Autopsy tissue trace elements in 8 long-term parenteral nutrition patients who received the current U.S. Food and Drug Administration formulation

Iron, zinc, copper, manganese, chromium, and selenium levels were measured in autopsy tissues of 8 people with short bowel syndrome who received home parenteral nutrition (HPN) and the U.S. Food and Drug Administration (FDA)-approved trace element formulation for an average duration of 14 years (range, 2-21). Iron, zinc, copper, manganese and selenium were measured by inductively coupled plasma methods; chromium, by graphite furnace atomic absorption spectrometry. The levels in the 4 tissues studied, heart, skeletal muscle, liver, and kidney, were compared with levels in 45 controls who died without chronic gastrointestinal disorders. Results showed normal HPN patient values for iron and selenium, mild elevation of zinc, and major elevations of copper, manganese, and chromium. The implications of these results for trace-element supplements in long-term PN adult patients are discussed, and the need for reformulation of commercially available multi-trace element products in the United States is stressed.     

Vitamin Serum Level Variations Between Cycles of Intermittent Parenteral Nutrition in Adult Patients With Short Bowel Syndrome

Background: An alternative form of nutrition therapy for patients with short bowel syndrome (SBS) who do not have home parenteral nutrition (PN) available is the administration of the PN cycle during regular hospital admissions and oral vitamin supplement at home. The aim of this study was to evaluate serum levels of folic acid and vitamins A, B₁₂, C, and E before and after the PN cycle in patients with SBS. Materials and Methods: This research was conducted with 10 patients with SBS (less than 15 minutes of total barium transit time) who were receiving the PN cycle and oral vitamin supplement at home. Patients were evaluated regarding total food ingestion and oral vitamin supplement intake. Serum levels of vitamins were evaluated immediately after the end of each PN cycle (phase 1) and before the beginning of the next PN cycle (phase 2). Results: Patients’ nutrient ingestion was in accordance with recommendations for healthy individuals. Regarding the oral vitamin supplement intake, 20% of the patients presented low adherence. Although all patients had a normal serum level of folic acid and vitamin B₁₂, PN vitamin infusion during hospitalization and home oral vitamin supplement were not enough to make the serum levels of vitamins A, C, and E achieve normal values. Conclusion: This study documented that patients did not receive an adequate administration of oral vitamin supplements of vitamins A, C, and E through PN. More studies need to be conducted investigating higher doses of vitamin administration (oral or intravenous administration), assessing differences between water and liposoluble supplements.     

Impact of the Nationwide Intravenous Selenium Product Shortage on the Development of Selenium Deficiency in Infants Dependent on Long‐Term Parenteral Nutrition

Background: For patients dependent on parenteral nutrition (PN), selenium must be supplemented intravenously. A nationwide intravenous selenium shortage began in April 2011. The impact of this shortage on PN‐dependent infants was evaluated by examining the provision of selenium, development of biochemical deficiency, and costs associated with the shortage. Materials and Methods: This single‐center, retrospective study included PN‐dependent infants aged ≤1 year who weighed ≤30 kg, received PN for ≥1 month, and had ≥1 serum selenium measurement. The primary outcome was the incidence of biochemical selenium deficiency. Secondary outcomes included severity of biochemical deficiency, clinical manifestations, costs, and relationship between serum selenium levels and selenium dose. Results: The average selenium dose decreased 2‐fold during the shortage (2.1 ± 1.2 µg/kg/d; range, 0.2–4.6 µg/kg/d) versus the nonshortage period (3.8 ± 1 µg/kg/d; range, 2.4–6 µg/kg/d; P < .001). A linear relationship between serum selenium concentration and selenium dose was observed (r² = 0.42), with a dose of 6 µg/kg/d expected to result in normal serum levels in most cases. Similar proportions of patients developed biochemical deficiency in both groups: shortage period, 59.1%; nonshortage, 66.7%; P = .13. The severity of biochemical deficiency was similar between groups. A significant increase in incremental cost during the shortage was observed. Conclusion: This is the first study examining the impact of the intravenous selenium shortage on PN‐dependent infants. Both groups exhibited similarly high incidences of biochemical selenium deficiency, suggesting higher empiric doses may benefit this population. However, ongoing shortages limit the ability to provide supplementation.     

