Hospital Pharmacy - December 2020 - 377

Dickerson et al
recommendations for multiple-trace element (MTE)
product reformulation and provide insight into individualized trace element prescribing during PN therapy.
Thirty-two unique PN components encompassing 65 different products were analyzed for manganese, copper,
chromium, selenium, and zinc contamination using
inductively coupled plasma mass spectrometry. The
extent of cumulative trace element exposure was then
extrapolated to theoretical PN formulations for adult,
pediatric, and neonatal populations. The results identified chromium and manganese as being the most prevalent contaminants, present in 65.6% and 51.5% of all
components analyzed, respectively. The products associated with the greatest chromium contamination were
potassium phosphate (0.21 mg/mL) and sodium phosphate (0.18 mg/mL) and those with the greatest manganese contamination were magnesium sulfate (3.01 mg/
mL) and calcium gluconate (0.15 mg/mL). Minimal contamination was found for selenium, zinc, and copper.
No detectable trace element contamination was found
in sterile water, dextrose 70%, lipid injectable emulsion
(intravenous lipid emulsion [ILE]), potassium chloride,
heparin (100 units/mL), vitamin K, and adult multivitamin injection (vial 2). In the theoretical adult, pediatric,
and neonatal PN formulations, calculated daily chromium contamination was 4.85, 1.5, and 0.28 mg, respectively. Manganese contamination was 25.18, 9.92, and
1.37 mg, respectively. The authors concluded that trace
element contamination is prevalent in PN components
and their findings support reformulation of adult, pediatric, and neonatal manufactured MTE products to
eliminate chromium, reduce manganese (elimination in
neonatal products), and supply full daily physiologic
requirements of selenium, zinc, and copper.
This study serves as a reminder that trace element
contamination continues to be a significant concern for
clinicians involved in PN management. ASPEN has published trace element dosing recommendations for adults,
pediatrics, and neonates.24 These recommendations
differ from commercially available MTE products, specifically with respect to chromium and manganese,
resulting in over-supplementation and the call for
MTE product reformulation. While chromium toxicity
is rare and not well characterized, manganese toxicity
can be significant, leading to neurological consequences
such as gait disturbances, lethargy, confusion,
Parkinsonian-like symptoms, seizures, neuropathy, and
memory loss The risk for hypermanganesemia is higher
for those on long-term PN support and those with liver
disease causing impaired biliary excretion of manganese
and increased manganese deposition in the liver and
brain. Until reformulation of MTE products occurs,
this study supports the omission of chromium supplementation, a reduction or omission of manganese supplementation, and use of individual trace element

377
components to better meet requirements in patients
receiving PN across the age spectrum, especially in
patients receiving long-term PN or those at risk for
over-supplementation. For the new U.S. Food and
Drug Administration (FDA)-approved trace element
products, testing for product contamination is warranted. During periods of individual trace element product shortages, use of the multiple trace element product
may be a practical solution with close monitoring for
toxicity in high-risk populations.
3. Huston et al.8 Calcium chloride and calcium gluconate
in neonatal parenteral nutrition solutions with added
cysteine: Compatibility studies using laser light obscuration methodology
Cysteine is often added to neonatal PN solutions as a
conditionally essential amino acid (AA) and to enhance
calcium phosphate solubility by lowering solution pH. A
recent study suggested that in the absence of cysteine,
calcium chloride, and calcium gluconate have comparable compatibility profiles with phosphate in neonatal PN
solutions.25 This study compared the compatibility of
calcium chloride to calcium gluconate at various concentrations from 0 to 20 mmol/L in neonatal PN solutions
with the addition of cysteine 50 or 100 mg/dL (equivalent to 20 and 40 mg/g AA, respectively). PN solutions
contained a final concentration of 2.5% AA (Premasol),
10% dextrose, potassium phosphate at concentrations
from 0 to 15 mmol/L, and other typical additives. PN
solutions were incubated at 37 C for 24 hours. The pH
of all solutions decreased after 24 hours of incubation.
Visual inspection that involved transilluminating the
solution with a bright beam of light in a dark room
before and after incubation showed no evidence of precipitation. Particle counts were determined by laser light
obscuration (LO) and microscopic particle counts,
which were consistent with the recommended Method
1 and Method 2 procedures in accordance to
USP<788> for evaluating calcium phosphate particle
formation. Microscopic particle counts for particles
10 lm and 25 lm were all fewer than 1 particle/mL
for all samples, suggesting no difference in compatibility
between the calcium salts in the presence of cysteine. In
contrast, results from the LO studies showed that all
calcium gluconate containing solutions, including the
sample with no phosphate, had particle counts that
greatly exceeded USP recommended guidelines using
the 10 lm diameter threshold. Acceptable particle
counts were found in control samples containing calcium
chloride with no phosphate, and calcium chloride with
potassium phosphate at concentrations not exceeding 15
and 12.5 mmol/L, respectively. Compared with the chloride salt, those solutions containing calcium gluconate
consistently had higher particle counts (>10-fold). The

Hospital Pharmacy - December 2020

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