Deficiencies are prevalent in HPN patients, especially in light of product shortages and inevitable non-adherance. Providers vigalent surveillance & supplementation is worthwhile, as it has potential to impact outcomes.
Falk A. Evaluating the effectiveness of a micronutrient assessment tool for long-term total parenteral nutrition patients. Nutr Clin Pract. 2002 Aug;17(4):240-5. PubMed PMID: 16214994
Namjoshi SS, Muradian S, Bechtold H, Reyen L, Venick RS, Marcus EA, Vargas JH, Wozniak LJ. Nutrition Deficiencies in Children With Intestinal Failure Receiving Chronic Parenteral Nutrition. JPEN J Parenter Enteral Nutr. 2017 Feb 1:148607117690528. doi: 10.1177/0148607117690528. [Epub ahead of print] PubMed PMID: 29187063.
Smith A, Feuling MB, Larson-Nath C, Karls C, Van Hoorn M, Walia CL, Leon C, Danner E, Opichka P, Duesing L, Martinez A, Goday PS. Laboratory Monitoring of Children on Home Parenteral Nutrition: A Prospective Study. JPEN J Parenter Enteral Nutr. 2016 Oct 11. pii: 0148607116673184. [Epub ahead of print] PubMed PMID: 27729404.
HPN outpatient laboratory monitoring schedule
Providers should monitor patients labs according to individual clinical judgement. Patients often require changes according to circumstances. The following is a general guideline for stable HPN outpatients:
|
Complete blood count |
Every 1-3 months |
|
PN profile |
Every 1-3 months |
|
C-reactive profile |
Every 1-3 months |
|
PT/INR |
Every 1-6 months |
|
Fatty acid profile |
Every 1-3 months |
|
Vitamin A with retinol binding protein |
Every year |
|
Vitamin E with cholesterol |
Every year |
|
Aluminum |
Every year |
|
Carnitine |
Every year |
|
Copper, Ceruloplasmin |
Every 6 months |
|
Selenium |
Every 6 months |
|
Zinc |
Every 6 months |
|
Vitamin 25-OH D |
Every 6 months (once during winter) |
|
Urine sodium |
As needed |
|
Iron, TIBC, ferritin |
Every 1-2 months on IV iron |
Trace elements and inflammation
Acute inflammation can alter measured concentrations of trace elements, because inflammation leads to changes in specific tissue proteins.
Shenkin A. Trace elements and inflammatory response: implications for nutritional support. Nutrition. 1995 Jan-Feb;11(1 Suppl):100-5. Review. PubMed PMID: 7749254.
Copper
- Deficiency:
- Hematologic - neutropenia, microcytic anemia
- Immunologic - impaired macrophage activation and cytokine production
- Osteoporosis
- Skin pigmentation.
- Excess:
- Cirrhosis
- Cardiac failure
- Kidney dysfunction
- Diabetes
- Psychosis
Requirement:
- Daily Amount Requirement: 200 mcg/kg
- Daily Amount Requirement Adult: 300-500 mcg/day
Monitoring:
- Check copper & ceruloplasm w/ CRP level every 6 months.
- Monitor trend in CBC with diff
- If copper level high or low on 2 consecutive occasions, consider 24-hour urine copper level.
- Consider liver biopsy for total copper content in patient who are on copper maximal doses but have persistently low levels of copper.
- If copper level level above upper limit of normal, decrease by 5 mcg/kg.
- If copper level level lower than lower limit of normal, increase by 5mcg/kg (to a max of 40mcg/kg/day).
- After copper dose titration, repeat copper level in 2-3 months.
- WARNING: Plasma levels may not be reflective of tissue levels.
- WARNING: Plasma level increases with inflammation, because increase in carier protein ceroplasmin.
Selenium
Deficiency:
- Cardiomyopathy
- Cartilage degeneration/necrosis
- Hypothyroidism
Requirement:
- Daily Amount Requirement 1-3 mcg/kg (max dose 40 mcg/day)
- Daily Amount Requirement Adult 20-60 mcg/day
Monitoring:
- Measure levels every 6 months
- If level is selenium level above the upper limit of normal, then decrease by 0.5 mcg/kg/day
- If level is selenium level below the lower limit of normal, then increase by 0.5 mcg/kg/day
- After selenium dose titration, repeat carnitine level in 2-3 months.
