Term Total Parenteral Nutrition Research Articles

MON-PO364: Proteome Characteristics of Liver Tissue in Patients with Liver Disease Induced by Long Term Total Parenteral Nutrition

MON-PO364: Proteome Characteristics of Liver Tissue in Patients with Liver Disease Induced by Long Term Total Parenteral Nutrition

PTH-212 High serum manganese levels in patients receiving long term total parenteral nutrition

Introduction In patients receiving long term total parenteral nutrition (TPN), high manganese (Mn) levels have been associated with nervous system disorders including parkinsonism. T1-weighted magnetic resonance imaging in these patients demonstrates high intensity signals in the globus pallidus which regresses on discontinuation of the Mn supplementation. NICE guideline (CG32) recommends checking Mn levels in patients on long term TPN every 3–6 months. The aim of the study was to assess serum Mn levels in patients on long term TPN and to establish if withdrawing Mn supplementation results in normalisation of serum Mn levels. Method Serum Mn levels were measured in all patients receiving long term TPN in the North East of England and Cumbria during the study period from Nov 2013 to Jan 2015. Of those with a high serum Mn, supplementation was withdrawn and the levels were rechecked within 12 months of withdrawal. Results In the North East of England and Cumbria, 77 patients were receiving long term TPN during the study period. Of these, 48 were female and 29 were male. The age range of patients was from 19 to 84 years. The indication for TPN included; 23 ischaemia, 21 inflammatory bowel disease, 10 intra-abdominal malignancy, 9 post-surgical complication, 5 enteric dysmotility, 4 radiation enteritis, 3 visceral myopathy, 1 connective tissue disorder and 1 congenital abdominal defect. Of the 77 patients, 46 had high serum Mn levels at initial measurement (mean 288nmol/l; range 90–1620). Serum Mn levels were rechecked in these patients within 12 months of Mn withdrawal. When rechecked, 26 patients had normal serum Mn levels and 11 patients had a reduced Mn levels but above normal limits. 9 patients did not undergo a repeat Mn level due to either acute illness, discontinuation of TPN or death. No patients reported any neurological symptoms to suggest toxicity. Conclusion The study demonstrated that high levels of Mn are found in 60% of all patients receiving long term TPN. Withdrawing Mn supplementation in these patients results in a normalisation of Mn levels in 57% and a reduction in Mn level in 20% within 12 months. Although no patients in the study showed signs of Mn toxicity, studies have shown a potential risk resulting in neurological disorders. This study highlights the importance of checking Mn levels in keeping with NICE guidance every 3–6 months and adjusting Mn supplementation for those with high levels to avoid potential toxicity. Mn is supplemented in combination with other trace elements some of which may not be replaced individually including molybdenum, iodine and chromium. Further studies are required to determine the clinical significance of withdrawing these trace elements. Disclosure of interest None Declared.

Fever Related to Fungemia Facilitated by Intralipid® Infusion

Purpose: A 62-year-old man with a history of small bowel pseudo-obstruction requiring long term total parenteral nutrition (TPN) with Intralipid® which he received via a tunneled central venous catheter presented to the clinic. He was well until approximately 6 weeks prior to admission when he developed fever and generalized malaise. He was hospitalized elsewhere on two prior occasions, treated empirically with antibiotics, and his blood cultures were negative. On his third admission, he had a catheter related bloodstream infection with Staphylococcus epidermidis requiring catheter exchange and intravenous antibiotics. Unfortunately, he presented again with his usual symptoms of fever, chills, and generalized malaise for a fourth time. Blood cultures were negative and he remained afebrile during hospitalization and was discharged home. During the admission, he was not given Intralipid® due to a nationwide shortage. At home, he developed fevers, but only on days he received Intralipid infusion. He was admitted a fifth time and blood cultures eventually grew Malassezia. His tunneled catheter was removed and he was treated with fluconazole. Malassezia species are lipophilic fungi that colonize the skin and can be associated with catheter related bloodstream infections, typically in the setting of TPN with Intralipid®. Specialized culture techniques utilizing sterilized lipid solutions are required to make the diagnosis, so a high index of suspicion must be maintained for patients receiving TPN and experiencing intermittent fevers.

Thrombosis and Thrombophilia in Children with Intestinal Failure Syndromes.

