Standard Parenteral Nutrition Research Articles

Preclinical trial of l-arginine monotherapy alone or with N-acetylcysteine in septic shock*

L-arginine supplementation in sepsis is controversial. Septic shock has been alternatively viewed as an L-arginine-deficient state or as a syndrome caused by excess nitric oxide, an end-product of L-arginine metabolism. Randomized, placebo-controlled, and double-blinded (investigators, veterinarians, and pharmacists). Laboratory. Purpose-bred, 1- to 2-yr-old, 10- to 12-kg beagles. The effects of parenteral L-arginine alone or in combination with N-acetylcysteine were compared with vehicle alone in a well-characterized canine model of Escherichia coli peritonitis. Two doses were studied that delivered approximately 1.5-fold (10 mg x kg(-1) x hr(-1)) and 15-fold (100 mg x kg(-1) x hr(-1)) the L-arginine dose typically administered with standard total parenteral nutrition. Animals in the low- and high-dose L-arginine arms were further randomized to receive vehicle alone or N-acetylcysteine (20 mg x kg(-1) x hr(-1)) as an antioxidant to prevent peroxynitrite formation. The main measurements were hemodynamics, plasma arginine and ornithine, serum nitrate/nitrite, laboratory studies for organ injury, and survival. Both doses of L-arginine similarly increased mortality (p = .02), and worsened shock (p = .001 for reduced mean arterial pressure). These effects were associated with significant increases in plasma arginine (p = .0013) and ornithine (p = .0021). In addition, serum nitrate/nitrite (p = .02), liver enzymes (p = .08), and blood urea nitrogen/creatinine ratios (p = .001) rose, whereas arterial pH (p = .001) and bicarbonate levels (p = .001) fell. N-acetylcysteine did not significantly decrease any of the harmful effects of L-arginine. Thus, parenteral L-arginine monotherapy was markedly harmful in animals with septic shock. These findings suggest that supplemental parenteral L-arginine, at doses above standard dietary practices, should be avoided in critically ill patients with septic shock.

Interleukin‐7 Dose‐Dependently Restores Parenteral Nutrition–Induced Gut‐Associated Lymphoid Tissue Cell Loss but Does Not Improve Intestinal Immunoglobulin A Levels

Without enteral nutrition, the mass and function of gut-associated lymphoid tissue (GALT), a center of systemic mucosal immunity, are reduced. Therefore, new therapeutic methods, designed to preserve mucosal immunity during parenteral nutrition (PN), are needed. Our recent study revealed that exogenous interleukin-7 (IL-7; 1 microg/kg twice a day) restores the GALT cell mass lost during intravenous (IV) PN but does not improve secretory immunoglobulin A (IgA) levels. Herein, we studied the IL-7 dose response to determine the optimal IL-7 dose for recovery of GALT mass and function during IV PN. We hypothesized that a high dose of IL-7 would increase intestinal IgA levels, as well as GALT cell numbers. Male mice (n = 42) were randomized to chow, IL-7-0, IL-7-0.1, IL-7-0.33, IL-7-1 and IL-7-3.3 groups and underwent jugular vein catheter insertion. The IL-7 groups were fed a standard PN solution and received IV injections of normal saline (IL-7-0), 0.1, 0.33, 1, or 3.3 microg/kg of IL-7 twice a day. The chow group was fed chow ad libitum. After 5 days of treatment, the entire small intestine was harvested and lymphocytes were isolated from Peyer's patches (PPs), intraepithelial (IE) spaces, and the lamina propria (LP). The lymphocytes were counted and phenotypes determined by flow cytometry (alphabetaTCR, gammadeltaTCR, CD4, CD8, B cell). IgA levels of small intestinal washings were also examined using ELISA (enzyme-linked immunoabsorbent assay). IL-7 dose-dependently increased total lymphocyte numbers in PPs and the LP. The number of lymphocytes harvested from IE spaces reached a plateau at 1 microg/kg of IL-7. There were no significant differences in any phenotype percentages at any GALT sites among the groups. IgA levels of intestinal washings were significantly higher in the chow group than in any of the IL-7 groups, with similar levels in all IL-7 groups. Exogenous IL-7 dose-dependently reverses PN-induced GALT cell loss, with no major changes in small intestinal IgA levels. IL-7 treatment during PN appears to have beneficial effects on gut immunity, but other therapeutic methods are needed to restore secretory IgA levels.