心脏病患者血清铜、锌、锰、铬、硒含量测定的临床意义

作者应用原子吸收光谱法和原子荧光光谱法测定了人血清铜、锌、锰、铬、及全血硒。测定对象分正常对照(40例),冠心病(36例),风湿性心脏瓣膜病(27例),扩张型心肌病(34例)4组。结果表明,正常人平均血铜值1.227±0.213μg/ml,锌1.0±0.149μg/ml,铬8.945±5.464ng/ml,锰12.163±4.21ng/ml,硒0.0625±0.03μg/ml,与文献报道值接近。其余三组心脏病人血铜值(1.448μg/ml,1.740μg/ml、1.746μg/ml)均显著升高(P<<0.001),血锌在冠心病、风心病组降低(P<0.01),铬三组无变化,锰仅在风心病组降低(P<0.01),硒在冠心病组增高(P<0.05),在扩张型心肌病组则显著降低(P<0.0001)。急性心肌梗塞(13例),血铜升高,而锌降低;心衰时血铜显著升高。以上变化对三种心脏病及急性心肌梗塞的诊断与鉴別、判断心脏的功能可能有一定意义。特别是扩张型心肌病呈现出特异性血硒降低,可能是该病的致病因素之一。     

Advances in Trace Element Supplementation for Parenteral Nutrition

Parenteral nutrition (PN) provides support for patients lacking sufficient intestinal absorption of nutrients. Historically, the need for trace element (TE) supplementation was poorly appreciated, and multi-TE products were not initially subjected to rigorous oversight by the United States Food and Drug Administration (FDA). Subsequently, the American Society for Parenteral and Enteral Nutrition (ASPEN) issued dosage recommendations for PN, which are updated periodically. The FDA has implemented review and approval processes to ensure access to safer and more effective TE products. The development of a multi-TE product meeting ASPEN recommendations and FDA requirements is the result of a partnership between the FDA, industry, and clinicians with expertise in PN. This article examines the rationale for the development of TRALEMENT^® (Trace Elements Injection 4*) and the FDA’s rigorous requirements leading to its review and approval. This combination product contains copper, manganese, selenium, and zinc and is indicated for use in adults and pediatric patients weighing ≥10 kg. Comprehensive management of PN therapy requires consideration of many factors when prescribing, reviewing, preparing, and administering PN, as well as monitoring the nutritional status of patients receiving PN. Understanding patients’ TE requirements and incorporating them into PN is an important part of contemporary PN therapy.     

Trace element balance in adults receiving parenteral nutrition: preliminary data

There have been many recommendations regarding trace element needs of adults receiving total parenteral nutrition. Balance studies for zinc, copper, manganese, chromium, selenium, and molybdenum were carried out in 3 critically ill patients in an intensive care unit. Results indicate that the need for zinc was great in them, but that for copper and manganese was lower. Small negative chromium and selenium balances were observed. Molybdenum, iron, cobalt, and iodine balances were attempted but proved difficult to interpret. The requirement of each trace element varied from patient to patient, and was influenced by the presence of gastrointestinal fluid loss and renal function.     

