamine in patients with systemic inflammatory response syndrome

Glutamine is an important substrate for enterocyte and other rapidly proliferating cells. Low plasma and tissue levels present in glutamine in critically ill patients suggest that demand may exceed endogenous supply. Because commercially available amino acid solutions do not contain glutamine because of its instability in aqueous solution, conventional total parenteral nutrition (TPN) does not prevent stress-induced glutamine depletion. In this study, we administered intravenous glutamine-supplemented TPN to patients with systemic inflammatory response syndrome (SIRS) to investigate the effect of glutamine supplementation on immune states. This study is a prospective, randomized clinical trial. All patients received TPN given continuously for 6 days. Thirty patients with SIRS were allocated to either a glutamine group ( l-glutamine 0.4g/[kg d]) (n = 15) or a control group (n = 15). Blood samples were collected on day 1 and day 6 after admission for C-reactive protein, immunoglobulin (Ig) M, IgG, IgA, C 3, C4, and lymphocyte analysis. The Acute Physiologic and Chronic Health Evaluation II score and the Simplified Acute Physiologic II (SAPS II) score were used to evaluate the patients after admission. Although there was a tendency for decreased T cytotoxic cells and natural killer cells in the control group, no significant difference was observed between the 2 groups. However, an increase in lymphocyte and lymphocyte subgroups in the glutamine group was observed; but there was no difference between the groups. A low SAPS II score was observed on the sixth day in the glutamine group, whereas no difference in SAPS II and Acute Physiologic and Chronic Health Evaluation II scores was observed between the 2 groups. There was no difference in IgM, IgG, IgA, C 3, and C4 levels and numbers of B-lymphocytes between the groups. Glutamine-added TPN significantly decreases leukocyte and natural killer cell count and therefore suppresses inflammation. Furthermore, total lymphocyte count, B- and T-lymphocytes, and their subgroups (helper T-lymphocytes, cytotoxic T-lymphocytes) are increased; although not statistically significant, these increases might be playing a role in improving the immune system.

Effects of parenteral glutamine supplementation on modulating the immune response in rats undergoing a total gastrectomy

The present study investigated the effect of parenteral glutamine (Gln) supplementation on cellular adhesion molecule expression and release of chemokines responsible for inflammatory cell recruitment in rats undergoing a total gastrectomy. Normal rats with internal jugular catheters were assigned to one control group and two experimental groups and received total parenteral nutrition (TPN). A total gastrectomy was performed in the experimental groups, whereas the control group received a sham operation (Sham). The TPN solutions were isonitrogenous and identical in nutrient composition except that the Sham group and one of the experimental group received conventional (Conv) TPN solution, whereas the other experimental group received 25% of the amino acid nitrogen as Gln. Half of the rats in each group were killed 1 or 3 d after surgery or the Sham to examine their immune response. The results showed that the surgery produced higher polymorphonuclear leucocyte CD11b/CD18 expressions, and Gln supplementation lowered CD11b/CD18 expressions compared with the Conv group post-operatively. The levels of monocyte chemotactic protein-1 and macrophage inflammatory protein-2 in peritoneal lavage fluid were higher in the Gln group than those in the Conv group 1 d post-operatively; these chemotactic proteins had returned to the levels comparable with those in the Sham group on post-operative day 3. These results suggest that Gln supplementation attenuated polymorphonuclear leucocyte integrin expression. In addition, Gln-enriched parenteral nutrition induced an earlier more intensive and rapid immune response to injury than the Conv parenteral nutrition after a total gastrectomy.

Effects of ω-3 fatty acids on inflammatory mediators and splenocyte cytokine mRNA expressions in rats with polymicrobial sepsis