Assessment of implementation of a standardized parenteral formulation for early nutritional support of very preterm infants

Parenteral nutrition (PN) plays an important role in the nutritional support of very preterm newborns. It has been suggested that a high proportion of PN orders could be standardized. In 2002, we implemented in our unit the preparation of three standardized formulations for PN adapted to the nutritional requirements of premature infants<32 weeks. Following this change of practice, a retrospective observational study was conducted to evaluate the relevance of the implemented standardized PN regime. Twenty premature inborn infants<32 weeks gestation who had received standardized (STD) PN in 2003 were matched for 20 infants who had received individualized (IND) PN in 2001. Adequacy of nutrition was assessed by comparing daily intravenous nutrient intake and biochemical parameters during the first week. Amino-acid intakes on day 3 were higher in the STD group (1.5+/-0.2 g/kg/d vs. 0.9+/-0.5, p<0.001), and the calcium phosphate intakes were better balanced. The cumulated intake of amino acids for the first week was greater in the STD group (+20% ; p=0.0003). Biochemical parameters were similar in both groups. Insulin infusions were less frequent in the STD group (p<0.06). Standardized parenteral formulations provided higher early intakes of amino acid and glucose, a better calcium phosphate ratio, and a greater amount of amino-acid intakes during the first week while maintaining the same biochemical parameters. This strategy forms part of an approach concerning quality control and the respect of good professional practice for the preparation of parenteral nutrition solutions.

Glutamine dipeptide for parenteral nutrition in abdominal surgery: A meta-analysis of randomized controlled trials

To assess the clinical and economical validity of glutamine dipeptide supplemented to parenteral nutrition (PN) in patients undergoing abdominal surgery. A meta-analysis of all the relevant randomized controlled trials (RCTs) was performed. The trials compared the standard PN and PN supplemented with glutamine dipeptide in abdominal surgery. RCTs were identified from the following electronic databases: the Cochrane Library, MEDLINE, EMBASE and ISI web of knowledge (SCI). The search was undertaken in April 2006. Literature references were checked by computer or hand at the same time. Clinical trials were extracted and evaluated by two reviewers independently. Statistical analysis was performed by RevMan4.2 software from Cochrane Collaboration. A P value of < 0.05 was considered statistically significant. Nine RCTs involving 373 patients were included. The combined results showed that glutamine dipeptide has a positive effect in improving postoperative cumulative nitrogen balance (weighted mean difference (WMD = 8.35, 95% CI [2.98, 13.71], P = 0.002), decreasing postoperative infectious morbidity (OR = 0.24, 95% CI [0.06, 0.93], P = 0.04), shortening the length of hospital stay (WMD= -3.55, 95% CI [-5.26, -1.84], P < 0.00001). No serious adverse effects were found. Postoperative PN supplemented with glutamine dipeptide is effective and safe to decrease the infectious rate, reduce the length of hospital stay and improve nitrogen balance in patients undergoing abdominal surgery. Further high quality trials in children and severe patients are required, and mortality and hospital cost should be considered in future RCTs with sufficient size and rigorous design.

Determinants of Insulin Availability in Parenteral Nutrition Solutions

Management of hyperglycemia in patients receiving parenteral nutrition (PN) often includes the addition of regular insulin to the PN solution. A literature review has shown insulin availability in such solutions to range from 10% to 95%. This discrepancy in availability may be due to differences in the composition of the PN solution, the final concentration of insulin, or the assay method used to determine insulin concentrations. The purpose of this study was to evaluate insulin recovery from a standard PN solution used at our medical center. Solutions were manually prepared in our pharmacy according to standard practice. Multivitamins and trace elements were added to 1 of 2 L of solution each day. Each of 3 simulated patients received 2 L of solution per day for 3 consecutive days. Samples from each bottle were drawn at baseline, 1 hour after the start of infusion, and 1 hour before the end of infusion and were subsequently analyzed for immunoreactive insulin levels by radioimmunoassay. Recovery of insulin from solutions containing multivitamins and trace elements was much greater (95%) than from those without (5%). The presence of multivitamins and trace elements is a major determinant of insulin availability in PN solutions. Additional research is necessary to determine the mechanism mediating this effect and to assess its clinical significance.

