Long-term Total Parenteral Nutrition Research Articles

New perspectives for children with microvillous inclusion disease: early small bowel transplantation.

Microvillous inclusion disease (MVID) is a congenital intestinal epithelial cell disorder leading to lifelong intestinal failure. Despite long-term total parenteral nutrition, life expectancy is extremely reduced because of metabolic or septic complications or liver failure. Twelve patients with early-onset MVID were evaluated between 1995 and 2002 for the possibility of small bowel transplantation (SbTx). Three patients died before they could be placed on the waiting list for SbTx, and one patient is still awaiting SbTx. SbTx was contraindicated in one patient. Seven of 12 patients (six boys and one girl) underwent transplantation (three SbTxs and four combined liver-SbTxs). Actuarial survival rates were 100% and 75% in the SbTx and combined liver-SbTx groups, respectively, with a mean follow-up of 3 years (1.1-8.5 years). In contrast, the survival rate was only 40% in the subgroup of five patients who did not undergo transplantation. After transplantation, all patients were weaned from parenteral nutrition: the five patients with an additional colon graft were weaned within 36 days as opposed to the others without colonic transplant who obtained full intestinal autonomy several months after transplantation. The only two surviving patients who did not undergo SbTx remain highly dependent on total parenteral nutrition, which is complicated by repeated episodes of metabolic decompensation. SbTx alone or in combination with the liver is highly successful in children with MVID, offering them a long-term perspective for the first time. Associated colon grafting markedly improves the outcome and quality of life after SbTx in patients with MVID.

Management of venous access problems before and after intestinal transplantation: case reports

Patients suffering irreversible loss of intestinal function require total parenteral nutrition (TPN). During long-term TPN, catheter infections are a common problem and intestinal transplantation (ITx) is indicated when patients experience loss of venous access. We report two patients with short bowel syndrome—one before and one after ITx. The patient listed for ITx had several catheter infections with septic temperatures. Staphylococcus aureus, detected in blood cultures, was treated with vancomycin. Packing of the central venous line (CVL) with vancomycin was not successful; the CVL was changed. Search for an infectious focus identified a septic femoral head destruction that was treated by incision and implantation of a hip endoprothesis. Thereafter, the patient was free from infection. The second patient underwent ITx on January 2, 2003, and is free from TPN. ITx was complicated by temporary acute renal failure and heparin-induced thrombocytopenia (HIT) syndrome. After compensation of kidney function, the patient required additional saline solution (1 to 2 L/d) to optimize renal perfusion. A CVL was placed in the external iliac vein (EIV) due to previous loss of venous access. At 2 months after ITx, the CVL was infected and the patient was septic. MR scan revealed only one jugular vein to provide vascular access. Therefore, the CVL was changed from the right to the left EIV. Postoperatively, the patient developed thrombosis of right iliac vein and a wound infection that is probably related to the nearby graft ileostomy. At present, the patient is in good condition with a functioning graft. In conclusion, recurrent CVL infections before ITx might reflect other infectious foci that require intensive diagnostic evaluation. After ITx, CVL infection may cause venous thrombosis. Therefore, a single upper venous access should be preserved for optimal care.

Improved outcome after intestinal transplantation at a single institution over 12 years

Purpose To evaluate the outcomes of patients undergoing intestinal transplantation (IT). Methods Retrospective review was undertaken using existing medical records and database. Results Between November 1991 and May 2003, 114 patients were referred for consideration for IT, of which 33 patients received 37 intestinal allografts. All patients had intestinal failure and all patients had significant complications from total parenteral nutrition (TPN). TPN was the predominant cause of liver failure (63%). Combined liver intestinal grafts were used in the majority of patients. Overall 1- and 3-year patient survival is 77% and 52% with patients transplanted since 1999 having a 1- and 3-year survival of 94% and 73%, respectively. The most common cause of death was sepsis. No graft or patient was lost to cytomegalovirus or Epstein-Barr virus disease. Twenty-seven percent of allografts were lost to rejection. Long-term TPN independence is 82% for grafts more than 30 days after IT. Statistical analysis revealed several important factors impacting outcome. Conclusions Successful IT defined as prolonged patient and graft survival and TPN independence can be readily achieved in select patients with IF and complications related to TPN therapy. Outcomes have improved with experience gained and control of viral infections and rejection.

