3/3/2014
Overview
• Role of essential fats in the body
• Risk factors for essential fatty acid
deficiency
• Drug shortages and EFAD
• Clinical manifestations & evaluation
process
• Treatment
• Case study
• Conclusion
Essential Fatty Acid
Deficiency
Kris M. Mogensen, MS, RD, LDN, CNSC
Team Leader Dietitian
Brigham and Women’s Hospital
Instructor
Boston University College of Health and Rehabilitation Sciences:
Sargent College
April 11, 2014
Overview
• Role of essential fats in the body
• Risk factors for essential fatty acid
deficiency
• Drug shortages and EFAD
• Clinical manifestations & evaluation
process
• Treatment
• Case study
• Conclusion
Role of Fat in the Body
•
•
•
•
•
Major source of energy & energy storage
Cushioning/insulation
A means to absorb fat-soluble vitamins
Cell membranes
Inflammatory mediators/cell signaling
systems
• Creation of steroid hormones
Fatty Acids Created from EFA
Essential Fatty Acids
• Cannot be synthesized in the body
• Two major EFAs:
– Alpha-linolenic acid (omega-3)
– Linoleic acid (omega-6)
*EFA
Hamilton C et al. Essential fatty acid deficiency in human adults during parenteral nutrition. Nutr Clin Pract. 2006;21:387394
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Overview
• Role of essential fats in the body
• Risk factors for essential fatty acid
deficiency
• Drug shortages and EFAD
• Clinical manifestations & evaluation
process
• Treatment
• Case study
• Conclusion
Risk Factors for EFAD
• Malabsorptive disorders
– Crohn’s disease
– Chronic pancreatitis
– Cystic fibrosis
– Short-bowel syndrome
Sites of Absorption
Prevalence of essential fatty acid deficiency in
patients with chronic gastrointestinal disorders.
Siguel EN and Lerman RG. Metabolism. 1996;45:12-23
• 47 patients with chronic intestinal disease
–
–
–
–
25 Crohn’s disease
11 UC
4 Celiac
7 Short bowel syndrome
• 56 healthy controls
• Blood samples analyzed for fatty acids
and triene:tetraene ratio
From Krause, 12th edition
Prevalence of essential fatty acid deficiency in patients
with chronic gastrointestinal disorders.
Siguel EN and Lerman RG. Metabolism. 1996;45:12-23
Prevalence of essential fatty acid deficiency in
patients with chronic gastrointestinal disorders.
Siguel EN and Lerman RG. Metabolism. 1996;45:12-23
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Essential fatty acid deficiency in patients with
severe fat malabsorption.
Essential fatty acid deficiency in patients with severe fat
malabsorption.
Jeppesen PB et al. AJCN. 1997;65:837-843
Jeppesen PB et al. AJCN. 1997;65:837-843
• 112 patients with GI disorders
–
–
–
–
–
–
66 Crohn’s disease
26 UC
16 bowel resection for varying reasons
2 celiac disease
1 radiation enteritis
1 cholestatic liver disease
• All had fecal fat analyzed
• Blood analyzed for fatty acids
• Stratified by % of fat malabsorption
Degree of
Malabsorption
<10%
(n=52)
10-25%
(n=21)
25-50%
(n=24)
>50%
(n=15)
% with EFAD based
on LA levels
0%
5%
38%
67%
Carnitine Shuttle
Risk Factors for EFAD
• Carnitine deficiency
– Necessary for metabolism of fat in the
mitochondria
– Required component for phospholipid
remodeling and biosynthesis
• Part of cell membranes!
– Reservoir for long-chain fatty acids that
will eventually be incorporated into cell
membranes
CPT-I, carnitine palmitoyltransferase-1; CPT-II, carnitine palmitoyltransferase-2; CACT, carnitine
acylcarnitine translocase; CrAT, carnitine acetyl transferase; OMM, outer mitochondrial membrane;
IMM, inner mitochondrial membrane. From Sharma & Black Drug Discov Today Dis Mech. 2009
Risk Factors for EFAD
• Patients with limited fat intake/delivery
– PN-dependent patients with
hypertriglyceridemia
– Allergy to intravenous fat emulsion
– Ultra-low fat diets
– Extracorporeal membrane oxygenation
(ECMO) patient receiving PN
From: Mogensen KM and Pfister DP. Carnitine supplementation: an update. Support Line. 2013;35:3-9
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Essential fatty acid deficiency in four adult patients
during total parenteral nutrition.
Richardson TJ and Sgoutas D. AJCN. 1975;28:258-263
Diet-induced essential fatty acid deficiency in
ambulatory patient with type I diabetes mellitus.
Piper CM et al. Diabetes Care. 1986;9:291-293
43 y.o. M who followed a 7% fat diet for 4 months.
Developed lethargy, fatigue, and a dry, scaly rash…
Essential fatty acid deficiency during total
parenteral nutrition.