Effect of low-calorie parenteral nutrition on the incidence and severity of hyperglycemia in surgical patients: A randomized, controlled trial

To determine the effect of a low-calorie parenteral nutrition (PN) regimen on the incidence and severity of hyperglycemia and insulin requirements. Prospective, randomized, clinical trial. Urban, university-affiliated, level-I trauma center. Consecutive surgical patients requiring PN. Patients were randomized to receive either a low-calorie PN formulation (20 nonprotein kilocalories per kg per day) or a standard PN formulation (30 nonprotein kilocalories per kg per day). Lipid-derived calories were standardized to 1000 kilocalories three times weekly for all patients; consequently, the number of calories varied only by the amount of carbohydrate administered. Protein requirements were individualized on the basis of estimated metabolic stress. Hyperglycemia was defined as a blood glucose level > or = 200 mg/dL. Forty patients were evaluated (low-calorie PN, n = 20; standard PN, n = 20). Demographics of the two groups were similar. The incidence of hyperglycemic events was significantly lower in the low-calorie group (0% [0-0.5] vs. 33.1% [0-58.4]; p = .001]. Additionally, the severity of hyperglycemia was also lower in the low-calorie group (mean glucose area under the curve = 118 +/- 22 [mg x hr]/dL vs. 172 +/- 44 [mg x hr]/dL; p < .001). This resulted in lower average daily insulin requirements (0 [0-0] units vs. 10.9 [0-25.6] units; p < .001.). The only predictor of hyperglycemia was a dextrose administration rate >4 mg/kg/min. : Administration of a low-calorie PN formulation resulted in fewer and less-severe hyperglycemic events and lower insulin requirements. PN regimens should not exceed a dextrose administration rate of 4 mg/kg/min to avoid hyperglycemic events.

Olive oil based nutrition in multiple trauma patients: a pilot study

A negative effect of hyperglycemia on clinical outcome has been proposed for patients treated under intensive care conditions. So far, however, the safety and effect of fat based nutrition regimen, especially of olive oil based emulsions, have not been systematically studied. Prospective, open-labeled, randomized, pilot study in a 14-bed surgical intensive care unit. Thirty-three consecutive, severe multiple trauma patients (injury severity score 31.6+/-11.5) were included; 18 (L group) received a parenteral lipid-based nutrition; 15 (G group) were given a standard parenteral glucose-based nutrition. The energy expenditure (EE) showed no difference between groups and no significant difference between the energy intake/EE ratio. The daily mean energy intake was lower in the L group (17.9+/-6.3 kcal/kg) than in the G group (22.3+/-4.2 kcal/kg). Triglycerides and nitrogen balance showed no significant differences between groups. The L group had significantly lower blood glucose (L 7.4+/-1.6, G 8.7+/-1.6 mmol/l), carbon dioxide production, and minute volume and shorter duration of mechanical ventilation (L 13.0+/-8.9, G 20.4+/-7.0 days), and stay in the ICU (L 17.9+/-11.2, G 25.1+/-7.0 days). Our findings suggest a good tolerance, a decrease in blood glucose, clinically relevant shortening of ICU stay, and shorter time on mechanical ventilation for patients treated with olive oil based than with conventional glucose-heavy nutrition.