- WARNING: Plasma level decreases with inflammation, because decrease in carier protein selenoprotein P.
Fleming CR, McCall JT, O'Brien JF, Forsman RW, Ilstrup DM, Petz J. Selenium status in patients receiving home parenteral nutrition. JPEN J Parenter Enteral Nutr. 1984 May-Jun;8(3):258-62. PubMed PMID: 6429362.
Zinc
- Excess (acute):
- Nausea
- Vomiting
- Diarrhea.
- Deficiency:
- Microcytic anemia
- Neutropenia
- Impaired immune system
- Low HDL
- Low alkaline phosphatase
Requirement:
- Daily Amount Requirement 3 mg ( 2kg)
- Daily Amount Requirement Adult 2.5-5.0 mg
Monitoring:
- Measure zinc level with CRP every 6 months.
- Monitor trend in alkaline phosphatase.
- If zinc level level is above the upper limit of normal, then decrease by 50-100 mcg/kg/day.
- If level is below the lower limit of normal, then increase by 50-100 mcg/kg/day (max dose, 5g/day).
- After zinc dose titration, repeat zinc level in 2-3 months.
- WARNING: WARNING: Plasma level decreases with inflammation, because decrease in carier protein albumin.
Sant VR, Arnell TD, Seres DS. Zinc Deficiency With Dermatitis in a Parenteral Nutrition-Dependent Patient Due to National Shortage of Trace Minerals. JPEN J Parenter Enteral Nutr. 2016 May;40(4):592-5. doi: 10.1177/0148607114566465. Epub 2015 Jan 6. PubMed PMID: 25564425.
Carnitine
Deficiency:
- Hypoglycemia
- Respiratory distress
- Delayed growth
- Hyperlipidemia
- Hypertriglyceridemia
- Developmental delay
- Progressive myopathy
Carnitine is a conditionally essential nutrient: Humans can synthesize carnitine if not obtained in the diet. The enzymatic pathway for synthesis requires ascorbic acid and iron (Fe2+). Deficiency can be inherited or acquired.
- Transporting long chain fatty acids as acylcarnitine into the mitochondria to generate energy
- Removing short chain fatty acids and medium chain fatty acids that accumulate in the mitochondria.
-
Acquired deficiency occurs from reduced intake or synthesis (preterm infants, newborns) or from increased requirements or excretion (critical illness, newborns, dialysis).
-
Levels can be measured in the plasma or urine as free, total, and free/total carnitine.
-
WARNING: Plasma and urine levels may not be reflective of tissue levels.
Monitoring laboratory reference ranges (total, fasting):
- 1-12 mo: 15-39 umol/L
- 1-7 yr: 18-37 umol/L
- 7-15 yr: 31-47 umol/L
Monitoring :
- Check free, total, free/total carnitine levels in inpatients after 1 month on parenteral nutrition.
- Check free, total, free/total carnitine levels every 6-12 months
- After carnitine dose titration, repeat carnitine level in 1-3 months
Requirement:
- Preterm/Infants/children: 8-16 mg/kg/day (usual starting dose = 10 mg/kg/day, max ~ 500 mg/day*)
- Primary carnitine deficiency/dialysis patients may require higher doses
- Adjust dose by ~5 mg/kg/day for low or high levels of total carnitine
- If persistently low levels despite increases in PN dose, check an acylcarnitine profile
- Consider empirically supplementing carnitine in patients on minimal enteral/oral nutrition (within 2-4 weeks)
Compatibility:
- There is limited compatibility information for the maximum amount of Carnitine that can be safely added to parenteral nutrition.
- Doses used for parenteral nutrition are typically considered compatible: 8-10 mg/kg/day up to 20 mg/kg/day
- Carnitine doses >1 gram/day should administered separately from the parenteral nutrition (typically intended to treat an inborn error of metabolism)
- Creaming of the IV lipid emulsion has been reported when carnitine has been added directly to a total nutrient admixture.
Aluminium
Toxicity:
- Encephalopathy
- Osteomalacia
- Microcytic/hypochromatic anemia
Monitoring:
- Check aluminum level annually
- If aluminum level > 25, notify HPN pharmacist who will review home medications and collaborate with home infusion company
- Blood products, albumin, sucralfate, heparin can contribute to aluminium load
- Uncorrected iron deficiency anemia can exacerbate aluminium toxicity
- If aluminum level 60-100 or any symptoms, consult toxicology.