Barr LH et al. Ann Surg. 1981;193:304-311
Risk Factors for EFAD
• National shortages of intravenous fat
emulsion
Overview
Drug Shortages
• Role of essential fats in the body
• Risk factors for essential fatty acid
deficiency
• Drug shortages and EFAD
• Clinical manifestations & evaluation
process
• Treatment
• Case study
• Conclusion
• A major problem over the past 5 years
– Intermittent shortages occurring for > 15
years
• In 2013 there were 324 medications in
shortage
– 70% were sterile injectables
Data from:
http://www.nutritioncare.org/Professional_Resources/Drug_Shortages_Update/#Why_do_drug_shortages_occur
accessed 2/20/14
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Nutrition Support Drug Shortages
•
•
•
•
IV multivitamins
IV multiple trace elements
Individual electrolytes
Macronutrients
– Intravenous fat emulsion
– Clinimix recall
New IVFE Available Soon!
•
•
•
•
Clinolipid
New product from Baxter
Blend of olive oil and soybean oil
Just FDA approved in October 2013
Physical Signs and Symptoms
of EFAD
A.S.P.E.N. Guidelines
• Rationing guidelines include reserving IVFE for neonates and
pediatric patients
• For non-malnourished adults, or those with mild or moderate
malnutrition, hold IV fat for the first two weeks of PN
• Provision of 100g fat total/week after the first two weeks of PN
• Also available at:
http://www.nutritioncare.org/Professional_Resources/Drug_Short
ages/PN_IV_Fat_Emulsions_Product/
Overview
• Role of essential fats in the body
• Risk factors for essential fatty acid
deficiency
• Drug shortages and EFAD
• Clinical manifestations & evaluation
process
• Treatment
• Case study
• Conclusion
Essential fatty acid deficiency in adults
receiving total parenteral nutrition.
Fleming CR et al. AJCN. 1976;29:976-983
• Dermatitis
– Dry, scaly rash
• Poor wound healing
• Impaired growth in children
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Essential fatty acid deficiency in surgical patients.
Essential Fatty Acid Deficiency in a Severely Malnourished Patient
Receiving Parenteral Nutrition.
O’Neill JA et al. Ann Surg. 1977;185:535-541
Duerksen D and McCurdy K. Diges Dis Sci 2005;12:2386-2388
Be careful of look-alikes!
Essential Fatty Acid Deficiency in a Child
http://images.medscape.com/pi/editorial/cmecircle/2002/1819/hansen/slide17.jpg accessed 2/16/06
Physical Signs and Symptoms
of EFAD
• Correlate physical exam with clinical
history
– Limited fat intake only?
– Other potential causes of a similar rash?
• Zinc deficiency alone, or superimposed on
EFAD?
• Other causes of skin rash
Other Signs and Symptoms of EFAD
•
•
•
•
•
•
•
Fatty liver
Elevated liver function tests
Hyperlipidemia
Hemolytic anemia
Thrombocytopenia
Reduced platelet aggregation
Increased susceptibility to infection
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Biochemical Evaluation
• Evaluate the triene:tetraene ratio
– Why?
– Mead acid (triene acid) production is
increased and linoleic and arachidonic
acid are decreased
– Triene:tetraene ratio evaluates the
mead:arachidonic acid ratio
– If > 0.2 (some references suggest 0.4),
the patient has EFAD
Timeframe of EFAD Development
• Typical EFAD onset occurs after 4
weeks of fat-free PN
• Other reports have shown earlier
onset of 10-20 days
• Most of EFAD is associated with
linoleic acid deficiency; few reports
of alpha-linoleic acid deficiency
Overview
• Role of essential fats in the body
• Risk factors for essential fatty acid
deficiency
• Drug shortages and EFAD
• Clinical manifestations & evaluation
process
• Treatment
• Case study
• Conclusion
Treating Deficiency
• For PN-Dependent patients
– The main IVFE available is intralipid
– 50% of the fat content is linoleic acid
– To give 10g linoleic acid, you must give
20g fat total
Treating Deficiency
• Prevent when you can!
– Provide at least 10% of energy from
polyunsaturated fats
– 2%-4% of total calories should be from
linoleic acid
Comparison of IV Fat Emulsions
Concentration
10%
20%
30%
kcal/mL
Fat g/L (9.3 kcal/g)
Phospholipid g/L (6 kcal/g)
1.1
100
12
2
200
12
2.9
300
12
Glycerol g/mL (4.2 kcal/g)
22.5
22.5
17
Example:
250 mL 20% IVFE = 500 kcals, 50 g fat (25 g as linoleic acid), 3 g
phospholipid, 5.625 g glycerol
Parenteral fat does NOT provide 10 kcal/gram!!!!
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Treating Deficiency
• For patients taking an oral diet, encourage
high intake of oils rich in essential fats
• Encourage fatty fish or omega-3 fatty acid
supplements
Oil
Safflower
Soybean
Sunflower
Linoleic acid
(g/tbsp)
2.0
6.9
8.9
Use of Topical Oils
• There is some cutaneous absorption of
essential fats
• The question: is that absorption
adequate?
Correction of the cutaneous manifestations of
essential fatty acid deficiency in man by
application of sunflower-seed oil to the skin.
Correction of the cutaneous manifestations of
essential fatty acid deficiency in man by
application of sunflower-seed oil to the skin.
