Days Of Total Parenteral Nutrition Research Articles

The Impact of Health Care Restructuring on Nosocomially Acquired Blood Stream Infections

To assess the impact of the health care restructuring, which occurred in Alberta in 1995, on the occurrence of nosocomial blood stream infection and risk factors for these infections at the University of Alberta Hospital. Changes in patient population, hospital bed numbers, admissions and hospital days for 1993 and 1994 (1993/94) were compared with those for 1996 and 1997(1996/97). Central venous catheter (CVC) use in intensive care units (ICU), days of total parenteral nutrition (TPN) and hemodialysis were compared for the two time periods. Prospectively collected data obtained by monitoring blood culture results on nosocomial blood stream infections in 1993/94 were compared with those obtained in 1996/97. Hospital bed number fell by 10% between 1993/94 and 1996/97. Annual admissions fell by 19% and patient days by 17%. Some services markedly increased patient days (neurosurgery 49%, nephrology 30%, orthopedic surgery 24%), and others markedly reduced patient days (obstetrics and gynecology 99%, ophthalmology 100%, adult medicine 41%, general paediatrics 38%). ICU use of CVCs increased by 41%, TPN days increased by 25% and hemodialysis runs increased by 9%. Annual nosocomial blood stream infections increased by 31% and the annual rate per 10,000 patient days increased by 60%. TPN-related blood stream infection rates and ICU CVC infection rates did not change from 1993/94 to 1996/97. Hospital restructuring has been associated with a 31% increase in nosocomial blood stream infection number and a 60% increase in rate. The increase has been associated with a change in patient populations and increases in risk factors for blood stream infection.

A Randomized Trial of 72- Versus 24-Hour Intravenous Tubing Set Changes in Newborns Receiving Lipid Therapy

To compare the microbial contamination rate of infusate in the intravenous tubing of newborns receiving lipid therapy, replacing the intravenous delivery system at 72-hour versus 24-hour intervals. Infants requiring intravenous lipid therapy were randomly assigned to have intravenous sets changed on a 72- or a 24-hour schedule, in a 3:1 ratio, in order to compare the infusate contamination rates in an equivalent number of tubing sets. A 35-bed, teaching, referral, neonatal intensive-care unit (NICU). All neonates admitted to the NICU for whom intravenous lipid was ordered. Patients were randomized in pharmacy, on receipt of the order for intravenous lipid therapy, to either 72- or 24-hour administration set changes, and followed until 1 week after discontinuation of lipids or discharge from the NICU. Microbial contamination of the infusate was assessed in both groups at the time of administration set changes. Contamination rates were analyzed separately for the lipid and amino acid-glucose tubing sets. Patient charts were reviewed for clinical and epidemiological data, including birth weight, gestational age, gender, age at start of lipid therapy, duration of parenteral nutrition, and type of intravenous access. During the study period, 1,101 and 1,112 sets were sampled in the 72- and 24-hour groups, respectively. Microbial contamination rates were higher in the 72-hour group than the 24-hour group for lipid infusions (39/1,101 [3.54%] vs 15/1,112 [1.35%]; P=.001) and for amino acid infusions (12/1,093 [1.10%] vs 4/1,103 [0.36%]; P=.076). Logistic regression analysis controlling for birth weight, gestational age, and type of venous access showed that only the tubing change interval was significantly associated with lipid set contaminations (odds ratio, 2.69; P=.0013). The rate of blood cultures ordered was higher in the 72- versus the 24-hour group (6.11 vs 4.99 per 100 patient days of total parenteral nutrition; P=.017), and a higher proportion of infants randomized to the 72-hour group died (8% vs 4%; P=.05), although the excess deaths could not clearly be attributed to bacteremia. Microbial contamination of infusion sets is significantly more frequent with 72- than with 24-hour set changes in neonates receiving lipid solutions. This may be associated with an increased mortality rate.

Total parenteral nutrition and tumor growth in malnourished patients with gastric cancer.