- WARNING: Plasma levels may not be reflective of tissue levels.
- WARNING: Plasma level increases with inflammation.
Gura KM. Aluminum contamination in parenteral products. Curr Opin Clin Nutr Metab Care. 2014 Nov;17(6):551-7. doi: 10.1097/MCO.0000000000000091. Review. PubMed PMID: 25023185.
Leung FY, Grace DM, Alfieri MA, Bradley C. Abnormal trace elements in a patient on total parenteral nutrition with normal renal function. Clin Biochem. 1995 Jun;28(3):297-302. PubMed PMID: 7554249.
Yokel RA, Unrine JM. Aluminum and Phthalates in Calcium Gluconate: Contribution From Glass and Plastic Packaging. J Pediatr Gastroenterol Nutr. 2017 Jan;64(1):109-114. doi: 10.1097/MPG.0000000000001243. PubMed PMID: 27111341.
Social Media
From Home Parenteral Nutrition at Boston Children's Hospital Facebook Program Group May 26, 2017.
"Hi it's Melissa, one of your HPN nurses. Let's talk about the vitamins that you add into the PN bag.
It can be confusing when you get a vitamin type that you are unfamiliar with.
Sometimes pharmacy needs to change vitamin type based upon shortages and availability.
Sometimes vitamins come mixed and some need to be mixed.
Please call your HPN Team with any questions!"
It can be confusing when you get a vitamin type that you are unfamiliar with.
Sometimes pharmacy needs to change vitamin type based upon shortages and availability.
Sometimes vitamins come mixed and some need to be mixed.
Please call your HPN Team with any questions!"
Vitamin D (see bone health)
Vitamin A
Monitoring:
- WARNING: Plasma level decreases with inflammation, because decrease in carier protein retinol binding protein.
Deficiency:
- Night blindness - degeneration of retina
- Xeropthtalmia
- Poor growth
- Hyperkeratosis
Toxicity:
- Idiopathic intracranial hypertension
- Hypercalcemia
- liver fibrosis (enlarged, lipid-laden stellate cells with variable degrees of sinusoidal fibrosis)
Retinol to retinol binding protein ratio* (Normal = 0.8-1)
- Toxicity > 1
- Deficiency
Retinol (vitamin A) to Retinol Binding Protein Ratio Caclulator
Vitamin B1 (Thiamine)
Function
- catalyst in conversion of pyruvate --> acetyl CoA (carbohydrate metabolism)
- nerve impulse propagation
Deficiency:
- Beriberi - heart failure with cardiomegaly. Older infants with neurological symptoms like agitation, seizures and altered mental status.
- Wernicke encephalopathy = memory disability out of proportion to other cognitive defects in setting of severe thiamine deficiency and other comorbidity (chronic alcoholism, malnutrition, cancer with chemotherapy, hyperemesis gravidarum).
Toxicity:
- No known toxicity - rapidly excreted from urine.
Monitoring
- Levels not routinely checked.
- WARNING: Plasma level decreases with inflammation
Arts NJ, Walvoort SJ, Kessels RP. Korsakoff's syndrome: a critical review. Neuropsychiatr Dis Treat. 2017 Nov 27;13:2875-2890. doi: 10.2147/NDT.S130078. eCollection 2017. Review. PubMed PMID: 29225466; PubMed Central PMCID: PMC5708199.
Romanski SA, McMahon MM. Metabolic acidosis and thiamine deficiency. Mayo Clin Proc. 1999 Mar;74(3):259-63. PubMed PMID: 10089995.
Schiano TD, Klang MG, Quesada E, Scott F, Tao Y, Shike M. Thiamine status in patients receiving long-term home parenteral nutrition. Am J Gastroenterol. 1996 Dec;91(12):2555-9. PubMed PMID: 8946985.
Folate
Testing:
- RBC folate level
- Folate level
B12
Deficiency
- Macrocytic anemia, pancytopenia, hypersegmented neutrophils
- Neurolopsychiatric changes
- Glossitis
Testing:
- B12 level - if level is normal or high, deficiency is unlikely. If level is borderline, recommend checking confirmatory testing with MMA and homocysteine.
- Methylmalonic acid (MMA) serum or urine - elevation consistent with B12 deficiency or folate deficiency
- Homocysteine level - elevation consistent with folate deficiency
- Autoantibodies to intrinsic factor (IF) and gastric parietal cell antigens if suspecting pernicious anemia
Vitamin C (absorbic acid)
Food sources: citrus fruits, vegetables, fruits.