Effects of perioperative parenteral glutamine-dipeptide supplementation on plasma endotoxin level, plasma endotoxin inactivation capacity and clinical outcome

We evaluated perioperative plasma endotoxin, plasma soluble CD14 molecule (sCD14), plasma endotoxin inactivation capacity (EIC) changes and clinical outcome after glutamine was provided in parenteral feedings to patients on whom gastrointestinal operations were performed using a prospective, randomized, double-blind study design. Forty patients undergoing gastrointestinal operations were randomized into two groups, each had 20 patients. One group received standard parenteral nutrition and the other received the same formulation but supplemented with the dipeptide alanyl-glutamine, the two groups were isonitrogenous. The infusion was started from 1 day before operation to the 3rd day after operation for 5 days. Blood samples were collected on the morning of 1 day before operation, 3h after operation, and on the morning of 1, 4 and 7 days after operation and analyzed for plasma endotoxin level, plasma sCD14 level and EIC. There were no differences between the two groups on plasma endotoxin level. After surgery a rapid reduction in plasma EIC was observed in both groups, a significant restoration of the plasma EIC was observed on the morning of 1 and 4 days after surgery in the study group (0.12+/-0.02 and 0.078+/-0.022 EU/mL, respectively, P < 0.01). A significant rise in plasma sCD14 level was found in the study group on the morning of 1 and 4 days after surgery (14.32+/-1.69 and 10.34+/-1.14 microg/mL, respectively, P < 0.01). Shortened hospital stay was observed in the study group (11.7+/-2.0 days in the control group and 10.6+/-1.2 days on the study group respectively, P = 0.03). Perioperative parenteral nutrition supplemented with dipeptide alanyl-glutamine ameliorated postoperative immunodepression without direct effect on endotoxemia.

Effects of Parenteral Nutrition Supplemented with Alanyl‐Glutamine on Nutrition Status in Rats

Glutamine, a nonessential amino acid, has received increasing attention because it becomes essential during stress and catabolic conditions. Many investigations have shown that during severe stress, the consumption of glutamine exceeds glutamine synthesis, resulting in depletion of glutamine stores. The aim of this study was to evaluate the effects of supplementing parenteral diets with a glutamine-containing dipeptide, L-alanyl-L-glutamine, on rat nutrition status. Male Wistar rats were used. Animals (n = 36) were centrally catheterized and randomly assigned to 1 of the following groups based on method of parenteral nutrition (PN): control group with oral nutrition and IV infusion of a saline solution; standard parenteral nutrition (SPN) group; or alanyl-glutamine-supplemented PN (ALA-GLN PN) group (20 g/L). Parenteral nutrition was isocaloric and isonitrogenous. Infusions were administered at a rate of 2.0 mL/h over 5 days. Nutrition status was assessed by body weight change, plasma proteins, accumulated urinary creatinine, and nitrogen balance. Accumulated urinary creatinine increased significantly after day 4 in the ALA-GLN PN group, compared with the SPN group and the controls. Body weight change significantly differed on day 5 between the ALA-GLN PN and SPN groups. After 3 days, nitrogen balance was significantly lower and nitrogen retention higher in the ALA-GLN PN group when compared with the SPN group. Albumin and transferrin concentrations decreased significantly in the SPN group, but did not differ from the controls in the ALA-GLN PN group. Weight, plasma proteins, urinary accumulated creatinine, and nitrogen retention showed a better evolution in the group supplemented with the glutamine dipeptide when compared with the SPN group. Our results suggest a more suitable nutrition support in animals receiving L-alanyl-L-glutamine.

Parenteral glutamine increases serum heat shock protein 70 in critically ill patients

Heat shock protein 70 (HSP-70) is protective against cellular and tissue injury. Increased serum HSP-70 levels are associated with decreased mortality in trauma patients. Glutamine (Gln) administration increases serum and tissue HSP-70 expression in experimental models of sepsis. Gln has been safely administered to critically ill patients and can improve clinical outcomes, but the effect of Gln administration on HSP-70 expression in humans is unknown. We examined whether Gln-supplemented parenteral nutrition (PN) increases serum HSP-70 levels in critically ill patients. Randomized, controlled, double-blind study in surgical intensive care units (SICU) in a university hospital. 29 patients admitted to the SICU and requiring PN for more than 7 days. Patients received either Gln-PN (containing alanyl-glutamine dipeptide; 0.5 g/kg per day; n=15) or standard Gln-free PN (control-PN) that was iso-nitrogenous to Gln-PN (n=14). Serum HSP-70 concentrations were measured at enrollment and at 7 days. Clinical outcome measures were also determined. HSP-70 concentrations were unchanged in control-PN subjects from baseline to day 7. In marked contrast, Gln-PN subjects demonstrated significantly higher (3.7-fold) serum HSP-70 concentrations than control subjects. In Gln-PN patients there was a significant correlation between increases in HSP-70 levels over baseline and decrease in ICU length of stay. Gln-PN significantly increases serum HSP-70 in critically ill patients. The magnitude of HSP-70 enhancement in Gln-treated patients was correlated with improved clinical outcomes. These data indicate the need for larger, randomized trials of the Gln effect on serum and tissue HSP-70 expression in critical illness and relationship to clinical outcomes.

