Bone Mineral Composition Among Long-Term Parenteral Nutrition Patients: Postmortem Assessment of Calcium, Phosphorus, Magnesium, and Select Trace Elements.

BACKGROUND: Patients receiving long-term parenteral nutrition (PN) treatment are at risk of developing metabolic bone diseases (MBDs). The bone compartment serves as a repository for a range of metal(loid)s that are administered intravenously to patients via PN solutions. Thus, the mineral composition of patient bones may be linked to the development of MBDs in this group. METHODS: We measured 12 elements in bone samples obtained post mortem from 7 long-term (2-21 years) PN patients and 18 control bones obtained from hip/knee replacement surgery. The samples were cleaned, digested, and subsequently analyzed using a method based on inductively coupled plasma tandem mass spectrometry. RESULTS: Compared with the control group, bones obtained from PN patients were significantly (P < 0.05) depleted in calcium (Ca), phosphorus (P), magnesium (Mg), chromium, and strontium and enriched in manganese (Mn), zinc, barium, cadmium (Cd), and uranium (U). No differences were observed for cobalt or lead. CONCLUSIONS: Depletion of major components of bone mineral (Ca, P, and Mg) and enrichment in known toxicants (Cd, Mn, U) are concerns for PN patients.

An assessment of exposure to rare earth elements among patients receiving long-term parenteral nutrition.

Patients receiving long-term parenteral nutrition (PN) are exposed to potentially toxic elements, which may accumulate in bone. Bone samples collected from seven PN patients (average = 14 years) and eighteen hip/knee samples were analyzed for Al as part of a previous investigation. Yttrium was serendipitously detected in the PN bone samples, leading to the present investigation of rare earth elements (REEs). A method for quantitating fifteen REEs in digested bone was developed based on tandem ICP-MS (ICP-MS/MS) to resolve spectral interferences. The method was validated against nine biological reference materials (RMs) for which assigned values were available for most REEs. Values found in two NIST bone SRMs (1400 Bone Ash and 1486 Bone Meal) compared favorably to those reported elsewhere. Method detection limits ranged from 0.9 ng g-1 (Tm) to 5.8 ng g-1 (Y). Median REE values in the PN patient group were at least fifteen times higher than the "control" group, and exceeded all previously reported data for eleven REEs in human bones. REE content in PN bones normalized to the Earth's upper crust revealed anomalies for Gd in two patients, likely from exposure to Gd-containing contrast agents used in MRI studies. A retrospective review of the medical record for one patient revealed an almost certain case of nephrogenic systemic fibrosis, associated with Gd exposure. Analysis of two current PN formulations showed traces of REEs with relative abundances similar to those found in the PN bones, providing convincing evidence that PN solutions were the primary source of REEs in this population.

A Call to Action to Bring Safer Parenteral Micronutrient Products to the U.S. Market.

The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) started an intensive review of commercially available parenteral vitamin and trace element (TE) products in 2009. The chief findings were that adult multi-TE products currently available in the United States (U.S.) provide potentially toxic amounts of manganese, copper, and chromium, and neonatal/pediatric multi-TE products provide potentially toxic amounts of manganese and chromium. The multivitamin products appeared safe and effective; however, a separate parenteral vitamin D product is needed for those patients on standard therapy who continue to be vitamin D depleted and are unresponsive to oral supplements. The review process also extended to parenteral choline and carnitine. Although choline and carnitine are not technically vitamins or trace elements, choline is an essential nutrient in all age groups, and carnitine is an essential nutrient in infants, according to the Food and Nutrition Board of the Institute of Medicine. A parenteral choline product needs to be developed and available. Efforts are currently under way to engage the U.S. Food and Drug Administration (FDA) and the parenteral nutrient industry so A.S.P.E.N.'s recommendations can become a commercial reality.

Excessive aluminum accumulation in the bones of patients on long-term parenteral nutrition: postmortem analysis by electrothermal atomic absorption spectrometry.

BACKGROUND: Aluminum (Al) contamination of parenteral nutrition (PN) solutions remains a concern for long-term PN patients. Al accumulates particularly in bone. Excessive exposure to Al may result in increased Al body burden and impaired bone formation and mineralization, leading to bone disease. Although the U.S. Food and Drug Administration (FDA) has limited Al contamination in large-volume parenteral solutions, small-volume parenterals may still contribute considerable amounts of Al to PN solutions. The goal of this study is to determine whether or not long-term adult PN patients remain at risk for increased bone Al accumulation. METHODS: We measured Al accumulation in autopsy bones from 7 patients who had received PN for 2-21 years and compared bone Al levels with those in living control patients undergoing hip or knee replacement. Electrothermal atomic absorption spectrometry was used for bone Al measurements. RESULTS: When compared with bone Al content in controls, markedly elevated Al levels (P < .0001) were found in the bones of all but 1 patient, who received PN for only 2 years before death. Even greater Al accumulation was found for PN patients who developed late renal impairment (P = .0159). CONCLUSIONS: We conclude that long-term adult PN patients continue to be at risk for Al toxicity.

A.S.P.E.N. position paper: recommendations for changes in commercially available parenteral multivitamin and multi-trace element products.

