The Role of an Intravenous Fat Emulsion Composed of Fish Oil in a Parenteral Nutrition-Dependent Patient With Hypertriglyceridemia

Abstract

Hypertriglyceridemia is a common complication in patients receiving parenteral nutrition (PN). Management typically involves withholding the IV fat emulsion (IVFE) until serum triglyceride levels normalize. In some instances, this practice may predispose patients to the development of essential fatty acid deficiency (EFAD) unless alternative therapies such as oral or topical oils are used. This is especially true in patients unable to tolerate enteral intake. We describe the management of hypertriglyceridemia in a 12-year-old boy dependent on PN who developed EFAD due to prolonged use of fat-free PN. His course was further complicated by PN-associated liver disease. Treatment involved the use of an IVFE derived from fish oils. Within 3 weeks, there was clinical improvement in EFAD and hypertriglyceridemia. The patient's triene:tetraene ratio decreased from 0.207 to 0.044 (normal: 0.013–0.05). Similarly, his serum triglyceride levels decreased from 628 mg/dL to 183 mg/dL (normal: <200 mg/dL). After 2 months of treatment, he was successfully transitioned to enteral feedings; hepatic function normalized, as did the essential fatty acid profile and serum triglycerides levels. This suggests that using fish-oil-based IVFE may be an effective alternative to conventional IVFE in PN-dependent patients whose clinical course is complicated by hypertriglyceridemia.

Get full access to this article

View all access options for this article.

References

Llop J, Sabin P, Garau M, et al; Hospital Pharmacy Artificial Nutrition Group of Catalonia. The importance of clinical factors in parenteral nutrition-associated hypertriglyceridemia. Clin Nutr. 2003 ;22:577– 583.

Gura KM, Parsons SK, Bechard LJ, et al. Use of a fish oil-based lipid emulsion to treat essential fatty acid deficiency in a soy allergic patient receiving parenteral nutrition. Clin Nutr. 2005 ;24:839– 847.

Gura KM, Duggan CP, Collier SB, et al. Reversal of parenteral nutrition associated liver disease in two infants with short bowel syndrome using parenteral fish oil: implications for future management. Pediatrics. 2006 ;118:e197– e201.

Haymore BR, Parks JR, Oliver TG, Glister BC. Hypertriglyceridemia. Hosp Physician. 2005 ;41:17– 24.

Veterans Health Administration, Department of Defense. VHA/DoD Clinical Practice Guideline for the Management of Dyslipidemia in Primary Care. Washington, DC: Veterans Health Administration, Department of Defense;2001.

Chait A, Brunzell JD. Severe hypertriglyceridemia: role of familial and acquired disorders. Metabolism. 1983 ;32:209– 214.

Henkin Y, Como JA, Oberman A. Secondary dyslipidemia: inadvertent effects of drugs in clinical practice. JAMA. 1992 ;267:961– 968.

Carpentier A, Patterson BW, Uffelman KD, Salit L, Lewis GF. Mechanism of highly active anti-retroviral therapy-induced hyperlipidemia in HIV-infected individuals. Atherosclerosis. 2005 ;178:165– 172.

Haumount D, Deckelbaum RJ, Richelle M, et al. Plasma lipid and plasma lipoprotein concentrations in low birth weight infants given parenteral nutrition with twenty or ten percent lipid emulsion. J Pediatr. 1989;115(5 Pt 1): 787–793.

10.

Dahlstrom KA, Goulet OJ, Roberts RL, Ricour C, Ament ME. Lipid tolerance in children receiving long-term parenteral nutrition: a biochemical and immunologic study. J Pediatr. 1988 ;113:985– 990.

11.

Krevsky B, et al. Hepatic complications of TPN. Nutrition Support Serv. 1983 ;3.

12.

Druml W, Grimm G, Laggner AN, Schneeweiss B, Lenz K. Hyperlipidemia in acute hemolysis. Klin Wochenschr. 1991 ;22:69:426– 429.

13.

Collier SB, Richardson DS, Gura KM, Duggan C. Parenteral nutrition. In: Hendricks KM, Duggan C, Walker WA, eds. Manual of Pediatric Nutrition. 3rd ed. Hamilton, Ontario, Canada: BC Decker;2000 : 242–287.

14.

Spear ML, Stahl GE, Hamosh M, et al. Effect of heparin dose and infusion rate on lipid clearance and bilirubin binding in premature infants receiving intravenous fat emulsions. J Pediatr. 1988 ;112:94– 98.

15.

Chen X, Ruis J, Boden G. Release, oxidation, and reesterification of fatty acids from infused triglycerides: effect of heparin. Metabolism. 1995 ;44:1590– 1595.

16.

Iriyama K, Tsuchibashi T, Urata H, et al. Elimination of fat emulsion particles from plasma during glucose infusion. Br J Surg. 1996;83:946– 948.