Objectives Many studies have shown that ω-3 fatty acids (FAs) have immunomodulatory effects. However, the influence of ω-3 FAs on septic conditions is not certain. This study examined the effect of fish oil (FO)–enriched diets before and/or ω-3 FA-containing total parenteral nutrition (TPN) after sepsis on the distribution of T-lymphocyte subpopulations and splenocyte cytokine mRNA expressions in rats with polymicrobial sepsis. Methods Rats were assigned to a control group and four experimental groups. The control group and groups 1 and 2 were fed a semipurified diet, and groups 3 and 4 had 20% soybean oil replaced by FO. After feeding the diets for 10 d, sepsis was induced by cecal ligation and puncture (CLP) in the experimental groups, whereas sham operation was performed on the control group. TPN was maintained for 3 d after CLP or sham operation. The control group and groups 1 and 3 were infused with conventional TPN, whereas the TPN solution of groups 2 and 4 was supplemented with FO. All rats were sacrificed 3 d after the operation to examine their immune responses. Results Messenger RNA expressions of interleukin-2 and tumor necrosis factor-α in splenocytes were higher in groups 3 and 4 than in the control group and group 1. Interleukin-10 mRNA expression in group 3 was higher than in the control group and group 2. Blood CD4 percentage and CD4/CD8 ratio in group 1 were significantly lower, whereas no differences were observed in FO-supplemented groups compared with the control group. Conclusion FO administration before and/or after CLP maintained blood T-lymphocyte subpopulations and modulated T-helper type 1 and 2 cytokine mRNA expressions in rats with polymicrobial sepsis.

Effects of ω-3 fatty acids on leukocyte Th1/Th2 cytokine and integrin expression in rats with gut-derived sepsis

Objectives This study examined the effect of fish oil (FO)-enriched diets before and/or ω-3 fatty acid–containing total parenteral nutrition (TPN) after sepsis on the distribution of the T-lymphocyte subpopulation, intracellular cytokine, and intestinal immunity in rats with gut-derived sepsis. Methods Rats were assigned to a control or one of four experimental groups. The control group and groups 1 and 2 were fed a semipurified diet, and groups 3 and 4 received FO instead of 20% soybean oil. After feeding the diets for 10 d, sepsis was induced by cecal ligation and puncture (CLP) in the experimental groups, whereas a sham operation was performed in the control group. TPN was maintained for 3 d after the CLP or sham operation. The control group and groups 1 and 3 were infused with conventional TPN, whereas the TPN solution used for groups 2 and 4 were supplemented with FO. All rats were sacrificed 3 d after the operation to examine their immune responses. Results Plasma and intestinal immunoglobin A levels were higher in the FO-supplemented groups than in the control group and group 1. Lymphocyte interferon-γ expression in groups 3 and 4 was significantly lower, whereas interleukin-4 expression was higher than those of the control group and groups 1 and 2. The splenocyte CD4 percentage in groups 3 and 4 and the CD4/CD8 ratio in group 4 were significantly higher than those in group 1. Conclusion These findings suggest that FO administration before and/or after CLP are not immunosuppressive. FO-enriched diets before or before and after CLP resulted in a T-helper type 2 response and enhanced immunoglobulin A secretion. In addition, the splenocyte CD4 levels and CD4/CD8 ratio were maintained in rats with gut-derived sepsis.

Branched chain amino acids as the protein component of parenteral nutrition in cancer cachexia

A prospective randomized trial was conducted to determine the effects of branched chain amino acids (BCAA) as the protein component of total parenteral nutrition (TPN) on protein kinetics in patients with intraabdominal adenocarcinoma. Nine malnourished patients were given both conventional TPN containing 19 per cent BCAA (AA) and isocaloric, isonitrogenous TPN containing 50 per cent BCAA (BCAA-TPN), in random order. Both [13C]leucine and [14C]tyrosine were employed as tracers to avoid the potential bias due to the different amino acid composition of the two TPN solutions. With BCAA-TPN, leucine and tyrosine flux increased significantly from (mean +/- s.d.) 158.0 +/- 37.2 to 243.5 +/- 75.8 mumol kg-1 h-1 (P less than 0.025) and from 35.0 +/- 8.4 to 42.6 +/- 11.0 mumol kg-1 h-1 (P less than 0.05) respectively. Leucine oxidation was significantly higher on BCAA-TPN (24.1 +/- 6.3 on AA versus 68.3 +/- 37.1 mumol kg-1 h-1, P less than 0.025) while tyrosine oxidation was significantly lower (3.7 +/- 1.8 mumol kg-1 h-1 on AA versus 2.5 +/- 2.0 mumol kg-1 h-1 on BCAA-TPN, P less than 0.05). Whole body protein synthesis and breakdown was significantly higher on BCAA-TPN by the tyrosine tracer (31.3 +/- 7.3 on AA versus 40.1 +/- 9.3 mumol kg-1 h-1, P less than 0.025 and 33.0 +/- 8.4 on AA versus 41.3 +/- 11.1 mumol kg-1 h-1, P less than 0.05) respectively. Using the leucine tracers both synthesis and breakdown were increased, but not significantly, from 133.8 +/- 40.0 to 175.3 +/- 65.1 mumol kg-1 h-1 and from 127.9 +/- 33.6 to 167.7 +/- 71.2 mumol kg-1 h-1 respectively. The fractional albumin synthetic rate increased significantly on BCAA-TPN from 4.3 +/- 2.9 on AA to 8.0 +/- 5.1 per cent per day (P less than 0.05). The reduction in tyrosine oxidation, suggesting improved protein utilization, coupled with an increase in protein and albumin synthesis, strongly support a positive benefit from BCAA-TPN in cancer cachexia.