Evidence that total parenteral nutrition (TPN) can stimulate tumor growth in humans is scanty and contradictory. The purpose of this study was to evaluate the impact of TPN on tumor cell proliferation in malnourished patients receiving preoperative TPN. We evaluated variations in the S-phase cell fraction, defined as 3H-thymidine labeling index (TLI), before and after 10 days of TPN or non-administration of nutritional support in 19 malnourished patients (weight loss, > or = 10%) with gastric cancer. TLI was determined on endoscopic biopsies at the time of diagnosis, and subsequently on the operative specimen or through intraoperative sampling. At diagnosis, a higher median TLI value was observed in the control than in the TPN group. Administration of TPN enhanced tumor cell proliferation in 50% of patients; however, at surgery there was no difference in the median TLI value of the two groups. The TPN regimen seems to be associated with increased tumor cell proliferation, even though this stimulating effect was moderate and at surgery the TLIs of TPN patients and controls were not different. Although the potential stimulation probably has little consequence for patients receiving short-term preoperative nutrition, it may call for further investigation in cancer patients undergoing long-term home TPN.

Oral and Parenteral Glutamine in Bone Marrow Transplantation: A Randomized, Double‐Blind Study

Total parenteral nutrition (TPN) supplemented with glutamine (GLN) has been reported to be effective for patients with bone marrow transplantation (BMT). Our aim was to evaluate enteral and parenteral glutamine in patients undergoing BMT. For evaluation of GLN in BMT, 66 patients with 43 hematologic and 23 solid malignancies (21 breast carcinomas), were randomized, double-blinded, to either oral GLN (n = 35) or glycine-control (GLY) (n = 31), 10 g three times daily. When TPN became necessary, patients who received GLN orally were given TPN with GLN (0.57 g/kg). Those who received GLY received standard TPN, isocaloric and isonitrogenous. Patients with hematologic malignancies received high-dose chemotherapy, total body irradiation, and either allogeneic (ALLO) BMT (n = 18) or autologous (AUTO) stem cell transplantation (n = 25). Patients with solid malignancies (n = 23) received AUTO. There were 14 in-hospital deaths without relationship to GLN administration. For respective comparisons of ALLO and AUTO transplants in the GLN and GLY hematologic groups and AUTO in the solid tumor groups, there were no significant differences in hospital stay, duration of stay after BMT, TPN days, neutrophil recovery >500/mm3, incidence of positive blood cultures, sepsis, mucositis, and diarrhea. Acute graft us host disease occurred in 1 of 10 hematologic patients receiving GLN and in 3 of 8 patients receiving GLY placebo (p > .05). Possible reduction in need for TPN and a suggestion of improved long-term survival were associated with GLN. Oral and parenteral GLN seemed to be of limited benefit for patients having AUTO or ALLO BMT for hematologic or solid malignancies. Further study of long-term effects of GLN in BMT seems warranted.

Hepatic and muscle glucose metabolism during total parenteral nutrition: impact of infection.

We examined the impact of infection on hepatic and muscle glucose metabolism in dogs adapted to chronic total parenteral nutrition (TPN). Studies were done in five conscious chronically catheterized dogs, in which sampling (artery, portal and hepatic vein, and iliac vein), infusion catheters (inferior vena cava), and Transonic flow probes (hepatic artery, portal vein, and iliac artery) were implanted. Fourteen days after surgery, dogs were placed on TPN. After 5 days of TPN, an infection was induced, and the TPN was continued. The balance of substrates across the liver and limb was assessed on the day before infection (day 0) and 18 (day 1) and 42 h (day 2) after infection. On day 0, the liver was a marked net consumer of glucose (4.3 +/- 0.6 mg. kg-1. min-1) despite near normoglycemia (117 +/- 5 mg/dl) and only mild hyperinsulinemia (16 +/- 2 microU/ml). In addition, the majority (79 +/- 13%) of the glucose taken up by the liver was released as lactate (34 +/- 6 micromol. kg-1. min-1). After infection, net hepatic glucose uptake decreased markedly on day 1 (1.6 +/- 0.9 mg. kg-1. min-1) and remained suppressed on day 2 (2.4 +/- 0.5 mg. kg-1. min-1). Net hepatic lactate output also decreased on days 1 and 2 (15 +/- 5 and 12 +/- 3 micromol. kg-1. min-1, respectively). This occurred despite increases in arterial plasma glucose on days 1 and 2 (135 +/- 9 and 144 +/- 9 mg/dl, respectively) and insulin levels on days 1 and 2 (57 +/- 14 and 34 +/- 9 microU/ml, respectively). In summary, the liver undergoes a profound adaptation to TPN, making it a major site of glucose disposal and conversion to lactate. Infection impairs hepatic glucose uptake, forcing TPN-derived glucose to be removed by peripheral tissues.