Practical aspects of multichamber bags for total parenteral nutrition

Ready-to-use all-in-one admixtures are standards for short and long-term parenteral nutrition. Their limited stability does not allow storage over prolonged periods of time. Multichamber bags represent industrially manufactured near complete standard parenteral nutrition premixes with extended shelf lives. This review focuses on the characterization of multichamber bags, their influence on parenteral nutrition practice, the need for individual parenteral nutrition compounding, and the role of the pharmacist in the nutrition team. The all-in-one admixture concept, its correlation with parenteral nutrition effectiveness, safety, and pharmaceutical issues are reviewed. Multichamber bags, the bag material, their use and practical handling are addressed. Newly developed container materials are mainly responsible for the increased stability of multichamber bag parenteral nutrition premixes. Multichamber bags are used for (standard) parenteral nutrition in adults. Multichamber bags cannot eliminate individualized all-in-one parenteral nutrition compounding. Pharmaceutical assistance with expertise in compatibility and stability is mandatory for the nutrition team to implement and control good parenteral nutrition practices, e.g. to convert multichamber bags into complete ready-to-use all-in-one admixtures or to compound individualized regimens. The incorporation of additional components into parenteral nutrition admixtures (pharmaconutrients, drugs) must rely on documented compatibility with the parenteral nutrition admixtures. Multichamber bags have their advantages and limitations. Studies on the effectiveness and costs of multichamber bags are needed to meet the expectations of pharmacists, physicians, nurses, and industry for optimal parenteral nutrition in patients.

Parenteral nutrition with standard solutions in paediatric intensive care patients

Paediatric intensive care patients often require parenteral nutrition (PN). Only very few standard mixtures are available for infants and children. Individual PN solutions need to be compounded manually on the ward, if preparation by the hospital pharmacy is not feasible. Since manual compounding is associated with a greater risk of compounding errors and microbial contamination, the use of standard solutions might be a preferable alternative. We evaluated the use of standard solutions on the paediatric intensive care unit of the von Hauner Children's Hospital at the University of Munich over a period of 8 months. PN solutions were either prescribed individually or as standard solutions. We evaluated the frequency of standard solution prescriptions and their modification, compared nutrient intakes with standard vs. individual PN solutions as well as the occurrence of laboratory anomalies. Standard PN solutions were prescribed in 68% of cases, individual PN solutions in 32%. Modifications of standard PN solutions were performed in 54%. The intake of a number of macronutrients and electrolytes was similar with individual and standard PN, but calcium and phosphate intakes were lower with individual total PN. Electrolyte imbalances occurred slightly more often with individual PN than with standard PN (34% vs. 26%, respectively). Standard PN solutions were used in the majority of patients on a paediatric intensive care unit. We did not detect indications for inadequacy of standard solutions in the majority of patients reviewed.

