September 2015 Issue

Parenteral Nutrition: Reverse Nutrient Deficiencies
By Kristi King, MPH, RDN, CNSC, LD
Today's Dietitian
Vol. 17 No. 9 P. 12

Learn more about the causes, the most common nutrient shortfalls, and treatment and management strategies.

Patients receiving parenteral nutrition (PN) tend to be a vulnerable population when it comes to developing nutrient deficiencies. They may absorb and meet their macronutrient needs orally, but they may not meet their micronutrient needs even when receiving PN.1

There's no consensus on how many of the estimated 33,000 PN patients have experienced nutrient deficiencies. Prevalence studies of this population haven't been published, so the medical community doesn't know the breadth of the deficiency issue. However, one PN pediatric study showed that at least 50% of subjects had at least one micronutrient or vitamin deficiency.2

To track PN patient outcomes, the American Society for Parenteral and Enteral Nutrition (ASPEN) developed the Sustain National Patient Registry for Nutrition Care, a voluntary database that practitioners can join. The database tracks diagnoses, PN formulation patterns, line infections, hospital readmissions, and mortality of PN patients. Data from the registry confirm the thought that the majority of PN patients suffer significant gastrointestinal (GI) disorders with 76% of the enrollees having short bowel, GI obstruction, GI fistulas, or motility disorders,3 which are associated with fluid losses that contribute to nutrient deficiencies.
This article discusses these and other causes of nutrient deficiencies, the common nutrient shortfalls in PN patients, and strategies for treatment and management.

Causes
Despite continued advances in health care, questions continue to arise about how and why nutrient deficiencies in the PN population occur. GI losses and malabsorption in the PN patient population help contribute to nutrient deficiencies, according to Robert J. Shulman, MD, a professor of pediatric nutrition at Baylor College of Medicine, and director of the Center for Pediatric Abdominal Pain Research at Texas Children's Hospital. GI fluid losses can cause deficiencies in zinc, sodium, copper, and bicarbonate. Unless these nutrients are measured regularly in GI fluid losses, it's difficult to quantify nutrient composition to determine which ones to replenish.

In addition to GI losses, the ongoing PN drug shortages help contribute to the nutrient shortfalls. Since 2009, nutrition professionals have seen significant shortages in PN additives, including but not limited to multivitamin packages, calcium gluconate, sodium acetate, magnesium sulfate, and trace elements.4 PN drug shortages aren't unique, as they occur approximately every 10 years. The first was reported in the late 1980s.4

Todd Canada, PharmD, BCNSP, FASHP, clinical pharmacy service manager at the University of Texas MD Anderson Cancer Center, says, "Nutrient deficiencies are quite common, especially with the current drug shortages. Due to product shortages, many homecare companies can't provide IV multivitamins or other minerals seven days a week, 365 days per year."

As a result of the shortages, dietitians have had to make difficult decisions about whether or not to include additives in PN care, and develop other remedies to help prevent nutrient deficiencies. 

Common Nutrient Shortfalls

Iron
Studies of adult PN patients have shown that 30% to 55% develop iron deficiency;5,6 pediatric studies show a wider percentage range of 40% to 84% of patients.2,7 Factors contributing to iron deficiency in the PN population include multiple blood draws, blood loss from surgery or bleeds, and increased GI losses.5 The main contributing factor is the exclusion of iron from packaged trace elements added to PN due to its incompatibility with IV fat emulsions.8

For patients on PN, dietitians should provide iron supplementation when clinically needed, but they must not overload. Bacteria and viruses both require iron to replicate; therefore, excess iron could potentially make this vulnerable population more prone to infection. If the patient has a duodenum (the main site of iron absorption), then theoretically, iron should be absorbed if given orally. However, if the patient has extreme upper small bowel dysmotility, iron absorption may be hindered. Dietitians should consider parenteral supplementation only when enteral supplementation fails. Iron sucrose, iron dextran, and ferrous gluconate all have been used and are deemed safe for infusion, but medical professionals should monitor patients closely due to risk of adverse reactions.5,9 Hardy and colleagues describe using 25 to 50 mg of iron once per month via IV.9 Dietitians can use the following calculations in determining how much iron is necessary for repletion: Replacement iron (Fe, mg): 0.3 x weight (lb) x [100-(actual hemoglobin x 100/desired hemoglobin)].9 The last resort would involve a blood transfusion.
Blood transfusions usually supply about three months' worth of iron at one time, so patients receiving multiple blood transfusions may never need supplemental iron.

Vitamin D
Vitamin D is essential for bone health, and is especially important in patients receiving PN since they have an increased risk of bone disease.1 As in healthy US adults, vitamin D tends to be a common nutrient shortfall in PN patients. Studies show that 30% to 87% of adults10,11 and 20% to 35% of children on PN are vitamin D deficient.2,7 Several factors can contribute to the deficiency, including malabsorption and limited sun exposure secondary to self-limiting behaviors such as avoiding lakes, pools, and beaches, since peripherally inserted central catheter and central lines should never get wet.