Effects of arginine-containing total parenteral nutrition on N balance and phagocytic activity in rats undergoing a partial gastrectomy

The present study investigated the effect of arginine (Arg)-containing parenteral nutrition on phagocytic activity to elucidate the possible roles of Arg in the secretion of anabolic hormones and N balance in rats undergoing gastrectomy. Rats were divided into two experimental groups and received total parenteral nutrition (TPN). The TPN solutions were isonitrogenous and identical in nutrient compositions except for differences in amino acid content. One group received conventional TPN, the other group replaced 2 % of the total energy as Arg. After receiving TPN for 3 d, one-third of the rats in each experimental group were killed as the baseline group. The remaining rats underwent a partial gastrectomy and were killed 1 or 3 d after surgery. The results showed that there were no differences in N balance, plasma growth hormone and insulin-like growth factor-1 levels between the two groups before or after surgery. The phagocytic activity of peritoneal macrophages was higher in the Arg group than in the control group 1 d after surgery. There were no differences in the phagocytic activities of blood polymorphonuclear neutrophils between the two groups at various time points. TNF-alpha levels in peritoneal lavage fluid were lower in the Arg group than in the control group on post-operative day 3. These results suggest that parenterally infused Arg enhances phagocytic activity and reduces the production of inflammatory mediators at the site of injury. However, Arg supplementation did not influence the secretion of anabolic hormones nor N balance in rats with a partial gastrectomy.

Effects of arginine supplementation on splenocyte cytokine mRNA expression in rats with gut-derived sepsis

To investigate the effects of arginine (Arg)-enriched diets before sepsis and/or Arg-containing total parenteral nutrition (TPN) after sepsis or both on cytokine mRNA expression levels in splenocytes of rats with gut-derived sepsis. Rats were assigned to four experimental groups. Groups 1 and 2 were fed with a semipurified diet, while groups 3 and 4 had part of the casein replaced by Arg which provided 2% of the total calories. After the rats were fed with these diets for 10 d, sepsis was induced by cecal ligation and puncture (CLP), at the same time an internal jugular vein was cannulated. All rats were maintained on TPN for 3 d. Groups 1 and 3 were infused with conventional TPN, while groups 2 and 4 were supplemented with Arg which provided 2% of the total calories in the TPN solution. All rats were killed 3 d after CLP to examine their splenocyte subpopulation distribution and cytokine expression levels. Plasma interleukin (IL)-2, IL-4, tumor necrosis factor-alpha (TNF-alpha) and interferon (IFN-gamma) were not detectable 3 d after CLP. There were no differences in the distributions of CD45Ra(+), CD3(+), CD4(+), and CD8(+) cells in whole blood and splenocytes among the four groups. The splenocyte IL-2 mRNA expression in the Arg-supplemented groups was significantly higher than that in group 1. IL-4 mRNA expression in groups 3 and 4 was significantly higher than that in groups 1 and 2. The mRNA expression of IL-10 and IFN-gamma was significantly higher in group 4 than in the other three groups. There was no difference in TNF-alpha mRNA expression among the four groups. The influence of Arg on the whole blood and splenic lymphocyte subpopulation distribution is not obvious. However, Arg administration, especially before and after CLP, significantly enhances the mRNA expression levels of Th1 and Th2 cytokines in the spleen of rats with gut-derived sepsis.