Abstract 4007Poster Board III-943 IntroductionIntestinal failure (IF) results from acquired or congenital loss of small bowel affecting absorption and digestion. The most common reason for this condition is prematurity combined with surgery to treat necrotizing enterocolitis. It is defined as <200 cm of intestines (small and large) or <100 cm of jejunum. Both situations can lead to malabsorption and the need for total parenteral nutrition (TPN). The average length of time children with IF require TPN is >48 months. However, some require it indefinitely due to failure of intestinal adaptation. These children require placement of multiple central venous catheters (CVC) to administer nutrition and fluids, and CVCs are complicated by infection and occlusion. Having IF and long term TPN can also lead to complications such as liver disease and vitamin deficiencies. The indications for intestinal transplant include impaired venous access, life-threatening sepsis or progressive liver disease with coagulopathy in a child who indefinitely requires TPN. Our center performed its first intestinal transplant in 2005. Since then, multiple children have been referred for transplant evaluation. ObjectiveTo determine prevalence of catheter-related thrombosis and thrombophilia in a population of children referred for intestinal transplant. MethodsRetrospective review of children being evaluated for IT between 2005 and 2008. Evaluation included review of vascular imaging results, thrombophilia testing and response to treatment with anticoagulation medications. ResultsThirteen children were evaluated. Magnetic resonance venography revealed that 11/13 (85%) had evidence of catheter-related DVT, with 7 (56%) having more than one vessel involved. Results of prothrombotic evaluation are included in the table.Protein C deficiency3/13 (23%)FV Leiden mutation1/12 (9%)Protein S deficiency3/13 (23%)Prothrombin mutation0/12 (0%Antithrombin deficiency7/13 (53%)Elevated Lipoprotein a0/5 (0%)Combined protein deficiencies4/13 (31%)Elevated Homocysteine0/9 (0%)Elevated FVIII5/9 (56%)APLA/LA0/11 (0%)Five children were treated with long-term (>3 months) anticoagulation therapy (warfarin in 1 and enoxaparin in 4). Prior to initiation of anticoagulation, the mean number of lines inserted per child was 4, post treatment 1.2 (p= 0.001). Before anticoagulation mean number of catheter-related bacteremia episodes per child was 3.8, after treatment 5 (p=0.55). DiscussionChildren with IF and chronic TPN use have very high rates of catheter-related DVT and loss of venous access. The most common thrombophilia associated with this population are persistently elevated FVIII activity and low levels of natural anticoagulant proteins. This is most likely a reflection of liver insufficiency and chronic inflammation of recurrent bacteremia. ConclusionAnticoagulant therapy appears to preserve venous access and reduce the need for CVC replacement. Though our study population is small, the results highlight the problem of acquired hypercoagulability in a subset of children who rely on long-term central venous access. Prospective studies are needed to determine if prophylactic anticoagulation initiated prior to loss of first or second catheter will benefit this growing population of children and possibly delay or even prevent the need for intestinal transplantation. Disclosures:Journeycake:Baxter Healthcare: Honoraria, Membership on an entity's Board of Directors or advisory committees. Off Label Use: anticoagulation in children.

Using Arteriovenous Fistulae as a Dual Access for Hemodialysis and Total Parenteral Nutrition Administration is Feasible with a Good Outcome: A Case Series

End stage renal failure patients requiring long term total parenteral nutrition (TPN) often have multiple central line placements due to line infection or occlusion. Sometimes this can cause central venous stenosis or even occlusion. We present three cases in this consecutive series, in which we have successfully used arteriovenous fistulae for both hemodialysis and long term TPN administration as an alternative route without any complications. We therefore think that native AVF and grafts can be used as dual access for hemodialysis and TPN administration provided careful case selection, counselling and follow-up.

The fungal DNA examination is useful as a sensitive parameter for the initiation and the quit of antifungal therapy in immunocompromised pediatric patients after surgery.

The purpose of this study is whether the fungal deoxyribonucleic acid (DNA) examination is useful as a sensitive parameter for pediatric surgical patients with mycosis. The eleven episodes of five cases (4 cases; progressive liver disease after biliary atresia operation, 1 case; short bowel syndrome and long term total parenteral nutrition with megacystis microcolon intestinal hypoperistalsis syndrome) with mycosis were divided into two groups according to the difference of therapeutic protocols. The sensitivity of fungal DNA examination, serum Candida antigen level, plasma beta-D glucan level, and blood culture were evaluated at the onset of infection and at the quit of antifungal medication under the protocols respectively. The duration of medication and the medication free interval in two groups were compared. The 6 episodes (3 cases) were diagnosed and treated under the protocol not including fungal DNA examination, while the 5 episodes (2 cases) under the protocol including fungal DNA examination. The occurrence rate was not significant. The sensitivity of fungal DNA examination was complete, but others were not. Using the fungal DNA examination, the duration of medication became significantly short. We conclude that the fungal DNA examination could be a sensitive parameter not only to start but to quit antifungal medication in pediatric patients with mycosis.