17.

American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). Administration of specialized nutrition support: issues unique to pediatrics. JPEN J Parenter Enteral Nutr. 2002 ;26(Suppl 1):97SA– 110SA.

18.

Mitchell ME. Carnitine metabolism in human subjects, I: normal metabolism. Am J Clin Nutr. 1978 ;31:293– 306.

19.

Argani H, Rahbaninoubar M, Ghorbanihagio A, Golmohammadi Z, Rashtchizadeh N. Effect of L-carnitine on the serum lipoproteins and HDL-C subclasses in hemodialysis patients. Nephron Clin Pract. 2005;101:c174– c179.

20.

Chitturi S, George J. Hepatotoxicity of commonly used drugs: nonsteroidal anti-inflammatory drugs, antihypertensives, antidiabetic agents, anticonvulsants, lipid-lowering agents, psychotropic drugs. Semin Liver Dis. 2002;22:169– 183.

21.

Hug G, McGraw CA, Bates SR, Landrigan EA. Reduction of serum carnitine concentrations during anticonvulsant therapy with phenobarbital, valproic acid, phenytoin, and carbamazepine in children. J Pediatr. 1991;119:799– 802.

22.

Arrigoni-Marteli E, Caso V. Carnitine protects mitochondria and removes toxic acyls from xenobiotics. Drugs Exp Clin Res. 2001;27:27– 49.

23.

Murphy JV, Groover RV, Hodge C. Hepatotoxic effects in a child receiving valproate and carnitine. J Pediatr. 1993 ;123:318– 320.

24.

Bryant AE, Dreifuss FE. Valproic acid hepatic fatalities, III: U.S. experience since 1986. Neurology. 1996 ;46:465– 469.

25.

Evans HM, Burr GO. A new dietary deficiency with highly purified diets. Proc Soc Exp Biol Med. 1927 ;24:740– 743.

26.

Kris-Etherton PM, Harris WS, Appel LJ. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Arterioscler Thromb Vasc Biol. 2003;23:e20– e30.

27.

Kris-Etherton PM, Harris WS, Appel LJ. Omega-3 fatty acids and cardiovascular disease: new recommendations from the American Heart Association. Arterioscler Thromb Vasc Biol. 2003 ;23:151– 152.

28.

von Schacky C, Angerer P, Kothny W, Theisen K, Mudra H. The effect of dietary omega-3 fatty acids on coronary atherosclerosis: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1999;130:554– 562.

29.

Mayser P, Grimm H, Grimminger F. n-3 Fatty acids in psoriasis. Br J Nutr. 2002 ;87(Suppl 1):S77– S82.

30.

Burr GO, Burr MM. A new deficiency disease produced by the rigid exclusion of fat from the diet. J Biol Chem. 1929 ;82:345– 367.

31.

Simopoulos AP. Importance of the ratio of omega-6/omega-3 essential fatty acids: evolutionary aspects. World Rev Nutr Diet. 2003;92:1– 22.

32.

Simopoulos AP. n-3 Fatty acid-enriched eggs, lipids, and Western diet: time for change. Nutrition. 1993 ;9:561– 562.

33.

Innis SM. Essential dietary lipids. In: Ziegler EE, Filer LJ, eds. Present Knowledge in Nutrition. 7th ed. Washington, DC: International Life Sciences Institute–Nutrition Foundation;1996 : 44–55.

34.

Fleming CR, Smith LM, Hodges RE. Essential fatty acid deficiency in adults receiving total parenteral nutrition. Am J Clin Nutr. 1976;29:976– 983.

35.

Frieman Z, Damon A, Stahlman MT, Oates JA. Rapid onset of essential fatty acid deficiency in the newborn. Pediatrics. 1976 ;58:640– 649.

36.

Holman R. The ratio of trienoic:tetranoic acids in tissue lipids as a measure of essential fatty acid requirements. J Nutr. 1970;60:405– 410.

37.

Siguel EN, Chee KM, Gong JX, Schaefer EJ. Criteria for essential fatty acid deficiency in plasma as assessed by capillary column gas-liquid chromatography. Clin Chem. 1987 ;33:1869– 1873.

38.

Wilmore D, Dudrick S. Growth and development of infant receiving all nutrients exclusively by vein. JAMA. 1968 ;203:860– 864.

39.

Bohles H, Bieber MA, Heird WC. Reversal of experimental essential fatty acid deficiency by cutaneous administration of safflower oil. Am J Clin Nutr. 1976 ;29:398– 401.

40.

Skolnick P, Eaglestein WH, Ziboh VA. Human essential fatty acid deficiency: treatment of topical applications of linoleic acid. Arch Dermatol. 1977 ;113:939– 941.

41.

Omegaven [package insert]. Bad Homburg, Germany: Fresenius Kabi AG;2001 .

42.