Parenteral vs. enteral nutrition in the critically ill patient: a meta-analysis of trials using the intention to treat principle

Controversy surrounds the use of parenteral nutrition in critical illness. Previous overviews used composite scales to identify high-quality trials, which may mask important differences in true methodological quality. Using a component-based approach this meta-analysis investigated the effect of trial quality on overall conclusions reached when standard enteral nutrition is compared to standard parenteral nutrition in critically ill patients. An extensive literature search was undertaken to identify all eligible trials. We retrieved 465 publications, and 11 qualified for inclusion. Nine trials presented complete follow-up, allowing the conduct of an intention to treat analysis. Aggregation revealed a mortality benefit in favour of parenteral nutrition, with no heterogeneity. A priori specified subgroup analysis demonstrated the presence of a potentially important treatment-subgroup interaction between studies of parenteral vs. early enteral nutrition compared to parenteral vs. late enteral. Six trials with complete follow-up reported infectious complications. Infectious complications were increased with parenteral use. The I(2) measure of heterogeneity was 37.7%. Intention to treat trials demonstrated reduced mortality associated with parenteral nutrition use. A priori subgroup analysis attributed this reduction to trials comparing parenteral to delayed enteral nutrition. Despite an association with increased infectious complications, a grade B+ evidence-based recommendation (level II trials, no heterogeneity) can be generated for parenteral nutrition use in patients in whom enteral nutrition cannot be initiated within 24 h of ICU admission or injury.

Perioperative administration of parenteral fish oil supplements in a routine clinical setting improves patient outcome after major abdominal surgery

Background & aims: It is hypothesized that provision of pre- and/or postoperative omega-3 fatty acids to surgical patients in clinical routine improves clinical outcome. Methods: Retrospective evaluation of a 2-year-longitudinal data base of ICU patients (n=249) elected for major abdominal surgery. Group I (n=110): postoperative standard parenteral nutrition (1.2g amino acids, 0.3g glutamine dipeptide, 0.6g lipids, 4g/kg glucose; energy ratio glucose to lipid 2:1); group II (n=86): part of postoperative lipid emulsion replaced by fish oil; group III (n=53): in addition 2–3 days preoperative fish oil supplementation (max. 100ml/d). Results: A decrease in mortality was observed in group III compared to group I (P=0.02). The number of patients requiring mechanical ventilation was lower with perioperative fish oil (n=34 in groups I and II. 10 in III, P<0.05). The number of days in ICU was not different (group I: 7.6 days, group II: 7.0, group III: 7.3), the length of hospital stay was shorter in group I (group I: 29.2 days, group II: 24.9, group III: 22.2, P<0.05 vs I). Conclusions: In a retrospective evaluation, perioperative provision of parenteral fish oil (ca. 10g/day) beneficially influences patient outcome probably by modulating the immune response.

Randomized, double-blind, controlled study of glycyl-glutamine-dipeptide in the parenteral nutrition of patients with acute leukemia undergoing intensive chemotherapy

Objective Glutamine has stimulatory effects on lymphocytes and mucosa cells in vitro and, when given with parenteral nutrition, has been shown to improve the clinical course of patients after bone marrow transplantation and in the critically ill. This study investigated the clinical and immunologic effects of parenteral glycyl-glutamine supplementation in patients with acute leukemia receiving intensive conventional chemotherapy without bone marrow transplantation. Methods A randomized, double-blind, controlled study compared a standard glutamine-free parenteral nutrition with a glycyl-glutamine–supplemented parenteral nutrition (Glamin, Baxter, Erlangen, Germany) containing 20 g of glutamine in adult patients with acute myeloid leukemia undergoing myelosuppressive chemotherapy. Clinical end points included the duration of neutropenia and the incidence and duration of neutropenic fever. To analyze the effects of glutamine on immunocompetent cells, CD4 + and CD8 + T cells and HLA-DR expression on monocytes were assessed by flow cytometry throughout the treatment course. Results Fifty-four adult patients entered the study and were randomized. In 45 of 127 chemotherapy cycles, parenteral nutrition was given, and 40 cycles (20 with and 20 without glutamine) were evaluated for comparison. The median durations of neutropenia were 18 d (range, 9–29 d) in the glutamine group and 22.5 d (range, 13–48 d) in the control group ( P = 0.052), whereas the median durations of neutropenic fever were 5.5 d (range, 0–13 d) and 5 d (range, 0–31 d), respectively ( P = 0.74). Using Kaplan-Meier analysis and controlling for the type of chemotherapy, we found a significantly faster neutrophil recovery in patients receiving glutamine than in the control group ( P = 0.040) in patients receiving a high-dose cytarabine regimen. There was no significant difference in the recovery of CD4 + or CD8 + lymphocytes or monocyte activation between groups. Conclusion In patients with acute myeloid leukemia requiring parenteral nutrition, glycyl-glutamine supplementation could hasten neutrophil recovery after intensive myelosuppressive chemotherapy. However, no impact of glutamine on neutropenic fever or other criteria of immunologic recovery was detected.