Total parenteral nutrition, intestinal adaptation, and short bowel syndrome

wenty-five years ago, in 1968, Wilmore and Dudrick1,2 published lmost simultaneously two papers that revolutionized surgery in eneral and gastrointestinal surgery in particular. An infant of 300 g with almost complete atresia of the small bowel and on the rink of death from inanition was fed intravenously for 44 d and emonstrated normal growth and development.1 This pivotal deelopment followed publication of an extensive experimental work y the same group from the University of Pennsylvania proving hat growth, development, and positive nitrogen balance can be chieved by long-term total parenteral nutrition (TPN) in beagle uppies.2 TPN has since been used in millions of patients all over the orld and for a myriad of indications. However, short bowel yndrome is probably the disease state where its effect was (as in he infant described by Wilmore and Dudrick) and still is the most ramatic one. TPN is used to enable intestinal adaptation and ltimately return to short bowel patients, completely or partly, the se of their bowel or is used as home TPN in those unfortunate nough not to be able to achieve adequate intestinal adaptation. Intestinal adaptation is aimed primarily at the restoration of the bsorptive function of the gut and secondarily at restoring intestial barrier function and gut immunologic function. Intestinal adptation is characterized by compensatory growth of all layers of he bowel wall of the intestinal remnant, leading to dilatation, engthening, and thickening. There is increased epithelial cell roliferation in the crypts and migration of cells into the villi. This yperplasic process results in increased mucosal cell mass, DNA, NA, and protein content.3 The stimulation of this complex proess of adaptation is dependent on pancreatobiliary secretions, on-nutritive factors such as enteroglucagon, growth hormone and ther growth factors, and a variety of nutritive factors.3 Some atients’ guts will be too short or too sick to undergo adequate ntestinal adaptation, and these patients will have to remain on

Síndrome de megavejiga-microcolonhipoperistaltismo intestinal. A propósito de un caso de supervivencia prolongada

Megacystis-microcolon-intestinal hypoperistalsis syndrome is a multisystemic disorder in which impaired intestinal motor activity causes recurrent symptoms of intestinal obstruction in the absence of mechanical occlusion, associated with bladder distention without distal obstruction of the urinary tract. It is an uncommon disorder with high morbidity and mortality, and long-term total parenteral nutrition may be required. We describe an 18-year-old girl with long-term survival, followed-up by our service since birth. With medical, surgical and nutritional management she currently presents a good oral tolerance and good quality of life, only requiring parenteral nutrition during periods of decompensation.

Glycyl-glutamine-supplemented long-term total parenteral nutrition selectively improves structure and function in heterotopic small-bowel autotransplantation in the pig

Glycyl-glutamine-supplemented long-term total parenteral nutrition selectively improves structure and function in heterotopic small-bowel autotransplantation in the pig

Warfarin therapy in children who require long-term total parenteral nutrition.

To determine whether warfarin can be safely administered to children who require long-term total parenteral nutrition (TPN), for the purpose of preventing central venous access device (CVAD)-related thrombosis. A prospective cohort study was conducted of 8 children with short-gut syndrome or small intestinal anomalies. All patients received oral anticoagulant therapy (warfarin) managed by the hematology department at a tertiary pediatric center. Data collected included demographic details, nutritional intake, age, weight, history of deep vein thrombosis, number and functional duration of CVADs, warfarin requirements, and adverse event rates. A total of 15.2 warfarin years were studied prospectively. The target therapeutic range was achieved 51.1% of time. The mean dose of warfarin required to achieve the target therapeutic range (international normalized ratio) of 2.0 to 3.0 was 0.33 mg/kg/d. The mean duration between warfarin monitoring tests was 6.6 days. The median vitamin K intake per patient was 0.367 mg/kg/d (range: 0.018-2.85 mg/kg/d). Before commencing anticoagulant therapy, the mean CVAD duration was 160.9 days. Concomitant warfarin therapy was associated with a mean CVAD duration of 351.7 days. There were no major bleeding events, and no clinical extension of thrombosis was observed. This is the first published study to report uniform warfarin prophylaxis for CVADs in children. Warfarin therapy can be administered safely in children who require long-term TPN. Warfarin prophylaxis seems to prolong CVAD survival.