Effects of glutamine supplementation on splenocyte cytokine mRNA expression in rats with septic peritonitis

To investigate the effects of glutamine (GLN)-enriched diets before and GLN-containing total parenteral nutrition (TPN) after sepsis or both on the secretion of cytokines and their mRNA expression levels in splenocytes of rats with septic peritonitis. Rats were assigned to a control group and 4 experimental groups. The control group and experimental groups 1 and 2 were fed a semipurified diet, while experimental groups 3 and 4 had part of the casein replaced by GLN which provided 25% of the total nitrogen. After rats were fed with these diets for 10 d, sepsis was induced by cecal ligation and puncture (CLP), whereas the control group underwent a sham operation, at the same time, an internal jugular vein was cannulated. All rats were maintained on TPN for 3 d. The control group and experimental groups 1 and 3 were infused with conventional TPN, while the TPN in experimental groups 2 and 4 was supplemented with GLN, providing 25% of the total nitrogen in the TPN solution. All rats were kiued 3 d after sham operation or CLP to examine their splenocyte subpopulation distribution and cytokine expression levels. Most cytokines could not be detected in plasma except for IL-10. No difference in plasma IL-10 was observed among the 5 groups. The IL-2, IL-4, IL-10, and TNF-alpha mRNA expression levels in splenocytes were significantly higher in experimental groups 2 and 4 than in the control group and group 1. The mRNA expression of IFN-gamma was significantly higher in the GLN-supplemented groups than in the control group and experimental group 1. The proportion of CD45Ra+ was increased, while those of CD3+ and CD4+ were decreased in experimental group 1 after CLP was performed. There were no differences in spleen CD3+ lymphocyte distributions between the control and GLN-supplemented groups. GLN supplementation can maintain T-lymphocyte populations in the spleen and significantly enhance the mRNA expression levels of Th1 and Th2 cytokines and TNF-alpha in the spleen of rats with septic peritonitis.

Glutamine-supplemented total parenteral nutrition attenuates plasma interleukin-6 in surgical patients with lower disease severity

Previous reports have shown that decrease in plasma glutamine (Gln) level following major surgery may contribute to the state of immunosuppression. Gln supplementation improves the depletion of body Gln pool, and may have indirect effect on reducing proinflammatory mediator release. This study evaluated whether the effect of Gln dipeptide-enriched total parenteral nutrition (TPN) on postoperative cytokine alteration depended on the disease severity of surgical patients. Forty-eight patients with major abdominal surgery were allocated to two groups to receive isonitrogenous (0.228 g nitrogen/kg per d) and isocaloric (30 kcal/kg per d) TPN for 6 d. Control group (Conv) using conventional TPN solution received 1.5 g amino acids/kg per day, whereas the test group received 0.972 g amino acids/kg per day and 0.417 g L-alanyl-L-glutamine (Ala-Gln)/kg per day. Blood samples were collected on d 1 and d 6 postoperatively for plasma interleukin (IL)-2, IL-6, IL-8, and interferon (IFN)-gamma analysis. Plasma IL-2 and IFN-gamma were not detectable. IL-6 concentrations were significantly lower on the 6(th) postoperative day in the Ala-Gln group than those in the Conv group in patients with APACHE II <=6, whereas no difference was noted in patients with APACHE II >6. There was no difference in IL-8 levels between the two groups. No difference in cumulative nitrogen balance was observed on d 2-5 after the operation between the two groups (Ala-Gln -3.2+/-1.6 g vs Conv -6.5+/-2.7 g). A significant inverse correlation was noted between plasma IL-6 levels and cumulative nitrogen balance postoperatively in the Ala-Gln group, whereas no such correlation was observed in the Conv group. TPN supplemented with Gln dipeptide had no effect on plasma IL-8 levels after surgery. However, Gln supplementation had a beneficial effect on decreasing systemic IL-6 production after surgery in patients with low admission illness severity, and lower plasma IL-6 may improve nitrogen balance in patients with abdominal surgery when Gln was administered.