Glutamine supplemented parenteral nutrition prevents intestinal ischemia- reperfusion injury in rats.

To examine whether glutamine prevents the injury to the intestinal mucosa after intestinal ischemia-reperfusion (I/R) in rats. Thirty male Sprague-Dawley rats were randomly divided into 3 groups: a standard parenteral nutrition (PN) group (n = 10); an I/R-PN group (n = 10); an I/R-glutamine enriched PN (I/R-Gln) group (n = 10). The superior mesenteric artery (SMA) was clamped. After 60 min of ischemia, reperfusion was initiated and infusion was started. All rats received isocaloric and isonitrogenous nutritional support for 48 h. Spleen, liver, mesenteric lymph nodes (MLN), and intestinal segments were removed for morphological and biochemical analyses, and blood samples were collected for bacterial culture and measurement of endotoxin levels. The permeability of intestinal mucosa was assayed by measurement of D-(-)-lactate levels in plasma. In I/R-PN group, extensive epithelial atrophy was observed, mucosal thickness, villous height, crypt depth and villous surface area were decreased significantly compared with PN group, whereas these findings did not occur in the I/R-Gln group. The incidence of intestinal bacterial translocation to spleen, liver, MLN, and blood was significantly higher in I/R-PN group than that in other groups. Plasma endotoxin levels significantly increased in the I/R-PN group compared with the I/R-Gln group. Remarkably higher values of D-(-)-lactate were also detected in PN group compared with that in I/R-Gln group. Glutamine protects the morphology and function of intestinal mucosa from injury after I/R in rats.

4-Hydroxynonenal is Markedly Higher in Patients on a Standard Long-term Home Parenteral Nutrition

Parenteral nutrition, a commonly used procedure in patients with gastrointestinal disorders, may lead with time to liver steatosis and fibrosis, whose pathogenesis has yet to be elucidated. Oxidative stress and particularly lipid peroxidation likely contribute to the expression of such hepatobiliary complications, by means of their recognized proinflammatory and profibrogenic effects. To evaluate the adequacy against oxidative insult of a standard micronutrient supplementation in patients under long term parenteral nutrition, a comprehensive patterns of redox indices has been determined on peripheral blood samples from forty one adults in comparison to fifty eight blood donors taken as controls. A sustained oxidative stress in peripheral blood of home parenteral patients was observed. Of the two lipid peroxidation markers found to be markedly increased, namely fluorescent plasma protein adducts with malondialdehyde and 4-hydroxynonenal, respectively, only the second was statistically correlated with all the antioxidant-related changes consistently detected in the patients, namely decreased plasma α-tocopherol and selenium intake and higher erythrocyte oxidized glutathione.Plasma level of 4-hydroxynonenal-protein adducts appears to be a reliable and easily measurable marker of oxidative status, particularly indicated to monitor the adequacy of dietary regimen during parenteral nutrition.

A Randomized, Controlled Trial of Parenteral Glutamine in Ill, Very Low Birth‐weight Neonates

ABSTRACTObjectiveThe role of “novel substrates” in neonatal nutrition has generated much interest in recent years. Glutamine has been recognized as a “conditionally essential” amino acid in critically ill adults, particularly for gut and immune function; however, its potential role in the neonate remains unclear. The authors examined the safety and benefits of parenteral glutamine in ill, preterm neonates.DesignRandomized controlled trial.MethodsThirty‐five ill preterm neonates of &lt;1000 g birth‐weight were randomized to receive either glutamine‐supplemented parenteral nutrition (PN) (n = 17) or standard PN (n = 18).ResultsThere were no significant differences in birth‐weight, gestational age, male‐to‐female ratio, or Clinical Risk Index for Babies (CRIB) score between the two groups. During PN there were no significant differences between the groups in white cell count, differential white cell count, blood urea nitrogen, plasma ammonia, lactate, pyruvate, plasma glutamine, or glutamate. The median time to achieving full enteral nutrition (FEN) was shorter in the study group (13 days vs. 21 days, P &lt; 0.05). The number of episodes of culture‐positive sepsis or age at discharge did not differ between groups.ConclusionsParenteral glutamine appears to be well tolerated and safe in the ill, preterm neonate. It may reduce the time to achieving FEN.