Trace element loss in urine and effluent following traumatic injury

BACKGROUND: Few data are available to establish recommendations for trace element supplementation during critical illness. This study quantified the loss of several elements and assessed the adequacy of manganese and selenium in parenteral nutrition (PN). METHODS: Men with traumatic injuries were grouped by renal status: adequate (POLY; n = 6), acute failure with continuous venovenous hemofiltration (CVVH; n = 2), or continuous venovenous hemodiafiltration (CVVHD; n = 4). PN supplied 300 microg/d manganese and 60 microg/d selenium. Urine and effluent (from artificial kidneys) were collected for 3 days and analyzed for boron, manganese, nickel, and silicon using inductively coupled plasma atomic emission spectrometry, and for selenium using atomic absorption spectrometry. RESULTS: POLY manganese and selenium excretion averaged (standard deviation [SD]) 7.9 (3.3) microg/d and 103.5 (22.4) microg/d, respectively. All elements except selenium were detected in dialysate (prior to use). CVVHD effluent contained 3.5 and 7.3 times more manganese and nickel than CVVH ultrafiltrate, respectively. Loss of manganese averaged 2.6%, 21%, and 73% of PN amounts for POLY, CVVH, and CVVHD groups, respectively. DISCUSSION: Minimal loss of manganese compared with the amount in PN suggests that excessive amounts are retained. POLY patients excreted more selenium than was in PN, indicating negative balance. POLY losses of boron and silicon were less than that published for healthy adults, reflecting less than typical intake, whereas loss during CVVH was in the normal reference range, possibly because of added intake from boron contamination of replacement fluids. All patients lost more nickel than amounts published for healthy adults. CONCLUSIONS: Current guidelines of 60-100 microg/d of parenteral manganese may be excessive for trauma patients. The uptake of manganese and nickel from contaminants in CVVHD dialysate should be investigated.     

严重烧伤病人微量元素的动态变化

目的：了解重度烧伤后血及２４ｈ尿中七种微量元素的变化规律。方法：选择烧伤面积，３０％的病人１０例，动态测定伤后至创面基本愈合时血、２４ｈ尿中锌、铜，铁、钼、硒、铬的浓度，同时选择未烧伤者３９例正常对照组。结果：２４ｈ尿中七种元素排泄量均增加，血锌明显下降，铜、铬、钼水平增加、铁、硒、锰未见明显变化。结论：严重烧伤后微量元素代谢发生较大变化，但是否需要补充及何时补充仍值得探讨。     

南京地区正常人和病人血中十一种元素含量的测定

本文报告用原子吸收光谱分析法(AAS),测定南京地区正常人血清中钙、镁、铜、锌、铁、铬、锰、镍、硒及全血中铅、镉元素的含量,经过分组统计处理,探讨了微量元素与性别及年龄的关系,同时通过大量病例测定,探讨了某些疾病与元素含量的关系。     

Poor zinc and selenium status in phenylketonuric children and adolescents in Brazil

Because of the restricted intake of high-biologic-value protein, children with phenylketonuria (PKU) may have lower than normal plasma concentrations of copper, zinc, and selenium. The purpose of the present study was to investigate erythrocyte zinc levels and serum copper and selenium levels in children and adolescents with PKU by analyzing the relation between their diet and the laboratory profiles of these elements. The study was conducted in 32 children and adolescents with PKU, who were on a special diet. Dietary records and blood samples were collected from each subject. Erythrocyte zinc and serum selenium levels were below normal in 37.5% and 90.6% of the subjects, respectively. Plasma copper levels were normal. Metabolic formulas were the only source of 86.9% of the zinc, 65.6% of the copper, and 32.4% of the selenium. Despite this, there was no significant correlation between the zinc formula supply and erythrocyte zinc levels (ρ = −0.143, P = .435) or the supply and serum levels for copper (ρ = −0.117, P = .523) and selenium (ρ = 0.113, P = .538). These results suggest that Brazilian patients with PKU present with low ingestion levels, low serum selenium levels, and low erythrocyte zinc levels.     