Prottey C. et al J Invest Dermatol 1975;64:228-234
Prottey C. et al J Invest Dermatol 1975;64:228-234
• 3 patients with short bowel syndrome and
known EFAD
• 7 controls on an unrestricted diet
• Intervention:
– 250 mg sunflower seed oil applied to the R arm
– 250 mg olive oil applied to the L arm
• Measured
– Various skin surface lipids
– Day 4, 8, 15 of the intervention
Human essential fatty acid deficiency. Treatment
by topical application of linoleic acid.
Skolnik P et al. Arch Dermatol. 1977;113:939-941
• Results
– Deficient patients had higher levels of linoleic
acid in the epidermis of the sunflower seed
oil arm
– No change in the olive oil arm
– Resolution of scaly lesions
– Epidermal changes not seen in the control
group
Human essential fatty acid deficiency. Treatment
by topical application of linoleic acid.
Skolnik P et al. Arch Dermatol. 1977;113:939-941
• 19 y.o. M with short bowel syndrome
from severe IBD
• Receiving fat-free PN
• Developed EFAD
• 150 mg linoleic acid rubbed into R thigh
once/day x 3 weeks
• Changed to safflower oil after 3 weeks
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Cutaneous application of safflower oil in
preventing essential fatty acid deficiency in
patients on home parenteral nutrition.
Cutaneous application of safflower oil in preventing essential fatty
acid deficiency in patients on home parenteral nutrition.
Miller DG et al. AJCN. 1987;46:419-423
Miller DG et al. AJCN. 1987;46:419-423
• Study of 5 HPN patients
– 4 weeks no IVFE
– 4-6 weeks of topical safflower oil (3 mg/kg/d
to provide 2.3 mg/kg/d of linoleic acid)
– 5 mL PO safflower oil once/day x 4 weeks
Failure of topical vegetable oils to prevent essential
fatty acid deficiency in a critically ill patient
receiving long-term parenteral nutrition.
Sacks GS et al. JPEN. 1994;18:274-277
Overview
• Case report of a critically ill trauma patient
requiring fat-free PN because of
hypertriglyceridemia
• Developed EFAD
• Received topical safflower oil per Miller
protocol
• No resolution of EFAD with use of topical oils
alone; resolved when IVFE could be resumed
• Role of essential fats in the body
• Risk factors for essential fatty acid
deficiency
• Drug shortages and EFAD
• Clinical manifestations & evaluation
process
• Treatment
• Case study
• Conclusion
IVFE Allergy Case
IVFE Allergy Case
•
•
•
•
•
•
79 y.o. F with multiple GI surgeries
Diverticulitis s/p sigmoid colectomy
Colostomy, ileostomy
Multiple SBOs, small bowel volvulus
Multiple small bowel resections
Presented with a high-output ECF
• Plan for PN and bowel rest
• If fistula didn’t close spontaneously, then
OR
• Pt was on PN in the past, had h/o
anaphylaxis with IVFE
• Fat-free PN was started
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IVFE Allergy Case
• Ideally, would have checked a fatty acid panel
prior to starting PN
• After one month of PN found:
– Low linoleic acid
– Low alpha-linolenic acid
– Triene:tetraene ratio of 0.034
• Lab uses the more sensitive measure, so EFAD is > 0.02 in
this case
– Pt discharged home on PN, returned 11 months
later
IVFE Allergy Case
• Repeat fatty acid panel done
1 month
11 months
fat free PN fat free PN
Linoleic acid
Normal range
1074
1627
2270-3850 nMol/mL
Alpha-linolenic acid
13
13
50-130 nMol/mL
Mead acid
12
39
7-30 nMol/mL
Arachidonic acid
352
850
520-1490 nMol/mL
0.034
0.046
0.010-0.038*
Triene:tetraene ratio
IVFE Allergy Case
• Pt was seen by a home infusion provider
– Recommended to take po:
• 1 tbsp canola oil + 1 tbsp fish oil daily
• Pt stopped fish oil many months prior to
readmission because she was worried about the
mercury content
• She increased to 2 tbsp canola oil daily
IVFE Allergy Case
• Pt went to the OR and had the fistula
taken down
• Diet advanced and pt went home on an
unrestricted oral diet!
*EFAD diagnosis should be made at > 0.02-0.04
IVFE Allergy Case
• What should we have done differently?
– Pushed for an allergy consult
– Counseled pt on appropriate fats to take po
• Sunflower, soybean, or safflower would have
been better choices
– Counseled pt to try topical oils
Overview
• Role of essential fats in the body
• Risk factors for essential fatty acid
deficiency
• Drug shortages and EFAD
• Clinical manifestations & evaluation
process
• Treatment
• Case study
• Conclusion
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Conclusion
•
•
•
•
•
Identify high-risk patients
Look for signs/symptoms of EFAD
Evaluate biochemical measures
Prevent EFAD when you can
Employ treatment options
Thank you!
– Appropriate IVFE dosing, when there isn’t a
shortage
– High intake of essential fats for patients taking an
oral diet
– Trial of topical oils rich in essential fats
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