Perioperative administration of parenteral fish oil supplements in a routine clinical setting improves patient outcome after major abdominal surgery

Background & aims: It is hypothesized that provision of pre- and/or postoperative omega-3 fatty acids to surgical patients in clinical routine improves clinical outcome. Methods: Retrospective evaluation of a 2-year-longitudinal data base of ICU patients ( n=249) elected for major abdominal surgery. Group I ( n=110): postoperative standard parenteral nutrition (1.2 g amino acids, 0.3 g glutamine dipeptide, 0.6 g lipids, 4 g/kg glucose; energy ratio glucose to lipid 2:1); group II ( n=86): part of postoperative lipid emulsion replaced by fish oil; group III ( n=53): in addition 2–3 days preoperative fish oil supplementation (max. 100 ml/d). Results: A decrease in mortality was observed in group III compared to group I ( P=0.02). The number of patients requiring mechanical ventilation was lower with perioperative fish oil ( n=34 in groups I and II. 10 in III, P<0.05). The number of days in ICU was not different (group I: 7.6 days, group II: 7.0, group III: 7.3), the length of hospital stay was shorter in group I (group I: 29.2 days, group II: 24.9, group III: 22.2, P<0.05 vs I). Conclusions: In a retrospective evaluation, perioperative provision of parenteral fish oil (ca. 10 g/day) beneficially influences patient outcome probably by modulating the immune response.

Parenteral nutrition in infants and children.

Parenteral nutrition (PN) came of age in 1964 with the demonstration that beagle puppies could be nourished successfully from 12 weeks of age to maturity by providing all nutrients intravenously (1). The first total parenteral nutrition of an infant with extreme short bowel syndrome followed in 1967 (1). Since them many lessons have been learned as a result of complications of PN. These have included nutrient deficiencies and excesses, infections, complications of inadequate or excessive energy and protein intake, liver disease, and toxicities from product contamination. Our patients have paid the price for these lessons, but fortunately improved survival has also resulted. These incidents have reinforced to us the physicians the axiom that “good judgment comes from experience . . . and experience comes from bad judgment.” (2). Along the way we have learned much about nutrition, infection, liver pathophysiology, and child development (e.g., yes, infants really can “unlearn” how to suck and swallow). Have we learned so much that administration of PN can now be placed on autopilot? The question posed to the authors when this review was solicited was whether the art and science of PN had reached the stage where administration could be treated as a routine clinical algorithm such as diarrhea or croup. Do we only need to check the weight, calculate the administration rate and check the box next to “Standard Child Solution” on the PN pharmacy order sheet? Is there really anything new in PN? Our immediate reaction was to take offense, feel hurt, and shake our heads in disbelief that anyone could be so foolish as to think such things. However, as we thought about it, we realized that the question is pertinent and perceptive. Like the clinical pathways set out for common illnesses such as diarrhea and croup, the question is not so much how to follow the roadmap but rather, when not to follow it. Thus, our review will focus on two areas: 1) Common misconceptions surrounding the use of PN; and 2) When should “standard PN” (i.e., checking the weight and the box on the order sheet) not be used. These questions have lead us to review recent developments in PN (in the past 5–7 years). Whenever possible we will take an evidenced-based approach to the data. Unless specified, the studies we will discuss were carried out in pediatric patients. The risk of any review is that it is old hat to some and very new to others. We have done our best to strike a middle ground. Because it could be a subject unto itself, we will not review PN-associated cholestasis, although when pertinent, some comments will be made.