Retinol and retinyl ester concentrations in rat tissues during total parenteral nutrition

We have previously observed that continuous total parenteral nutrition (TPN) that supplies retinyl palmitate induces a strong decrease of the circulating retinol, which is associated with an impaired hepatic production of retinol-binding protein. We have investigated the effect of 7 days of TPN on the retinol and retinyl ester concentrations in rat tissues, relative to the vitamin A status [ n = 30 for vitamin A-sufficient (A +) and n = 30 for deficient (A −)]. Rats were cannulated for intravenous feeding ( n = 12 for TPN-A +, n = 12 for TPN-A −) and were compared with their per os pair-fed counterparts ( n = 12 for O-A + and n = 12 for O-A −). Retinol and retinoic acid in serum and retinol and retinyl ester concentrations in liver, kidney, lung, heart, and testis were measured by high performance liquid chromatography. TPN induced a dramatic decrease in circulating retinol of A + rats, whereas retinoic acid concentration in serum was unchanged. When TPN was given to A − rats, retinol concentration in serum remained low. Lower retinol and retinyl ester concentrations were measured in the livers of TPN rats compared with orally pair-fed rats, no matter the initial vitamin A status ( P < 0.02 for A + and P < 0.01 for A −). By contrast, in extrahepatic tissues, retinol and retinyl ester concentrations were similar in TPN rats compared with orally pair-fed rats. Our results indicate that TPN induced a decrease of retinol in serum and retinyl esters in liver. However, TPN was able to maintain retinol and retinyl ester concentrations in extrahepatic tissues of vitamin A-sufficient rats and to restore retinol and retinyl ester concentrations in extrahepatic tissues of vitamin A-deficient rats, albeit a low circulating retinol.

Nutritional support of the cancer patient.

Malnutrition, a common problem in cancer patients, adversely affects survival and quality of life. It results from several factors that alter nutritional intake and cause massive metabolic disturbances. Anticancer therapies may compound the malnutrition. Optimal nutrition improves therapeutic modalities and the clinical course and outcome. Oral nutrition should be used whenever possible; in patients unable to ingest adequate amounts orally, enteral and parenteral feedings are safe and effective.

Tumor growth inhibition and nutritional effect of D-amino acid solution in AH109A hepatoma-bearing rats.

We examined the inhibitional and nutritional effects of total parenteral nutrition (TPN) containing D-amino acids (D-phenylalanine, D-Phe; D-valine, D-Val; D-leucine, D-Leu; D-methionine, D-Met) on tumor growth in AH109A hepatoma-bearing rats. Five experimental groups were examined: a control amino acid solution group (control group), D-Phe group, D-Val group, D-Leu group and D-Met group. The analysis of tumor volume and weight revealed significant tumor growth inhibition in the D-Val group as compared with the control group. In the D-Val group, decreases of DNA and protein contents in the tumor tissues were also observed. The D-Leu and D-Met groups showed a tendency toward tumor growth inhibition. The protein content in the liver tissues of these two groups was significantly higher as compared with the control group. The DNA content in the liver tissue was also significantly higher in the D-Met group. The body weight including the tumor (on the final day of TPN) was significantly lower in the D-Val group as compared with the control group, but there was no significant difference in the groups for body weights not including tumors (carcass body weight). The hematocrit and hemoglobin values, indicators of anemia, were significantly higher in the D-Val group as compared with the control group. From these results, regarding tumor growth inhibition, the D-Val solution had the strongest inhibitory effect with no negative influence on the host, and improvement of nutritional status was also suggested in the rats that received the D-Leu or D-Met solutions.

Total parenteral nutrition influences both endocrine and exocrine function of rat pancreas.

The aim of this study was to examine the effect of total parenteral nutrition (TPN) on the endocrine and exocine function of the pancreas. Endocrine function was investigated using an intravenous glucose tolerance test (IGTT) in rats with TPN for 7 or 14 days. Exocrine function was evaluated by measuring amylase secretion from isolated acini as well as pancreatic weight, water content, protein, and enzymes after 7 days of TPN. When the TPN rats were compared with the controls, the glucose tolerance curve after an IGTT was unchanged, the basal plasma insulin levels were slightly lower and the insulin secretory response to intravenous glucose was markedly impaired. No differences could be seen between the insulin response after 7 days and that after 14 days of TPN. The weight of pancreas, the total content and concentration of pancreatic protein, and the total amylase content of the pancreas were lower, whereas the total content of both chymotrypsin and trypsin was higher. The concentration of DNA remained intact, whereas the total DNA content decreased. The levels of lipolytic enzymes, except for carboxylesterlipase, were unaffected. After TPN treatment, the insulin secretory response to glucose is impaired, the exocrine pancreas is hypoplastic and the storage pattern of pancreatic exocrine enzymes is altered.