Growth hormone to improve short bowel syndrome intestinal autonomy: a pediatric randomized open-label clinical trial

Background: The ability of growth hormone (GH) to promote the weaning‐off of parenteral nutrition (PN) in short bowel syndrome (SBS) is unclear. No randomized controlled study is available in children. This study was undertaken to determine if GH could enhance the weaning off of PN in PN‐dependent children with SBS. Methods: A prospective randomized open‐label multicenter study was performed in 14 patients (mean age, 9 ± 1.4 years) with SBS (average small bowel length, 33 cm) and long‐term PN dependency (8 years) on an unrestricted diet. A standardized PN decrease with and without GH (0.14 mg/kg/d) was conducted. The patients were randomized to either a GH group (4 months of GH) or a control (CTR) group (4 months without GH, followed by 4 months with GH). Blood tests and a nutrition assessment of enteral and parenteral intakes were performed. Groups were compared with the Wilcoxon test. Results: Treatment with GH did not improve the weaning off of PN (decrease in PN caloric intake of 32.5% ± 9.6% in the GH group vs 35.2% ± 8.7% in the CTR group, nonsignificant). In the CTR group, GH treatment induced an additional but not statistically significant decrease of 8.8% ± 12.4% in daily calories. Parenteral needs returned to near basal rates 6 months after GH discontinuation (GH: 77.6% ± 10.6% vs CTR: 73.2% ± 7.4%). Weight decreased slightly in both groups. No biological parameters varied significantly. Conclusions: GH did not improve the weaning off of PN in PN‐dependent children with SBS.     

Serum vitamins in adult patients with short bowel syndrome receiving intermittent parenteral nutrition

Background: Short bowel syndrome (SBS) occurs after massive intestinal resection, and parenteral nutrition (PN) therapy may be necessary even after a period of adaptation. The purpose of this study was to determine the vitamin status in adults with SBS receiving intermittent PN. Methods: The study was conducted on hospitalized adults with SBS who were receiving intermittent PN therapy (n = 8). Nine healthy volunteers, paired by age and sex, served as controls. Food ingestion, anthropometry, plasma folic acid, and vitamins B₁₂, C, A, D, E, and K were evaluated. Results: The levels of vitamins A, D, and B₁₂ in both groups were similar. SBS patients presented higher values of folic acid (21.3 ± 4.4 vs 14.4 ± 5.2, P = .01) and lower values of vitamin C (0.9 ± 0.4 vs 1.2 ± 0.3 mg/dL, P = .03), α‐tocopherol (16.3 ± 3.4 vs 24.1 ± 2.7 µmol/L, P < .001), and phylloquinone (0.6 ± 0.2 vs 1.0 ± 0.5 nmol/L, P < .03). Eight‐seven percent of patients had vitamin D deficiency, and all patients presented with serum vitamin E levels below reference values. Conclusions: Despite all efforts to offer all the nutrients mentioned above, SBS patients had lower serum levels of vitamins C, E, and K, similar to those observed in patients on home PN. These findings suggest that the administered vitamins were not sufficient for the intermittent PN scheme and that individual adjustments are needed depending on the patient's vitamin status.     

Nutrition and immunological status in long-term follow up of children with short bowel syndrome

BACKGROUND: Little is known about the long-term evolution, nutrition status, growth, and eventual deficiencies of patients with short bowel syndrome (SBS) adapted to oral feeding after parenteral nutrition (PN). Because there are not absolute criteria for weaning from parenteral or enteral nutrition to oral feeding, new nutrient deficiencies may develop. Subtle nutrition deficits could induce subclinical immune deficiencies; therefore, we studied long-term growth, nutrition status, and the state of the immune system in 10 patients with SBS after weaning PN for at least 2 years. METHODS: Ten children with SBS (3-12 years old; mean, 7.4 years) who had not received PN for at least 2 years were studied. Anthropometric measurements, hemoglobin values, and indicators of iron, zinc, copper, folate and vitamin B(12) nutrition status were evaluated, along with immunoglobulins, lymphocyte subpopulations, and polymorphonuclear candidicidal activity. RESULTS: Weight-for-height was normal in 8 children; height-for-age was low in 5 children whose SBS was established early in life. Fat body mass was also low in 5 subjects. Four children presented macrocytosis, 2 with anemia. Low serum levels of vitamin B(12) (1 child), folates (4 children), and ferritin (2 children) were observed. Diminished candidicidal activity (4 children) was the only remarkable immunological abnormality. Conclusion: Many biologic and growth deficiencies are frequently seen in patients with SBS, even in children adapted to enteral feeding. This finding and the existence of previously unreported decreased candidicidal activity in some patients with SBS deserve long-term clinical and biologic follow up.     