Candidal Retinitis

Mr. R.T. was a 49 year old male with recurrent Hepatitis C infection after orthotopic liver transplant, who presented with complications related to hemorrhagic pancreatitis. While on long term total parenteral nutrition, he developed blurry vision and Candida albicans fungemia. A fundus photograph revealed fungal endopthalmitis with focal areas of chorioretinitis. His vision improved significantly with serial intravitreal antifungal injections.

Preterm Birth Affects the Intestinal Response to Parenteral and Enteral Nutrition in Newborn Pigs

Maturation of gastrointestinal (GI) function in neonates is stimulated by enteral nutrition, whereas parenteral nutrition induces GI atrophy and malfunction. We investigated whether preterm birth alters the GI responses to parenteral and enteral nutrition. Pigs were delivered either preterm (107 d gestation) or at term (115 d gestation) and fed total parenteral nutrition (TPN) or enteral sow's milk (ENT) for 6 d after birth. Immaturity of the preterm pigs was documented by reduced blood pH, oxygen saturation and neutrophil granulocyte function, impaired intestinal immunoglobulin G uptake from colostrum, and altered relative weights of visceral organs (small intestine, liver, spleen, pancreas, and adrenals). For both ages at delivery, increases occurred in pancreatic weight (30-75%) and amylase activity (0.5- to 13-fold) after birth, but much more in ENT than in TPN pigs (P < 0.05). Six days of TPN feeding was associated with reduced intestinal weight for both delivery groups (60% of values in ENT, P < 0.001), but only in term TPN pigs was the weight lower than at birth (-20%, P < 0.05). Likewise, it was only in term TPN pigs that intestinal maltase activity increased, compared with ENT, and the absorption of glucose and proline decreased. Only in preterm pigs did TPN feeding increase lactase activity (+50% compared with ENT, P < 0.05). For both delivery ages, the mRNA of lactase-phloridzin hydrolase and sodium-coupled glucose transporter 1 (SGLT-1) were increased in TPN, compared with ENT. In conclusion, the trophic effect of enteral vs. parenteral nutrition on the GI tract is also present after preterm birth, but the postnatal maturation of many GI functions is modified, compared with term birth. The effects of nutritional regimen on the maturation of the gut epithelium in neonates depend on gestational age at birth.

Chronic intestinal pseudo-obstruction: treatment and long term follow up of 44 patients

AIMSTo document the long term course of chronic idiopathic intestinal pseudo-obstruction syndrome (CIIPS) in children with defined enteric neuromuscular disease, and the place and type of surgery used in their...

Paradoxical Aspects of Inter-Professional Disagreements in the Management of Short Gut † 153

In the management of short gut, alternatives to long term total parenteral nutrition (TPN) exist, ranging from enteral feeding only to interventional, surgical management such as gut transplant or gut lengthening procedures. To understand attitudes and practice concerning short gut management, a survey was sent in the spring of 1997 to the directors of 102 Neonatology (Neo) and 47 Gastroenterology (GI) fellowship programs with 70% and 85% response respectively. Chi square with Yates correction and Wilcoxon matched paired analysis are used as appropriate.