Effect of medium-chain triglyceride emulsion in total parenteral nutrition on experimental hepatic metastasis in the rat.

This study evaluated the effect of total parenteral nutrition (TPN) regimens containing a medium-chain triglyceride (MCT) emulsion on tumor metastasis. Tumor metastasis development was assessed by the number of metastatic foci on the liver surface in rats inoculated with ACL-15 tumor cells via the portal vein. Rats received one of the following TPN regimens: TPN containing an MCT emulsion (group M), in which tricaprylin emulsion served as the MCT and comprised 50% of nonprotein calories (NPC); TPN containing a long-chain triglyceride (LCT) emulsion (group L), in which soybean oil served as the LCT and comprised 50% of NPC; and TPN without lipid emulsion (group G), in which dextrose comprised 100% of NPC. The number of metastatic foci was greatest in rats receiving TPN containing the MCT emulsion on day 11 after tumor cell inoculation and either 11 days of TPN or 2 days of TPN followed by 9 days standard rat chow. TPN containing MCT emulsion increases liver metastasis early in its administration.

Recovery of gut-associated lymphoid tissue and upper respiratory tract immunity after parenteral nutrition.

The authors characterize the recovery of parenteral nutrition-induced changes in gut-associated lymphoid tissue (GALT) and upper respiratory tract immunity with enteral nutrition and provide further information defining the effects of enteral feeding on mucosal immunity. The small intestine plays a prominent role in development and maintenance of mucosal immunity, both intestinal and extraintestinal, primarily through immunoglobulin A (IgA)-mediated mechanisms. Prior research has shown that mice fed total parenteral nutrition (TPN) have reduced GALT T and B cells, the cells responsible for IgA production, as well as impaired upper respiratory tract immunity to viral challenge of previously immunized animals. The recovery of TPN-induced changes in GALT and upper respiratory tract immunity after enteral refeeding is studied. Male institute of Cancer Research mice received 5 days of TPN followed by 0 to 4 days of chow. Small intestinal GALT was characterized by flow cytometry. In a second experiment, animals were immunized intranasally with moused-adapted influenza virus. Three weeks later, one group received a 5-day course of TPN followed by enteral refeeding for 5 days. A second group received TPN alone. Both groups were challenged with intranasal virus and killed 40 hours postchallenge to determine viral shedding from the upper respiratory tract. Animals fed TPN only had significantly fewer GALT lymphocytes compared with those chow-fed control subjects. Peyer's patch counts increased after a single day of refeeding, returning to normal levels by 48 hours. Lamina propria counts remained significantly depressed after 24 hours of refeeding, but also returned to normal after 48 hours of refeeding. The T-cell and B-cell populations mimicked total cell patterns. Lamina propria CD4+/CD8+ ratio returned to normal only after 72 hours of refeeding. None of the 9 animals refed enterally for 5 days were positive for viral shedding, compared with 8 of 12 matched TPN-fed animals. Enteral refeeding after TPN is associated with rapid repletion of GALT cellularity, initially within Peyer's patches and subsequently within the lamina propria. Refeeding corrects the impairment of IgA-mediated upper respiratory tract antiviral immunity occurring with TPN administration. This work further enhances the authors' knowledge of the underlying immunologic differences influenced by routes of nutrition.

Reprioritization of liver protein synthesis resulting from recombinant human growth hormone supplementation in parenterally fed trauma patients: the effect of growth hormone on the acute-phase response.