Effects of glutamine-containing total parenteral nutrition on phagocytic activity and anabolic hormone response in rats undergoing gastrectomy

To investigate the effect of glutamine (Gln)-containing parenteral nutrition on phagocytic activity and to elucidate the possible roles of Gln in the secretion of anabolic hormones and nitrogen balance in rats undergoing a gastrectomy. Rats with an internal jugular catheter were divided into 2 experimental groups and received total parenteral nutrition (TPN). The TPN solutions were isonitrogenous and identical in nutrient compositions except for differences in amino acid content. One group received conventional TPN (control), and in the other group, 25% of the total amino acid nitrogen was replaced with Gln. After receiving TPN for 3 d, one-third of the rats in each experimental group were sacrificed as the baseline group. The remaining rats underwent a partial gastrectomy and were killed 1 and 3 d, respectively, after surgery. Plasma, peritoneal lavage fluid (PLF), and urine samples were collected for further analysis. The Gln group had fewer nitrogen losses 1 and 2 d after surgery (d1, 16.6+/-242.5 vs -233.4+/-205.9 mg/d, d2, 31.8+/-238.8 vs -253.4+/-184.6 mg/d, P<0.05). There were no differences in plasma growth hormone (GH) and insulin-like growth factor-1 levels between the 2 groups before or after surgery. The phagocytic activity of peritoneal macrophages was higher in the Gln group than in the control group 1 d after surgery (A 1185+/-931 vs 323+/-201, P<0.05). There were no differences in the phagocytic activities of blood polymorphonuclear neutrophils between the 2 groups at the baseline or on the postoperative days. No significant differences in interleukin-1beta or interleukin-6 concentrations in PLF were observed between the 2 groups. However, tumor necrosis factor-alpha level in PLF was significantly lower in the Gln group than in the control group on postoperative d 3. TPN supplemented with Gln can improve the nitrogen balance, and enhance macrophage phagocytic activity at the site of injury. However, Gln supplementation has no effect on phagocytic cell activity in the systemic circulation, GH and insulin-like growth factor-1 might not be responsible for attenuating nitrogen losses in rats with a partial gastrectomy.

Effects of glutamine supplementation on innate immune response in rats with gut-derived sepsis

The present study examined the effect of glutamine (Gln)-enriched diets before sepsis or Gln-containing total parenteral nutrition (TPN) after sepsis, or both, on the phagocytic activity and blood lymphocyte subpopulation in rats with gut-derived sepsis. Rats were assigned to a control group or one of four experimental groups. The control group and groups 1 and 2 were fed a semipurified diet; groups 3 and 4 had part of casein replaced by Gln. After feeding the diets for 10 d, sepsis was induced by caecal ligation and puncture (CLP); TPN was maintained for 3 d after CLP. The control group and groups 1 and 3 were infused with conventional TPN and groups 2 and 4 were supplemented with Gln in the TPN solution. All rats were killed 3 d after CLP or sham operation to examine their immune responses. The results showed that compared with the control group, the phagocytic activities of peritoneal macrophages were enhanced in groups 3 and 4, but not in groups 1 and 2. The proportion of CD3+ cells in group 1 was significantly lower (P<0.05) than that of the control group, whereas no differences were observed among the control and Gln-supplemented groups. The CD4+ cell proportion was significantly lower (P<0.05) in group 1 compared with the control group and groups 3 and 4. These findings suggest that Gln-enriched diets before CLP significantly enhanced peritoneal macrophage phagocytic activity, preserved CD4+ cells and maintained blood total T lymphocytes in gut-derived sepsis. However, parenteral Gln administration after caecal ligation and puncture had no favourable effects on modulating immune response in septic rats.

Glutamine supplementation enhances mucosal immunity in rats with Gut-Derived sepsis

