Drug Shortages and Selenium Deficiency

If you participate in the care of patients who are dependent on parenteral nutrition, then you are familiar with frequent component drug shortages.  Generally, attempts to manage these shortages involve rationing and targeting those with the greatest need.  In one institution, this was not effective in preventing biochemical deficiency of selenium (JPEN 2013; DOI 10.1177/0148607113486005).  Thanks to Kipp Ellsworth for this reference.

The authors describe five pediatric patients who were completely dependent on parenteral nutrition due to intestinal failure.  During a 9-month shortage of intravenous selenium, all five who were previously selenium replete had deficiency identified (level <20 ng/mL).

After these deficiencies were identified, the patients were placed on Multitrace-5 (MTE-5).  This multivitamin contains 20 mcg/mL of selenium.  While patients prior to the shortage typically received 50-75 mcg/day, after instituting MTE-5, they received 10-26 mcg/day.  Nevertheless, this helped prevent any clinical evidence of deficiency.  In patients with selenium deficiency, there is an increased risk of cardiomyopathy, chronic illness, and death.

The authors note that their preference is to individually dose the specific trace elements and that MTE-5 can contribute to elevated levels of manganese and chromium with long-term usage.

Related blog links:

Related references:

  • -Gastroenterol 2009; 137: S61-S69.
  • -J Pediatr 2011; 159: 39.

Copper in Cholestasis

More data indicate that copper levels in infants receiving parenteral nutrition are usually not affected by cholestasis (JPEN 2013; 37: 92-96).

A retrospective study reviewed all patients younger than 1 year who had copper levels measured between 1999-2009 at Riley Hospital for Children.  Inclusion criteria: parenteral nutrition for at least 50% of caloric needs and cholestasis (direct bilirubin >2 mg/dL).

Key findings:

  • 26 of 28 patients had gastrointestinal disorders.  82% were receiving standard parenteral nutrition (PN) dose of copper (20 mcg/kg/day).
  • Only one elevated copper level was found in a child with congenital heart disease.
  • 46% (n=13) of cholestatic infants had low copper levels.  Three of theses infants had no copper in their PN.
  • There was no correlation between bilirubin level and measured copper values.

Bottomline:

Measure copper values periodically in patients requiring parenteral nutrition.  Most patients, even cholestatic patients, will require standard dosing but some will need less and some more.

Additional References:

  • -JPGN 2010; 50: 650-54.  n=28.  (only 2 had elevated Cu). Typical Cu supplementation in HAL did not lead to significant increase in Cu toxicity or worsening of liver disease in cholestatic infants.  Study prompted by single infant who developed Cu deficiency/anemia.
  • -Clin Gastro & Hepatol 2004; 2: 1074. Two patients with Cu deficiency after bariatric surgery
  • -JPGN 2000; 31: 102-111. (review)

Minimizing malnutrition in Biliary Atresia

A retrospective study in Liver Transplantation reviews a single center experience with the use of parenteral nutrition (PN) in patients with end-stage liver disease due to biliary atresia (Liver Transpl 2012; 18: 121-129).  In this study which spanned the past twenty years, 25 PN BA patients were compared to 22 non-PN BA patients –all patients were younger than 36 months.  PN was started when maximal enteral nutrition failed to improve markers of malnutrition (triceps skinfold thickness, & mid-arm circumference).  Among the PN BA patients, there was a higher gastrointestinal bleeding rate and ascites; however, there was no difference in the rates of bacteremia, length of intensive care unit stay after liver transplantation, or patient/graft survival.  The authors speculate that the outcome for the PN BA patients would have been much worse without the PN as malnourished BA patients are at increased risk for graft failure and post-transplant complications.  It is noteworthy that PN patients did have progression of their liver disease that seemed to accelerate with the administration of PN, perhaps due to PN-associated cholestasis.  Specific changes included higher bilirubin levels, lower platelet counts, worsened coagulopathy, and higher calculated PELD scores.

Additional References:

  • Hepatology 2007; 46: 1632-38.  Growth failure and outcomes in infants with BA.
  • J Pediatr 2005; 147: 180-85.  Outcomes of 755 BA patients listed for liver transplantation.