One of the major components of the metabolic response to severe trauma is the alteration in concentrations of a large number of plasma proteins referred to as acute-phase proteins (APP). The principle mediators of these liver-synthesized APP are mainly the cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). We have measured the plasma levels of IL-6, TNF alpha, and 20 APP in 24 adult, severely injured, hypermetabolic and highly catabolic patients with multiple injuries within 48-60 hours after injury, when they were receiving maintenance fluids without calories or nitrogen, and subsequently during 7 days of total parenteral nutrition with (n = 12) or without (n = 12) recombinant human growth hormone supplementation (rhGH, 0.15 mg/kg/d). Baseline positive APP due to severe trauma include C-reactive protein (CRP), alpha-1 antichymotrypsin, alpha-1 acid glycoprotein, alpha-1 antitrypsin, fibronectin, and factor B. Negative APP include IgG, IgM, complement-3, prealbumin, transferrin, ceruloplasmin, and albumin. Except for CRP, alpha-1 antichymotrypsin, and albumin, all the APP levels increase during 7 days of nutritional support. Plasma levels of cytokines IL-6 and TNF-alpha, although initially markedly increased after injury, decrease with parenteral refeeding. There is a linear correlation between CRP and IL-6 levels and also between the transport proteins prealbumin and transferrin. Trauma-induced increases in CRP and IL-6 levels decreased with nutrition alone, but did not change with rhGH supplementation. An immunosuppressed state of injury is evident from the decreased immunoglobulin levels (IgG, IgM, IgA) in the trauma patients. Total parenteral nutrition alone increases the immunoglobulin levels to normal. However, with adjuvant rhGH, only IgA levels are normalized. Adjuvant rhGH therapy does not attenuate the reprioritization of acute liver protein synthesis and results in only limited restoration of host defenses. The clinical implications of these findings await further study.

TOTAL PARENTERAL NUTRITION WITH OR WITHOUT LIPIDS INDUCES AN OXIDATIVE STRESS IN RAT LIVERS.

Introduction: Total Parenteral Nutrition (TPN)-associated cholestasis pathophysiology remains unclear. The role of specific components of TPN solution have been studied. We have previously demonstrated that both amino acids and lipids can induce a cholestasis in a rat model and that S-adenosyl-methionine can prevent this complication. The aim of this study was to further investigate the liver oxidative stress induced by TPN. Material and methods: 18 rats were divided in 3 groups. Gr D/aa received a TPN composed by dextrose (D) and aa, as Gr D/aa/L was added with lipids (L). Both groups were compared to weight matched controls (C), receiving D IV and chow orally. On TPN, Gr D/aa received 10.2 g of D and 3.4 g of aa daily, as Gr D/aa/L received 6.8 g of D, 3.4 g of aa and 1.5 g of L with the aim to maintain a constant caloric intake of 50 Kcal/day. After 5 days of TPN, rats were anaesthetised and bile collected during 2 hours. After that, they were sacrificed and their liver rapidly removed to prepare homogenates, in which Glutathione (GSH), Thiobarbituric acid-reactive peroxide (TBARS) and carbonylated proteins (CO-prot) were measured to test the level of oxidative stress. Blood levels of SGOT and g-GT were also determined. Statistics was made using ANOVA. Results: Both groups were not different for weight at the beginning of TPN (Gr D/aa: 210±14 g;Gr D/aa/L: 194±5 g). After TPN, both groups lost ≅ 5% of weight and remained similar. Liver weight was also not different (respectively 7.1±0.1 vs 7.7±0.3 g). Results: Table Furthermore, Transaminases were significantly increased in both TPN-groups, but not g-GT. Conclusions: TPN with or without lipids induced an oxidative stress, which is not related to GSH content. Even if bile flow was decreased by TPN, oxidative stress was not directly related to bile flow. However, the liver injury was confirmed by a biological significant increase of cytolysis.

Safety and efficacy of total parenteral nutrition delivered via a peripherally inserted central venous catheter.

Central venous catheters for total parenteral nutrition (TPN) have traditionally been inserted via direct cannulation of the subclavian vein, but this technique requires physician participation and is associated with well-described complications. We report the single largest institutional experience with peripherally inserted central venous catheters (PICC lines) used exclusively for TPN in non-intensive care unit patients. From July 1991 to March 1994, 135 PICC lines were placed in 126 patients via the antecubital vein, advanced into the central venous system, and used only for TPN. Complication rates were determined and compared with those for TPN administered through a subclavian vein-inserted central catheter. Patient demographics were similar in each group with respect to age, type of disease process, acuity of illness, and indications for nutrition support. A cumulative number of 1381 TPN days (mean = 11 days per patient) comprised the PICC line experience. Comparison was made with 135 successive standard (subclavian) central lines inserted in 105 patients for TPN administration (1056 TPN days, mean = 10 days per patient). There was no difference in the overall rate of complications between the two groups. There were no major complications that prolonged hospitalization (eg, catheter-related sepsis or pneumothorax) in the PICC group compared with three such complications in the standard group. PICC lines can be used safely and effectively for TPN and are associated with an acceptable rate of complications.