Early developments and clinical applications of total parenteral nutrition.

This article recounts the conditions and status of surgical nutrition support in the 1960s and the antecedent basic and clinical investigational work leading to the development of a practical and efficacious method of adequate nourishment entirely by vein in Beagle puppies; describes the subsequent clinical application of the knowledge, techniques, and technology to the first successful long-term total parenteral nutrition (TPN) support of critically ill pediatric and adult patients; and admonishes nutritionists of all backgrounds that some need for parenteral nutrition will likely always exist and that it is incumbent upon everyone to continue endeavors to advance the germinal methodology to perfection. The relevant indications, limitations, hindrances, motivational factors, and studies regarding the development of TPN are reviewed, and the fundamental investigational work culminating in the first successful growth and development of Beagle puppies and a human infant fed entirely by vein are described firsthand. The details of the orderly and logical scientific development of the principles and components of the techniques in animals, infants, and adults are related. Knowledge, techniques, and technologic constituents of the first successful long-term TPN system were developed in the basic biochemical and animal laboratories initially in 6 puppies and subsequently adapted clinically for the efficacious long-term i.v. support of 6 critically ill surgical adult patients and a newborn infant before its widespread clinical application. Long-term TPN was inaugurated successfully as a safe and effective i.v. feeding technique nearly 4 decades ago. However, basic and clinical investigations must continue to be encouraged, supported, and carried out in the quest to perfect the current rudimentary technology, methodology, and outcomes.

Fibrin glue as a sealant for high-risk anastomosis in surgery for morbid obesity.

Fibrin sealants promote hemostasis and wound healing. Complex revisional surgery is performed for morbid obesity, and high-risk patients undergo weight loss surgery routinely. Fibrin sealant, Tisseel, was used by one surgeon on 120 consecutive patients at the gastrojejunal anastomosis in Roux-en-Y gastric bypass (RYGBP). We hypothesized that the application of fibrin sealant would decrease anastomotic leaks. One surgeon (Surgeon A) used fibrin sealant for 120 consecutive patients, while two other surgeons (Surgeons B & C) served as controls and did not use fibrin glue for their last 120 patients. Surgeon A did not use fibrin glue in 120 patients to serve as an internal control. All 480 patients underwent a RYGBP. Fibrin glue was applied at the gastrojejunal anastomosis. The fibrin sealant group did not have any documented leaks on the previous 120 patients, while 5 patients with Surgeon B, 2 patients with Surgeon C and 1 patient with Surgeon A without fibrin sealant experienced enteric leaks requiring re-operation, drainage, or long-term total parenteral nutrition (N = 480 total patients). Fibrin sealant may be useful in preventing leaks and promoting healing of the "high risk" anastomosis during complex gastrointestinal surgery. While the cost of fibrin glue is to be considered, re-operation and management of subsequent enterocutanous fistulas or anastomotic strictures may be more costly than routine use for high-risk morbidly obese patients.

Selenium Deficiency in a Patient with Crohn's Disease Receiving Long-term Total Parenteral Nutrition.

We report a case of selenium deficiency in a patient with Crohn's disease on long-term total parenteral nutrition (TPN). She manifested lassitude of the legs, discoloration of the nail beds, and macrocytosis. Since her plasma selenium level was found to be below the measurable level, we diagnosed this case as selenium deficiency. After intravenous administration of sodium selenite, her symptoms were reversed. Careful attention should be paid to selenium deficiency when a patient receives long-term TPN; supplementary administration of selenium via TPN may be required because selenium is often not routinely added to TPN formulations.

Crohn's disease with Parkinsonism due to long-term total parenteral nutrition.

Crohn's disease with Parkinsonism due to long-term total parenteral nutrition.