Objective Supplemental glutamine (Gln) has been demonstrated to improve the immunologic response and reduce mortality in rodents with sepsis. However, the effects of Gln on gut-associated lymphoid tissue function after infection and sepsis are not clear. We investigated the effects of Gln-supplemented diets before sepsis, Gln-enriched total parenteral nutrition (TPN) after sepsis, or both on the intestinal immunity in rats with gut-derived sepsis. Methods Male Wistar rats were assigned to control and four experimental groups. The control and experimental groups 1 and 2 were fed a semi-purified diet; in experimental groups 3 and 4, part of the casein in the diets was replaced with Gln. After feeding rats the respective diets for 10 d, sepsis was induced by cecal ligation and puncture (CLP) in the experimental groups, whereas the control group underwent a sham operation; at the same time, the internal jugular vein of all rats was cannulated. All rats were maintained on TPN for 3 d. The control group and groups 1 and 3 were infused with conventional TPN, and groups 2 and 4 were given a TPN solution supplemented with Gln, which provided 25% of total amino acid nitrogen. All rats were killed 3 d after the sham operation or CLP. Intestinal immunoglobin A levels, total lymphocyte yields, and lymphocyte subpopulations in Peyer's patches were analyzed. Results Total Peyer's patch lymphocyte numbers were significantly higher in the Gln-supplemented groups than in the control group. Distributions of CD3 + and CD4 + in group 1 were significantly lower than those in the control group, whereas no differences were observed among the control and Gln-supplemented groups. Plasma immunoglobulin A levels were higher in the Gln-supplemented groups than the control group and group 1. Intestinal immunoglobulin A levels were significantly higher in groups 2 and 4 than in the control group and group 1. Conclusions Preventive use of a Gln-supplemented enteral diet before CLP or intravenous Gln supplementation after CLP have similar effects in promoting proliferation of total lymphocyte in gut-associated lymphoid tissue, enhancing IgA secretion, and maintaining T-lymphocyte populations in Peyer's patches. Gln administered before and after CLP did not seem to have a synergistic effect on enhancing mucosal immunity in rats with gut-derived sepsis.

Effect of total parenteral nutrition (TPN) with and without glutamine dipeptide supplementation on outcome in severe acute pancreatitis (SAP)

Objective: To investigate the effect of total parenteral nutrition (TPN) and glutamine-supplemented TPN in patients with serious acute pancreatitis (SAP). Methods: Sixty-four patients with SAP were randomly divided into three therapeutic groups. Twenty-three cases (group I) were treated by traditional therapeutic program combined with traditional therapy, the 21 cases in group II and 20 cases in group III were treated by TPN and glutamine-supplemented TPN, respectively. The concentration of serum albumin was determined, recovery time of blood amylase, the incidence of complications, mortality, length of hospital stay (LOS) and body mass of the patients in each group were monitored. Results: The concentrations of serum albumin were low in all three groups at admission. After 2 weeks of treatment, the serum albumin concentration increased in groups II and III, while it remained almost the same in group I. Mortalities for groups I, II, and III were 43.5% (10/23), 14.3% (3/21, vs. group I P<0.05) and 0% (vs. group I P<0.01), respectively. The incidence of complications in group I (21/23) was much higher than those in group II (11/21, P<0.01) and group III (4/20, P<0.01), and in group III they were less frequent than in group II (P<0.05). In fact no pancreatic infection occurred in group III with glutamine dipeptide supplementation. The loss of body mass in group I was more profound than in groups II and III, P<0.05. The length of stay (LOS) in group I (39.1±10.60 d) was longer than those of group II (28.6±6.90 d, P<0.05) and III (25.3±7.60 d, P<0.01). Conclusions: Combined with conventional therapy, TPN and glutamine dipeptide-supplemented TPN therapy can reduce mortality and the incidence of infectious complications, shorten the LOS, and improve the nutritional status of patients with SAP. Glutamine-supplemented TPN therapy can apparently prevent the occurrence of pancreatic infection.

Effects of arginine supplementation on mucosal immunity in rats with septic peritonitis