The parenteral multivitamin preparations that are commercially available in the United States (U.S.) meet the requirements for most patients who receive parenteral nutrition (PN). However, a separate parenteral vitamin D preparation (cholecalciferol or ergocalciferol) should be made available for treatment of patients with vitamin D deficiency unresponsive to oral vitamin D supplementation. Carnitine is commercially available and should be routinely added to neonatal PN formulations. Choline should also be routinely added to adult and pediatric PN formulations; however, a commercially available parenteral product needs to be developed. The parenteral multi-trace element (TE) preparations that are commercially available in the U.S. require significant modifications. Single-entity trace element products can be used to meet individual patient needs when the multiple-element products are inappropriate (see Summary/A.S.P.E.N. Recommendations section for details of these proposed modifications).

Complex home care: Part I--Utilization and costs to families for health care services each year.

As many as 120 persons per million people in the United States are dependent on the lifelong, complex, technology-based care of home parenteral nutrition (HPN) infusions. However, data for costs paid by families for HPN-related health care services and for non-reimbursed expenditures are rarely tabulated and most often underestimated. The goals of this study were to describe health care services used by families to manage HPN, report the frequency of each service used annually, and estimate the average annual non-reimbursed costs to families for these health services. The numerous and varied types of services reported and the time required to coordinate and access HPN services illustrates the challenges faced by patients and their family caregivers. The lack of a coordinated and efficient system for delivering complex chronic care results in poorer outcomes for HPN patients and their families on-reimbursed costs and the extensive amount of time required to coordinate multi-professional services negatively impacts the clinical outcomes and quality of life of complex chronic home care.

Micronutrients in parenteral nutrition: too little or too much? The past, present, and recommendations for the future.

This research workshop in 2009 grew out of a concern in the United States, Europe, and other countries with advanced medicine that it was time to revisit the parenteral requirements for a number of micronutrients. Critical questions sought to be answered included the following: Were there micronutrients not routinely added that should be part of a parenteral nutrition (PN) formula? Were other micronutrients present but in inappropriate amounts? How are various micronutrient requirements altered in the critically or chronically ill?

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.

Home parenteral nutrition: survival, cost, and quality of life.

This article summarizes what is known about which factors influence survival of patients on home parenteral nutrition, the costs related to this therapy, and the quality of life for patients living on home parenteral nutrition. The article refers to both North American and European experiences with this complex therapy.

Nutrition in the perioperative patient.

The association of malnutrition with surgical morbidity and mortality is well recognized. The question of whether this relationship is causal or simply an association in sick patients has been hotly debated. The field of nutrition support has grown out of the belief that correcting malnutrition will modify associated risks for poor outcome. It has been easier to substantiate this belief in some clinical situations than in others. The evidence for nutrition support during the perioperative period is reviewed and recommendations are made about where nutrition support is most useful and where it may be counterproductive. Some of the important unanswered questions about perioperative nutrition support are raised.

Management of complications in patients receiving home parenteral nutrition.

Patients receiving long-term home parenteral nutrition tend to fall under the care of adult and pediatric gastroenterologists. This article reviews the management of potential infectious, mechanical and metabolic complications and describes common psychosocial issues related to the therapy. The point at which to refer the patient to an intestinal failure program offering autologous bowel reconstruction and small bowel transplantation is discussed.

Home parenteral nutrition: does affiliation with a national support and educational organization improve patient outcomes?

BACKGROUND: For patients receiving home parenteral nutrition (HPN), catheter-related bloodstream infection (CRBSI) and reactive depression may significantly impact quality-of-life. This study evaluated the influence of patient affiliation with a national organization promoting HPN education and peer support on these outcome variables. METHODS: Using a case-control design, we compared 2 groups of affiliated patients with nonaffiliated controls, who were matched for diagnosis, HPN duration, sex, and age. Group 1 data were obtained from patients in large HPN medical practice programs. Group 2 data were obtained from patients in small medical practices with a small number of HPN patients. All participants were evaluated by structured interviews every 6 months over 18 months. RESULTS: In both data collection groups, affiliated patients (A) had significantly higher (mean +/- SD) quality-of-life scores compared with nonaffiliated patients (NA): (Gr 1: A, 19.8 +/- 4.7 versus NA, 17.6 +/- 5.6, p = .05; Gr 2: A, 20.4 +/- 5.2 versus NA, 17.3 +/- 4.8, p = .05). Affiliated patients also had lower depression scores (Gr 1: A, 10.9 +/- 10.4 versus NA, 20.4 +/- 13.6, p = .01; Gr 2: A, 12.5 +/- 9.6 versus NA, 18.5 +/- 10.8, p = .03) and a lower incidence of catheter-related infections (Gr 1: A, 0.10 +/- 0.3 versus NA, 0.60 +/- 0.55, p = .01; Gr 2: A, 0.27 +/- 0.55 versus NA, 0.71 +/- 0.64, p = .02) than nonaffiliated patients. CONCLUSIONS: Affiliation with an organization that provides ongoing HPN education and peer support was associated with significantly better HPN outcomes. Alternative explanations are discussed in relation to limitations of the case-control design.

The Neurologic Syndrome of Vitamin E Deficiency: Laboratory and Electrophysiologic Assessment.

A human requirement for vitamin E was established in the 1960s; however, its role in neurologic function has been recognized only for the past 10 years. The neurologic syndrome of vitamin E deficiency is seen in patients with chronic steatorrhea and principally affects functions of the spinal cord posterior column and retina; however, it can also involve other parts of both the central and peripheral nervous system and the proximal muscles. This review examines the clinical and laboratory assessment of patients suspected of having vitamin E deficiency and points out the importance of recognizing the syndrome since many of the incapacitating symptoms are largely reversible.