Total parenteral nutrition-stimulated activity of inducible nitric oxide synthase in rat pancreatic islets is suppressed by glucagon-like peptide-1.

Long-term total parenteral nutrition (TPN) is associated with elevated plasma lipids and a marked decrease of glucose-stimulated insulin release. Since nitric oxide (NO) has been shown to modulate negatively the insulin response to glucose, we investigated the influence of TPN-treatment on isoforms of islet NO-synthase (NOS) activities in relation to the effect of glucagon-like peptide-1 (GLP-1), a known activator of glucose-stimulated insulin release. Isolated islets from TPN rats incubated at basal glucose (1 mmol/l) showed a modestly increased insulin secretion accompanied by an enhanced accumulation of islet cAMP and cGMP. In contrast, TPN islets incubated at high glucose (16.7 mmol/l) displayed an impaired insulin secretion and a strong suppression of islet cAMP content. Moreover, islet inducible NOS (iNOS) as well as islet cGMP content were greatly increased in these TPN islets. A dose-response study of GLP-1 with glucose-stimulated islets showed that GLP-1 could overcome and completely restore the impaired insulin release in TPN islets, bringing about a marked increase in islet cAMP accumulation concomitant with heavy suppression of both glucose-stimulated increase in islet cGMP content and the activities of constitutive NOS (cNOS) and iNOS. These effects of GLP-1 were mimicked by dibutyryl-cAMP. The present results show that the impaired insulin response of glucose-stimulated insulin release seen after TPN treatment is normalized by GLP-1. This beneficial effect of GLP-1 is most probably exerted by a cAMP-induced suppression of both iNOS and cNOS activities in these TPN islets.

Glycyl-glutamine-supplemented long-term total parenteral nutrition selectively improves structure and function in heterotopic small-bowel autotransplantation in the pig.

Marked atrophy and impaired absorptive and barrier function occur in transplanted small intestinal graft during total parenteral nutrition (TPN), TPN is required by all the patients after small bowel transplantation (SBT). Glutamine (Gln) is a conditional indispensable amino acid that is not included in regimens for parenteral nutrition because of its chemical instability in aqueous solution. Glutamine-containing dipeptide, however, is heat-stable. With this study, we determine whether the glycyl-glutamine-supplemented long-term TPN improves mucosal structure and function in heterotopic transplanted small intestinal graft in the pig. Ten outbred pigs, randomly divided into two groups, underwent heterotopic small bowel autotransplantation. In the STPN group, the animals received standard TPN without glycyl-glutamine (Gly-Gln) and in the GTPN group, the animals received isonitrogenous (0.3g kg day(-1)) and isocalories (nonprotein calories, 30 kcal kg day(-1)) TPN with Gly-Gln (3% Gln) for 28 days. At the end of TPN, there was no significant difference in the body weight loss between two groups ( P>0.05). The mucosal contents of Gln and protein were significantly higher in the GTPN group than in the STPN group ( P<0.05). The mucosal disaccharidase activities in the homogenate of the graft mucosa of the GTPN group were significantly higher than that of the STPN group ( P<0.05). The villous height, surface area, mucosal thickness were significantly higher in the GTPN group than in the STPN group ( P<0.05). There was no significant difference in crypt depth between the two groups ( P>0.05). These results suggest that glycyl-glutamine-supplemented long-term TPN improves graft mucosal structure in heterotopic autotransplanted small bowel grafts in the pig. Long-term (4 weeks) TPN supplemented with Gln could alleviate small intestinal graft atrophy, but could not completely eliminate atrophy.

The impact of iron and selenium deficiencies on iodine and thyroid metabolism: biochemistry and relevance to public health.