实验性动脉粥样硬化对血清铜、锌、铬、锰、硒的影响

本研究观察高胆固醇血症和实验性动脉粥样硬化形成对必需微量元素Cu、Zn、Cr、Mn、Se代谢的影响。将22只家兔随机分为动脉粥样硬化造型组和对照组。造型组每只家兔每天喂胆固醇0.5g,该组在形成高胆固醇血症和动脉粥样硬化的4个月过程中,血清Cu均值逐渐升高,Zn逐渐降低,Ca/Zn比值逐渐增大,前后对比差异显著。对照组血清Cu、Zn无显著变化。两组的血清Cu、Zn同次测定值对比有显著或高度显著差异。血清Cr、Mn、Se均无显著变化。相关性检验证实,造型组血清胆固醇均值与血清Ca均值无显著相关(P>0.5),而与血清Zn均值呈高度负相关(P<0.01)。结果表明,在形成实验性动脉粥样硬化的过程中,高胆固醇食物及高胆固醇血症可引起血清Zn降低,又通过锌铜拮抗,使血清Cu升高。     

Effect of Recombinant Human Growth Hormone on Intestinal Absorption and Body Composition in Children With Short Bowel Syndrome

This prospective study aimed to establish the effect of recombinant human growth hormone (rhGH) on intestinal function in children with short bowel syndrome (SBS). Eight children with neonatal SBS were included. All were dependent on parenteral nutrition (PN) for >3 years (range, 3.8–11.6 years), with PN providing >50% of recommended dietary allowance for age (range, 50%–65%). The subjects received rhGH (Humatrope) 0.13 mg/kg/d subcutaneously over a 12‐week period. The follow‐up was continued over a 12‐month period after rhGH discontinuation. Clinical and biological assessments were performed at baseline, at the end of the treatment period, and 12 months after the end of treatment. No side effects related to rhGH were observed. PN requirements were decreased in all children during the course of rhGH treatment. Between baseline and the end of treatment, significant increases were observed in concentrations (mean ± standard deviation) of serum insulin‐like growth factor 1 (103.1 ± 49.9 µg/L vs 153.5 ± 82.2 µg/L; P < .01), serum insulin‐like growth factor–binding protein 3 (1.7 ± 0.6 mg/L vs 2.5 ± 0.9 mg/L; P < .001), and plasma citrulline (16.5 ± 14.8 µmol/L vs 25.2 ± 18.3 µmol/L; P < .05). A median 54% increase in enteral intake (range, 10%–244%) was observed (P < .001) and net energy balance improved significantly (P < .002). It was necessary for 6 children to be maintained on PN or restarted after discontinuation of rhGH treatment, and they remained on PN until the end of the follow‐up period. A 12‐week high‐dose rhGH treatment allowed patients to decrease PN, but only 2 patients could be definitively weaned from PN. Indications and cost‐effectiveness of rhGH treatment for SBS pediatric patients need further evaluation.     

