Special Interest

A.S.P.E.N. Statement on Aluminum in Parenteral NutritionSolutions

The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Aluminum Task ForcePamela J. Charney, MS, RD, LD, CNSD, Chair

Aluminum is one of the most common elementsfound in the soil. Although it has no known func-tions in the human body, it can be found in smallamounts in most mammalian tissue. Until recently,little was known of the effects of aluminum accumu-lation in human tissue. Increased tissue aluminumlevels have now been implicated in some pathologicconditions in susceptible patient populations.

Exposure to aluminum occurs through a varietyof sources. Aluminum is present in cooking utensils,aluminum cans, utensils, and containers. Manymedications contain aluminum as a contaminant oras a component of the raw materials. Skin exposureto aluminum occurs through aluminum containingantiperspirants, although it is not known if skinexposure leads to tissue accumulation. It is esti-mated that humans ingest 5 to 20 mg of aluminumper day. Less than 1% of orally consumed aluminumis absorbed, with 99% of absorbed aluminum lost inthe urine. However, circulating aluminum is highlyprotein bound (95%) in plasma. Plasma binding issaturable so in healthy individuals, urine excretionincreases when intake increases. Therefore, the vastmajority of the population is not at risk for alumi-num toxicity from oral or enteral intake.

Certain patient populations may be at risk foraluminum accumulation in tissue and resulting alu-minum toxicity. In the early 1980s, it was noticedthat some patients with end-stage renal disease ondialysis developed signs and symptoms thought tobe associated with aluminum toxicity, includingencephalopathy and bone pain. It was determinedthat aluminum present in dialysate was responsible,leading to the subsequent removal of aluminumfrom dialysis solutions. Accumulation of aluminumin bone, serum, and tissue of neonates receivinglong-term parenteral nutrition has also been noted.Tissue accumulation of aluminum would be muchless in infants who receive total parenteral nutrition

for shorter periods. The true significance of tissuealuminum accumulation is not known at this time.

Current StatusIn 1990, the US Food and Drug Administration

(FDA) published an intent to propose regulation ofaluminum content of parenteral solutions. In 2000,a final rule was published, with a proposed effectivedate in 2001. The effective date was postponed, withthe final effective date set for July 26, 2004. Large-volume parenteral solutions will be required to con-tain �25 �g/L of aluminum. Small-volume paren-teral solution products will be required to be labeledwith the maximum aluminum content at expiration.

All large- and small-volume parenterals (large-volume parenterals include amino acids, dextrose,fat emulsions, sterile water for injection, saline, andelectrolyte solutions [IV fluids with added electro-lytes]; small volume parenterals include calciumsalts [gluconate, chloride, and gluceptate], potas-sium salts [acetate, chloride, and phosphates],sodium salts [acetate, lactate, and phosphates],magnesium salts [only sulfate was mentioned in themandate, not chloride], multiple electrolyte additivesolutions, parenteral multivitamins, trace elementsand single-entity parenteral vitamins) used in par-enteral nutrition compounding will contain the fol-lowing warning in their product literature: “WARN-ING: This product contains aluminum that may betoxic. Aluminum may reach toxic levels with pro-longed parenteral administration if kidney functionis impaired. Premature neonates are particularly atrisk because their kidneys are immature, and theyneed large amounts of calcium and phosphate solu-tions, which contain aluminum. Research indicatesthat patients with impaired kidney function, includ-ing premature neonates, who receive parenterallevels of aluminum at �4 to 5 �g/kg/day accumulatealuminum at levels associated with central nervoussystem and bone toxicity. Tissue loading may occurat even lower rates of administration.”

The FDA requirements are summarized as fol-lows:

● Large-volume parenterals* will be required tocontain �25 �g/L of aluminum.

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● Small-volume parenteral solutions will berequired to be labeled with the maximum alu-minum content at expiration.

● These requirements are meant to encouragemanufacturers to lower the aluminum contentof parenteral solutions.

Recommendations for PracticeBecause there is risk of aluminum toxicity in

some patient populations, it is recommended thataluminum exposure be minimized in all patientsreceiving parenteral nutrition. In many patients,particularly the neonatal population, it may beimpossible to provide �4–5 �g/kg aluminum. Pa-tient safety should remain the first and foremostconsideration when compounding parenteral nutri-tion solutions.

● The FDA regulation applies to industry only;however, those ordering and preparing paren-teral nutrition solutions should be aware of thepotential aluminum contaminants present inthe components of these solutions

● Compounding pharmacies may desire todevelop a database containing the aluminumcontent of products used in parenteral nutritionsolutions.

● Clinicians may want to purchase equivalentproducts with the lowest aluminum contentwhen possible and should monitor changes inthe pharmaceutical market that may affect alu-minum concentrations.

In addition to products used in preparing paren-teral nutrition solutions, clinicians must be aware ofother sources of aluminum:

● Heparin● Albumin● Blood products● L-cysteine

ConclusionsIn light of the potential link between aluminum

contamination of parenteral solutions and morbidityamong patients receiving parenteral nutrition, theFDA is issuing a rule to regulate aluminum contentand to establish labeling requirements for large andsmall volume parenterals used in the compoundingof parenteral nutrition solutions. All healthcare pro-viders involved in the provision of parenteral nutri-tion should ensure that aluminum exposure is lim-ited when possible in at risk populations. Patientmonitoring for aluminum toxicity may not be possi-ble or reliable in most settings.

Suggested Resources1. Federal Register, 2000; 65:4103 to 11.2. Federal Register, 2002; 67:52429 to 31.3. ASCN/A.S.P.E.N. workgroup on standards for aluminum con-

tent of parenteral solutions. Am J Clin Nutr. 1991;53:399–402. Available at: http://www.naspgn.org/sub/position_papers/aluminum.asp.

*Large volume parenterals include: amino acids,dextrose, fat emulsions, sterile water for injection,saline, and electrolyte solutions (IV fluids withadded electrolytes). The FDA regulation applies toamino acid and dextrose solutions used in com-pounding parenteral nutrition solutions.

Small volume parenterals include calcium salts(gluconate, chloride, and gluceptate), potassiumsalts (acetate, chloride, and phosphates), sodiumsalts (acetate, lactate, and phosphates), magnesiumsalts (only sulfate was mentioned in the mandate,not chloride), multiple electrolyte additive solutions,parenteral multivitamins, trace elements, and sin-gle-entity parenteral vitamins. The FDA regulationapplies to vitamin and electrolyte solutions used incompounding parenteral nutrition solutions.

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