Hepatic oxidant injury and glutathione depletion during total parenteral nutrition in weanling rats.

Hepatobiliary dysfunction occurs commonly in infants on prolonged parenteral nutrition alimentation; however, the underlying mechanisms causing liver injury are poorly understood. We postulated that oxidant stress played a significant role in parenteral nutrition-induced liver abnormalities and tested this hypothesis in a rat model. Weanling male rats received 8 days of total parenteral nutrition (TPN) through a central venous catheter (TPN group), pair feeding of rat chow and placement of a central venous catheter (sham group), or ad libitum feedings of rat chow (control group). After 8 days of TPN, serum alanine aminotransferase and cholylglycine levels were elevated, hepatocellular steatosis was present, hepatic mitochondria had dilated intracristal spaces, and lipid peroxidation of mitochondria was increased compared with sham and control groups. Hepatic glutathione levels decreased to 16% of control values after 5 days of TPN; this was followed by mitochondrial lipid peroxidation and elevated serum cholylglycine levels after 8 days of TPN. Sham and control rats showed no evidence of mitochondrial lipid peroxidation or liver injury after 8 days. Removal of metabisulfate from TPN solutions and addition of cysteine HCl or choline had no major effect on these findings. Bacterial translocation was not increased in TPN rats. These data suggest that glutathione depletion and oxidant stress are important factors in the pathogenesis of TPN-induced liver abnormalities in the weanling rats.

Alanyl-glutamine dipeptide-supplemented parenteral nutrition improves intestinal metabolism and prevents increased permeability in rats.

The authors determined the effects of alanyl-glutamine-supplemented total parenteral nutrition (TPN) on mucosal metabolism, integrity, and permeability of the small intestine in rats. Male Sprague-Dawley rats were randomized to receive TPN supplemented with a conventional amino acids mixture (STD group) or the same solution supplemented with alanyl-glutamine; both solutions were isocaloric and isonitrogenous. On the seventh day of TPN, D-xylose and fluorescein isothiocyanate (FITC)-dextran were administered orally. One hour later, superior mesenteric vein (SMV) D-xylose and plasma FITC-dextran concentration were measured. Intestinal blood flow and calculated intestinal substrates flux were measured with ultrasonic transit time flowmetery. Plasma FITC-dextran increased significantly in the STD group. Intestinal blood flow and SMV D-xylose concentration did not differ between the groups. Mucosa weight, villus height, mucosal wall thickness, mucosal protein, and DNA and RNA content in jejunal mucosa were significantly increased in the alanyl-glutamine group. Jejunal mucosal glutaminase activity and net intestinal uptake of glutamine (glutamine flux) were significantly higher in the alanyl-glutamine group as compared with the STD group. Addition of alanyl-glutamine dipeptide to the TPN solution improves intestinal glutamine metabolism and prevents mucosal atrophy and deterioration of permeability.

Early enteral feeding in the pediatric intensive care unit.

The purpose of this study was to evaluate the feasibility and safety of early enteral feedings of critically ill pediatric patients. The subject population of 42 critically ill patients ranged in age from 5 days to 18 years (mean 5.8 years), mean weight 17 kg. Transpyloric nasoenteric tubes were placed in all patients by a nonfluoroscopic bedside technique. All subjects were mechanically ventilated; 32 (76%) were on one or more vasoactive medications. Six (15%) patients were fed for more than 13 days while on vasoactive support and pharmacological paralysis. There were no documented complications of early enteral feeding, including aspiration. All patients were able to achieve caloric goals within 48 hours of beginning enteral feedings. All patients developed regular stool patterns despite periodic absence of bowel sounds. Enteral feedings replaced 256 days of total parenteral nutrition. Estimated patient charge savings averaged $425 for each day of enteral feedings. Early enteral feedings are feasible, well tolerated, and cost effective in critically ill pediatric patients.

Biliary lithocholate and cholestasis during and after total parenteral nutrition: an experimental study.