EFFECT OF INTRALIPID ON HEPATIC CHOLESTEROL UPTAKE : IMPLICATIONS FOR TOTAL PARENTERAL NUTRITION

Total parenteral nutrition (TPN) offers the chance of survival to children who have had extensive gut resections or suffer from severe gut failure. Long term TPN in infants is, however, often complicated by cholestatic liver disease, the actiology of which still remains unclear. It has been suggested that the lipid emulsions used in TPN may be responsible. Studies were undertaken to examine the effect of a lipid emulsion. 20% Intralipid (IL), on the loading of cholesterol into cultured Hep G2 cells. In a pilot study the net uptake of cholesterol by cells incubated with culture medium containing IL (1:1v/v) for 24 hours was greatly decreased compared to controls without added IL (3.8×10-4 and 1.2×10-2 μmoles/μg protein respectively). Hep G2 cells incubated for 24 hours with culture medium supplemented with IL in concentrations from 50:1v/v to 5:1v/v also took up considerably smaller amounts of cholesterol than controls (e.g. 50:1v/v 5.6×10-4, 5:1v/v 2.8×10-4, controls 3.6×10-3 μmoles/μg). Time course studies were carried out over a 24 hour period in culture medium with and without IL (50:1v/v). Controls showed a maximum net uptake of cholesterol of 3.5×10-3 μmoles/μg after 8 hours exposure, whereas those cells incubated with IL accumulated 1.6×10-4, 2.1×10-4 and 3.3×10-4 μmoles/μg after 4, 8, and 24 hours respectively. Preincubation of cells for up to 4 hours with culture medium containing IL (50:1v/v), followed by washing had no effect on the subsequent uptake of cholesterol by Hep G2 cells from culture medium alone. IL did not affect cell viability or sequester the cholesterol in the culture medium. Thus, IL appears to have a selective and reversible effect on the net cholesterol uptake by Hep G2 cells. Since these effects were observed with concentrations of IL similar to those found in the plasma of infants receiving intravenous IL, they suggest that IL could interfere with hepatic cholesterol uptake in vivo.

Current status of small bowel transplantation in children.

Small bowel transplantation is gradually changing from an experimental procedure to a very desirable and viable treatment option in children with irreversible intestinal failure due to either short bowel syndrome or functional impairment. Long term total parenteral nutrition and home parenteral nutrition would be necessary to manage these children in the absence of a small bowel transplant programme. Parenteral nutrition is also associated with complications which can result in chronic liver disease. In India, there is no infrastructure for this treatment option and even if it was there the cost of this method of treatment is likely to be more than the cost of post-operative immunosuppression. Small bowel can be transplanted as an isolated graft, in combination with the liver or as part of a multivisceral transplant. The operative techniques have been standardised. Major post-operative complications result from sepsis and lymphoproliferative diseases. The best results have been obtained with a combined liver and small bowel transplant.

Ursodeoxycholic acid for treatment of cholestasis in children on long- term total parenteral nutrition: A pilot study

BACKGROUND & AIMS: Cholestatic liver disease (CLD) is a frequent and sometimes fatal complication of total parenteral nutrition (TPN) that may require withdrawal of TPN. The aim of this pilot study was to evaluate ursodeoxycholic acid (UDCA) as treatment of TPN-associated CLD. METHODS: Seven children (4 boys and 3 girls) undergoing long-term TPN because of intractable diarrhea syndrome developed cholestasis and were treated with UDCA. Treatment efficacy was evaluated by monitoring clinical and biochemical markers of CLD, including gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), conjugated bilirubin, and alanine aminotransferase (ALT). RESULTS: In all children, UDCA was associated with the disappearance of signs of CLD and with normalization of biochemical markers of cholestasis within 4-8 weeks. A rebound increase of GGT, ALP, and ALT serum levels was observed in 3 children in whom UDCA was temporarily discontinued while they were still undergoing TPN. However, after reinstitution of UDCA, markers of cholestasis normalized in all cases. UDCA was withdrawn on reinstitution of full oral feeding; there was no relapse of cholestasis. Six children fully recovered. One child died because of the lack of vascular access. CONCLUSIONS: UDCA appears to be an effective treatment for TPN-related cholestasis in children. (Gastroenterology 1996 Sep;111(3):716-9)

Restricting Food Intake Does Not Exacerbate the Effects of a Choline-Deficient Diet on Tissue Carnitine Concentrations in Rats

Previous reports in animals indicate that choline deficiency alters carnitine metabolism. Recent studies in humans suggest that choline deficiency occurs in individuals during long term total parenteral nutrition. Malnutrition is also a frequent complication in this population. We therefore examined the effect of restricting the intake of a choline-deficient diet on carnitine concentrations in plasma and tissues. Adult male rats were randomly assigned to one of four dietary regimens: control, choline deficient, restricted control (85% of control), or restricted choline deficient for 42-43 d. At the end of the experimental period, restricted animals weighed significantly less than their respective controls (P < 0.01). Liver weight relative to body weight and fat concentration were greater in choline-deficient animals (P < 0.01 and 0.001, respectively). Choline-deficient rats fed free access had elevated plasma carnitine concentration (P < 0.01). Urinary carnitine excretion was elevated in both groups of choline-deficient rats (P < 0.01), while liver, heart and muscle carnitine concentrations were lower than in controls (P < 0.05). Restricting dietary intake reduced plasma carnitine concentration in choline-deficient animals (P < 0.01), but did not alter tissue or urine carnitine concentrations in either group. Restricted, choline-deficient animals did not exhibit a worsening of the sequelae of choline deficiency. We conclude that choline deficiency alters carnitine concentrations in plasma and tissues and that restricting the intake of a choline-deficient diet does not alter this effect in tissues.