Several minerals and trace elements are essential for normal thyroid hormone metabolism, e.g., iodine, iron, selenium, and zinc. Coexisting deficiencies of these elements can impair thyroid function. Iron deficiency impairs thyroid hormone synthesis by reducing activity of heme-dependent thyroid peroxidase. Iron-deficiency anemia blunts and iron supplementation improves the efficacy of iodine supplementation. Combined selenium and iodine deficiency leads to myxedematous cretinism. The normal thyroid gland retains high selenium concentrations even under conditions of inadequate selenium supply and expresses many of the known selenocysteine-containing proteins. Among these selenoproteins are the glutathione peroxidase, deiodinase, and thioredoxine reductase families of enzymes. Adequate selenium nutrition supports efficient thyroid hormone synthesis and metabolism and protects the thyroid gland from damage by excessive iodide exposure. In regions of combined severe iodine and selenium deficiency, normalization of iodine supply is mandatory before initiation of selenium supplementation in order to prevent hypothyroidism. Selenium deficiency and disturbed thyroid hormone economy may develop under conditions of special dietary regimens such as long-term total parenteral nutrition, phenylketonuria diet, cystic fibrosis, or may be the result of imbalanced nutrition in children, elderly people, or sick patients.

Trends in the management and outcome of jejuno-ileal atresia.

The aim of this study was to evaluate contemporary patterns of presentation and trends in the management and outcome of newborn infants with jejuno-ileal atresia at a regional paediatric surgical centre in the United Kingdom. The hospital neonatal surgical registry was used to identify patients with jejuno-ileal atresia (n = 83) admitted between 1976 - 1998, excluding those associated with gastroschisis. The clinical records were reviewed and antenatal information, patient demographics, associated anomalies, operative treatment, post-operative management and outcomes were analysed in three time periods to identify trends in management and survival: Group 1 1976 - 1982 (n = 32), Group 2 1983 - 1990 (n = 21), and Group 3 1991 - 1998 (n = 30). Overall survival was 90 %. The number of patients with associated anomalies were Group 1, 10 (31 %); Group 2, 7 (33 %); and Group 3, 11 (37 %). Cystic fibrosis was encountered in 4 (13 %), 1 (5 %) and 4 (13 %) patients, respectively. Resection with primary anastomosis was the definitive management in most of patients: Group 1, 25 (78 %); Group 2, 17 (81 %); and Group 3, 27 (90 %). Initial stoma followed by delayed primary anastomosis was performed in 14 infants; eight patients had divided stomas while 6 had Bishop-Koop stoma. Tapering was used in 10 patients (12 %) with proximal jejuno-ileal atresia. Parenteral nutrition was increasingly utilised over the three time periods studied. There were no deaths in Group 3 compared to 6 deaths in Group 1 and 2 in Group 2 (P = 0.02). Most of the deaths were due to overwhelming sepsis. Mortality did not correlate significantly with the TYPE of atresia, presence of associated anomalies or the need for long-term total parenteral nutrition. The overall complication rate in survivors was 18 %. In the infants undergoing Bishop-Koop operation the complication rate was 50 %. This study has shown a significant reduction in mortality from jejuno-ileal atresia, which may be attributed primarily to advances in perioperative management, including parenteral nutrition. Generous resection of the atretic segment with primary anastomosis is more frequently employed in preference to initial stoma formation. Cystic fibrosis remains an important co-morbid condition that must be excluded promptly in all newborns.

Motility of the gastrointestinal tract and gallbladder during long-term total parenteral nutrition in dogs.

The motility of the gastrointestinal tract during total parenteral nutrition (TPN) remains poorly understood. The objective of this study was to determine the motility pattern not only in the gastrointestinal tract but also in the gallbladders of dogs maintained by TPN. Central venous catheters were inserted through the external jugular vein of 5 dogs and 6 strain gauge force transducers were sewn to the stomach, small intestine, and gallbladder. Two weeks later, oral food was discontinued and motility was recorded for 24 hours after the first migrating motor complex (MMC) was confirmed in the stomach as pre-TPN. TPN was started and continued for 4 weeks, and patterns of motor activity during TPN were recorded for 24 hours at the end of each week. The durations of MMC in the stomach, duodenum, and gallbladder in pre-TPN were 118 +/- 3 minutes, 118 +/- 2 minutes, and 118 +/- 2 minutes, respectively, but in the first week of TPN they were 432 +/- 56 minutes, 431 +/- 56 minutes, and 386 +/- 29 minutes, respectively. TPN times were significantly longer than those of pre-TPN (corrected p < .005). The durations of MMC in jejunoileum did not alter between pre-TPN and TPN. The occurrences of phase III in the stomach, duodenum, and gallbladder in pre-TPN were 12/d, but during TPN they were reduced significantly (corrected p < .005). TPN did not affect the motility of the jejunoileum but did inhibit the motor activities of the stomach, duodenum, and gallbladder. The inhibition of gallbladder contraction observed during TPN may be one of the factors inducing gallbladder disease.