MacLean CH, Mojica WA, Newberry SJ, et al. Systematic review of the effects of n-3 fatty acids in inflammatory bowel disease. Am J Clin Nutr. 2005;82:611– 619.

43.

Schwartz J, Weiss ST. The relationship of dietary fish intake to level of pulmonary function in the first National Health and Nutrition Survey (NHANES I). Eur Respir J. 1994 ;7:1821– 1824.

44.

Hoff S, Seiler H, Heinrich J, et al. Allergic sensitisation and allergic rhinitis are associated with n-3 polyunsaturated fatty acids in the diet and in red blood cell membranes. Eur J Clin Nutr. 2005 ;59:1071– 1080.

45.

James MJ, Cleland LG. Dietary n-3 fatty acids and therapy for rheumatoid arthritis. Semin Arthritis Rheum. 1997 ;27:85– 97.

46.

Bates D, Cartlidge NE, French JM, et al. A double-blind controlled trial of long chain n-3 polyunsaturated fatty acids in the treatment of multiple sclerosis. J Neurol Neurosurg Psychiatry. 1989 ;52:18– 22.

47.

Horrobin DF. Omega-3 Fatty acid for schizophrenia. Am J Psychiatry. 2003;160:188– 189; author reply 189.

48.

Wander RC, Hall JA, Gradin JL, Du SH, Jewell DE. The ratio of dietary (n-6) to (n-3) fatty acids influences immune system function, eicosanoid metabolism, lipid peroxidation and vitamin E status in aged dogs. J Nutr. 1997;127:1198– 1205.

49.

Berge RK, Madsen L, Vaagenes H, Tronstad KJ, Gottlicher M, Rustan AC. In contrast with docosahexaenoic acid, eicosapentaenoic acid and hypolipidaemic derivatives decrease hepatic synthesis and secretion of triacylglycerol by decreased diacylglycerol acyltransferase activity and stimulation of fatty acid oxidation. Biochem J. 1999 ;343(Pt 1):191– 197.

50.

Siddiqui RA, Shaikh SR, Sech LA, Yount HR, Stillwell W, Zaloga GP. Omega 3-fatty acids: health benefits and cellular mechanisms of action. Mini Rev Med Chem. 2004 ;4:859– 871.

51.

Omacor [package insert]. Liberty Corner, NJ: Reliant Pharmaceuticals, Inc; 2005.

52.

American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists medical guidelines for the clinical use of dietary supplements and nutraceuticals. Endocr Pract. 2003;9:417– 470.

53.

Lu G, Windsor SL, Harris WS. Omega-3 fatty acids alter lipoprotein subfraction distributions and the in vitro conversion of very low density lipoproteins to low density lipoproteins. J Nutr Biochem. 1999;10:151– 158.

54.

Friedberg CE, Janssen MJ, Heine RJ, Grobbee DE. Fish oil and glycemic control in diabetes: a meta-analysis. Diabetes Care. 1998;21:494– 500.

55.

Farmer A, Montori V, Dinneen S, Clar C. Fish oil in people with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2001 ;(3):CD003205 .

56.

Gerbi A, Maixent JM, Ansaldi JL, et al. Fish oil supplementation prevents diabetes-induced nerve conduction velocity and neuroanatomical changes in rats. J Nutr. 1999 ;129:207– 213.

57.

Calder PC. n-3 Fatty acids, inflammation, and immunity: relevance to postsurgical and critically ill patients. Lipids. 2004 ;39:1147– 1161.

58.

Novak TE, Babcock TA, Jho DH, Helton WS, Espat NJ. NF-kappa B inhibition by omega-3 fatty acids modulates LPS-stimulated macrophage TNF-alpha transcription. Am J Physiol Lung Cell Mol Physiol. 2003;284:L84– L89.

59.

Fakhrzadeh H, Poorebrahim R, Shooshtarizadeh P, Raza M, Hosseini S. The effects of consumption of omega 3 fatty acidenriched eggs on insulin and CRP. Nutr Metab Cardiovasc Dis. 2005 ;15:329– 330.

60.

Liu T, Li G. Anti-inflammatory effects of long-chain omega 3 fatty acids: potential benefits for atrial fibrillation. Med Hypotheses. 2005;65:200– 201.

61.

Weiss G, Meyer F, Matthies B, Pross M, Koenig W, Lippert H. Immunomodulation by perioperative administration of n-3 fatty acids. Br J Nutr. 2002 ;87(Suppl 1):S89– S94.

62.

Heller AR, Fischer S, Rossel T, et al. Impact of n-3 fatty acid supplemented parenteral nutrition on haemostasis patterns after major abdominal surgery. Br J Nutr. 2002 ;87(Suppl 1):S95– S101.

63.

Heller AR, Rossler S, Litz RJ, et al. Omega-3 fatty acids improve the diagnosis-related clinical outcome. Crit Care Med. 2006 ;34:972– 979.