Vitamin D is included in a patient's daily multivitamin package before it's added to PN for administration. However, there are other options to consider to boost vitamin D levels since there's no individual PN additive nutrition professionals can give to patients diagnosed with a vitamin D deficiency. These options include the following:

• Increase the daily multivitamin dose, but note the risk of other nutrient overload.

• Administer high doses of vitamin D orally. Patients without a jejunum seem to be at increased risk of vitamin D deficiency,10 presumably due to increased malabsorption. Yet, patients with any length of remaining functioning bowel should be able to absorb at least minimal amounts of vitamin D.12

• Recommend patients ask their doctors about increasing sun exposure or using sunlamps to boost vitamin D levels, and the benefits/risks of ultraviolet rays.

Trace Elements

Zinc
Studies show that 10% of adult PN patients have a zinc deficiency,13 and infants and children have much higher rates at 20% to 30%.2,7 According to Laura Matarese, PhD, RDN, CNSC, LDN, an associate professor at East Carolina University in Greenville, North Carolina, "Zinc is probably the most likely deficiency to occur because many of these patients have large stool/ostomy losses where zinc is lost."

With no functional stores or zinc reserves in the body, assessment of this trace element can be difficult. Invisible hemolysis can cause serum levels to be higher than plasma zinc.9 Hypozincemia doesn't occur until advanced deficiency,9 although clinical signs and symptoms may be present before the patient reaches this stage. Signs of zinc deficiency can include significant hair loss, skin rash, mental slowness, taste changes, and growth failure in children. Even if energy and amino acid stores are repleted, the growth pattern may not improve until zinc status is fully corrected.14

Zinc is part of the trace element package that RDs should add daily to the PN mixture. Trace element packages tend to be dosed based on weight; however, in children, the weight dosage may underestimate the patient's individual needs.15 Catabolic patients may require an additional 2.5 to 4 mg per day of zinc, whereas those with significant output may need as much as 12 to 17 mg or an additional 200 mcg/kg per day for each liter of intestinal fluids lost.9,16 Conversely, practitioners should be cautious about administering excess zinc, as doses greater than 150 mg per day can interfere with copper and iron metabolism and cause more metabolic issues.16

The PN product shortage has significantly impacted trace element packages. Shortages of trace element packages have forced medical teams to choose more individual trace element additives, thus causing a shortage of individual elemental zinc additives. The three forms of zinc—zinc sulfate, zinc chloride, and zinc gluconate—all have been shown to be stable and appropriate for use in PN.9

Copper
Copper is a trace element needed for red blood cell production, immune function, and bone health. And, unfortunately, copper has been hit hard by the PN shortages, contributing to current deficiencies. High zinc administration, iron and vitamin C supplementation, and gastric-acid suppression regimens all can interfere with copper metabolism.8

Studies have shown deficient serum levels in 30% to 56% of PN patients, including adults and children.2,7,10,13 When monitoring for copper deficiency, nutrition professionals should look at biochemical presentation as well as clinical presentation. Serum levels don't correlate directly with accumulation in the liver.13 Other ways to check copper levels include ceruloplasmin and 24-hour urine copper collection. Deficiency can present as aching joints, poor wound healing, neutropenia, and microcytic anemia that's unresponsive to iron replacement therapy.15

Patients with increased biliary and jejunal losses may find themselves at increased risk of copper deficiencies. It's been reported that pediatric patients with increased losses may require an additional 10 to 15 mcg/kg per day of copper in their PN.16 There have been questions about whether to minimize the dose for cholestatic PN patients, but Corkins and colleagues showed that cholestasis doesn't impair copper excretion.17

Monitoring
Because of GI fluid losses and the drug shortages, monitoring patients is key to preventing nutrient deficiencies in the PN population. Dietitians may find it helpful to practice previsit planning, which entails reviewing the patient's chart one to two days before the visit. This allows the RD to determine whether additional lab tests are needed, communicate with the physician, and develop a preliminary plan before the clinic visit. Nicole Lidyard, RD, who works at the University Hospitals Case Medical Center in Cleveland, finds that developing a database of individual spreadsheets for patients helps her monitor how frequently serum levels are checked, as they may be affected by ongoing physiological responses. "Checking baseline levels during infection, sepsis, or postoperatively may influence serum levels from an acute phase response," Canada says, thus indicating that laboratory values in these situations may be influenced by confounding factors causing unreliable results.

Treatment Strategies
The best strategies nutrition professionals can use to reverse nutrient shortfalls in PN patients are those that are tailored to meet patients' individual needs, according to Lidyard and Shulman, who note that both IV replacement and long-term oral replacement may be necessary.

ASPEN recommends nutrition professionals give patients oral supplements if they can tolerate them. If patients can't tolerate oral supplements, health care practitioners can administer certain nutrients, such as iron, intravenously, and vitamin A and vitamin B12 intramuscularly. However, dietitians may find the need to add other elements such as trace minerals individually to the PN mixture. Other options include administering various medications to improve intestinal absorption, although dietitians must discuss this with patients and physicians.