Toxicity: Increase oxalate formation --> risk of calcium oxalate kidney stones
Deficiency: Scurvy (level
- petechiae
- perifollicular hemorrhage
- bruising
- gingivitis
- arthralgias
- impaired wound healing
- pulmonary hypertension
Duvall MG, Pikman Y, Kantor DB, Ariagno K, Summers L, Sectish TC, Mullen MP. Pulmonary hypertension associated with scurvy and vitamin deficiencies in an autistic child. Pediatrics. 2013 Dec;132(6):e1699-703. doi: 10.1542/peds.2012-3054. Epub 2013 Nov 4. PubMed PMID: 24190688.
Weinstein M, Babyn P, Zlotkin S. An orange a day keeps the doctor away: scurvy in the year 2000. Pediatrics. 2001 Sep;108(3):E55. PubMed PMID: 11533373.
Vitamin K
- Dependent clotting factors: II (prothrombin), VII, IX and X.
- Anticoagulation proteins: C, S and Z
If INR >1.4 and suspect vitamin K deficiency, consider supplementation for 3 days as follows:
|
Age |
Dose (mg/kg/day) |
|
1 |
1 |
|
2 |
2 |
|
3 |
3 |
|
4 |
4 |
|
≥5 |
5 |
Repeat INR within 1 week after repletion dose.
Vitamin E Deficiency
Deficiency:
- Peripheral neuropathy
- Ataxia
- Hemolytic anemia
Monitoring:
- Vitamin E to total lipid concentration ratio, deficiency:
- If concerned about deficiency, check blood smear (acanthocytes)
Manganese
- Levels not routinely measured
- Consider brain MR or neurology consultation for movement disorders, especially with Parkinson’s features.
Chromium
Deficiency:
-
glucose intolerance
-
persistent hyperglycemia
-
insulin resistance
Monitoring:
- Levels not routinely measured
Multi-trace solutions
|
Contents of Trace Elements per 1 ml
|
|
|
|
|||
|
Element
|
MTE-4
|
PTE-4
|
MTE-5
|
MTE-5
|
Peditrace
|
Units
|
|
(non-concentrate)
|
(concentrate)
|
(Fresnius)
|
||||
|
Chromium
|
4
|
1
|
4
|
10
|
25
|
mcg
|
|
Copper
|
0.4
|
0.1
|
0.4
|
1
|
0.02
|
mg
|
|
Manganese
|
0.1
|
0.03
|
0.1
|
0.5
|
0.001
|
mg
|
|
Zinc
|
1
|
0.5
|
1
|
5
|
0.25
|
mg
|
|
Selenium
|
0
|
0
|
20
|
60
|
2
|
mcg
|
|
Iodine
|
0
|
0
|
0
|
0
|
1
|
mcg
|
|
Fluoride
|
0
|
0
|
0
|
0
|
57
|
mcg
|
IV Multi-vitamin solutions
|
|
Pediatric MVI per 5ml
|
MVI-12 (adult) per 10ml
|
Vitalipid N
10 ml
|
|
Vitamin C
|
80mg
|
200mg
|
|
|
Vitamin A
|
2300 IU (0.7mg)
|
3300 IU
|
Vitamin A 2300 IU
|
|
Vitamin D3 (cholecalciferol)
|
x
|
200 IU
|
(D2) 400
|
|
Vitamin D2 (ergocalciferol)
|
400 IU (10mcg)
|
x
|
|
|
Thiamine (B1)
|
1.2mg
|
6mg
|
|
|
Riboflavin (B2)
|
1.4mg
|
3.6mg
|
|
|
Pyridoxine (B6)
|
1mg
|
6mg
|
|
|
Niacinaminde
|
17mg
|
40mg
|
|
|
Dexpanthenol
|
5mg
|
15mg
|
|
|
Vitamin E
|
7 IU (7mg)
|
10 IU
|
7 IU
|
|
Vitamin K
|
200mcg
|
150mcg
|
200 mcg
|
|
Folic Acid
|
140mcg
|
600mcg
|
|
|
Biotin
|
20mcg
|
60mcg
|
|
|
Cyanocobalamin (B12)
|
1mcg
|
5mcg
|
|