Anemia and Leukopenia in a Long‐Term Parenteral Nutrition Patient During a Shortage of Parenteral Trace Element Products in the United States

Recently, drug shortages in the United States have affected multiple components of the parenteral nutrition (PN) solution. A 62‐year‐old patient with systemic sclerosis who was dependent on home PN due to intestinal dysmotility developed anemia and leukopenia approximately 4 months after parenteral copper was withheld from her PN solution due to drug shortages. The patient was not able to tolerate a sufficient amount of oral multivitamins with trace elements due to severe dysphagia. Her serum copper and ceruloplasmin concentrations were undetectable, confirming the diagnosis of severe copper deficiency. The hematological abnormalities promptly resolved with copper supplementation. This report emphasizes the importance of close monitoring for nutrient deficiencies during drug shortages and supplementing with oral or enteral nutrition when feasible, particularly in high‐risk patients such as those with intestinal malabsorption or short bowel syndrome who are dependent on long‐term PN.     

Prospective analysis of serum carotenoids,vitamin A,and tocopherols in adults with short bowel syndrome undergoing intestinal rehabilitation

ObjectiveCarotenoids, vitamin A, and tocopherols serve important roles in many key body functions. However, availability of these compounds may be decreased in patients with short bowel syndrome (SBS) due to decreased oral intake of fruits and vegetables and/or decreased intestinal absorption. Little information is available on serum concentrations of carotenoids, vitamin A, and tocopherols during chronic parenteral nutrition (PN) or during PN weaning. The aim of this study was to prospectively examine serum concentrations of a wide variety of carotenoids, vitamin A, and tocopherols in patients with SBS undergoing an intensive 12-wk intestinal rehabilitation program.MethodsTwenty-one PN-dependent adult patients with SBS were enrolled in a 12-wk intestinal rehabilitation program, which included individualized dietary modification, multivitamin supplementation, and randomization to receive subcutaneous placebo (n = 9) or human growth hormone (0.1 mg · kg^?1 · d^?1; n = 12). PN weaning was initiated after week 4 and advanced as tolerated. Serum concentrations of carotenoids, vitamin A, and tocopherols were determined at baseline and at weeks 4 and 12.ResultsA significant percentage of subjects exhibited low serum concentrations for carotenoids and α-tocopherol at study entry, and a few subjects had low concentrations of retinol (5%). Carotenoid and vitamin A valves did not improve over time, while α-tocopherol levels rose. Serum α-tocopherol concentration was negatively associated with PN lipid dose (r = ?0.34, P < 0.008).ConclusionPatients with SBS are depleted in diet-derived carotenoids despite oral and intravenous multivitamin supplementation and dietary adjustment during intestinal rehabilitation and PN weaning. Reduction of PN lipid infusion may improve serum α-tocopherol concentrations.     

Correlation of cholestasis with serum copper and whole-blood manganese levels in pediatric patients.

Many institutions reduce or eliminate copper (Cu) and manganese (Mn) in parenteral nutrition (PN) solutions when cholestasis develops. Little data exist to support this practice. Fifty-four subjects with known serum Cu, whole-blood Mn, and serum-conjugated bilirubin levels were evaluated in this prospective, observational study. Subjects ranged in weight from 760 g to 65.2 kg. Subjects weighing <25 kg received a daily parenteral dose of 20 microg/kg Cu and 5 microg/kg Mn. Subjects weighing > or =25 kg received a dose of 500 microg/d Cu and 150 microg/d Mn. Cholestasis was defined as a conjugated bilirubin level > or =2 mg/dL. Of the 54 subjects, 20 had cholestasis. Fifteen patients had elevated Cu levels, and 21 had high Mn levels. Seven of the subjects had both high Cu and high Mn levels. The regression model comparing cholestasis as a predictor of high, low, or normal Cu level was not significant (P = .9588). Cholestasis was not a significant predictor of high, low, or normal Mn levels (P = .6533). No correlation between Cu and Mn levels was found. The authors found no significant relationship between conjugated serum bilirubin levels > or =2.0 mg/dL, serum Cu, and whole-blood Mn levels. They found insufficient evidence to support the practice of dosing Mn from a Cu level or vice versa. They recommend obtaining Cu and Mn levels on all pediatric patients who develop cholestasis prior to adjusting parenteral doses and at regular intervals for all long-term PN patients.