RDs can use growth hormones in pediatric PN patients, especially in those with intestinal failure, due to their ability to increase intestinal fluid and nutrient absorption. Tedugliatide, a glucagonlike peptide 2 analogue, which helps to increase absorption of fluids and nutrients in the bowel, also may be an option. Tedugliatide has been FDA approved for adults, and researchers continue to study its effectiveness in the pediatric population.

Nutrient deficiencies present challenges and tend to be associated with significant GI disorders and fluid losses even while patients are receiving PN care. Dietitians can be proactive in managing nutrient shortfalls by anticipating the likelihood of their development. "The dietitian is an integral part of our nutrition support team," Shulman says. "My colleagues and I rely heavily on their nutrition assessment and input to determine the likelihood of nutrient deficiencies, to decide if there are additional laboratory studies which may be helpful, and to help develop a sound nutrition plan."

— Kristi King, MPH, RDN, CNSC, LD, is a senior pediatric dietitian at Texas Children's Hospital. Her clinical expertise includes gastrointestinal disorders, including short bowel syndrome, inflammatory bowel disease, motility disorders, and nutrition support.

References
1. Howard L, Nassan N. Home parenteral nutrition. 25 years later. Gastroenterol Clin North Am. 1998;27(2):481-512.

2. Ubesie AC, Kocoshis SA, Mezoff AG, Henderson CJ, Helmrath MA, Cole CR. Multiple micronutrient deficiencies among patients with intestinal failure during and after transition to enteral nutrition. J Pediatr. 2013;163(6):1692-1696.

3. Winkler MF, DiMaria-Ghalili RA, Guenter P, et al. Characteristics of a cohort of home parenteral nutrition patients at the time of enrollment in the Sustain registry [published online May 13, 2015]. JPEN J Parenter Enteral Nutr. pii:0148607115586575.

4. Sant VR, Arnell TD, Seres DS. Zinc deficiency with dermatitis in a parenteral nutrition-dependent patient due to national shortage of trace minerals [published online January 6, 2015]. JPEN J Parenter Enteral Nutr. pii: 0148607114566465.

5. Hwa YL, Rashtak S, Kelly DG, Murray JA. Iron deficiency in long-term parenteral nutrition therapy [published online May 13, 2015]. JPEN J Parenter Enteral Nutr. pii: 0148607115587329.

6. Khaodhiar L, Keane-Ellison M, Tawa NE, Thibault A, Burke PA, Bistrian BR. Iron deficiency anemia in patients receiving home total parenteral nutrition. JPEN J Parenter Enteral Nutr. 2002;26(2):114-119.

7. Yang CF, Duro D, Zurakowski D, Lee M, Jaksic T, Duggan C. High prevalence of multiple micronutrient deficiencies in children with intestinal failure: a longitudinal study. J Pediatr. 2011;159(1):39-44.

8. Szeszycki E, Cruse W, Beitzel M. Evaluation and monitoring of pediatric patients receiving specialized nutrition support. In: Corkins MR, ed. The A.S.P.E.N. Pediatric Nutrition Support Core Curriculum. 2nd ed. Silver Spring, MD: American Society for Parenteral and Enteral Nutrition; 2015:615-639.

9. Hardy G, Menendez AM, Manzanares W. Trace element supplementation in parenteral nutrition: pharmacy, posology, and monitoring guidance. Nutrition. 2009;25(11-12):1073-1084.

10. Braga CB, Vannucchi H, Freire CM, Marchini JS, Jordão AA Jr, da Cunha SF. Serum vitamins in adult patients with short bowel syndrome receiving intermittent parenteral nutrition. JPEN J Parenter Enteral Nutr. 2011;35(4):493-498.

11. Bharadwaj S, Gohel TD, Deen OJ, et al. Prevelance and predictors of Vitamin D deficiency and response to oral supplementation in patients receiving long-term home parenteral nutrition. Nutr Clin Pract. 2014;29(5):681-685.

12. Boullata J, Compher C, Schiavone P, Stoner N, Hoff K, Kinosian B. Oral vitamin D repletion in patients with parenteral nutrition dependent intestinal failure. Nutr Clin Pract. 2009;24(1):138-139.

13. Btaiche IF, Carver PL, Welch KB. Dosing and monitoring of trace elements in long-term home parenteral nutrition patients. JPEN J Parenter Enteral Nutr. 2011;35(6):736-747.

14. Livingstone C. Zinc: physiology, deficiency, and parenteral nutrition. Nutr Clin Pract. 2015;30(3):371-382.

15. Crill CM, Gura KM. Parenteral nutrition support. In: Corkins MR, ed. The A.S.P.E.N. Pediatric Nutrition Support Core Curriculum. 2nd ed. Silver Spring, MD: American Society for Parenteral and Enteral Nutrition; 2015:593-614.

16. Wong T. Parenteral trace elements in children: clinical aspects and dosage recommendations. Curr Opin Clin Nutr Metab Care. 2012;15(6):649-656.

17. Corkins MR, Martin VA, Szeszycki EE. Copper levels in cholestatic infants on parenteral nutrition. JPEN J Parenter Enteral Nutr. 2013;37(1):92-96.