To evaluate the role of lithocholic acid (LCA) in the etiology of parenteral nutrition-associated cholestasis (PN-AC), we studied (i) the changes in the percentage of biliary LCA and (ii) the emergence and resolution of cholestatic changes in the liver after total parenteral nutrition (TPN) and after 6 weeks of oral feeding following the TPN. We compared these changes in rabbits on TPN support (via a central vein) for 14 days (TPN, n = 8) with those after 6 weeks of refeeding (Post-TPN, n = 8). Age-matched rabbits on lab chow served as controls (CHOW, n = 8). At the end of the diet regimens, the common bile duct was cannulated under anesthesia, and hepatic bile collected for measurements of bile flow and bile acid (BA) secretion rates, and BA profiles. The 60-min biliary excretion of sulfobromophthalein (BSP) after an intravenous bolus (5 mg/kg) was determined. A liver biopsy was taken for light microscopy. After 14 days of TPN, bile flow was reduced by 60%, bile acid secretion by 52%, and BSP excretion by 38%. On refeeding, only the BSP excretory rate recovered fully. In the TPN group, histology of the liver showed hepatocellular degeneration and portal tract inflammation; these resolved after refeeding leaving a mild portal fibrosis in 4/8 rabbits. Total colonic stasis occurred during TPN. With TPN, a decrease in the percentage of biliary glycochenodeoxycholate and an increase in LCA% were seen, whereas after refeeding the increase was in the percentage of glycoursodeoxycholate. An LCA% > or = 6 was associated with liver cell damage. After 6 weeks of refeeding, the structural cholestasis disappeared, but the decreases in basal bile flow and bile acid secretion (functional cholestasis) persisted. These data associate an increase in biliary LCA with the emergence of cholestasis during TPN in rabbits.

Gastroschisis: A simple technique for staged silo closure

In conjunction with the Neonatology Department at Loma Linda University Children's Hospital, a new protocol has evolved for the management of infants with gastroschisis, which obviates both risks associated with primary and staged silo closure. After stabilization of the infant in the neonatal intensive care unit, under sterile conditions, a 5- or 7-cm SILASTIC ® silo with a spring-loaded ring is placed over the exposed viscera, under the fascial defect. No sutures are required. A fentanyl drip is given, and the bowel is gradually reduced over the next few days. The transparent material of the silo allows for continuous monitoring of the condition of the bowel. Second-stage closure in the operating room is performed using a purse-string suture in the fascia to create a pseudoumbilicus. From October 1992 to April 1994 the authors managed 10 infants using this protocol. The results are compared with those of infants with gastroschisis treated at the same institution between August 1982 and June 1993. Outcome parameters to be compared include time until closure, time on ventilation, days of total parenteral nutrition, time until start of oral feeding, time until toleration of full-volume oral feeding, and time until discharge. The authors conclude that silo closure in the neonatal intensive care unit is simple, quick, and effective. It eliminates multiple trips to the operating room, allows the natural accommodation of the bowel into the abdominal cavity with little edema and minimal vascular compromise, and has become the authors' treatment of choice for infants with gastroschisis.

High-calorie total parenteral nutrition reduces hepatic insulin-like growth factor-I mRNA and alters serum levels of insulin-like growth factor—Binding protein-1, -3, -5, and -6 in the rat

High-calorie total parenteral nutrition (TPN) is associated with hepatic dysfunction and steatosis. Because TPN-induced steatosis might compromise hepatic expression of insulin-like growth factor-I (IGF-I) and thereby limit its potential nutritional benefit, we examined hormonal and IGF-I responses in male Sprague-Dawley rats (270 to 300 g) fed by continuous intravenous infusion with high-calorie, high-dextrose (350 kcal/kg) TPN solutions for O (control), 2, 4, and 8 days. Since IGF-binding proteins (IGFBPs) are thought to modulate the biological effects of IGFs in target tissues, we also determined serum levels of IGFBPs. Animals developed hepatic steatosis after 2 to 8 days of TPN, as reflected by a sevenfold to 15-fold increase in hepatic triacylglycerol content (P < .001 v control on each day). Serum corticosterone and insulin levels were significantly higher after 2 and 4 days of TPN, whereas serum growth hormone levels were reduced after 4 and 8 days. Serum IGF-I levels were not significantly different during TPN. However, there was a coordinate reduction in the three major hepatic IGF-I transcripts (7.0, 1.9, and 1.0 kb) after 2, 4, or 8 days of TPN, and IGF-I transcripts corresponding to multiple initiation sites within exons 1 and 2 were coordinately downregulated with TPN. Western ligand blotting indicated that serum levels of 38K to 43K, 30K to 34K, and 24K IGFBPs were increased approximately twofold after 4 and 8 days of TPN as compared with control values.(ABSTRACT TRUNCATED AT 250 WORDS)