長期経管栄養施行中の重症心身障害者に対する亜セレン酸ナトリウム内服液投与の有用性

Selenium is a component of glutathione peroxidase (GPx), which metabolizes oxygen radicals. Generally, selenium is obtained from such foods as grains and fish. Therefore, for patients with severe motor and intellectual disabilities (SMID) who cannot orally consume meals, a selenium deficiency remains a problem. To overcome this problem, selenium oral solution was administered to SMID patients under long-term total parenteral nutrition, and the usefulness of selenium oral solution was evaluated using the serum selenium concentration and GPx activity as indices.Before selenium oral solution administration, the serum selenium concentration of SMID patients was 3.0 ± 0.7, μg/dL, which is an extremely the low value compared with 11.2 ± 1.2, μg/dL which is the normal value for a healthy adult. Moreover, the GPx activity of 48.5 ± 12.3 n mol/min/mL was also extremely low in comparison to a healthy adult' s value of 112.6 ± 5.6 n mol/min/mL. When a selenium oral solution (6, μg/kg) was administered to SMID patients for two weeks once per day, the serum selenium concentration and the GPx activity increased, and there was no difference from a normal healthy adult' s value. Although the selenium oral solution thereafter decreased to 1.5μg/kg once per day, the serum selenium concentration and the GPx activity were mostly maintained in the normal region. Moreover, a significant positive correlation was observed between the serum selenium concentration and the GPx activity. (p< 0.001)These results suggested that the administration of oral selenium solution to patients with selenium deficiency diseases, such as SMID, and patients under long-term total parenteral nutrition, thus improved the serum selenium concentration and GPx activity.

Choline and vitamin B12 deficiencies are interrelated in folate-replete long-term total parenteral nutrition patients.

Choline has recently been recognized as an essential nutrient, in part based on deficiency data in long-term home total parenteral nutrition (TPN) patients. Choline, a methyl donor in the metabolism of homocysteine, is intricately related to folate status, but little is known about choline and vitamin B12 status. Long-term TPN patients are also subject to vitamin B12 deficiency. The objective of the study was to evaluate any interaction between choline, vitamin B12, and folate in patients with severe malabsorption syndromes, requiring long-term TPN. Plasma free choline, serum and red blood cell (RBC) folate, serum vitamin B12 methylmalonic acid, B6, and plasma total homocysteine concentrations were assayed by standard methods. Low choline was defined as values that fall 1 to < or =3 and marked low choline concentration as >3 SD below the control mean. Both low choline concentrations (52% were marked low, 33% low, 14% normal) and elevated methylmalonic acid concentrations (47%) were prevalent. Choline concentration was significantly lower and RBC folate higher in patients with elevated methylmalonic acid. Total homocysteine elevations were rare (3 of 21) and mild. These data suggest a strong interaction between vitamin B12 and choline deficiencies and folate status in this population, which may be due in part to variations in vitamin and choline delivery by TPN. Folate adequacy may increase B12 use for homocysteine metabolism, thus limiting B12 availability for methylmaIonic acid metabolism. Choline use may also increase, and choline deficiency may worsen if choline substitutes when the vitamin B12 side of the homocysteine metabolic pathway cannot be used.

Outcome after intestinal transplantation: results from one center's 9-year experience; discussion 1031-2.