Starvation adaptation in children treated with long term-total parenteral nutrition (TPN)

Starvation adaptation in children treated with long term-total parenteral nutrition (TPN)

Plasma levels of fat-soluble vitamins A and E in neonates, after administration of two different vitamin solutions

The aim of this study was to compare the effects of 2 different vitamin solutions on plasma levels of vitamin A and E during and after short term total parenteral nutrition (TPN), after neonatal surgery. 2 compounds were compared, one with a higher vitamin A content (100 μ g/ml) and no vitamin E and one with vitamin E (0.64 mg/ml) and a lower vitamin A content (69 μ g/ml). 2 randomly chosen groups of 10 neonates were studied each with gastrointestinal malformations. The groups were comparable regarding gestational age (GA), weight and length. Diagnoses within the groups were similar. TPN was given after corrective surgery for a median time of 6.5 days to both groups. Vitamin A and retinol binding protein (RBP) levels increased significantly (p < 0.05) above the pre-treatment level in patients receiving supplementation with a higher dosage of vitamin A (100 μ g/ml). In patients receiving the lower dose of vitamin A (69 μ g/ml) plasma levels of this vitamin were unchanged but RBP levels fell significantly (p < 0.05). There was no significant difference in plasma vitamin E levels in the group of patients receiving vitamin E supplementation as compared with the unsupplemented group. In both groups vitamin E levels increased significantly (p < 0.005) after introduction of oral feeding. The results indicate that even during short term TPN endogenous stores of vitamin A might become depleted. In spite of the fact that no vitamin A deficiency was noted it seems obvious that a higher vitamin A intake is advisable which is in accordance with the recommendations from the Subcommittee on Paediatric Parenteral Nutrient Requirements from the Committee on Clinical Practice Issues of The American Society for Clinical Nutrition.

Low plasma free choline is prevalent in patients receiving long term parenteral nutrition and is associated with hepatic aminotransferase abnormalities

Hepatic transaminase abnormalities have been previously reported in patients receiving long term total parenteral nutrition (PN). We sought to determine if such abnormalities are caused by choline deficiency-induced hepatocyte damage. In 41 subjects (19 male, 22 female) aged 45.1 ± 24.3 years (range 0.1–79 years) who have received PN for 5.5 ± 4.7 years (range 0.1–14.5 years). We determined plasma free and phospholipid bound choline levels, serum albumin, ALT and AST. We also determined the daily volume of intravenous lipid emulsion received by the patients as well as the concentration of free choline and phospholipid bound choline in the lipid emulsion. Plasma free choline was low in 33 41 subjects (mean 7.15 ± 2.5 nmol/ml, range 3.3–15.6, normal 11.4 ± 3.7). Phospholipid bound choline was normal in 34 41 subjects (mean 2157 ± 620 nmol/ml, range 1026–3887, normal 2364 ± 774). Elevations in ALT and AST were significantly correlated with plasma free choline (r = −0.34, p = 0.03, r = −0.37, p = 0.02 respectively) but not with phospholipid bound choline. No relationship was found between age, PN duration or daily volume of intravenous lipid and plasma free or phospholipid bound choline. The lipid emulsion contained 24 ± 6 nmol/ml of free choline and 11 630 ± 552 nmol/ml of phospholipid bound choline. We conclude that low plasma free choline is prevalent in patients receiving long term PN and this abnormality is associated with elevated serum aminotransferases. Furthermore, intravenous lipid emulsion is an inadequate source of choline for this patient group.

Anemia and Neutropenia due to Copper Deficiency During Long Term Total Parenteral Nutrition

Anemia and Neutropenia due to Copper Deficiency During Long Term Total Parenteral Nutrition

Plasma aluminium concentrations in children administered long term total parenteral nutrition

Plasma aluminium concentrations in children administered long term total parenteral nutrition

Effect of long term total parenteral nutrition on morphological and cytoproliferative pattern of human small intestinal mucosa

Effect of long term total parenteral nutrition on morphological and cytoproliferative pattern of human small intestinal mucosa