Background: Supplemental Arginine (Arg) has been demonstrated to improve the immunologic response and reduce mortality in rodents with sepsis. However, the effects of Arg on gut-associated lymphoid tissue function after infection and sepsis are not clear. The aim of this study was to study the effect of Arg-supplemented diets before and Arg-enriched total parenteral nutrition (TPN) after sepsis or both on the intestinal immunity of rats with septic peritonitis. Methods: Rats were assigned to four groups. Groups 1 and 2 were fed a semipurified diet, while in the diets of groups 3 and 4, part of the casein was replaced with Arg. After feeding the experimental diets for 10 days, sepsis was induced by cecal ligation and puncture (CLP); at the same time, the internal jugular vein was cannulated. All rats were maintained on TPN for 3 days. Groups 1 and 3 were infused with conventional TPN, while groups 2 and 4 were given a TPN solution supplemented with Arg, which replaced 10% of the total amino acids. All rats were sacrificed 3 days after CLP. Intestinal immunoglobin (Ig) A levels, total lymphocyte yields, and lymphocyte subpopulations in Peyer's patches were analyzed. In vitro cytokine secretion by splenocytes and Peyer's patch lymphocytes were also measured. Results: Total lymphocyte yields in Peyer's patches, and small intestinal immunoglobulin A (IgA) secretion in group 4 were significantly higher than the groups 1 and 2. No differences were observed between groups 3 and 4. There were no differences in the interleukin (IL)-2 and interferon- γ levels among all groups when splenocytes were stimulated with mitogen. However, in vitro splenocyte IL-10 production in group 4 was significantly higher than those of groups 1 and 2, and had no difference from group 3. There were no differences in the ratios of B and T lymphocyte subpopulations in Peyer’s patches among all groups. Conclusions: Enteral Arg supplementation before sepsis tended to enhance total lymphocyte yields in Peyer's patches and intestinal IgA secretion. Arg administered both before and after CLP had a synergistic effect on improving intestinal immunity, possibly by enhancing systemic IL-10 secretion. However, intravenous Arg administration after CLP had no favorable effects on mucosal immunity in rats with septic peritonitis.

Arginine supplementation enhances peritoneal macrophage phagocytic activity in rats with gut-derived sepsis.

Previous reports have shown that arginine (Arg) enhances phagocytic activity of macrophages and is required for macrophage-mediated toxicity toward tumor cells. Few studies have addressed the importance of Arg supplementation on macrophage and neutrophil function after infection and sepsis. This study examined the effect of Arg-supplemented diets before and Arg-enriched total parenteral nutrition (TPN) after sepsis or both on the phagocytic activity of peritoneal macrophages and blood polymorphonuclear cells in rats with gut-derived sepsis. Male Wistar rats were assigned to 4 groups. Groups 1 and 2 were fed a semipurified diet, while groups 3 and 4 had part of the casein replaced with 2% of total calories as Arg. After the experimental diets were administered for 10 days, sepsis was induced by cecal ligation and puncture (CLP); at the same time, an internal jugular vein was cannulated. All rats were maintained on TPN for 3 days. Groups 1 and 3 were infused with conventional TPN, while groups 2 and 4 were supplemented with Arg, replacing 10% of total amino acids in the TPN solution. Survival rates were recorded for 3 days after CLP, and all surviving rats were killed 3 days after CLP to examine their immune responses. Aerobic and anaerobic bacteria colony counts in peritoneal lavage fluid were significantly reduced, and the phagocytic activity of peritoneal macrophages was enhanced in groups 3 and 4 but not in the other 2 groups. There were no significant differences in the phagocytic activities of blood polymorphonuclear cells and survival rates among the 4 groups. Enteral Arg supplementation before sepsis significantly enhanced peritoneal macrophage phagocytic activity and reduced total bacterial counts in peritoneal lavage fluid. Arg administered before and after CLP seemed to have a synergistic effect on enhancing phagocytic activity and on bacterial clearance. However, IV Arg administration after CLP had no favorable effects on phagocytic activity or survival rates in rats with gut-derived sepsis.

Effect of glutamine-enriched total parenteral nutrition in patients with acute pancreatitis

Background: The management of acute pancreatitis (AP) frequently includes parenteral nutrition, but conditionally essential amino acids such as glutamine are not included in conventional total parenteral nutrition (TPN). Aim: This study was conducted to determine whether the inclusion of glutamine has a beneficial effect in patients with AP receiving TPN. Methods: In a randomized, controlled study 28 patients with AP received either a standard TPN with 1.5 g/kg body weight protein or an isonitrogen, isocaloric TPN which contains 0.3 g/kg L -alanine- L -glutamine. Patients were assessed for nutritional and inflammatory parameters, infectious complications, length of TPN, length of hospital stay (LOS) and cost of TPN. Results: There were no side-effects related to glutamine substitution observed. Glutamine was associated with a significant increase of cholinesterase, albumin and lymphocyte count in AP as well a decrease of C-reactive protein compared to standard TPN at day 14. There was a reduced length of TPN (10 [6–16] vs 16 [10–18] days, P<0.05) and a trend of reduced LOS (21 [14–32] vs 25 [19–40] days) in AP patients receiving glutamine. The overall cost per patient for TPN did not differ (gln+: 929±586 vs gln−: 981±507 euro/patient). Conclusion: Our results suggest that glutamine substitution is beneficial and does not increase the overall cost of parenteral feeding in patients with acute pancreatitis.