Outcomes after intestinal transplantation have improved during the past decade with refinements in surgical techniques as well as advances in immunosuppression and antimicrobial therapy. Retrospective analysis. Tertiary care medical center, August 1991 through December 2000. Adult (5) and pediatric (12) patients with intestinal failure. All developed complications from long-term total parenteral nutrition therapy. Median age was 8.6 years and median weight was 22 kg. Primary intestinal transplantation with (n = 14) or without (n = 3) the liver. Patient and graft survival, viral infections, rejection, and nutritional autonomy. Twenty-one intestinal grafts were transplanted into the 17 recipients. All donors were cadaveric and were matched by ABO blood group and size. Patient survival at 1 and 3 years was 63% and 55%, respectively. Death-censored graft survival at 1 and 3 years was 73% and 55%, respectively. There were 1.5 acute cellular rejection episodes per graft and 3 grafts were lost to rejection. Incidences of infection with the Epstein-Barr virus and cytomegalovirus were negligible with aggressive prophylaxis and preemptive therapy. Nutritional autonomy was achieved in 69% of grafts surviving more than 30 days after intestinal transplantation. Intestinal transplantation is now the standard of therapy for patients with intestinal failure and complications resulting from total parenteral nutrition. Outcomes have markedly improved since initiation of the program. Aggressive immunosuppression as well as prophylaxis and preemptive antiviral therapy have led to low incidences of acute cellular rejection, Epstein-Barr virus, and cytomegalovirus. Finally, nutritional autonomy can be achieved after successful intestinal transplantation.

Organ heavy-metal accumulation during parenteral nutrition is associated with pathologic abnormalities in rats

OBJECTIVES: Metabolic bone disease, hepatic abnormalities, splenic insufficiency, and nephropathy have been associated with long-term total parenteral nutrition (TPN). We determined the heavy-metal contamination in TPN solutions and investigated whether it was associated with organ deposition and pathologic organ damage. METHODS: Five representative TPN solutions (two adult standard solutions, one renal solution, and one standard pediatric solution to reflect clinical practice) and 28 TPN components were analyzed with inductively coupled plasma mass spectrometry. Twenty-six male Fisher 344 rats were assigned to two groups (chow/NaCl = 8 and TPN = 18). TPN or NaCl was infused at a rate of 50 mL/d. After 14 d, serum, femurs, spine, liver, kidneys, brain, spleen, and testes were analyzed for heavy-metal deposition by using inductively coupled plasma mass spectrometry. Tissues were fixed in formalin, sectioned, and stained with hematoxylin and eosin, periodic acid Schiff, and Masson’s trichrome stain. Kidneys were fixed in gluteraldehyde for ultrastructural examination with scanning electron microscopy. RESULTS: The predominant sources of contaminants in TPN were amino acids (Al, As, Cr, Ge, Pb, Sn), dextrose (As, Ba, Cr, Sn), Ca gluconate (Al), K 2PO4 (Al), lipid emulsion (As, Sn), and vitamins (As). Significant variations in the level of contamination depended on TPN formulation and brand of constituents. In the kidney, Pb, Cr, and Mn concentrations were greater than in controls, although there was no correlation with serum creatinine. Hepatic Cr and Pb concentrations were greater in TPN rats, although there was no correlation with serum aspartate aminotransferase or total bilirubin. Splenic Ba, Cr, Ge, Pb, Mn, and Sn concentrations were greater in TPN rats. Only serum Cr concentration was significantly correlated with splenic concentration ( r = 0.46, P = 0.04). Brain and serum Ba concentrations were significantly correlated ( r = 0.60, P = 0.007). No significant correlations were observed between any other metal in serum and that metal’s respective organ concentration. No increase in heavy-metal accumulation was seen in the femur, spine, or testis. There were no significant depositions of As, Cd, Hg, St, or V in any of the organs examined. Serum Al and Cr concentrations were significantly increased in TPN rats, although there was no correlation with tissue concentrations. No significant increases in heavy-metal concentrations in tissue or plasma were observed for any of the other metals measurable by inductively coupled plasma mass spectrometry. Histologically in the TPN group, 50% of the rats had mild to moderate hepatic steatosis and 33% to 50% developed renal morphologic abnormalties; brains and spleens remained histologically normal. CONCLUSIONS: We found significant heavy-metal contamination of TPN solutions, and this contamination can lead to organ deposition and subsequent histologic abnormalities.