Total nutrient admixtures appear safer than lipid emulsion alone as regards microbial contamination: growth properties of microbial pathogens at room temperature.

The extraordinary growth properties of most microorganisms in 10% and 20% lipid emulsions has led to the Centers for Disease Control and Prevention recommendation that if lipids are given through an i.v. line, the administration set should be replaced every 24 hours rather than the usual 72-hour interval used for crystalloid solutions, including those used for conventional total parenteral nutrition. For nearly 15 years, parenteral alimentation has been given as a total nutrient admixture (TNA), with the glucose, amino acids, and lipid mixed within the same bag and infused continuously over 24 hours. We prospectively studied in a representative TNA (17.6% glucose, 5% amino acids, 4% lipid; pH 5.6, osmolality 1778) and in a control solution, 5% dextrose-in-water (D5%/W), the growth properties at 4, 25, and 35 degrees C of three isolates each of Staphylococcus epidermidis, Staphylococcus aureus, Enterobacter cloacae, Klebsiella oxytoca, Serratia marcescens, Acinetobacter calcoaceticus, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, Burkholderia cepacia, Flavobacterium spp, and Candida albicans, and two isolates of Staphylococcus saprophyticus, the species that are most likely to contaminate TNA during preparation or administration and that have been implicated in >95% of all outbreaks and sporadic cases of nosocomial bloodstream infections traced to contaminated parenteral admixtures reported in the world literature. Growth in TNA at 25 and 35 degrees C occurred with only two species, C. albicans and S. saprophyticus, and only after 24 to 48 hours; D5%/W allowed growth at 25 degrees C of two gram-negative species, S. marcescens and B. cepacia. We conclude that TNA is a poor growth medium for most nosocomial pathogens and is no better than D5%/W. The need to replace administration sets every 24 hours with TNA should be reconsidered and ideally be studied in a prospective randomized trial.

Glutamine dipeptides-supplemented parenteral nutrition reverses gut mucosal structure and interleukin-6 release of rat intestinal mononuclear cells after hemorrhagic shock.

Glutamine is an essential substrate for gut mucosal structure, but the role for gut immune function is not fully known. To determine the effect on gut cytokine release in relation to bacterial translocation and gut morphology, a nonlethal hemorrhagic shock (30 min, 30 mmHg) was performed in male Wistar rats followed by 4 days of different way of feeding. A conventional total parenteral nutrition (TPN) solution was compared with an isocaloric and isonitrogenous TPN solution supplemented with alanin-L-glutamine and glycyl-L-glutamine. An enteral chow-fed control group was included. Gut mononuclear cells and splenic macrophages were obtained and endotoxin-induced supernatant tumor necrosis factor-alpha (TNF) and interleukin-6 (IL-6) bioactivity was measured. Histological specimen of the small bowel were taken and mesenteric lymph nodes (MLN) were separated. Enteral feeding following hemorrhagic shock was accompanied by a normal mucosal structure and no bacterial translocation could be detected. TPN was characterized by suppression of cytokine release in gut mononuclear cells and splenic macrophages compared with the enteral-fed control (p < .05). Decreased TNF and IL-6 release was associated with a significantly increased mucosal injury score (p < .05) and a high incidence of bacterial translocation to MLN (66%, p < .05 vs. control). Supplementation of glutamine-dipeptides did not prevent TPN-induced bacterial translocation to MLN (p < .05 vs. control) but significantly improved mucosal injury (p < .05 vs. TPN). Down-regulation of TNF release in TPN-fed rats could not be reversed by glutamine dipeptides while IL-6 release was significantly increased compared with TPN-fed animals (p < .05), and no difference to enteral-fed controls could be found. Enteral nutrition following hemorrhagic shock is superior to parenteral nutrition with regard to mucosal structure, cytokine release, and bacterial translocation. Supplementation of TPN with glutamine dipeptides could reverse TPN-induced suppression of IL-6 release and improved mucosal structure, which may be beneficial in various disease conditions in which TPN is an integrated part of patients management.